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Myocyte death in heart failure.
Decompensated eccentric ventricular hypertrophy characterizes the transition from compensated pressure or volume over-load hypertrophy to myocardial dysfunction and failure. Myocyte loss is the major etiologic factor of wall thinning and chamber dilation and may condition the progression of the cardiac myopathy. Myocyte death can occur by apoptosis or necrosis, but the activation of the suicide program of myocytes exceeds necrotic cell death in the pathologic heart of ischemic origin. Whether reactive fibrosis constitutes a primary event in the initiation of ventricular dysfunction or a secondary reaction to myocyte death is an important unanswered question.
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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MMR scare. In the wake of Wakefield.
Marcovitch describes the failure of an independent body to investigate research fraud because of lack of mandatory powers and long term funding,1 and, although Kennedy reassures us that the UK Research Integrity Office is still …
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,101
An Empirical Regularity in the Market for Risk and Insurance Research Output
This study provides a means for evaluating the research productivity and output concentration of risk and insurance researchers by identifying an empirical regularity in the frequency distribution of article publications in six major risk and insurance journals. Our results reveal a strong bibliometric regularity, which provides a useful tool for assessing the likelihood of multiple publications in the insurance literature. Assuming that the publishing behavior of risk and insurance researchers is stable over time, we predict that less than four percent of all publishing risk and insurance researchers will publish six or more coauthored articles in the next fifteen years, and less than two percent will publish ten or more articles.
AbstractRATIONALE: Delivery of pulmonary rehabilitation (PR) varies widely across Canada. There is a need for evidence-based quality indicators (QI) that can be used to identify variations in the q...
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Magnetic resonance imaging as a potential gold standard for infarct quantification.
Accurate diagnosis, characterization, and quantification of myocardial infarction (MI) is essential to assess the impact of therapy and to aid in predicting prognosis of patients with ischemic heart disease. Delayed contrast-enhanced magnetic resonance (DE-MR) imaging has the potential of being the gold standard for quantification of MI. It has also been useful in correlating electrocardiography abnormalities with the location and transmurality of infarction. The focus of this review is to address the strengths and limitations of DE-MR imaging in the detection and quantification of MI for clinicians and investigators in the field of electrocardiology. The biological rationale and technical background for detecting MI by DE-MR imaging were reviewed as well as the different approaches for quantification of the DE-MR images, exemplified by patient cases.
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,103
“It Was Not Me That Was Sick, It Was the Building”: Rhetorical Identity Management Strategies in the Context of Observed or Suspected Indoor Air Problems in Workplaces
Suffering from a contested illness poses a serious threat to one’s identity. We analyzed the rhetorical identity management strategies respondents used when depicting their health problems and lives in the context of observed or suspected indoor air (IA) problems in the workplace. The data consisted of essays collected by the Finnish Literature Society. We used discourse-oriented methods to interpret a variety of language uses in the construction of identity strategies. Six strategies were identified: respondents described themselves as normal and good citizens with strong characters, and as IA sufferers who received acknowledge from others, offered positive meanings to their in-group, and demanded recognition. These identity strategies located on two continua: (a) individual- and collective-level strategies and (b) dissolved and emphasized (sub)category boundaries. The practical conclusion is that professionals should be aware of these complex coping strategies when aiming to interact effectively with pe...
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,104
Statistical methods for lifetime verification and failure rate analysis
In the powertrain of a heavy vehicle, several sensors and electronic control units are mounted. These components need to have a long lifetime and high reliability. The quality is secured by robust ...
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,105
From symbolic surge to closing courts: The transformation of international criminal justice and its professional practices☆
The creation of the International Criminal Tribunal for the former Yugoslavia (ICTY) in 1993 began a striking proliferation of international criminal tribunals. Now, however, in the wake of this phase of international institution building that followed from the surge of symbolic support for an emergent legal field, international criminal justice is characterized by closing courts and a declining number of professional positions. Developing a framework inspired by structural sociology, this article will analyze the professional practices of the agents that created this field and are now affected by the closure of the courts. These practices constitute a professional response to larger geopolitical transformations in which international criminal justice is no longer politically in vogue. As the article will show, geopolitical structures alone are not wholly definitive for developments of international law: professional agency is actively reshaping the field of international criminal justice.
BACKGROUND/OBJECTIVE ::: The goal of this update in hospice and palliative care is to summarize and critique research published between January 1 and December 31, 2014 that has a high potential for impact on clinical practice. ::: ::: ::: DESIGN ::: To identify articles we hand searched 22 leading journals, the Cochrane Database of Systematic Reviews, and Fast Article Critical Summaries for Clinicians in Palliative Care. We also performed a PubMed keyword search using the terms "hospice" and "palliative care." ::: ::: ::: MEASUREMENTS ::: We ranked candidate articles based on study quality, appeal to a breadth of palliative care clinicians, and potential for impact on clinical practice. ::: ::: ::: RESULTS ::: In this manuscript we have summarized the findings of eight articles with the highest ratings and make recommendations for clinical practice based on the strength of the resulting evidence.
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Antenatal ultrasound screening using check list before delivery for predicting a non-reassuring fetal status during labor.
AbstractObjective: To clarify the effectiveness of ultrasound screening at 36 weeks’ gestation for predicting a non-reassuring fetal status during labor (NRFS).Methods: A prospective cohort study was conducted between 2012 and 2013. Ultrasound evaluations of umbilical cord and placental abnormalities and fetal biometry were performed among pregnant females at 36 weeks’ gestation. Patients who underwent ultrasound screening were divided into three risk level groups according to their abnormalities. After delivery, NRFS and emergency Cesarean section (eCS) rate were compared between the risk groups.Results: A total of 790 subjects were analyzed. Elective Cesarean section was performed in 111 cases. Consequently, 34 cases in the high-risk group, 45 cases in the middle-risk group and 600 cases in the low-risk group were analyzed. NRFS was diagnosed in 17.6%* of the patients in the high-risk group, 11.1%* of the patients in the middle-risk group and 5.6% of the patient’s in the low-risk group. eCS was performe...
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Medical emergency team admittance to intensive care versus conventional admittance: characteristics and outcome
The purpose of the medical emergency team (MET) is to find and treat deteriorating ward patients. Suboptimal care and delays on general wards before admission to intensive care have an effect on mortality [1] and patients admitted from general wards have a worse outcome than from the operating room (OR) or emergency department (ED) [2]. MET patients have a high rate of ICU admissions but whether their outcome differs from other patients admitted from the wards has not been studied before. We evaluated characteristics and outcome of ICU patients based on mode of admittance, via the MET versus the conventional way.
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Cooperation, Not Competition, in the Health Professions
Medical care has become a complex science that involves not only physicians but also many other professionally trained people. Some health professions such as dentistry, nursing, and pharmacy, are licensed to perform specific services and have well defined roles in the health care system. Many other recognized groups also work as a team with the physician and perform highly technical and skilled tasks that result in high-quality and efficient care for the patient. Unfortunately, persons with limited training and licensed to perform limited procedures may sometimes try to substitute for a fully trained medical specialist. Comprehensive schooling in the biological sciences, followed by intensive training and supervision in the clinical sciences, makes the physician the best equipped person to deal with illness in all its forms. Therefore, the AMA believes that the diagnosis and selection of treatment for any disease is best performed by a physician. When each professional group
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,109
An Empirical Study on Risk Assessment and Household Characteristics in Thailand
This study identifies the type of risks experienced by rural households and examines their relationships with the socio-economic characteristics of the households in rural Pattani province, Thailand. A multi-stage sampling technique is used to select 600 households, which are divided into 12 districts in Pattani province. Structured questionnaire is developed to collect information from the respondents. Data is analyzed using descriptive statistics and Logistic regression model. Evidences from descriptive analysis indicate that the major risks faced by the households in the rural area of Pattani province include job loss, flooding and household member sick or crippled. Furthermore, the results of logistic regression suggest that gender of household heads, household size and location of houses significantly influence exposure to risks, whereas education level of household heads is found to be insignificant in affecting exposure to risks by the rural households.
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,110
Workplace Health and Safety: International Perspectives on Worker Representation
In many countries the regulation of health and safety at work underwent a new turn in the 1970s and 80s. This book brings together research that reviews the coverage and effectiveness of the consequent arrangements for worker representation on health and safety that exist in the EU generally, within this specifically in the UK, Spain, France and Sweden, and beyond this in Australia, Canada and the Baltic States. It examines the effectiveness of these arrangements in different countries and how they operate in different sectors and in organisational of different size. It also considers in some detail the conditions that support or constrain these arrangements in different countries, which are generally found wanting, and especially the impact upon them of major political and economic changes in recent years.
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,111
The Stress of Residency: A Review of the Literature
• A review of empiric studies of the stresses of residency training and descriptions of intervention programs and mental health resource surveys published since 1980 indicated that inadequate sleep and fatigue are major stressors for residents, but they are only part of a more complex situation influenced by time demands, social support, and maturational factors. Other important stressful aspects of training appear to be those that interfere with social support. Increased anger, not depression, is emerging as the predominant mood change during residency, but the effects of any mood change on patient care have not been studied. Despite growing evidence of the need for change in training programs, especially attention to the affiliative needs of residents, few intervention programs have been reported. (Arch Intern Med1988;148:1428-1435)
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Bias in alternative medicine is still rife but is diminishing.
EDITOR—In 1995, journals of alternative medicine published virtually no studies with negative results, which suggests that the literature was far from objective.1 To determine whether the situation has changed we analysed last year's volumes of three journals originally evaluated and compared our results with those …
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Say Dr No to shifting from falls to osteoporosis
As clinicians, we agree with shifting the focus in fracture prevention from osteoporosis to falls,1 and consider that loss of bone mineral is a risk factor rather than a disease. ::: ::: This shift is seriously challenged in information campaigns targeted at the public. In the timeless women campaign promoted by the …
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Project 3000 by 2000 -- Racial and Ethnic Diversity in U.S. Medical Schools
Only 30 years ago, 93 percent of medical students in the United States were men, and 97 percent were non-Hispanic whites. Today, the profile of U.S. medical students has changed dramatically. Forty percent of the 67,000 students in the nation's 126 allopathic medical schools are women, and 31 percent belong to racial or ethnic minority groups. Producing a physician work force that draws on the knowledge and skills of people from all segments of our society has long been a key element of this country's health-manpower policies1 as well as those of the Association of American Medical Colleges (AAMC)2. . . .
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Lose a piece of the rock: physician liability for failing to notify private third parties of HIV risk.
Since 1851, individuals have successfully sued physicians for injuries sustained through infectious disease transmission from the physicians' patients. Liability to third parties must be considered in the management of patients with infectious diseases. Because of this potential liability, physicians with human immunodeficiency virus-infected patients must consider notifying identified third parties of their respective risks of infection.
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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Hinder, Henry Vincent Critchley - Biographical entry - Index to the AMA archive
Hinder, Henry Vincent Critchley - Biographical entry - Index to the AMA archive - NAME is a biographical, bibliographical and archival database of SUBJECT with links to related articles and images. ADD MORE DESCRIPTION AS REQUIRED
From April next year the NHS in England is to have a new measure of hospitals’ performance, a regular report on the numbers of patients dying in hospital in each trust. ::: ::: Called the summary hospital level mortality indicator (SHMI), the measure draws on experience gathered by companies such as Dr Foster and Caspe Healthcare Knowledge Systems (CHKS) in comparing hospitals by how many patients die. The Dr Foster measure, the hospital standardised mortality ratio, originally developed by Brian Jarman at Imperial College London, forms an important part of Dr Foster’s annual Good Hospital Guide ( BMJ 2009;339:b5242, doi:10.1136/bmj.b5242). ::: ::: Discrepancies between the ratings given by Dr Foster and those derived from inspections by the Care Quality Commission (Dr Foster rated Mid Staffordshire NHS Foundation Trust among its “most improved” at a time when it was branded “appalling” …
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27,117
The High Cost of Low-Frequency Events
Abstract We conducted a one-year prospective survey to identify adverse outcomes due to error during care in the field of general surgery. We identified 36 such cases among 5612 surgical admissions to the Peter Bent Brigham Hospital, but in 23 cases the initiating mishap had occurred in another hospital before transfer. In two thirds of the cases the mishap was due to an error of commission: an unnecessary, defective, or inappropriate operative procedure. Twenty of these patients died in the hospital, and in 11 death was directly attributable to the error. Five of the 16 survivors left the hospital with serious physical impairment. A satisfactory outcome was achieved in only 11 cases (31 per cent). The average hospital stay was 42 days, with the duration ranging from one to 325 days; the total cost for the 36 patients was $1,732,432. We suggest that all hospitals develop comprehensive methods to identify and prevent these costly and unnecessary events. (N Engl J Med. 1981; 304:634–7.)
Background: Cardiac resynchronization therapy (CRT) has significant nonresponse rates. We assessed whether machine learning (ML) could predict CRT response beyond current guidelines. Methods: We an...
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US analyst awards NHS top marks
A US health analyst says the NHS is close to becoming the best healthcare system in the world.
Leading British shares managed to finish the day in positive territory as falls in New York were offset as blue chip insurers clawed back losses in the wake of last week's probe in the US.
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Care Quality Commission: 1,200 practices may not be providing safe care . Watchdog has categorised 864 surgeries in England as of 'highest concern' Failings include misdiagnosis, inadequate care and appointments delays .
The Care Quality Commission has identified 1,200 GP practices in England which may not be providing safe care (file picture, posed by model) One in six GP surgeries could be putting tens of thousands of patients at risk, according to the NHS watchdog. The Care Quality Commission has identified 1,200 practices in England which may not be providing safe care, including 864 it has categorised as of ‘highest concern’. Failings include misdiagnosing cancer, inadequate care of the elderly and making patients wait too long for appointments. CQC chief inspector Professor Steve Field said most surgeries were managing to provide good care despite high demand, but added: ‘We’re sadly finding some very poor practices. ‘These typically are chaotic, have very poor leadership and a lack of learning culture. They also have a poor skill mix – some don’t have any nurses. 'Patients could be at risk by simple things such as by prescribing out-of-date medicines and vaccines. ’ The poorly performing surgeries will be prioritised for vigorous, day-long spot checks over the next two years, which could lead to the worst being closed down. Preliminary assessments of nearly all 8,000 surgeries in England were carried out as part of a new Ofsted-style ratings system based on 38 categories covering safety and basic care. The surgeries have been placed into one of six categories ranging from ‘highest concern’ to ‘lowest concern’. Patients can go to the CQC website to see how their surgery is performing in comparison with neighbouring practices and how they rate according to national standards. Criteria include detection rates for cancer and dementia, opening hours, giving patients the flu jab and the numbers of frail, elderly patients ending up in A&E because they are not properly looked after. The consequences for patients of any one of these failings can be catastrophic. Scroll down for video . Several practices have been identified as having high rates of patients whose cancers are only detected in A&E – because the GP failed to diagnose it in previous appointments. By this stage, the cancer has often spread to other organs and may have become untreatable. The CQC also identified 217 surgeries which could be putting young women at risk by not offering them screening for cervical cancer. A further 228 are making patients wait far too long to see a doctor or nurse. The surgeries were given a score for each of the 38 indicators. These were added together to give an overall score, with the final result determining which of the six bands they were placed in. There were 864 surgeries in band 1 (‘highest concern’) and 332 in band 2. By comparison there were 3,979 surgeries in band 6 (‘lowest concern’). Failings identified by the health watchdog include misdiagnosing cancer, inadequate care of the elderly and making patients wait too long for appointments. It has categorised 864 surgeries as of ‘highest concern’ Prof Field, who is also a GP in Edgbaston, Birmingham, added: ‘GPs are under a lot of pressure but they are demonstrating that even in deprived areas they can provide fantastic care. I do have concerns about access to practices. But we need to do more to encourage people to take better care of themselves and to make better use of pharmacies.’ Prof Field said he expected that only about 160 practices (two per cent) would be put in special measures, where officials from NHS England would step in and instruct them to make urgent improvements. If these are not carried out, the surgeries could be closed down and patients taken on by others nearby. Roger Goss, of Patient Concern, said: ‘The patients at these high-risk practices should be told so they have the option of going elsewhere. ‘That is part of the NHS’s duty of candour, its obligation to be honest and open. Over the past 18 months there has been a rise in the number of patients contacting us with concerns – most notably not being able to get an appointment, which is fundamental.’ GPs are being warned not to close early over the festive period. NHS officials have written to surgeries over concerns they will close their doors mid-afternoon on Christmas Eve and New Year’s Eve when it is traditionally quiet. Last year NHS England found that one in 20 GPs had shut by 4pm and left patients in the hands of out-of-hours firms. A letter sent to practices last week – obtained by Pulse magazine – reminds them that Christmas Eve and New Year’s Eve are ‘normal working days’. Katherine Murphy, chief executive of the Patients’ Association, added: ‘The NHS must be open and transparent and patients should be provided with as much information as possible about their GP practice. ‘We know that if patients are provided with information, they are able to make more meaningful choices about their healthcare. The more transparent and honest a GP surgery and its staff are, the more confidence the public will have in the system.’ Patients can check their surgery’s rating by going to www.cqc.org.uk/content/our-intelligent-monitoring-gp-practices and inserting their postcode. However, the website has already been criticised by some patients as being riddled with jargon and difficult to interpret. Joyce Robins, co-director of Patient Concern, said: ‘There are just too many patients and not enough doctors. Many are just stretched to the limit and that is why so many patients are ending up in A&E.’ Dr Maureen Baker, chairman of the Royal College of General Practitioners, added: ‘Many practices are struggling to meet quality standards due to factors beyond their control, such as lack of funding, significant increases in patient consultations and difficulties in trying to recruit sufficient GPs to meet patients’ needs.’ Mike Bewick, deputy medical director at NHS England, said: ‘We’re pleased this report shows that despite the increased pressure on GPs there are so many good and outstanding practices across the country.’
By . Sara Malm . PUBLISHED: . 06:21 EST, 18 October 2012 . | . UPDATED: . 09:24 EST, 18 October 2012 . The proportion of GCSE students scoring at least five Cs, including in English and maths, has fallen for the first time, official figures show. The drop is said to be down to fewer English entries from private schools, but the harsh grading of this June's GCSE English exam is likely to have played a part. The news comes as more than 45,000 pupils prepare to resit their English GCSE exams in November. Tough exams: The number students achieving at least five A*-C GCSEs has dropped for the first time . The number of students in England who achieved five A*-C grades, including the two key subjects, is down almost half a per cent from 2011. This year 58.6 per cent of pupils in England achieved five A*-C grades, according to Government data. Thousands of pupils received lower than expected results in GCSE English in the summer after grade boundaries were raised between the January and June exams. Not improving: The proportion of students achieving at least five C's is down by half a per cent since last year . A report compiled by the Association . of School and College Leaders published last week blames the summer exam . for ‘enormous and unprecedented’ fluctuations in results. The number of sixth-formers awarded with at least three top A-level grades has fallen for the first time in four years. One in eight students at all English schools and colleges achieved at least three A*s or As in their exams, down from 13.1 per cent in 2011, according to Government statistics. The Department for Education data also shows that private school students are three times more likely to score top grades than their state-educated peers. The proportion of private school pupils achieving three or more A*-A grades dwarfed state schools with 30.6 per cent compared to 10.7 per cent and 7.9 per cent of those at further education colleges. Overall, 91.7 per cent of all students achieved two or more A-levels at grade E or higher, down from 94.1 per cent in 2011. And more boys than girls achieved three or more A-levels at grade A or higher (12.7 per cent compared with 12.2 per cent). One in four secondaries saw at least a 10 . per cent drop in the proportion of pupils securing a C and a fifth . suffered at least a 15 per cent fall. The report concludes sudden changes in . pass marks between January and June’s English GCSE sittings led to . large swings in results. In a . letter to the Commons education select committee, ASCL’s secretary . Brian Lightman said pupils had suffered a ‘gross injustice’. He renewed his demands for the English exams to be re-graded and for an independent inquiry. A . document attached to the letter shows one in four out of 3,000 state . secondary schools, some 750, saw large drops in their results. However, the official Government figures show a rise in pupils entered for all the subjects in the Government’s English Baccalaureate, with 25 per cent and 18.1 per cent achieving the EBacc. The EBacc qualifications is awarded to pupils who score a C grade or higher in English, maths, science, history or geography, and a language. This year’s EBacc results are up on last year, when 23.8 per cent entered and 17.6 per cent achieved it.
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Major incident reportedly declared at Colchester Hospital following inspection . Unannounced visit said to focus on A&E and emergency assessment unit . Care Quality Commission reportedly raised 'safety concerns' after visit . Hospital chief executive says 'it's a difficult time for the trust' Patients reportedly told only to go to A&E in 'serious or life threatening condition' In July CQC rated hospital as 'requires improvement'
A major incident was reportedly declared at a hospital in Essex over concerns raised by the health regulator following a surprise inspection. The Care Quality Commission (CQC) apparently inspected Colchester Hospital's accident and emergency department and emergency assessment unit on Wednesday and told the trust of 'safeguarding concerns'. Following the unannounced visit the watchdog found patients being inappropriately restrained, sedated without consent and do not resuscitate signs being ignored, the Guardian reported. A major incident has reportedly been declared at Colchester Hospital over 'safeguarding concerns' raised by the Care Quality Commission . Professor Mike Richards, the CQC's chief inspector, told the newspaper that they had carried out the unannounced inspection following 'concerns.' 'Following the inspection, we gave feedback to the trust about our safeguarding concerns so that it could take appropriate action to ensure the safety and wellbeing of its patients,' he told the Guardian. A spokesman for the hospital trust said it could not responded to the specific allegations made by the Guardian because they had not seen the CQC's full report . In July the CQC gave the hospital an overall rating of 'requires improvement'. Peter Wilson, acting chairman of Colchester Hospital University NHS Foundation Trust told the Guardian it was facing 'unprecedented demand' on its services. Professor Mike Richards, the CQC's chief executive, said they carried out the surprise inspection in response to concerns . The trust's interim chief executive, Dr Lucy Moore, said it was 'a difficult time for the trust'. She said: 'The Care Quality Commission raised a small number of safeguarding concerns when its team gave immediate feedback at the end of the inspection on Wednesday. 'The Trust takes safeguarding extremely seriously and is now investigating to find out whether our policies had been followed appropriately.' In the wake of the announcement more staff were said to have been drafted into the hospital, non urgent surgery rescheduled and where safe to do so patients discharged. Mr Wilson said they were disappointed that the CQC felt the situation at the hospital had not improved, and confirmed it had declared a major incident to review various aspects of service at the hospital. The trust said the major incident is likely to last a week, and appealed to members of the public only to visit the accident and emergency department if they have a 'serious or life-threatening condition'. The CQC said it will publish its latest report on the hospital 'in due course', and added that it will carry out further inspections at the trust. The major incident was declared at the hospital the day after Health Secretary, Jeremy Hunt, announced that the NHS was to receive an additional £300 million to help them cope this winter.
By . Jenny Hope . PUBLISHED: . 19:11 EST, 19 May 2013 . | . UPDATED: . 19:11 EST, 19 May 2013 . Some High Street pharmacies are giving customers poor quality and even dangerous advice about their medicines, claims a new survey. Almost three-quarters of pharmacists did not warn about the hazards of mixing prescription drugs with a heartburn remedy. The survey showed pharmacies in big chains and supermarkets give a better service than High Street independents. Almost three-quarters of pharmacists did not warn about the hazards of mixing prescription drugs with a heartburn remedy . Which? sent trained undercover mystery shoppers into 122 pharmacies across the UK and an expert panel of three experienced pharmacists rated the advice they received. It found some pharmacies are giving out advice without asking the right questions, with potentially serious consequences for their customers’ health. Advice from pharmacies was given an unsatisfactory rating in around four in ten (43 per cent) visits overall, almost 10 per cent higher than a previous survey in 2008. Which? sent mystery shoppers into 122 pharmacies . There was a marked difference in the quality of advice given from different types of pharmacies.Independent pharmacies gave unsatisfactory advice more than half of the time compared to a third of the time for the leading chains and supermarkets – with no change on the last survey. In one scenario, a customer taking the drug warfarin to prevent blood clots requested a heartburn remedy called Pantoloc Control . Pharmacies should have asked basic but important questions about existing prescription medication because it can interfere with warfarin levels in the blood, leading to bleeding problems and even hospitalisation. But the advice was rated unsatisfactory in 71 per cent of the visits – the worst finding. On visits where counter assistants dealt with mystery shoppers without consulting a pharmacist, two thirds gave poor advice compared with one in four when involving a pharmacist. Which? executive director, Richard Lloyd, said ‘Too many pharmacies are still failing their customers, with some potentially serious consequences. ‘We’re pleased that the Royal Pharmaceutical Society and the General Pharmaceutical Council recognise our concerns and are taking steps to tackle these issues. ‘Consumers should be able to trust the advice they receive from any pharmacy they visit.’ In a separate snapshot study, Which? also discovered that two-thirds of pharmacies did not follow the professional guidance by failing to explain there is no scientific evidence that homeopathy works. Martin Astbury, president of the Royal Pharmaceutical Society, said ‘The pharmacists I know won’t recognise their own practice in the results Which? have shared with us. Which? said that chains and supermarkets performed better in their study . ‘The RPS wants to understand the underlying reasons for the differences highlighted by this report and how to improve consistency of the advice the public receive when they purchase medicines from a pharmacy. There are some areas which require improvement. ‘We have commissioned the University of Nottingham to look internationally for best practice on the sale of medicines through pharmacy.  We will use the outcomes of this to make recommendations as to how pharmacists’ skills can be used most effectively in Great Britain to ensure the public get the best possible advice.’
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CNN asks 1,023 adult Americans about their trust in government . Federal government rates the lowest at 23%; local government rates 52% . Suburbanites rate highest level of trust with local government .
Washington (CNN) -- When it comes to the trust Americans put in government, a new national poll indicates it's a matter of location, location, location. According to a CNN/Opinion Research Corporation survey released Tuesday, only 26 percent of the public trusts the federal government most of the time or always. A third of the people questioned in the poll say they trust their state government most or all of the time. But that number surges to 52 percent for those who say they trust local government most or all of the time. "How broken is government in the mind of most Americans? It depends on how close that government is to them," said CNN Polling Director Keating Holland. "Suburbanites are happiest with their local government, with 55 percent of them saying they trust their local government all or most of the time. That same figure for city folk is 50 percent, and for rural Americans, it is 47 percent." Democrats may want to take pause over the 26-percent trust figure. The number is as low as it was in 1994 when the GOP swept the midterm elections and won control of Congress. According to CNN poll numbers released Sunday, Americans overwhelmingly think that the government in this country is broken, but the public overwhelmingly holds out hope that what's broken can be fixed. The CNN/Opinion Research Corporation poll was conducted February 12-15, with 1,023 adult Americans questioned by telephone. The survey's sampling error is plus or minus 3 percentage points for the overall survey. CNN Deputy Political Director Paul Steinhauser contributed to this report.
Doctors and nurses have been warned by David Cameron that ‘standards are not good enough' after one in three patients said they would not recommend their local hospital to family and friends. The Prime Minister said the new test would give a single measure for the quality of NHS care across the country. The first set of results revealed patients in 36 hospital wards across England would not recommend them to loved ones. Care: David Cameron said the new Friends and Family Test would expose areas where healthcare is poor . The first wave of the ‘Friends and Family’ test also saw one English A&E department get a ‘negative score’ - at Chase Farm Hospital, part of the Barnet and Chase Farm Hospital NHS Trust, in north London. Patients are simply asked whether they would recommend the hospital where they were treated to their loved ones. Each hospital is then given a score based on patient satisfaction levels - if every single patient says they would be ‘extremely likely’ to recommend the service the ward would receive a score of 100, if every single patient said they would be ‘neither unlikely nor likely’, ‘unlikely’ or ‘extremely unlikely’ to recommend the service, the trust receives a score of minus 100. Mr Cameron, who is on holiday in Portugal, said: ‘I am determined to give patients a far greater voice within the NHS as a way of highlighting the best and worst of care within our hospitals. Health minister Anna Soubry claims the Mid-Staffs scandal could have been prevented if the test had been in place . ‘With the 'Friends and Family' test, we now have a single measure that looks at the quality of care across the country. ‘I want the NHS to put patient satisfaction at the heart of what they do and expect action to be taken at hospitals where patients and staff say standards are not good enough.’ Health minister Anna Soubry suggested that the test could have highlighted earlier the Mid-Staffs NHS scandal, in which up to 1,200 people died needdessly as a result of poor care. She told BBC News: 'We are clearing away some of the smokescreen, some of the systems that prevented people from knowing what's actually happening in their hospitals. 'People in Stafford had known what was happening in their hospital had they been listend to then hopefully some of those people that died wouldn't have died if people had taken proper action considerably sooner.' More than 400,000 NHS hospital inpatients or A&E attendees completed the test during April, May and June. NHS England will now publish monthly updates to ensure patients can regularly give feedback about the care they receive. By the end of next year, NHS England hopes to roll the test out to include GP practices, community services and mental health services. All other services will be included by April 2015. Tim Kelsey, NHS England's national director for patients and information, said: ‘This is the boldest move yet to promote real openness in the NHS and to concentrate our focus on improvement in care. ‘At the heart of Robert Francis's report into the tragedy at Stafford hospital was one basic message: to ensure the NHS delivers high quality care for all, we need transparency of the patient and carer experience. It is the absence of this transparency that often allows poor care to go undetected.’ But Jocelyn Cornwell, director of new patient charity the Point of Care Foundation, said the data are ‘not meaningful’. She said: ‘The way in which the data for the friends and family test is collected varies widely and is open to gaming. ‘People who respond are not part of a random sample, but are self-selecting or, worse, are encouraged to respond by staff. ‘Clearly there is a temptation for staff to encourage responses from patients who they feel will respond positively, especially as a positive result is linked to financial reward.’ Under the new Friends and Family test, patients are asked if they would recommend their ward to their loved ones. The number who give a negative rating is then deducted from the number who give a positive response. This figure is then used to produce a Friends and Family Test Score. NHS England said that in the first set of results a total of 36 out of 4,500 wards had a negative rating. However, some of the hospitals point out that the score can be based on just one rating from a patient.
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BRIEF-S&P says Papua New Guinea ratings affirmed at 'B+/B'; outlook remains negative
April 6 (Reuters) - * S&P - Papua New Guinea ratings affirmed at 'B+/B'; outlook remains negative * S&P - Papua New Guinea outlook remains negative, reflecting the risk that external and fiscal imbalances remain large for an extended time * S&P-Papua New Guinea ratings reflect constraints inherent in lower middle-income economy dependent on extractive industries, served by weak institutions * S&P - in the near term, low global energy prices continue to weigh on the Papua New Guinea economy, export receipts, and government revenues Source text - bit.ly/2p3qZLY
(CBS Detroit) – A nationwide hospital safety analysis has found that 23 hospitals in Michigan received an “A” grade for preventing medical errors, accidents, injuries and infections, which collectively are the third leading cause of death in America. On the flip side, 5 hospitals received a “D” or worse, including around Metro Detroit, Pontiac and Lansing. Michigan is one of only 10 states to have a hospital with an “F” grade: Hurley Medical Center in Flint. The Leapfrog Group released it’s bi-yearly hospital safety grades on Tuesday, finding that hospitals overall have improved in reducing the number of avoidable deaths. The group assessed roughly 2,500 hospitals. Of those, 30 percent earned an “A,” 28 percent earned a “B,” 35 percent a “C,” 6 percent a “D” and 1 percent an “F.” “The national numbers on death and harm in hospitals have alarmed us for decades. What we see in the new round of Safety Grades are signs of many hospitals making significant improvements in their patient safety record,” Leah Binder, president and CEO of Leapfrog, said in a release. The assessment system assigns school-style letter grades to general acute-care hospitals. The hope is to determine a patient’s risk of further injury or infection if they visit a certain hospital. Click here to continue.
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Tribunals urged after study finds 'unacceptable' variations in healthcare access
Local health bodies should have to face a tribunal board if they have " overly restrictive commissioning policies", a new report suggests. The recommendation comes after researchers found that there is "unacceptable" variation in access to care for patients across England. After examining data concerning each of the 209 clinical commissioning groups (CCGs) across England in relation to certain treatments, researchers highlighted a number of variations in access to care and waiting times including: :: Less than one patient (0.173) per 100,000 population in Southampton was referred for a computed tomography colonoscopy - a diagnostic tool for bowel cancer - compared with nearly 59 patients per 100,000 in Fareham and Gosport. :: The authors found vast differences in the rate of stroke patients being admitted to a specialist unit with four hours of arrival at hospital - from 84.5% in Hillingdon to 21% in Wyre Forest. :: In some regions, there were 207 hip replacements being performed for every 100,000 people living in that area, but in others the rate was just 54 per 100,000 population. :: In urology and ophthalmology, the worst performing CCGs only hit the 18 referral to treatment time target about 80% of the time, the authors said. This means that one in every five patients from those regions get treatment in the required time frame. The authors said that NHS England should establish a tribunal board to consider whether individual CCGs have overly restrictive commissioning policies which are contrary to national guidelines. The report, by the Medical Technology Group (MTG) - a collaboration of pharmaceutical companies, patient groups, research charities and medical device manufacturers - also examined whether CCGs were falling behind on waiting times for patients. After examining referral to treatment times, researcher s created league tables for CCGs for waiting times for a number of medical treatments such as pacemakers, cataract surgery, and hip and knee replacements. They found that seven of the 10 "worst performers" at hitting the 18-week referral- to-treatment time target were actually rated as good or outstanding by NHS England. The authors said: "CCGs currently go through an Ofsted-style assessment programme. "Each CCG is given one of four ratings: inadequate, requires improvement, good, or outstanding. "The MTG does not believe that these ratings are sufficient to give patients an overview of how their CCG is performing. "The key factors for patients are gaining access to treatment and successful, quick recoveries. It is not clear from the current rating system that there is sufficient weighting given to these aspects of care." The authors suggested that p erformance against the 18-week wait should have a stronger impact on each CCGs' 'Headline Rating'. Barbara Harpham, MTG chairwoman, said: "Delivering high-quality healthcare, no matter where you live, is one of the fundamental principles of the NHS. But budget cuts and rationing is having a huge impact on the service patients receive, and the outcome they can expect. "There is an unprecedented strain on the health service and patients are not being given equal access to the treatment - and most importantly - the technology they need." An NHS England spokeswoman said: "Although this report by companies seeking to sell products to the NHS is largely a rehash of old and previously published data, the NHS RightCare programme is helping local areas identify which treatment differences are linked to local need, and which aren't. "But as the Academy of Medical Royal Colleges has pointed out through its Choosing Wisely initiative, over-treatment is often as much of an issue as under-treatment."
Here are some of the top stories in healthcare, telemedicine, and mobile health that our sister site mHealthWatch has been monitoring this past week. AdvancedMD Touts New Doctor Reputation Tool MHW learned this morning that AdvancedMD — a pioneer in integrated provider and patient workflow for independent physician practices — has just launched AdvancedReputation. NewYork-Presbyterian Named New York’s Top Hospital By U.S. News & World Report This morning, NewYork-Presbyterian Hospital — one of the largest and most comprehensive academic medical centers in the nation — is ranked New York’s No. 1 hospital for the 17th consecutive year (and No. 8 in the United States). Reliq Health Technologies Touts Go-Live with Paz Home Health Reliq Health Technologies Inc. — a developer of mobile health and telemedicine solutions for the Community-Based Healthcare market — has just announced the go-live of its remote patient monitoring and telemedicine solution with Paz Home Health LLC in Texas. eWellness, Total Release Physical Therapy Ink Integration and Marketing Agreement MHW learned Wednesday that eWellness Healthcare Corporation — a provider of telehealth solutions for clinical practices — has forged a new partnership with Total Motion Release Seminars (TMR). CEO Departs ATA After 24 Years After nearly a quarter-century of service, the longtime Chief Executive Officer of the American Telemedicine Association, Jon Linkous, announced that he is stepping down. Want to get the latest mHealthWatch news and insight delivered straight to your inbox every morning? If so, sign up for our free newsletter today.
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Nine out of 10 children survive blood cancer
Nine out of ten children in Norway, who are affected by leukaemia survive the disease, according to a major international survey. The Norwegian Cancer Register has participated in the survey, which shows that only Germany, Austria and Canada are getting better results, than Norway, according to NRK. Eva Widing from the National Quality Register for Childhood Cancer is not surprised by the figures. “We are at the in the top slice of the world because we have been good at changing the treatment according to the new researches.” Through Nordic cooperation, all blood-cancer-affected children receive equal treatment. The Nordic region has been a leader in leukemic treatment for children since the 1980s, she says. Every year around 140 Norwegian children under 15 years get cancer, a number that has been stable for a long time. In the 1970s, half of the affected children with cancer died. Today, 8 out of 10 survive. © NTB Scanpix / Norway Today
Ochsner Medical Center – Baton Rouge (OMCBR) is celebrating a familiar commendation. OMCBR was awarded an ‘A’ for its efforts in protecting patients from harm and meeting the highest safety standards in the U.S. RELATED: Learn more about Ochsner Medical Center - Baton Rouge It’s an award the Ochsner Medical Center has earned six consecutive times before from the Leapfrog Group, a Washington D.C.-based organization aiming to improve health care quality and safety for consumers and purchasers. OMCBR was one of 750 hospitals awarded an ‘A’ by the Leapfrog Group when they released the new Leapfrog Hospital Safety Grades. The Safety Grade assigns an A, B, C, D or F grade to hospitals across the country based on their performance in preventing medical errors, infections and other harms among patients in their care. “All of our healthcare providers and staff are focused on improving health outcomes,” said OMCBR CEO Eric McMillen. “Ochsner believes in always putting patients first, which is why our quality and safety continue to be among the best in the country.” OMCBR has been named a Distinguished Hospital for Clinical Excellence by Healthgrades and earned the Healthgrades Patient Safety Excellence Award each year since 2015. It is the only hospital in the Capital Region ranked among IBM Watson Health’s 100 Top Hospitals. “This is the only national rating of how well hospitals protect patients from preventable harm and death, such as medical errors, infections, and injuries,” said Leah Binder, president and CEO of The Leapfrog Group. “Receiving an ‘A’ Safety Grade means a hospital is among the best in the country for preventing these terrible problems and putting their patients first, 24 hours a day.” For more information or to schedule an appointment with an Ochsner practitioner, call 225-761-5200. Copyright 2018 WAFB. All rights reserved.
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Study compared death rates in the two countries from 2004 to 2010 . A third more British patients died than in Sweden within a month of attack . Research by University College London said Brits received inferior care . Professor Harry Hemingway: 'Our findings are a cause for concern'
Care: A study has found a third more heart attack patients died a month later in Britain than Sweden . More than 11,000 deaths of heart attack patients could have been avoided if British care was as good as Sweden's, a study has claimed. A third more Britons than Swedes died within a month of having a heart attack, according to the research on half a million patients. Scientists from University College London examined death rates in the two countries between 2004 and 2010. They said a key reason for the striking difference between the two was that British patients are not receiving the best possible treatment. Professor Harry Hemingway, from University College London, said: 'Our findings are a cause for concern. 'The uptake and use of new technologies and effective treatments recommended in guidelines has been far quicker in Sweden. This has contributed to large differences in the management and outcomes of patients.' In total, the team analysed records relating to 391,077 patients from 242 hospitals in the UK and 119,786 from 86 hospitals in Sweden. They found that 30 days after a heart attack, 10.5 per cent of patients discharged from hospital were dead in the UK compared with 7.6 per cent in Sweden. At the start of the study the difference was even more stark, with almost 50 per cent more patients dying in the UK than in Sweden. But by 2010, the gap had narrowed to 20 per cent. Taking into account age and sex differences, heart attack severity, risk factors including rates of smoking and diabetes, and other influences, the scientists estimated that over the study period 11,263 British lives could have been saved by matching Swedish standards. Co-author Dr Tomas Jernberg, from the Karolinska University Hospital in Sweden, said: 'Our findings suggest that failure to get the best treatment is one likely reason why short-term survival for heart attack patients is lower in the UK.' Concerning: The study, which looked at half a million patient records, said surgery and drugs like beta blockers were offered earlier and more often Sweden than in Britain, and processes must be improved . The study found drugs such as beta . blockers were less likely to be prescribed to British patients and surgery on constructed coronary arteries were used earlier and more often in Sweden - 59 per cent of the time compared with 22 per cent in the UK. The research was published in the medical journal The Lancet. Dr Mike Knapton, associate medical director at the British Heart Foundation, said: 'The reasons behind the differing survival rates are complex, but one explanation could be the speed with which the two countries adopted primary angioplasty as an emergency treatment. 'Sweden's early adoption meant they saw the benefits quicker and this is reflected in the figures. However, the UK has caught up and last year the majority of patients received this treatment. 'The lesson here for the UK is that we need to be led by the research and introduce pioneering practices quickly and on a large scale.'
A major incident was reportedly declared at a hospital in Essex over concerns raised by the health regulator following a surprise inspection. The Care Quality Commission (CQC) apparently inspected Colchester Hospital's accident and emergency department and emergency assessment unit on Wednesday and told the trust of 'safeguarding concerns'. Following the unannounced visit the watchdog found patients being inappropriately restrained, sedated without consent and do not resuscitate signs being ignored, the Guardian reported. A major incident has reportedly been declared at Colchester Hospital over 'safeguarding concerns' raised by the Care Quality Commission . Professor Mike Richards, the CQC's chief inspector, told the newspaper that they had carried out the unannounced inspection following 'concerns.' 'Following the inspection, we gave feedback to the trust about our safeguarding concerns so that it could take appropriate action to ensure the safety and wellbeing of its patients,' he told the Guardian. A spokesman for the hospital trust said it could not responded to the specific allegations made by the Guardian because they had not seen the CQC's full report . In July the CQC gave the hospital an overall rating of 'requires improvement'. Peter Wilson, acting chairman of Colchester Hospital University NHS Foundation Trust told the Guardian it was facing 'unprecedented demand' on its services. Professor Mike Richards, the CQC's chief executive, said they carried out the surprise inspection in response to concerns . The trust's interim chief executive, Dr Lucy Moore, said it was 'a difficult time for the trust'. She said: 'The Care Quality Commission raised a small number of safeguarding concerns when its team gave immediate feedback at the end of the inspection on Wednesday. 'The Trust takes safeguarding extremely seriously and is now investigating to find out whether our policies had been followed appropriately.' In the wake of the announcement more staff were said to have been drafted into the hospital, non urgent surgery rescheduled and where safe to do so patients discharged. Mr Wilson said they were disappointed that the CQC felt the situation at the hospital had not improved, and confirmed it had declared a major incident to review various aspects of service at the hospital. The trust said the major incident is likely to last a week, and appealed to members of the public only to visit the accident and emergency department if they have a 'serious or life-threatening condition'. The CQC said it will publish its latest report on the hospital 'in due course', and added that it will carry out further inspections at the trust. The major incident was declared at the hospital the day after Health Secretary, Jeremy Hunt, announced that the NHS was to receive an additional £300 million to help them cope this winter.
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What is Plymouth's National Health Service hospital?
Plymouth is served by Plymouth Hospitals NHS Trust and the city's NHS hospital is Derriford Hospital 4 miles (6 km) north of the city centre. The Royal Eye Infirmary is located at Derriford Hospital. South Western Ambulance Service NHS Foundation Trust operates in Plymouth and the rest of the south west; its headquarters are in Exeter.
Southampton as a Port and city has had a long history of administrative independence of the surrounding County; as far back as the reign of King John the town and its port were removed from the writ of the King's Sheriff in Hampshire and the rights of custom and toll were granted by the King to the burgesses of Southampton over the port of Southampton and the Port of Portsmouth; this tax farm was granted for an annual fee of £200 in the charter dated at Orival on 29 June 1199. The definition of the port of Southampton was apparently broader than today and embraced all of the area between Lymington and Langstone. The corporation had resident representatives in Newport, Lymington and Portsmouth. By a charter of Henry VI, granted on 9 March 1446/7 (25+26 Hen. VI, m. 32), the mayor, bailiffs and burgesses of the towns and ports of Southampton and Portsmouth became a County incorporate and separate from Hampshire.
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In what year were comprehensive schools first created?
In these schools children could be selected on the basis of curriculum aptitude related to the school's specialism even though the schools do take quotas from each quartile of the attainment range to ensure they were not selective by attainment. A problem with this is whether the quotas should be taken from a normal distribution or from the specific distribution of attainment in the immediate catchment area. In the selective school system, which survives in several parts of the United Kingdom, admission is dependent on selection criteria, most commonly a cognitive test or tests. Although comprehensive schools were introduced to England and Wales in 1965, there are 164 selective grammar schools that are still in operation.[citation needed] (though this is a small number compared to approximately 3500 state secondary schools in England). Most comprehensives are secondary schools for children between the ages of 11 to 16, but in a few areas there are comprehensive middle schools, and in some places the secondary level is divided into two, for students aged 11 to 14 and those aged 14 to 18, roughly corresponding to the US middle school (or junior high school) and high school, respectively. With the advent of key stages in the National Curriculum some local authorities reverted from the Middle School system to 11–16 and 11–18 schools so that the transition between schools corresponds to the end of one key stage and the start of another.
Imperial College Healthcare NHS Trust was formed on 1 October 2007 by the merger of Hammersmith Hospitals NHS Trust (Charing Cross Hospital, Hammersmith Hospital and Queen Charlotte's and Chelsea Hospital) and St Mary's NHS Trust (St. Mary's Hospital and Western Eye Hospital) with Imperial College London Faculty of Medicine. It is an academic health science centre and manages five hospitals: Charing Cross Hospital, Queen Charlotte's and Chelsea Hospital, Hammersmith Hospital, St Mary's Hospital, and Western Eye Hospital. The Trust is currently the largest in the UK and has an annual turnover of £800 million, treating more than a million patients a year.[citation needed]
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What was formed on the 1st October 2007?
Imperial College Healthcare NHS Trust was formed on 1 October 2007 by the merger of Hammersmith Hospitals NHS Trust (Charing Cross Hospital, Hammersmith Hospital and Queen Charlotte's and Chelsea Hospital) and St Mary's NHS Trust (St. Mary's Hospital and Western Eye Hospital) with Imperial College London Faculty of Medicine. It is an academic health science centre and manages five hospitals: Charing Cross Hospital, Queen Charlotte's and Chelsea Hospital, Hammersmith Hospital, St Mary's Hospital, and Western Eye Hospital. The Trust is currently the largest in the UK and has an annual turnover of £800 million, treating more than a million patients a year.[citation needed]
Kinnock then resigned as leader and was replaced by John Smith. Smith's leadership once again saw the re-emergence of tension between those on the party's left and those identified as "modernisers", both of whom advocated radical revisions of the party's stance albeit in different ways. At the 1993 conference, Smith successfully changed the party rules and lessened the influence of the trade unions on the selection of candidates to stand for Parliament by introducing a one member, one vote system called "OMOV" — but only barely, after a barnstorming speech by John Prescott which required Smith to compromise on other individual negotiations.
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In what year was the Medal of the Order of the British Empire established?
At the foundation of the Order, the "Medal of the Order of the British Empire" was instituted, to serve as a lower award granting recipients affiliation but not membership. In 1922, this was renamed the "British Empire Medal". It stopped being awarded by the United Kingdom as part of the 1993 reforms to the honours system, but was again awarded beginning in 2012, starting with 293 BEMs awarded for the Queen's Diamond Jubilee. In addition, the BEM is awarded by the Cook Islands and by some other Commonwealth nations. In 2004, a report entitled "A Matter of Honour: Reforming Our Honours System" by a Commons committee recommended to phase out the Order of the British Empire, as its title was "now considered to be unacceptable, being thought to embody values that are no longer shared by many of the country’s population".
Imperial College Healthcare NHS Trust was formed on 1 October 2007 by the merger of Hammersmith Hospitals NHS Trust (Charing Cross Hospital, Hammersmith Hospital and Queen Charlotte's and Chelsea Hospital) and St Mary's NHS Trust (St. Mary's Hospital and Western Eye Hospital) with Imperial College London Faculty of Medicine. It is an academic health science centre and manages five hospitals: Charing Cross Hospital, Queen Charlotte's and Chelsea Hospital, Hammersmith Hospital, St Mary's Hospital, and Western Eye Hospital. The Trust is currently the largest in the UK and has an annual turnover of £800 million, treating more than a million patients a year.[citation needed]
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A Victorian university building in Aberystwyth could be transformed into a postgraduate centre under plans for a new "cultural quarter".
A £60,000 feasibility study will examine how to alter Aberystwyth University's Old College and the costs. The building opened in 1865 as a hotel, but was later bought by a group of philanthropists who founded the university. It is home to various departments and is used for teaching. The university said the Old College was one of finest examples of the work of gothic revival architect John Pollard Seddon. It is one of the town's most recognisable buildings with spires, towers, gargoyled parapets and steep-pitched roofs "like a French Renaissance chateau". Plans include creating a "cultural quarter" based around the Old College, a postgraduate centre providing world-class teaching, learning and study spaces, an art gallery, and lecturing and performance facilities. University vice-chancellor Prof April McMahon said: "Research consistently shows that Aberystwyth University is recognised as one of the best locations to study for undergraduates. "We want to build on that and develop a world class postgraduate centre. "However, the Old College should have a community focus as well as an academic one. "We want to provide a resource for residents and visitors as well as students and staff. "Our vision is for state-of-the-art learning facilities, exhibition space, a university shop and a first point of contact for local businesses - truly bringing the town and gown together in a new cultural quarter." Regeneration Minister Huw Lewis said: "The Old College is an iconic building in Aberystwyth and resonates with present and past students of the university. "Its location in the centre of the town can provide a focal point to the area's regeneration and the potential ideas put forward sound extremely exciting." The final feasibility study, which will also include a number of other university properties, is expected to be finished in March 2013. It will be funded by a Welsh government regeneration fund and the university. Aberystwyth has been identified as a regeneration area by the Welsh government and up to £10.3m has been made available to invest, which is being used on a number of projects in the town.
Inspectors found problems with the way Queen Elizabeth Hospital in Birmingham runs its heart unit after a high death rates compared with other hopsitals. The trust ignored repeated warnings over high death rates, the report said. The trust said patient safety remained its "number one priority". University Hospitals Birmingham NHS Foundation Trust has now been ordered to make improvements and send weekly surgery results to the Care Quality Commission (CQC). Read more news for Birmingham The report said the trust has only recently started a quality improvement programme (QIP), despite concerns being identified in 2013 and consultants approaching the executive team in 2014 with concerns around patient deaths and outcomes. The trust was also informed that its death rates were outside the national average in March last year. England's chief inspector of hospitals, Prof Sir Mike Richards, said: "Initial data regarding surgery outcomes in the months since our inspection show an improvement but we need to continue to monitor the service." Data from the Society for Cardiothoracic Surgeons showed the cardiac surgical unit at Queen Elizabeth Hospital had an above average death rate over the three years from April 2011 to March 2014. A spokeswoman for University Hospitals Birmingham NHS Foundation Trust said on Tuesday: "None of the cardiac surgeons currently working at UHB are outliers for mortality outcomes and we are confident they will continue to offer the highest standards of care and expertise in delivering their service. "The trust established a QIP for the cardiac surgery service in July 2015, which is ongoing and subject to external review. "At the time of the CQC inspection in December 2015, the QIP had already improved outcomes and internal issues within the service. "The subsequent report has added awareness and pace to what is considered a valuable exercise to enhance both staff and, more importantly, patient benefit."
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The human rights group Liberty has called for a public inquiry into physical and sexual abuse at the Deepcut army barracks in Surrey.
It said many current and former soldiers had given accounts of suffering violence or abuse there. A coroner recently ruled the death of Pte Cheryl James, 18, was suicide and criticised army welfare standards. Liberty said Pte James' inquest had exposed a "toxic, violent and sexualised" culture at the barracks. It also said other accounts of abuse at the camp emerged in two recent BBC documentaries, Deepcut - the Army's Shame, and Week In Week Out - A Family's Fight for the Truth. It has written to Defence Secretary Michael Fallon to request a "thorough and independent" inquiry on behalf of the families of Privates James, Sean Benton and James Collinson - three out of four young soldiers found dead with gunshot wounds between 1995 and 2002. Last week Pte Benton's twin brother Tony and sister Tracey Lewis lodged an application for a fresh inquest into the circumstances surrounding his death. Liberty said it was also acting for former Deepcut recruits Mark Harrison, who says he was a victim of sexual assault and rape, and Dan Griffiths, who alleges an army instructor beat him unconscious. Mr Harrison said: "The man who did this to me was known by the Army to be a risk to young people because he committed sexual offences before he came to Deepcut. "His actions changed my life forever and I still struggle deeply today as a consequence. "I want to be heard and I want to be assured that this could never happen again." Pte James' father, Des said: "The MoD has wasted many years avoiding a public inquiry into Deepcut and even denying an abusive culture existed until very recently. "A public inquiry may finally draw a line under this dark stain on the reputation of the British Army." Liberty said in 2002-3 Surrey Police compiled a dossier of 118 "duty of care and bullying issues", mainly at Deepcut. An independent review in 2006 by Nicholas Blake QC concluded there was no need for a public inquiry. In a statement, a Ministry of Defence spokesperson said: ""We believe in the importance of transparency through any method deemed most appropriate, and we have not objected to any of the further Deepcut inquests raised to date. "However Sir Nicholas Blake's review concluded a public inquiry into the circumstances at Deepcut barracks was not necessary, and this view was shared by the House of Commons Defence Committee."
Sherwood Forest Hospitals NHS Foundation Trust has failed to take adequate action to cut its high death rates, a healthcare report stated. The Care Quality Commission (CQC) found a number of "serious problems" which were "extremely concerning". The trust's chief executive apologised for letting patients down. The trust, which runs Kings Mill Hospital, Newark Hospital and Mansfield Community Hospital, was placed in special measures two years ago because of concerns about death rates and standards of care. The latest CQC report said the trust had almost double the national average rate of deaths from sepsis, a bloodstream infection. "In 2010 and 2012, we raised mortality outlier alerts with the trust when information showed there were a higher number of deaths than expected for patients with sepsis," the report said. "The trust had identified a third mortality outlier for patients with sepsis in the period April 2014 to January 2015." CQC inspectors found major concerns, including resuscitation equipment not being on trolleys, which would leave patients suffering a cardiac arrest in crisis. The report added the trust should remain in special measures, with the BBC understanding it could be taken over by another trust or the government if improvement is not made within around three months. Analysis - Rob Sissons, East Midlands Health Correspondent In medicine, a patient's condition rarely stays the same, they either improve or get worse - this can also be said of failing hospitals. So, there is some shock at the news that Sherwood Forest Hospitals NHS Foundation Trust has gone in the wrong direction. The Care Quality Commission rating moving from 'requires improvement' to 'inadequate'. So what happens now? Closing the hospital isn't realistic - where would people go? Changes in management, or a takeover by another health trust may be considered, and after six chief executives in four years, the idea that one person at the top can solely change the culture may be wishful thinking. However, the trust can at least breath a sigh of relief in the knowledge its staff are considered to be kind and caring. Patients I spoke to outside King's Mill were generally very supportive of the hospital and impressed at the treatment they received. Professor Sir Mike Richards, the chief inspector of hospitals, said: "The trust's special measures action plan had 18 high-level action points to be completed by March 2015. "Only one of these areas had been completed by the June inspection." Karen Fisher, the trust's acting chief executive, said since the inspection it has seen a "downward trend in our mortality rates" from sepsis and now met national standards. "We are sorry that we have let our patients down and are not meeting the quality standards that our patients rightly deserve," she said. "There are a number of challenges that we now need to face." Managers from other hospitals have been brought in to make improvements. The trust provides services for people across north and mid-Nottinghamshire as well as parts of Derbyshire and Lincolnshire.
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Patient satisfaction with Scotland's health service continues to rise according to this year's inpatient experience survey.
The Quality of Healthcare Experience National Indicator has risen to 82.8, the highest it has been since the survey began in 2010. This represents a rise of 1.1 from the previous survey in 2014. The 2016 survey, published today, found that 90% of patients rated their care as good or excellent. Good or excellent care in A&E has also increased to 88% and the number of people who thought their ward was clean has increased from 95% to 96% since the last survey in 2014. Overall satisfaction with the hospital environment increased from 88% to 89% since the last survey, and overall satisfaction with hospital staff has remained at 91%. Health Secretary Shona Robison said: "It is encouraging to see that satisfaction in Scotland's hospitals continues to rise against a backdrop of increasing patient numbers. It's especially pleasing to see even more people rating their overall care as good or excellent, including in areas like accident and emergency. "We are determined to continue to push up standards. "This is why we are providing financial support to all health and social care partnerships in the form of £90 million over three years, specifically to reduce delays in patients leaving hospital, plus an additional £250 million for investment in social care in 2016/17."
Springfield House Medical Centre in Oldham was given the lowest possible grade when assessed by the Care Quality Commission for safety, effectiveness, and quality of leadership. The CQC said the Huddersfield Road surgery also "requires improvement" when it comes to the care it provides patients and its "responsiveness". The practice has yet to comment. Inspectors in September found staff training "was not well-monitored". A previous inspection in 2015 rated the practice as "requiring improvement". Alison Holbourn, deputy chief inspector of general practice at the CQC, said patients "aren't getting the high quality care which everyone should expect". "It was worrying to see that training at the practice wasn't well-monitored and there was no evidence of all staff completing the appropriate training to carry out their role. "We found that the practice weren't responsive to the needs of the people using the service, for example we saw no extended opening times, or programmes for specific groups such as carers." The CQC said the surgery would be kept under review and could face closure unless sufficient improvements are made during the next six months.
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More than 2,000 defibrillators for use in public places like railway stations and schools have a potentially faulty component and might not deliver an electric shock in an emergency.
The models LIFEPAK CR Plus and LIFEPAK EXPRESS Automatic External Defibrillators (AED) were the ones affected, the Medicines and Healthcare products Regulatory Agency said. The manufacturers have sent out safety instructions for the devices. No patient incidents have occurred. The defibrillators, made by Physio-Control, are public access defibrillators (PAD) - so called because anyone can use them in an emergency. Approximately 2,600 devices are thought to be defective. The MHRA said the fault was caused by an internal component that could become stuck in the closed position. This means the device could fail to deliver an electric shock to resuscitate a patient in cardiac arrest. It advised people to carry out a safety check on their devices and arrange for the component to be replaced. If they have not received the manufacturer's safety alert, they should locate the serial number on the label on the back of the device and call the manufacturer's customer support number or visit their website to seek further advice. John Wilkinson, MHRA's director of medical devices, said: "These devices deliver lifesaving treatment and it is vital that they work in an emergency. "Those responsible for them should carry out the instructions by the manufacturer. "If you have any questions, or have not got the manufacturer's safety alert, call Physio-Control's customer support on 0808 258 0094."
Colchester Hospital's leadership was labelled "poor" by the Care Quality Commission (CQC), which put the hospital in special measures in 2013. End-of-life patients did not always receive "safe or effective care", the watchdog also found. The hospital said the report did not reflect the improvements it had made. Operations were regularly cancelled and some cancer patients had to wait more than 100 days for treatment, the CQC found. Outpatients were often placed "at high risk of avoidable harm" because of a "real lack of understanding" of waiting lists, it said. Many items of equipment had not been tested "for several years", despite this being raised as a concern at a previous inspection. Mothers were not treated "with sufficient dignity and respect" on the postnatal ward, inspectors found. Staff were praised for being "dedicated" but inspectors said they "felt let down" because many agency workers did not show the same level of commitment. Prof Sir Mike Richards, the Chief Inspector of Hospitals, said the hospital has a "serious number of problems" and has shown "only limited capacity to improve". "While the staff have been working hard through many issues to drive improvements locally, their efforts have been affected by poor leadership and a high use of agency staff, some of whom are unsuitable in terms of their skills and knowledge," he said. He recommended the trust remains in special measures for the next three months, during which time it must submit a weekly improvement plan. The trust's council of governors said the report might have an impact on recruitment and was "likely to have a negative effect on the morale of our dedicated and loyal staff". All high-risk medical devices have been checked since the inspection, it added. Chief executive Frank Sims said he was "disappointed" with the report but will use it as a "blueprint for improvement".
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A 15-year-long study into the affect childhood lifestyle has on adult health will continue with new funding.
The EarlyBird study has followed 300 young people from the age of five since 2000 to measure the impact of childhood diet and exercise on later life. Plymouth University academics behind the study believe it is the only one of its kind in the world to follow the same children for such a long period. Funding of £500,000 will now allow the project to continue until 2017. EarlyBird3 has won the funding from Plymouth University, Plymouth Hospitals NHS Trust, the Clinical Research Network: South West Peninsula, which is part of the National Institute for Health Research, and Nestlé Institute of Health Sciences Ltd. The study has weighed, measured and investigated children in the Plymouth area to see how their lifestyles, diet and exercise patterns affect their health - especially diabetes. EarlyBird previously found modern children were "at quite substantial risk" of the condition. The third phase of the project will also explore the childhood origins of dental, psychological and respiratory health problems. Jonathan Pinkney, professor of endocrinology and diabetes at Plymouth University Peninsula Schools of Medicine and Dentistry, said: "Not only will this give us a better understanding of how such diseases develop, it will also help us to identify methods for disease prevention and when in our life development it is best to implement those." The study organisers are re-recruiting members of the original group.
Colchester Hospital's leadership was labelled "poor" by the Care Quality Commission (CQC), which put the hospital in special measures in 2013. End-of-life patients did not always receive "safe or effective care", the watchdog also found. The hospital said the report did not reflect the improvements it had made. Operations were regularly cancelled and some cancer patients had to wait more than 100 days for treatment, the CQC found. Outpatients were often placed "at high risk of avoidable harm" because of a "real lack of understanding" of waiting lists, it said. Many items of equipment had not been tested "for several years", despite this being raised as a concern at a previous inspection. Mothers were not treated "with sufficient dignity and respect" on the postnatal ward, inspectors found. Staff were praised for being "dedicated" but inspectors said they "felt let down" because many agency workers did not show the same level of commitment. Prof Sir Mike Richards, the Chief Inspector of Hospitals, said the hospital has a "serious number of problems" and has shown "only limited capacity to improve". "While the staff have been working hard through many issues to drive improvements locally, their efforts have been affected by poor leadership and a high use of agency staff, some of whom are unsuitable in terms of their skills and knowledge," he said. He recommended the trust remains in special measures for the next three months, during which time it must submit a weekly improvement plan. The trust's council of governors said the report might have an impact on recruitment and was "likely to have a negative effect on the morale of our dedicated and loyal staff". All high-risk medical devices have been checked since the inspection, it added. Chief executive Frank Sims said he was "disappointed" with the report but will use it as a "blueprint for improvement".
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A body representing health professionals in Scotland has said major changes are needed to address "systemic failures" in the NHS.
The Academy of Medical Royal Colleges and Faculties said staffing and leadership were particular concerns. It recommended the Scottish government and NHS boards agree minimum safe staffing levels for all professions in hospitals. The Scottish government said NHS staffing was at its highest-ever level. The academy set up a working group to look at how the health service could learn from past failures. It followed three previous reports into serious failings of care in the Scottish health service. They looked at problems of staffing and leadership at Aberdeen Royal Infirmary (ARI); above-average mortality rates at NHS Lanarkshire; and the worst-ever outbreak of C-difficile infection, at Vale of Leven Hospital. The academy's report, Learning from Serious Failings in Care, identified key issues to be addressed, including: The working group was chaired by Prof Alan Paterson of Strathclyde University and involved senior experts from the Royal Colleges in Scotland. Prof Paterson said: "It is clear that serious failings in team working between clinical staff and NHS management played a significant role in the failings in care identified. "These failings are deep-rooted and systemic. They must not be ignored if we are to learn from them and to prevent repetition. "It is also clear that a combination of factors led to some appalling failings in care, a loss of basic compassion and the prioritisation of inappropriate targets over patient care. In addition, leadership and accountability were all too often sadly lacking and bullying endemic. "While there have been responses to the individual published reports of inquiries and reviews into failings in care, there is little evidence to suggest that we are tackling the underlying systemic failings which exist." The report recommended that hospital staffing levels should be based on "best evidence". It said priority should be given to developing minimum safe staffing for acute medicine and medicine for the elderly wards. Among its 20 recommendations was a suggestion that there should be less reliance on locum and agency staff, and a call for quality of care to be put ahead of meeting targets, It also raised concerns about staff sickness, saying this could be an indication of deteriorating morale and should be used as "an early warning system". Royal College of Nursing Scotland Director Theresa Fyffe said: "These are hard-hitting recommendations and will make uncomfortable reading for many managers and leaders in our health service." She added: "Too often, failures in care are down to unsafe staffing levels. We know that quality of care is inextricably linked to having the right number of suitably skilled staff in the right place at the right time, with the right balance between registered nurses and unregistered staff. "Having appropriately trained and experienced staff must be a priority for all health boards if they are to deliver safe, high quality care to patients." The Scottish government's national clinical director for healthcare quality, Prof Jason Leitch, said: "We are committed to driving up standards in our NHS which is why we have led the way in responding to the reports detailed in the Scottish Academy's report. "We are absolutely clear about the value we place on staff and the safe and effective service they deliver to patients. "We currently have the highest staffing levels across our NHS than ever before, with increases under this government of over 1,300 more consultants, and 2,300 more qualified nurses and midwives." Prof Leitch added: "We are constantly striving to further improve health care in Scotland and will review the recommendations within this report and take forward any learning that will benefit NHS Scotland, either as part of the follow up work to the Vale of Leven, Grampian and Lanarkshire reviews."
Colchester Hospital's leadership was labelled "poor" by the Care Quality Commission (CQC), which put the hospital in special measures in 2013. End-of-life patients did not always receive "safe or effective care", the watchdog also found. The hospital said the report did not reflect the improvements it had made. Operations were regularly cancelled and some cancer patients had to wait more than 100 days for treatment, the CQC found. Outpatients were often placed "at high risk of avoidable harm" because of a "real lack of understanding" of waiting lists, it said. Many items of equipment had not been tested "for several years", despite this being raised as a concern at a previous inspection. Mothers were not treated "with sufficient dignity and respect" on the postnatal ward, inspectors found. Staff were praised for being "dedicated" but inspectors said they "felt let down" because many agency workers did not show the same level of commitment. Prof Sir Mike Richards, the Chief Inspector of Hospitals, said the hospital has a "serious number of problems" and has shown "only limited capacity to improve". "While the staff have been working hard through many issues to drive improvements locally, their efforts have been affected by poor leadership and a high use of agency staff, some of whom are unsuitable in terms of their skills and knowledge," he said. He recommended the trust remains in special measures for the next three months, during which time it must submit a weekly improvement plan. The trust's council of governors said the report might have an impact on recruitment and was "likely to have a negative effect on the morale of our dedicated and loyal staff". All high-risk medical devices have been checked since the inspection, it added. Chief executive Frank Sims said he was "disappointed" with the report but will use it as a "blueprint for improvement".
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Campaigners want hospital managers to rethink plans for a £4.5m shake-up of healthcare in a Flintshire town.
About 100 people attended a meeting in Flint to discuss plans for single-site facility for GPs, clinics and other health and welfare services. They want facilities reinstated following the closure of the town hospital with the loss of ward beds and a minor injuries unit. The local health board said its plans offered an "exciting opportunity". But Flint Hospital Campaign Group accused officials at the meeting of not listening to people's views. Chairman Mike Evans said members were now considering putting forward a candidate to stand at the next Welsh assembly election in 2016 if people's concerns are not addressed. "None of us what to become politicians," he said. "We have made great effort to be apolitical. But patients' voices - voters - have not been heard." Betsi Cadwaladr University Health Board pledged to consider residents' views following the meeting on Wednesday. Project director Robin Wiggs said: "We really do understand and appreciate the strong feelings that have been expressed about the closure of the old hospital. "However we have an exciting opportunity to develop a range of more integrated services that should mean people get much more of the primary and community healthcare they need locally in the town." He explained that an "enhanced care at home service" started last month in Flint following the closure of the community's hospital and its ward beds. "By investing in this early support and treatment we can help people to stay healthier and prevent minor illness from developing into something more serious, so many people don't get to a point where they need to go into hospital," he said. The health board's plans for the hospital are on display in Flint Library throughout September. A funding case will be submitted to the Welsh government in early 2014 and it expected that a new facility could be open by early 2016. The health board is looking for a site for the new facilities and the former hospital is still being considered as a possible location.
The North Tees and Hartlepool NHS Foundation Trust is one of nine in England found to have higher than predicted mortality rates last year. The figures include deaths in hospital, or within 30 days of discharge. North Tees and Hartlepool NHS Trust medical director, Dr David Emerton, said it was "reviewing the care of all patients who die". Dr Emerton said the figures - higher than expected for the second year running - were skewed by the number of patients treated without being admitted to hospital. Some patients, such as those in care homes nearing the end of their lives, where sent to hospital "when not much really can be done", he said. The Health and Social Care Information Centre (HSCIC), who compiled the data, says the categorisation does not mean a hospital is failing or unsafe and does not take levels of social deprivation into account. Its figures should "instead should be viewed as a 'smoke alarm' which requires further investigation by the trust", a spokeswoman said. The SHMI is available from April 2010 and the latest data covers July 2013 to June 2014. The expected risk of the patient dying in hospital, or within 30 days of discharge, is estimated based on the patient's condition, age, sex and how they were admitted to hospital. Dr Mike Smith, from the Patients Association, said the figures should be viewed in the context of the area's poverty and unemployment rate. "If people have, locally, a high mortality and morbidity rate, that means to say people are dying more than the rest of the nation and/or are sicker than the rest of the nation, then you mustn't necessarily think it's the hospital's fault," he said.
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when are the new quality measures added to the five star rating
announced that five of the six new quality measures for skilled nursing facilities will be phased into the Five-Star Quality Ratings system on July 27, 2016. While the initial phase-in will begin July 27th, the new measures won't carry full weight in determining a nursing home's ranking until January 2017. The measures that will be added to the Five-Star include:
Five Star Rating. To meet NSSF's criteria of a Five Star facility, a range must demonstrate excellence in all aspects of management and operations. Ranges are rated on appearance, management, customer service, amenities, customer development and community relations. 1 Five Star Ranges. 2 Four Star Ranges.
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is the kaiser family foundation biased
For those who may not follow health care policy closely, the Kaiser Family Foundation is one of the few independent think tanks that neither side of the political aisle is likely to criticize for being partisan as the organization’s record for impartiality is so well established.
I have worked at Kaiser since 2008 and the experience has been mixed. Overall the facility and the Core values are great but the staff tend to be less than friendly and supportive to new nurses. The management team is aware and try to help but it's up to the Charge nurses to make sure you do not fail.
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A 27-year-old woman who was 34 weeks pregnant was admitted in a semicomatose state. Five days later she gave birth to an infant who demonstrated significant CNS depression. Elevated blood levels confirmed bromide intoxication in both the mother and infant secondary to chronic maternal bromide ingestion (Nervine). Simultaneous determinations revealed a higher initial serum bromide level in the infant compared to that of the mother in spite of a subsequent more rapid rate of disappearance in the neonate. It is suggested that the drug history obtained from the pregnant woman include nonprescription medications containing bromides. This possibility should also be included in the differential diagnosis in infants exhibiting evidence of CNS depression, particularly those born to mothers classified as neurotic or psychotic.
OBJECTIVE ::: To critically evaluate and summarize available information on the safety of potassium bromide in dogs. ::: ::: ::: DESIGN ::: Systematic review. ::: ::: ::: SAMPLE ::: 111 references reporting safety information relevant to potassium bromide published between 1938 and 2011. ::: ::: ::: PROCEDURES ::: PubMed searches without date limitations were conducted with the terms "potassium bromide" and "sodium bromide" in December 2009 and October 2011. Additional articles were identified through examination of article reference lists and book chapters on seizures in dogs and pharmacology. ::: ::: ::: RESULTS ::: Reversible neurologic signs were the most consistently reported toxicoses and were generally associated with adjunctive potassium bromide treatment or high serum bromide concentrations. Dermatologic and respiratory abnormalities were rare in dogs. Insufficient information was available to assess the effects of potassium bromide on behavior or to determine the incidence of vomiting, weight gain, polyphagia, pancreatitis, polyuria, polydipsia, or reproductive abnormalities associated with potassium bromide administration. Evidence suggested that administration of potassium bromide with food may alleviate gastrointestinal irritation and that monitoring for polyphagia, thyroid hormone abnormalities, and high serum bromide concentrations may be beneficial. ::: ::: ::: CONCLUSIONS AND CLINICAL RELEVANCE ::: Results suggested that potassium bromide is not an appropriate choice for treatment of every dog with seizures and that practitioners should tailor therapeutic regimens and clinical monitoring to each dog. Abrupt dietary changes or fluid therapy may compromise seizure control or increase the likelihood of adverse events. Availability of an appropriately labeled, approved potassium bromide product could provide better assurance for veterinarians and their clients of the quality, safety, and effectiveness of the product for veterinary use.
Two new model systems for use within the rapidly develop- ing ultrafast time resolved x-ray scattering techniques have been prepared. Their photoisomerisation from norbornadiene to quadricyclane was found to be a suitable reaction to fol- low. Simulations of scattering patterns (not included in this report) showed that if heavy atoms are included in these molecular structures, then the transformation can be followed by transient X-ray scattering techniques. Two new bromosub- stituted norbornadienes were synthesised and characterised. Absorption spectroscopy showed that the norbornadienes are converted quantitatively to quadricyclanes under ultra- violet irradiation. Nuclear magnetic resonance (NMR) studies showed that the process was fully reversible and that the norbornadienes could be completely recovered even without addition of catalysts. Furthermore, it was shown that the formation of quadricyclane from norbornadiene was unaf- fected by triplet sensitisers. The two new model systems synthesised thus are strong candidates for use in time- resolved X-ray scattering studies in both gas and condensed phases.
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Standard Methods of Clinical Chemistry: Volume II
Plasma Ascorbic Acid Levels and G-6-PD Activities in Symptomatic, Asymptomatic Malaria and Malaria Negative Subjects
Lipoprotein Electrophoresis Should Be Discontinued as a Routine Procedure
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This rapid fluorescence polarization immunoassay for urinary vanillylmandelic acid (VMA) involves use of our previously described antiserum and label and the program for 5-hydroxyindoleacetic acid in the Abbott TDx fluorimeter. Urine samples were measured directly, without pretreatment. The minimum detectable concentration was 0.3 mg/L, and the range of the standard curve was 0.3-200.0 mg/L. Precision, analytical recovery, and correlation of results with those by the Pisano method (Clin Chim Acta 1962;7:285-91) were all satisfactory. With this procedure one can determine the VMA concentration in 10 urine sample in 22 min. This is the first report of a clinical immunoassay for VMA and should greatly simplify screening for neural crest tumors.
The development of a separation fluoroimmunoassay for urinary normetanephrine is described. Antiserum specific to normetanephrine was coupled, using cyanogen bromide, to magnetizable cellulose; and fluorescein labelled normetanephrine was synthesized from fluoresceinthiocarbamylethylene diamine and a previously described normetanephrine derivative. Using these reagents it was possible to construct a reproducible standard curve, covering a wide range of concentrations, and to accurately measure the concentration of this metabolite in acid-hydrolysed urine samples. Cross-reactivities of structurally similar compounds were low and the fluoroimmunoassay showed good correlation with an established gas-chromatographic assay. The procedure is rapid; it is possible to accurately determine the normetanephrine concentration of urine samples approximately 2 h after hydrolysis, resulting in an overall assay time of approximately 4 h. This is the first report of a non-isotopic immunoassay for normetanephrine.
Ofloxacin was administered to 26 males infected with Ureaplasma urealyticum. The infection was confirmed by urine or semen culture. Ofloxacin, administered at daily dose of 300-600 mg for 7 to 28 days, eradicated U. urealyticum in 25 of 26 patients (92.2%).
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Earlier studies suggested that the dose of 6-mercaptopurine (6-MP) can be reduced substantially when the drug is given with allopurinol. We studied the effect of allopurinol on the kinetics of oral and intravenous 6-MP. Studies conducted initially in rhesus monkeys and subsequently in man with 6-MP doses of 100 mg/m2 and 75 mg/m2, demonstrated that allopurinol pretreatment resulted in a nearly 400% increase in peak plasma concentration of oral 6-MP in monkeys (from a mean of 0.54 microM to a mean of 2.1 microM) and a 500% increase in man (0.74 microM to 3.7 microM). Allopurinol pretreatment also led to a 300% increase in plasma AUC in monkeys after oral 6-MP (from a mean of 121 microM/min to a mean of 391 microM/min) and a 500% increase in AUC in man (from a mean of 142 microM/min to a mean of 716 microM/min). In contrast, allopurinol pretreatment had no effect on the kinetics of intravenous 6-MP. This difference was found to be due to inhibition of first-pass metabolism of oral 6-MP as the result of the action of allopurinol on liver or intestinal xanthine oxidase. Our results indicate that, although dose reduction of oral 6-MP given in conjunction with allopurinol is appropriate, it is not necessary when 6-MP is injected intravenously.
The plasma concentrations and tissue distribution of thiopurines were studied in mice after oral administration of 50 mg/kg azathioprine (AZA) using HPLC analysis. Peak concentrations of AZA and three other thiopurine metabolites in plasma [thiouric acid (TUA) greater than 6-mercaptopurine (6-MP) greater than AZA greater than 8-hydroxy-AZA] were observed as early as 10 min after drug application, thus indicating fast absorption and extensive metabolism of AZA, and were followed by a rapid decline. The extraction of thiopurines from organs (intestinal mucosa, liver, kidney, testes, spleen, and bone marrow) and from red blood cells (RBCs) was preceded by an acid hydrolysis procedure resulting in the release of thiopurine bases from their corresponding ribonucleotides. 6-MP, 6-thioxanthene (6-TX), 6-thioguanine (6-TG), TUA, and 8-hydroxy-6-MP (8-OH-6-MP) were extracted from the organs, whereas only 6-MP and 8-OH-6-MP were found in the processed RBCs. Initially, high concentrations of TUA, the endpoint of metabolic AZA degradation, were detected in the intestinal mucosa and in the liver. This provides evidence for a first-pass metabolism of AZA in these two organs. The initial concentrations of 6-MP extracted from the organs were about 10-fold those found in plasma. This indicates rapid cellular uptake of 6-MP and an accumulation of 6-MP derivatives that can be explained by formation of the 6-MP ribonucleotide thioinosine monophosphate (TIMP). With the exception of plasma and RBCs, 6-TG, which may originate from intracellular 6-thioguanosine nucleotides (TGNs), was extracted from all organs examined in the study. From the sequence of appearance of 6-MP, 6-TX, and 6-TG extracted from spleen and bone marrow homogenates, it can be assumed that formation of TGN occurs via the nucleotide interconversion pathway TIMP----6-thioxanthosine monophosphate----6-thioguanosine monophosphate. The highest concentrations of 6-TG derivatives were found in the spleen and bone marrow. This correlates with the clinical and experimental observation that AZA cytotoxicity mainly affects bone-marrow stem cells and lymphocytes and supports the hypothesis (derived from in vitro experiments) that the incorporation of TGN into DNA is the cytotoxic mechanism of AZA and 6-MP.
How should complementarities affect antitrust merger policy? I introduce a two-stage strategic model in which complementary-input monopolists offer supply schedules to producers and then engage in bilateral bargaining with producers. The main result is that there is a unique weakly dominant strategy equilibrium, the equilibrium attains the joint-profit-maximizing outcome, and output equals that of a bundling monopoly. The result holds with perfect competition in the downstream market with both unit capacity and multiunit capacity. The result also holds with oligopoly competition in the downstream market. The result contrasts with the Cournot effect, which states that complementary-input monopolists choose total prices that are greater than the bundled-monopoly level. The analysis shows that consumers' surplus and total producers' surplus are greater with supply schedules and bargaining than with posted-price competition. The analysis has implications for antitrust policy toward vertical and conglomerate mergers.
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Natural dipeptides of skeletal muscles, carnosine (β-alanylhistidine) and anserine (β-alanyl-1-methylhistidine), have been demonstrated to be myosin ATPase activators, the latter being much more effective than the former under identical experimental conditions. At low ionic strengths of K+, Mg++, and Ca++ the activating effect of carnosine was marked at optimal concentration of ATP, and at levels of ATP in which there was apparent substrate inhibition the effect was very pronounced. The effect of carnosine appears to be specific rather than an ionic strength effect. The lowest concentrations of carnosine and anserine found to be activating were comparable to concentrations found in tissue.
Essence of chicken is a popular Asian nutritional supplement that is often taken to improve metabolism and general health. Although used as a traditional remedy for combating fatigue and general health, there has been few studies investigating the ergogenic properties of chicken essence and its associated mechanism. We conducted a study to investigate the anti-fatigue and anti-oxidant properties of essence of chicken (EC) after exercise. Six weeks old male Institute of Cancer Research (ICR) mice were divided to four groups (10 mice/group) and were provided different doses of Essence of Chicken (EC): (1) Vehicle (water), (2) EC-0.5X (558 mg/kg), (3) EC-1X (1117 mg/kg), and (4) EC-2X (2234 mg/kg). EC supplementation could improve endurance and grip strength (p < 0.0001) and it had significant effects on the fatigue-related biochemical markers: ammonia, blood urea nitrogen (BUN), and creatine kinase (CK) levels were significantly lowered, while glucose blood levels and lactate clearance were improved after exercise challenge. Muscle and liver glycogen levels, muscle and liver superoxide dismutase (SOD), hepatic catalase (CAT), and glutathione (GSH) levels were observed to increase with EC supplementation. Preliminary in vitro data suggests that EC may have a beneficial effect in muscle mass and strength. No abnormalities were observed from pathohistological examination. Our study suggests that the EC could significantly improve exercise performance and endurance capacity and that the anti-oxidant properties of EC may be an important contributing factor to its anti-fatigue effects.
Long-term (1987-2012) water quality monitoring in 36 acid-sensitive Swedish lakes shows slow recovery from historic acidification. Overall, strong acid anion concentrations declined, primarily as a result of declines in sulfate. Chloride is now the dominant anion in many acid-sensitive lakes. Base cation concentrations have declined less rapidly than strong acid anion concentrations, leading to an increase in charge balance acid neutralizing capacity. In many lakes, modeled organic acidity is now approximately equal to inorganic acidity. The observed trends in water chemistry suggest lakes may not return to reference conditions. Despite declines in acid deposition, many of these lakes are still acidified. Base cation concentrations continue to decline and alkalinity shows only small increases. A changing climate may further delay recovery by increasing dissolved organic carbon concentrations and sea-salt episodes. More intensive forest harvesting may also hamper recovery by reducing the supply of soil base cations.
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The relative importance of two plasma inhibitors C1 inhibitor and α_2-macroglobulin in the inhibition of plasma kallikrein was studied using the synthetic substrate PPAN. The inhibition of plasma kallikrein by purified inhibitors as well as by normal plasma and inhibitor-depleted plasma was determined. The sensitivity of purified kallikrein, kallikrein complex and kallikrein endogenously generated in plasmas to the inhibitors was similar. There was a marked difference between the two inhibitors in the kallikrein inhibition. Initially, C1 inhibitor very rapidly inactivated the kallikrein activities, but the process proceeded only slowly towards completion. This was in contrast to α_2-macroglobul in which only caused a very slow decrease in the kallikrein activities. The absence of C1 inhibitor in plasmas led to a change in the kallikrein inhibition pattern i.e. a decrease in the inhibition of the amidolytic activity, indicating the importance of C1 inhibitor for rapid kallikrein inhibition in plasma.
::: Human plasma kallikrein is inactivated by plasma protease inhibitors. This study was designed to determine the nature of these protease inhibitors and to assess their relative importance in the inactivation of kallikrein. Therefore, the kinetics of kallikrein inactivation and the formation of kallikrein inhibitor complexes were studied in normal plasma and in plasma depleted of either alpha 2-macroglobulin (alpha 2M), C1 inhibitor, or antithrombin (AT III). Prekallikrein was activated by incubation of plasma with dextran sulfate at 4 degrees C. After maximal activation, kallikrein was inactivated at 37 degrees C. Inhibition of kallikrein amidolytic activity in AT III-deficient plasma closely paralleled the inactivation rate of kallikrein in normal plasma. The inactivation rate of kallikrein in alpha 2M-deficient plasma was slightly decreased compared with normal plasma, but in contrast to normal, C1 inhibitor-deficient, and AT III-deficient plasma, no kallikrein amidolytic activity remained after inactivation that was resistant to inhibition by soybean trypsin inhibitor. Suppression of kallikrein activity in C1 inhibitor-deficient plasma was markedly decreased, and this was even more pronounced in plasma deficient in both C1 inhibitor and alpha 2M. The pseudo first-order rate constants for kallikrein inactivation in normal, AT III-deficient, alpha 2M-deficient, C1 inhibitor-deficient plasma, and plasma deficient in both alpha 2M and C1 inhibitor, were 0.68, 0.60, 0.43, 0.07, and 0.016 min-1, respectively. Sodium dodecyl sulfate gradient polyacrylamide slab gel electrophoresis showed that during inactivation of kallikrein in plasma, high-Mr complexes were formed with Mr at 400,000-1,000,000, 185,000, and 125,000-135,000, which were identified as complexes of 125I-kallikrein with alpha 2M, C1 inhibitor, and AT III, respectively. In addition, the presence of an unidentified kallikrein-inhibitor complex was observed in AT III-deficient plasma. 52% of the 125I-kallikrein was associated with C1-inhibitor, 35% with alpha 2M, and 13% with AT III and another protease inhibitor. A similar distribution of 125I-kallikrein was observed when the 125I-kallikrein inhibitor complexes were removed from plasma by immunoadsorption with insolubilized anti-C1 inhibitor, anti-alpha 2M, or anti-AT III antibodies. These results suggest that only covalent complexes are formed between kallikrein and its inhibitors in plasma. As a function of time, 125I-kallikrein formed complexes with C1 inhibitor at a higher rate than with alpha 2M. No difference was observed between the inactivation rate of kallikrein in high-Mr kininogen-deficient plasma and that in high-Mr kininogen-deficient plasma reconstituted with high-Mr kininogen; this suggests that high-Mr kininogen does not protect kallikrein from inactivation in the plasma milieu. These results have quantitatively demonstrated the major roles of C1 inhibitor and alpha 2M in the inactivation of kallikrein in plasma.
::: Human plasma kallikrein is inactivated by plasma protease inhibitors. This study was designed to determine the nature of these protease inhibitors and to assess their relative importance in the inactivation of kallikrein. Therefore, the kinetics of kallikrein inactivation and the formation of kallikrein inhibitor complexes were studied in normal plasma and in plasma depleted of either alpha 2-macroglobulin (alpha 2M), C1 inhibitor, or antithrombin (AT III). Prekallikrein was activated by incubation of plasma with dextran sulfate at 4 degrees C. After maximal activation, kallikrein was inactivated at 37 degrees C. Inhibition of kallikrein amidolytic activity in AT III-deficient plasma closely paralleled the inactivation rate of kallikrein in normal plasma. The inactivation rate of kallikrein in alpha 2M-deficient plasma was slightly decreased compared with normal plasma, but in contrast to normal, C1 inhibitor-deficient, and AT III-deficient plasma, no kallikrein amidolytic activity remained after inactivation that was resistant to inhibition by soybean trypsin inhibitor. Suppression of kallikrein activity in C1 inhibitor-deficient plasma was markedly decreased, and this was even more pronounced in plasma deficient in both C1 inhibitor and alpha 2M. The pseudo first-order rate constants for kallikrein inactivation in normal, AT III-deficient, alpha 2M-deficient, C1 inhibitor-deficient plasma, and plasma deficient in both alpha 2M and C1 inhibitor, were 0.68, 0.60, 0.43, 0.07, and 0.016 min-1, respectively. Sodium dodecyl sulfate gradient polyacrylamide slab gel electrophoresis showed that during inactivation of kallikrein in plasma, high-Mr complexes were formed with Mr at 400,000-1,000,000, 185,000, and 125,000-135,000, which were identified as complexes of 125I-kallikrein with alpha 2M, C1 inhibitor, and AT III, respectively. In addition, the presence of an unidentified kallikrein-inhibitor complex was observed in AT III-deficient plasma. 52% of the 125I-kallikrein was associated with C1-inhibitor, 35% with alpha 2M, and 13% with AT III and another protease inhibitor. A similar distribution of 125I-kallikrein was observed when the 125I-kallikrein inhibitor complexes were removed from plasma by immunoadsorption with insolubilized anti-C1 inhibitor, anti-alpha 2M, or anti-AT III antibodies. These results suggest that only covalent complexes are formed between kallikrein and its inhibitors in plasma. As a function of time, 125I-kallikrein formed complexes with C1 inhibitor at a higher rate than with alpha 2M. No difference was observed between the inactivation rate of kallikrein in high-Mr kininogen-deficient plasma and that in high-Mr kininogen-deficient plasma reconstituted with high-Mr kininogen; this suggests that high-Mr kininogen does not protect kallikrein from inactivation in the plasma milieu. These results have quantitatively demonstrated the major roles of C1 inhibitor and alpha 2M in the inactivation of kallikrein in plasma.
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Using six different cultured cell models representing osteoblast, intestine, kidney and keratinocyte, we have demonstrated that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) is metabolized into 3-epi-1alpha,25(OH)2D3 in vitamin D-target cells. Although differences existed in the amount of 3-epi-1alpha,25(OH)2D3 formed with different cell types, it was apparent that 1alpha,25(OH)2D3 was subjected to metabolism both through the C24-oxidation and 3-epimerization pathways. Time course and dose response studies showed that the production of 3-epi-1alpha,25(OH)2D3 was enzymatic. It is interesting to note that this epimerization proceeded from 3beta towards 3alpha unidirectionally, and this conversion was not inhibited by ketoconazole. These data suggest that cytochrome P450 related enzymes including the 24-hydroxylase would not affect this reaction. The biological activity of 3-epi-1alpha,25(OH)2D3 was found to be lower than the native 1alpha,25(OH)2D3 in suppressing of proliferation of HL-60 cells, while the affinity of 3-epi-1alpha,25(OH)2D3 for vitamin D-binding protein was 2.5-fold higher than that of 1alpha,25(OH)2D3. The results indicate that 3-epimerization may change the pharmacokinetics and catabolism of 1alpha,25(OH)2D3 in vitamin D-target cells.
Background The complexity of vitamin D metabolites especially the contribution of C3-epimers of 25-hydroxyvitamin D (C3-epimers) in human sera remains unclear. We hypothesized that genetic polymorphisms in the vitamin D-related gene pathway contribute to variation in C3-epimer levels. Therefore, we investigated candidate single nucleotide polymorphisms (SNPs) concerning C3-epimer levels. Methods The candidate SNPs, including DHCR7/NADSYN1 (rs12785878), CYP2R1 (rs2060793) and GC (rs2282679), were genotyped in 1727 members of the third project of the Electricity Generating Authority of Thailand 3/1 cohort investigation. Each SNP was tested under three genetic effects (dominant, recessive and additive models) concerning the levels of total serum 25(OH)D [the sum of 25(OH)D 2+3 and 3-epi-25(OH)D 2+3 ], non-C3-epimers [25(OH)D 2+3 ] and C3-epimers [3-epi-25(OH)D 2+3 ], using linear regression analysis. Results Among the participants, the median (range) levels of non-C3-epimers and C3-epimers were 22.7 (6.4–49.2) ng/mL and 1.3 (0.01–14.2) ng/mL, respectively. In regression analysis, we found the genetic variation of two SNPs, the DHCR7/NADSYN1 (rs12785878; G > T) and GC (rs2282679; T > G) under additive genetic models, explained the variation of C3-epimer levels about 1.5% ( p = 1.66 × 10 −7 ) and 1.1% ( p = 1.10 × 10 −5 ), respectively. Interestingly, participants carrying the minor T-allele of rs12785878 exhibited a trend to increase C3-epimer levels, while those carrying the minor G-allele of rs2282679 exhibited a trend to decrease levels of both non-C3-epimers and C3-epimers. In addition, CYP2R1 (rs2060793; G > A) was clearly associated only with non-C3-epimer levels ( p = 2.46 × 10 −8 ). In multivariate analyses, sex, age and BMI were predictors for variation in C3-epimer concentration; sex and age for variation in non-C3-epimers. Conclusion To the best of our knowledge, this is the first study to demonstrate genetic models concerning the variation in C3-epimer levels. Our results emphasize that genetic determinants and the potential factors of C3-epimers differ from non-C3-epimers. This study contributes fundamental knowledge of the endogenous vitamin D pathway.
A combination of Novozym 435-catalyzed methanolysis and amidation using racemic N-methyl-5-acetoxytridecan- and tetradecanamides as a substrate proceeded in good enantioselectivity to afford the corresponding (R)-N-methyl-5-acetoxyalkanamides, (S)-N-methyl-5-hydroxyalkanamides, and (S)-N-cyclohexyl-5-hydroxyalkanamides. Both enantiomers of δ-tri- and δ-tetradecalactones were synthesized in over 90% enantiomeric excesses from the corresponding (R)- or (S)-alkanamides. Addition of cyclohexylamine to Novozym 435-catalyzed methanolysis shortened 24-hour reaction time to reach about 50% conversion. Enantiomers of optically active δ-tri- and δ-tetradecalactones had different odors and thresholds.
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Ultraviolet absorption spectroscopy was used as a non-intrusive probe to measure OH radical temperature in the plume of a 2.5-in. hybrid rocket motor. Continuous radiation from a xenon arc lamp was passed through the rocket plume onto the entrance slits of a monochromator equipped with an intensified charge-coupled device array detector and absorption was measured around 306 nm. The data are analyzed using a multi-parameter curve-fitting routine. This program utilizes 153 rotational transitions over the three vibrations band, R1, R2, and Q2, in these spectral regions (306-312 nm). The program determines number density (concentration) and temperature of the OH radical. The OH concentration was measured in the hybrid rocket motor plume over a range of oxidizer flow values. The results show that the OH concentration does increase with flow rate at low flow, level off at intermediate flow, and drop at higher values
: A windowed strand burner with a propellant feed mechanism has been used to characterize the steady-state combustion of solid propellants over a pressure environment of 0.1-2.0 MPa nitrogen. Under conditions where a line of sight measurement is meaningful, temperatures and absolute concentrations can be extracted from optical absorption spectra An arc lamp light source and spectrometer-intensified photiode array detector systems provided the means to absorption spectra for NO through the dark zone burning solid propellants. Additionally, OH absorption spectra were obtained in the luminous flame region. A least-squares fitting program applied to these absorption spectra resulted in a determination of temperature profiles and absolute NO concentrations for JA-2, M-9, and HMX2 solid propellants over a pressure range of 03-2.0 MPa. Measured dark zone temperatures ranged from about 1,300 K to 1,600 K and NO concentrations varied from about 15 to 30 mole percent depending upon the propellant type and pressure. Where possible these values are compared with literature data. Temperatures in the luminous flame computed from OH absorption spectra reached values in agreement with adiabatic flame temperatures. Video records of each propellant burn allowed a determination of the propellant bum rate and length of the dark zone as a function of pressure. absorption; solid propellant; temperature; concentration; dark zone; spectroscopy; nitric oxide.
Adrenal glands and ovaries of nu/+and nu/nu female mice were examined histochemically throughout the postnatal life for changes in distribution, intensity and appearance of activities of 3 steroid-converting enzymes. While the 3β-OH-steroid- and pregnenolone-dehydrogenase did not reveal any difference, the 20α-hydroxysteroid-dehydrogenase (20α-OH SDH) showed a constant behaviour: the onset of the enzyme activity was detectable in the adrenals of nu/+ mice after the second week of age, in nu/nu mice 3–4 weeks later. The localization of 20α-OH-SDH was strictly confined to the zone of small cells, a zone lying between the x-zone and the zona fasciculata. In nu/+ mice, after reached sexual maturity at about 6–8 weeks of age, the enzyme progressively disappeared from the adrenals and simultaneously appeared in the ovaries. In nu/nu mice, which had been kept separated from mating animals, the 20α-OH SDH persisted in adrenals even in adult stages. After pregnancy, both —nu/nu and nu/+, showed 20α-OH SDH-activity only in ovaries and none in adrenals. In both, the enzyme was localized in involuting corpora lutea, whilst in nu/nu it was also present in the interstitial cells.
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Optimization of ethanol production from Garcinia kola (bitter kola) pulp agrowaste
Optimization options for production of ethanol from bitter kola (Garcinia kola) pulp wastes were investigated. The methods are degumming, saccharification, acid hydrolysis, alkaline hydrolysis. Degumming was effectively achieved at 96 h of saccaharification. The concentration of reducing sugar for the treated sample (acid hydrolysed and saccharification) and control sample (saccharification) was maximum at 144 h (86.2 g/100g) and 96 h (31.5 g/100 g), respectively. Ethanol yield from treated sample and control sample using baker’s yeast was maximum at 120 h (70.7 g/L) and 192 h (29.3 g/L), respectively. Alkaline hydrolysis with 0.25 M sodium hydroxide has no significant effect on concentration of reducing sugar and ethanol yield. Acid hydrolysis with 2.5 M sulphuric acid and saccharification using Aspergillus niger are better methods for optimizing ethanol production from bitter kola pulp waste. Solar drying of the bitter kola pulp waste significantly enhanced ethanol production.
Objective: To observe the influence of Nourishing Kidney and Dredging Collaterals Recipe on the content of NO/ET-1 in serum of MCAO rats. Methods: Established MCAO rats model. MCAO rats were randomly divided into sham operated group, model control group, high-dose group of Chinese Medicine, low-dose group of Chinese Medicine and western medicine group. Following 20 days’intragastric administration, took rats’blood from abdominal vena, detected the content of NO and ET-1 in serum by chemical method and Radioimmunoassay, calculate the ratio of NO/ET-1. Results: Nourishing Kidney and Dredging Collaterals Recipe can increase the content of NO, and reduce the content of ET in Serum, then increase the ratio of NO/ET-1. Conclusion: Nourishing Kidney and Dredging Collaterals Recipe could regulate the vascular tone, increase local blood flow, recover the vessel homostasis by improving the function of injured endothelia and regulate the secretion and the release of vasoactive substances.
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High-Quality Factor MEMS Based Oscillator Silicon 9 MHz Oscillator with Low Phase Noise and High Quality Factor
In this paper, an oscillator based on a Vibrating Body Field Effect Transistor (VB-FET) working at 9.4MHz is presented. The electrical characteristics of this active MEM resonator are detailed for static and dynamic operation. The benefit of the intrinsic gain for oscillator design is analyzed and an oscillator design is proposed based on these findings. The reported oscillator performance shows the advantages of an active MEM resonator for the construction of MEM based oscillators with respect to the reduced requirements on the electronics. © 2009 by Department of Microelectronics & Computer Science.
We established a simple, sensitive, and reproducible method to analyze the histamine and tyramine levels in Japanese soy sauce and its mash (called moromi) using hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC–MS/MS). Histamine and tyramine quantification was performed using their stable isotopes for electrospray ionization–tandem mass spectrometry in the selected reaction monitoring mode. The sample pretreatment process was a simple, one-step liquid–liquid extraction. HILIC separation was performed with a gradient elution of aqueous ammonium formate and acetonitrile. Because of validation tests, the linearity, the accuracies, and precisions were sufficient. The limit of detection and the limit of quantification were 0.09 and 0.29 ppm for histamine and 0.13 and 0.42 ppm for tyramine, respectively. We successfully applied this method to histamine and tyramine determination in four kinds of commercial Japanese soy sauces and also in moromi samples during soy sauce production.
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New method for the estimation of bulk HgCdTe composition by infrared transmission
A new method for compositional estimation in bulk Hg1−xCdxTe (MCT) has been studied. The infrared (IR) transmission curves as a function of various compositions and thicknesses were simulated using the theoretical IR transmission model. From these results, a new equation for calculating the composition of bulk MCT was obtained. This equation is related to the wavenumber (Z12) of the 50% Tmax transmission point, where Tmax is the maximum transmission value. The new equation is as follows: x = 0.0675 + 9.907 × 10−5 + (−0.00818 + 5.29 × 10−7 × Z12) × ln(10/d), where d is the sample thickness in μm. The compositions can be calculated easily using the new equation with an accuracy of ±0.002 in the range of 0.17 ⩽ x ⩽ 0.3. The new method can be also applied successfully for samples with low transmission.
Abstract Peptide and protein samples are often complex mixtures that contain a number of individual compounds. The initial HPLC separation of such samples typically results in the poor resolution of one or more band pairs. Various means have been suggested tor varying separation selectivity so as to minimize this problem. In this study of a tryptic digest of recombinant human growth hormone, the simultaneous variation of temperature and gradient steepness was found to be a convenient and effective means of varying selectivity and optimizing the separation. The use of computer simulation greatly facilitated this investigation.
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Use of 3.6 mg/L (anhydrous) sodium thiosulfate will reduce 1.0 mg chlorine/L (APHA, 1992).
Use of 3.6 mg/L (anhydrous) sodium thiosulfate will reduce levels of 1.0 mg chlorine/L
Use of 3.6 mg/L (anhydrous) sodium thiosulfate has no effect on levels of 1.0 mg chlorine/L.
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Concentration and pH-dependent aggregation behavior of an l-histidine based amphiphile in aqueous solution
Self-assembling systems based on quaternized derivatives of 1,4-diazabicyclo[2.2.2]octane in nutrient broth as antimicrobial agents and carriers for hydrophobic drugs.
Checking for completeness of 24-h urine collection using para-amino benzoic acid not necessary in the Observing Protein and Energy Nutrition study
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5-Hydroxy-L-lysine excretion in cystinuria
Transport of glycyl-L-proline into intestinal and renal brush border vesicles from rabbit.
A straightforward route to enantiopure 2-substituted-3,4-dehydro-β-proline via ring closing metathesis
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Thiourea as a complexing agent for reduction of copper interference in the determination of selenium by hydride generation/atomic absorption spectrometry
Selenium measurement in sulphides by hydride generation high-resolution inductively coupled plasma mass spectrometry
Project Thyia: A Forever Gameplayer
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A dynein ATPase inhibitor isolated from a commercial ATP preparation.
Effect of Vanadate on Bean Leaf Movement, Stomatal Conductance, Barley Leaf Unrolling, Respiration, and Phosphatase Activity
A review of analytical methods for the determination of four new phosphodiesterase type 5 inhibitors in biological samples and pharmaceutical preparations
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Identification of the absorbed components and metabolites of Zhi-Zi-Da-Huang decoction in rat plasma by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry
Chemotaxonomic Classification Applied to the Identification of Two Closely-Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics
Synthesis of nanosized ZSM-5 zeolite using extracted silica from rice husk without adding any alumina source
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Quantification of Intracellular Polyhydroxyalkanoates by Virtue of Personalized Flow Cytometry Protocol
Fluorometric measurement of poly-β hydroxybutyrate in Alcaligenes eutrophus by flow cytometry and spectrofluorometry
High-speed running performance is largely unaffected by hypoxic reductions in aerobic power
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Determination of 3,7-dimethyl-1-(5-oxohexyl)-xanthine (pentoxifylline) and its 3,7-dimethyl-1-(5-hydroxyhexyl)-xanthine metabolite in the plasma of patients with multiple diseases using high-performance liquid chromatography.
SimultaneousDeterminationof Pentoxifyllineand Three Metabolitesin BiologicalFluidsby LiquidChromatography
5-(6-Hydroxy-6-methyl-5-oxoheptan-2-yl)-2-methyl Phenyl Acetate
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Rapid and selective determination of multi-sulfonamides by high-performance thin layer chromatography coupled to fluorescent densitometry and electrospray ionization mass detection
HPTLC Screening of Folic Acid in Food: In Situ Derivatization with Ozone-Induced Fluorescence
Inability of the Submaximal Treadmill Stress Test to Predict the Location of Coronary Disease
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Solvent extraction of platinum group metals with N, N-diethyl-n'-benzoylthiourea
Liquid Anion Exchange Chromatographic Extraction and Separation of Platinum(IV) with n-Octylaniline as a Metallurgical Reagent: Analysis of Real Samples
N-nitrosodiethylamine initiation of carcinogenesis in Japanese medaka (Oryzias latipes): hepatocellular proliferation, toxicity, and neoplastic lesions resulting from short term, low level exposure.
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In order to separate liquid mixtures, common distillation is not always suitable, especially if relative volatility of the mixture components is close to or equals unity, thus avoiding separation based on the vapor enrichment by more volatile component. To overcome this limitation of distillation, several alternatives were suggested including pressure swing and extraction distillation. Another, principally different, separation method used for the liquid mixtures separation is liquid-liquid extraction. Separation effi ciency of this method is closely related to the basic extraction solvent characteristics, capacity and selectivity. In order to minimize costs connected with extraction, new extraction solvents are developed, among which ionic liquids show high potential due to their tunable properties. Here, effi ciency of traditional extraction solvent, benzene, was compared to that of tetradecyltrihexylphosphonium bis(trifl uoromethylsulfonyl)imide ionic liquid in separation of ethanol from its aqueous solution. The comparison was assessed on the base of results of a counter-current extractor simulation. Further, some economic aspects of this separation procedure were discussed. Optimum consumption of extraction solvent was identifi ed taking into account alcohol-to-water molar (mass) ratio in the fi nal extract as optimization criterion.
The kinetics of uranium, plutonium and americium electrodeposition on steel targets from organic solutions of diphenyl-(N,N-dibutyl) carbamoylmethylphosphine oxide supplemented with the ionic liquid of trihexyltetradecylphosphonium hexafluorophosphate ([PH4]+PF6 −) in ethanol or N,N-dimethylformamide has been studied. When running a process in a dimethylformamide medium, and 0.05 M concentration of [PH4]+PF6 − americium deposition degree exceeds 95 % at the electrolysis time of 2 h. Alpha-spectra resolution of obtained target does not exceed 40 keV.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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In the present study, a dimeric glucosamine binding lectin, designated as CHL, was purified from Phaseolus coccineus L. var. albonanus Bailey through three chromatographic steps. The molecular weight of CHL was approximately 66kDa. Its hemagglutinating activity toward rabbit erythrocytes was dependent on carbohydrates, especially glucosamine, and was stable at temperatures between 20 and 70°C, and at pH between 1 and 13. Intriguingly, further characterization showed that CHL served as a potent antioxidant to prevent erythrocytes from haemolysis induced by 2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in a dose-dependent manner. Moreover, it exerted antitumor activity against human nasopharyngeal carcinoma CNE1 cells, hepatoma HepG2 cells, and breast cancer MCF7 cells but was devoid of antifungal activity. In addition, the CHL could bring about a significant dose-dependent increase in the production of mRNAs of pro-inflammatory cytokines including interferon-gamma and interleukin-2. These results suggest the potential therapeutic utility of CHL.
The physicochemical, functional, antioxidant and anticancer properties of protein isolates from the seeds of Soybean (SP), Black soybean (BSP), Adzuki bean (ABP), and Mung bean (MBP) were comparatively characterized. The difference was found in the protein composition and physicochemical properties of the four types of legume proteins, which affected the functional properties and bioactivities. BSP and SP had six predominant proteins with a molecular weight (MW) range of 20-95 kDa, whereas ABP and MBP showed the most intense bands of 48 kDa. ABP with higher essential amino acids content and the highest solubility exhibited the highest antioxidant activities among the four types of proteins. While BSP with higher content of acidic amino acids, low content of the hydrophobic amino acids and higher WHC, may have potential nutraceutical uses.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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Summary ::: ::: Tuna liver is fish by-product, which is normally discarded and/or used as fish meal and animal feed because of poor functionality. In this study, we attempt to recover functional peptides from tuna liver protein by enzymatic hydrolysis using various proteases, and further hydrolysates were fractionated into four categories base on their molecular weight (MW) by ultrafiltration membranes. All fractionated hydrolysates produced by Alcalase, Neutrase and Protamex following Flavourzyme hydrolysis showed excellent antioxidant activities against DPPH, hydrogen peroxide and hydroxyl radical scavenging, and reducing power. Their bioactivity was dependent on treated enzymes, and antioxidant activities of fractions dependent on employing bioassay. Moreover, they confirmed antioxidant ability toward the protection effects on hydroxyl radical-induced DNA damage by the measuring the conversion of supercoiled pBR322 plasmid DNA to the open circular form. In addition, all fractionated hydrolysates inhibited acetylcholinesterase activity, which is involved in Alzheimer’s diseases, and high MW fractions showed high AChE inhibition activity than those of low MW fractions.
OBJECTIVE ::: The objective of this study was to optimize ultrasonic-assisted enzymatic hydrolysis conditions, including enzyme-to-substrate (E/S) ratio, pH, and temperature, for producing porcine liver hydrolysates (PLHs) with the highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity by using response surface methodology (RSM). ::: ::: ::: METHODS ::: The study used RSM to determine the combination of hydrolysis parameters that maximized the antioxidant activity of our PLHs. Temperature (40°C, 54°C, and 68°C), pH (8.5, 9.5, and 10.5), and E/S ratio (0.1%, 2.1%, and 4.1%) were selected as the independent variables and analyzed according to the preliminary experiment results, whereas DPPH free radical scavenging activity was selected as the dependent variable. ::: ::: ::: RESULTS ::: Analysis of variance showed that E/S ratio, pH, and temperature significantly affected the hydrolysis process (p<0.01). The optimal conditions for producing PLHs with the highest scavenging activity were as follows: E/S ratio, 1.4% (v/w); temperature, 55.5°C; and initial pH, 10.15. Under these conditions, the degree of hydrolysis, DPPH free radical scavenging activity, ferrous ion chelating ability, and reducing power of PLHs were 24.12%, 79%, 98.18%, and 0.601 absorbance unit, respectively. The molecular weight of most PLHs produced under these optimal conditions was less than 5,400 Da and contained 45.7% hydrophobic amino acids. ::: ::: ::: CONCLUSION ::: Ultrasonic-assisted enzymatic hydrolysis can be applied to obtain favorable antioxidant hydrolysates from porcine liver with potential applications in food products for preventing lipid oxidation.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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A new drug-in-adhesive transdermal patch was developed to deliver both estradiol and levonorgestrel through the skin over a 7-day period, but at different rates. This report elucidates the in vitro and in vivo biopharmaceutical studies that were necessary during the development of this product. Three test patches had to be manufactured, all delivering estradiol at the same rate, but delivering levonorgestrel at three different rates so that a levonorgestrel dose response could be studied in the clinic. An in vitro hairless mouse skin model (HMS) using modified Franz diffusion cells was used to select the test products delivering levonorgestrel in the order of 1:2:3. HMS experiments also demonstrated that the presence of estradiol did not affect the flux of levonorgestrel. Two in vivo studies in postmenopausal women showed that at steady state (four weeks of once-weekly dosing) the three test products all delivered estradiol at comparable rates. Similarly, the levonorgestrel deliveries for the three test products were in the order expected. The target fluxes of both drugs were achieved in these three test products by varying the drug loads and patch size. That this approach was successful is evidence of the value of using the HMS penetration experiments in transdermal product development and should provide useful insights for other formulations having to develop complex systems. One of the test products is now marketed as Climara Pro.
PURPOSE ::: To screen crystallization inhibitors, perform accelerated stability testing and predict saturation solubility of levonorgestrel in drug-in-adhesive patches. ::: ::: ::: METHODS ::: Differential scanning calorimetry (DSC) studies were compared against slide crystallization studies for screening additives. Release studies were performed from crystallized and supersaturated patches. Die cutting was used for accelerated stability testing of patches. Time lag experiments were performed to predict saturation solubility of levonorgestrel in acrylate adhesive, DuroTak-2516. ::: ::: ::: RESULTS ::: DSC studies indicated poloxamer to be the best additive whereas slide crystallization studies showed polyvinylpyrrolidone to be better. Supersaturated patches showed higher release profiles relative to crystallized patches. Crystals were observed in crystallized patches even after 96 h of release studies. Die-cutting of patches helped in development of crystals in less time as compared to uncut sheets indicating its usefulness in accelerated stability testing. Saturation solubility of levonorgestrel in DuroTak-2516 was predicted to be 0.09% w/w which was in close agreement with value of 0.1% w/w from solubility calculator on vendor's website. ::: ::: ::: CONCLUSIONS ::: Crystallization was shown to have negative impact on drug release and patch performance. Slide crystallization studies, die cutting and time lag experiments can be used as tools to help stabilize the otherwise unstable patches.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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Levels of homovanillic acid and dopamine were measured in rat corpus striatum by gas chromatography—mass fragmentography. Steady-state levels of the compounds were 4.1 and 57 nmole/g respectively. After pargyline, 75 mg/kg, i.v., levels of homovanillic acid declined exponentially with a half life of 12 min. Dopamine increased about 40% within 80 min. From the steady-state level of homovanillic acid and its half life after monoamine oxidase inhibition the turnover rate of homovanillic acid in rat corpus striatum was calculated to 14 nmole/g/hr.
Dopamine levels in the neostriatum of the rat were estimated at various times after pargyline (75 mg/kg), pheniprazine (4 mg/kg) and tranylcypromine (20 mg/kg) intraperitoneal injections. Depending on the inhibitor used, the amine levels reached 135 to 150% of control values within 10 min. During the 20 min which followed this rapid linear rise, DA levels increased in tissues at a much slower rate. As indicated by the estimation of MAO activity using14C-tyramine or kynuramine as substrates, the three drugs induced a complete inhibition of the enzyme activity within 5 min. A similar effect was seen after pheniprazine and tranylcypromine with14C-dopamine as substrate, but the maximal inhibition never exceeded 80% after pargyline treatment. As revealed by the “in vivo” 3 min initial accumulation of3H-H2O seen at the end of a local infusion of L. 3. 5-3H-tyrosine, the rate of the first step of DA synthesis was unchanged 5 min after pargyline treatment but significantly reduced 10 min after the drug injection. This explains the sudden interruption in the rise of DA levels observed shortly after the MAO inhibitors injection. DA synthesis rate was calculated from the initial (5 min) rate of DA accumulation and was found to be 148 to 190 nmole/g/hr depending on the inhibitor used.
Polyamines (PAs) are natural compounds involved in many growth and developmental processes in plants, and, specifically in fruits, play a vital role regulating its development, ripening and senescence processes. Putrescine (PUT), spermine (SPE), and spermidine (SPD) are prominent PAs applied exogenously to extend shelf life of fruits. They also originate endogenously during developmental phases of horticultural crops and simultaneously affect the quality attributes and shelf life. Their anti-ethylene nature is being exploited to enhance the shelf life when exogenously applied on fruits. In growth and development of fruits, PA levels generally fall, which marks the beginning of senescence at postharvest phase. PUT, SPE and SPD treatments are being applied during postharvest phase to prolong the shelf life. They enhance the shelf life of fruits by reducing respiration rate, ethylene release and enhance firmness and quality attributes in fruits. PAs have a mitigating impact on biotic and abiotic stresses including chilling injury (CI) in tropical and sub-tropical fruits. PAs are environment friendly in nature and are biodegradable without showing any negative effect on environment. Biotechnological interventions by using chimeric gene constructs of PA encoding genes has boosted the research to develop transgenic fruits and vegetables which would possess inherent or in situ mechanism of enhanced biosynthesis of PAs at different stages of development and thereby will enhance the shelf life and quality in fruits. Internal and external quality attributes of fruits are improved by modulation of antioxidant system and by strengthening biophysical morphology of fruits by electrostatic interaction between PAs and phospholipids in the cell wall.
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The possibility of improving the detection sensitivity for boron with the use of mannitol as a chemical modifier in electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICP-MS) is presented. Experiments were performed by adding mannitol to a boron analyte solution to form a boron–mannitol complex and then injecting the resulting product into the ETV-ICP-MS system for determination. The effect of mannitol on the signal pulse of boron was investigated by monitoring the analyte through a heating cycle from 150 to 2600 °C. The appearance of several marked signal pulses at temperatures between 425 and 1500 °C was observed and assumed to result from the vaporization of boron–mannitol complexes. The signal intensity of boron in the presence of mannitol was found to be considerably enhanced in comparison with that in its absence. The optimization of the ETV and ICP parameters and the amount of mannitol added and the comparison of mannitol with different modifier systems were subsequently investigated. It was found that by following the established method the sensitivity for boron in the presence of mannitol can be improved by a factor of 84 compared with that without the modifier, and the limits of detection (3 s) achieved in the presence of mannitol can be as low as 0.2 ng ml–1 with a 20 µl injection. The large boron sensitivity enhancement in the presence of mannitol in ETV-ICP-MS is attributed to the formation of a boron–mannitol complex that is subsequently vaporized from the graphite surface and transported with the assistance of mannitol to the plasma. A novel application with mannitol, which acts both as a preconcentrating agent for boron in the chemical separation process and as a modifier in the ETV-ICP-MS for the determination of boron in trichlorosilane, is also presented.
This paper reviews techniques for determining B concentration and isotopic ratio and their application to soil and plant samples. Boron concentration has been determined utilising spectrophotometry, potentiometry, chromatography, flame atomic emission and absorption spectrometry, inductively coupled plasma (ICP) optical emission (OES) and mass spectrometry (MS), and neutron activation analysis using neutron radiography and prompt-γ activation analysis. Isotopic ratios of B have been measured by ICP–MS, thermal ionisation mass spectrometry (TIMS) and secondary ion mass spectrometry (SIMS). For isotopic measurements, TIMS and SIMS are more sensitive and provide higher degrees of accuracy and resolution than ICP–MS, however, extensive sample preparation and purification, and time-consuming measurements limit their usefulness for routine analyses.
A 49-year-old woman with traumatic brain injury after an automobile accident is found to have raised intracranial pressure, and hyperosmolar therapy is recommended. Hyperosmolar therapy with either hypertonic saline or mannitol reduces intracranial pressure by reducing brain volume.
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Therapeutic drug monitoring of immunosuppressive agents is a critical and essential part of patient therapy after organ transplantation. We have developed high-throughput, robust, and rapid liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) methods with common pretreatment procedures for simultaneous quantification of four immunosuppressive agents (everolimus, sirolimus, tacrolimus, and cyclosporin A) in whole blood and one immunosuppressant (mycophenolic acid) in plasma. The new approach used in this work is based on improved sample preparation procedures allowing the analysis of five immunosuppressive drugs. Whole blood was prepared by transferring 100 μL of blood into a 1.5-mL silanized conical test tube. Zinc sulfate solution (150 μL), containing deuterated internal standards, was added to perform hemolysis. The samples were vortexing for 10 s, followed by the addition of 250 μL acetonitrile, containing internal standard for cyclosporin A, to precipitate proteins. The mixture was vortexed for 1 min and centrifuged for 2 min at 14,000 rpm. The whole supernatant was transferred to a vial. To prepare blood plasma, the hemolysis step involving the addition of zinc sulfate was omitted and, instead of acetonitrile, methanol was used as the solvent for the internal standard (mycophenolic acid-d3). The volumes of chemicals used in this procedure were the same as those used in the procedure for immunosuppressants in whole blood. The basic validation parameters for the analytical methods were limits of detection (0.5 ng/mL for everolimus, sirolimus and tacrolimus, 25 ng/mL for cyclosporin A and 100 ng/mL for mycophenolic acid), precision ( 84%), repeatability and reproducibility. Possible mutual ion suppression was eliminated in the presence of internal standards. The method developed for the quantitation of immunosuppressants in whole blood was used to analyze 276 patient samples containing tacrolimus and 55 samples containing cyclosporin A. The results from LC/MS/MS were compared to those obtained from immunoassays of the same samples. Immunoassays significantly overestimated the concentrations of immunosuppressants.
The paper discusses some of the problems associated with the preparation and reversed-phase HPLC analysis of sirolimus samples in mixtures of water with methanol or acetonitrile with different content of the latter. It was shown that when the sirolimus samples were evaporated to dryness in polypropylene tubes, almost quantitative irreversible adsorption of the substance occurred. The loss of sirolimus can be avoided by using glass tubes for sample preparation when a complete removal of a solvent is necessary. Preparation of sirolimus samples in water–methanol or water-acetonitrile mixtures can lead to a gradual adsorption of the substance on the walls of a glass vial in case of a low organic solvent content. It was shown that a reconstitution solution containing about 50% of an organic solvent should be used to analyze sirolimus by the RP-HPLC method, since the analysis of samples dissolved in pure acetonitrile or methanol is limited by the amount of sample injected due to broadening or distortion of the chromatographic peak.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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Novel phenethylpyridone derivatives were identified as potent human melanin-concentrating hormone 1 receptor (MCH-1R) antagonists. A search for surrogates for the 4-(2-aminoethoxy)phenyl moiety of 1 resulted in discovery of 2-[4-(aminomethyl)phenyl]ethyl substructure as in 6a. Successive optimization of the right-hand moiety led to the identification of a number of potent derivatives.
Hypothalamic receptors for neuropeptide Y, melaninconcentrating hormone, melanocortins and orexins/ hypocretins as well as for the downstream signaling corticotrophic factor have been discussed broadly for their influence on food intake and reward but also on several psychiatric disorders. For the development of non-peptide ligands for the in vivo detection of alterations in density and affinity of such G-protein coupled (GPCRs) peptide receptors the requirements to affinity and pharmacokinetics have been shifted to thresholds markedly distict from classical GPCRs to dissociation constants ported originally as potential therapeutics in the treatment of obesity among which some are suitable candidates for labeling as PET or SPECT-tracers providing receptor affinities even below 0.1 nM. These could be unique tools not only for better understanding of the mechanism of obesity but also for investigations of extrahypothalamic role of “feeding receptors” at the interface between neuroendocrine and mental diseases.
Transfusion-dependent patients such as those suffering from β-thalassaemia develop a fatal secondary haemosiderosis and consequently a selective iron chelator must be used to relieve such iron overload. 3- Hydroxypyridin-4-ones are selective for iron(III) under most biological conditions, but unlike desferrioxamine, are efficiently absorbed when administered orally. In this study, the synthesis and determination of partition coefficients (Kpart) of a range of 1-substituted-2-ethyl-3-hydroxypyridin-4-ones, as orally active iron chelators, are described. All of the 1-substituted-2-ethyl-3-hydroxypyridin-4-ones were synthesized via a three step synthetic pathway. The commercially available 2-ethyl-3-hydroxypyran-4-one (ethyl maltol) was benzylated in aqueous methanol. The reaction product of the benzylated ethyl maltol with an excess of the suitable primary aryl amines was heated in a thick-walled sealed glass tube at 150-160 oC to give 1-aryl-2-ethyl-3-benzyloxypyridin-4-one derivatives which were isolated as the free-bases. Removal of the benzyl group under acidic conditions was performed by catalytic hydrogenation to yield the bidentate chelators as HCl salt in good yield. In this work, final following compounds of 1-phenyl-2-ethyl-3- hydroxypyridin-4-one, 1-(4-methylphenyl)-2-ethyl-3-hydroxypyridin-4-one, 1-(4-methoxylphenyl)-2-ethyl- 3-hydroxypyridin-4-one, and 1-(4-nitrophenyl)-2-ethyl-3-hydroxypyridin-4-one were synthesized. Identifcation and structural elucidation of ligands were achieved by 1HNMR, IR, elemental analysis, mass spectra and through physical experiments. The Kpart values of the compounds were also determined in an aqueous/octanol system using an automated continuous flow method (a filter probe method).
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A sensitive and selective aptasensor using tri(2,2'-bipyridyl)ruthenium(II)-doped silica nanoparticles (Ru(bpy)3(2+)-doped SNPs) as DNA tags for detection of thrombin is developed based on the target protein-induced strand displacement of the DNA probe. For the proposed aptasensor, the aptamer was assembled on the surface of the Au electrode through Au-S binding. The hybridization event between the DNA probe labeled by the Ru(bpy)3(2+)-doped SNPs and the aptamer was evaluated by electrogenerated chemiluminescence (ECL) measurements. Then, the DNA probe was displaced by thrombin and the binding event between the thrombin and the aptamer was monitored by ECL measurements again. The difference of ECL intensity (deltaI(ECL)) of the two events could be used to quantify the thrombin. Other proteins, such as bovine serum albumin and bovine hemoglobin, had almost negligible deltaI(ECL). Under the optimal conditions, the deltaI(ECL) was linearly related to the concentration of the thrombin in the range of 10 fM to 10 pM and the detection limit was down to 1.0 fM since SNPs containing a large number of Ru(bpy)3(2+) molecules were labeled on the DNA probe.
The article describes a method for the determination of thrombin that is based on the use of gold nanoparticles (AuNPs) functionalized with an aptamer labeled with a horseradish peroxidase mimick. The assay is based on (a) the high affinity between aptamer and thrombin, and (b) on the finding that AuNPs display HRP-like properties in catalyzing the oxidation of 3,3,5,5-tetramethylbenzidine to give a blue reaction product with an absorption maximum at 652 nm. The limit of detection for thrombin is as low as 0.02 pM, and the analytical range extends from 0.1 pM to 0.1 μM thrombin. The aptamer-based assay was successfully applied to the quantitation of thrombin in spiked human serum. This method is simple, inexpensive and highly sensitive.
We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero.
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Sudan I is a carcinogenic and mutagenic azo-compound that has been utilized as a common adulterant in spice and spice blends to impart a desirable red color to foods. A novel biosensor combining molecularly imprinted polymers (MIPs), thin layer chromatography (TLC) and surface enhanced Raman spectroscopy (SERS) could determine Sudan I levels in paprika powder to 1 ppm (or 2 ng/spot). Sudan I spiked paprika extracts (spiking levels: 0, 1, 5, 10, 40, 70 and 100 ppm) were prepared. Sudan I imprinted polymers were synthesized by employing the interaction between Sudan I (template) and methacrylic acid (functional monomer), followed by washing to remove Sudan I leaving the Sudan I-binding sites exposed. MIPs were used as a stationary phase for TLC and could selectively retain Sudan I at the original spot with little interference. A gold colloid SERS substrate could enhance Raman intensity for Sudan I in this MIP-TLC system. Principal component analysis plot and partial least squares regression (R(2)=0.978) models were constructed and a linear regression model (R(2)=0.983) correlated spiking levels (5, 10, 40, 70 and 100 ppm) with the peak intensities (721 cm(-1)) of Sudan I SERS spectra. Both separation (30-40s) and detection (1s or 0.1s) were extremely fast by using both commercial bench-top and custom made portable Raman spectrometers. This biosensor can be applied as a rapid, low-cost and reliable tool for screening Sudan I adulteration in foods.
Food colorants are inalienable part of human life. Since ancient times, they have become firmly established and have undergone a number of changes. During this time, the attitude towards them has changed. The desire to color the food now raises questions about the various side effects of their use. With the development of methods of toxicology and obtaining data on the toxicity of food coloring, restrictions and standards for their content in food have emerged. The development of methods for the analysis of dyes in various food products is becoming increasingly in demand. Development of screening immunoanalytical methods such as enzyme-linked immunoassay and immunochromatographic one suitable for simultaneous analysis of a large number of samples at the same time allows to avoid serious costs when operating the chromatographic equipment. Reduction of the analysis time and simple sample preparation is what unites immunoassay techniques. This review shows the possibilities of modern immunoanalytical methods for analyzing samples and determining food dyes belonging to different classes. Graphical
We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero.
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Epoxyeicosatrienoic acids (EETs) are cytochrome P-450 metabolites of arachidonic acid involved in the regulation of vascular tone. The method of microbore column high-performance liquid chromatography with fluorescence detection was developed to determine 14,15-EET, 11,12-EET, and the mixture of 8,9-EET and 5,6-EET. Tridecanoic acid (TA) was used as an internal standard. EETs were reacted with 2-(2,3-naphthalimino)ethyl trifluoromethanesulfonate (NT) to form highly fluorescent derivatives. A C18 microbore column and a water-acetonitrile mobile phase were used for separation. Samples were excited at 259 nm, and the fluorescence was detected at 395 nm. The overall recoveries were 88% for EETs and 40% for TA. EETs were detected in concentrations as low as 2 pg (signal-to-noise ratio = 3). The method was used to determine the EET production from endothelial cells (ECs). Bradykinin and methacholine (10−6 M) stimulated an increase in the production of EETs by ECs two- and fivefold, respectively. This sensitive ...
Oxylipins are potent lipid mediators derived from polyunsaturated fatty acids, which play important roles in various biological processes. Being important regulators and/or markers of a wide range of normal and pathological processes, oxylipins are becoming a popular subject of research; however, the low stability and often very low concentration of oxylipins in samples are a significant challenge for authors and continuous improvement is required in both the extraction and analysis techniques. In recent years, the study of oxylipins has been directly related to the development of new technological platforms based on mass spectrometry (LC–MS/MS and gas chromatography–mass spectrometry (GC–MS)/MS), as well as the improvement in methods for the extraction of oxylipins from biological samples. In this review, we systematize and compare information on sample preparation procedures, including solid-phase extraction, liquid–liquid extraction from different biological tissues.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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Background ::: Methylene blue was used as a vital stain for the assessment of viability of protoscolices from hydatid cysts taking advantage of the chemical nature of the dye as a redox indicator and the kinetically distinct molecular transfer systems of Echinococcus protoscolex for uptake of materials across the tegument. ::: ::: ::: Aim ::: The present study attempts to validate the application of methylene blue staining for assessment of viability of protoscolices. ::: ::: ::: Methods ::: To validate the criteria by which viability is assessed, control tests were performed using normal protoscolices and protoscolices previously treated with distilled water at 60°C for 5 minutes. Performance of methylene blue was further studied at intervals over a period of 50 minutes after protoscolex exposure using 1% dye concentration. ::: ::: ::: Results ::: Normal protoscolices were able to adsorb and reduce the dye and have, therefore, lost the blue color. Protoscolices previously treated with warm water on the other hand, being functionally dead, failed to reduce the adsorbed dye and permanently retained the blue color. Results also indicated that a clear distinction between dead and alive protoscolices can be made within 1 minute. Reading of the test after 10 minutes would be misleading giving a false result. ::: ::: ::: Conclusion ::: These findings suggest that viability of protoscolices can be assessed on the basis of acquisition and loss/retaining of the dye blue color. Increasing the concentration of methylene blue to 1% was noticed to be associated with remarkable enhancement of contractility, sucker movement, and evagination. Such an excitatory action of the dye may be exploited in viability tests which adopt these criteria.
Protoscoleces of Echinococcus granulosus (horse strain) were found to absorb, by a combination of mediated transport and passive diffusion, 10 L-amino acids, 1 D-amino acid (D-alanine) and D(+)glucose. The L-amino acids enter the protoscolex through four, kinetically distinct, transport systems. Secondary hydatid cysts were also found to absorb and accumulate 4 amino acids, but at a far slower rate than the protoscoleces. Entry into the cyst wall component appears to occur by passive diffusion but, for L-threonine at least, entry into the fluid-filled interior is by mediated transport. A synthetic polymer (PVP) was found to enter the cyst by endocytosis. Analysis of hydatid fluid and host blood indicates that amino acids are accumulated to varying degrees in the cyst, the values obtained resembling those achieved during in vitro experiments. The relevance of these studies to drug targeting is discussed.
By using a superluminescent diode as the light source and a depolariser inside the fibre coil, a constant scale factor is achieved without using polarisation control elements. For long-term behaviour an RMS-bias drift of 10 degrees/h is obtained.
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We have developed a new, quick and efficient method of high-performance liquid chromatography (HPLC) for the isolation and quantitative determination of phospholipids in hepatocyte membranes. A silica gel column was used for the isolation and determination, and an isocratic mixture of acetonitrile, methanol and 85% phosphoric acid (130:5:1.7, v/v/v) was used as a mobile phase. Six kinds of phospholipids, i.e. phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphinogomyelin (SPH), in this order, were completely isolated within 45 min. The phospholipid composition of sinusoidal membrane vesicles (SMV) and canalicular membrane vesicles (CMV) obtained from rat liver, as well as of human erythrocyte ghosts were determined by this HPLC method. The level of SPH in CMV was significantly higher than that in SMV, and the level of PC in CMV was significantly lower than that in SMV. These results were considered attributable to the low fluidity of CMV. The phospholipid composition of human erythrocyte membrane was different from that of rat SMV and CMV. The present technique is suitable for quantitative determination of phospholipids in cell membranes.
The effects of the ionic strength and pH of the hemolyzing solution on the hemoglobin content of human erythrocyte ghosts were studied in phosphate buffers and found to have a pronounced influence upon hemoglobin binding in the ghosts. Buffer concentrations between 10 and 20 ideal milliosmolar (imOsm), at pH values 5.8 – 8.0, resulted in maximum hemoglobin removal from ghosts. The pH optimum for hemoglobin binding to ghosts was between 5.8 and 5.9 in a 20 imOsm buffer. The influence of these variables suggest an electrophysical interaction of hemoglobin with membrane constituents. This study provides a basis for comparison of existing methods for ghost preparation, as well as a means for prediction of the conditions required for preparation of ghosts containing any desired amount of hemoglobin. Conditions were found that allowed the preparation of hemoglobin-free ghosts by single-stage hemolysis and washing. Hemoglobin-free ghosts were prepared in 20 imOsm phosphate buffer at pH 7.4. Essentially all the lipid was recovered in the ghosts, but non-hemoglobin nitrogen-containing substances were lost. The pyridine hemochromogen method for hemoglobin determination was adapted for the measurement of very small quantities of hemoglobin through use of the Soret band (418 mμ) for absorbancy measurements.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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A simple, sensitive, rapid, precise, cost effective and reproducible UV spectrophotometric method has been developed for estimation of Rizatriptan Benzoate in bulk and tablet dosage form. Rizatriptan benzoate shows maximum absorbance at 225 nm with molar absorptivity of 8.9583×104 l/mol.cm. Beer's law was obeyed in the concentration range of 1–10 μg/ml. Results of analysis were validated by statistical analysis and by recovery studies. The method was validated with respect to linearity, precision, LOD, LOQ, Sandell's sensitivity and specificity. The proposed method was found to be accurate and precise for routine estimation of Rizatriptan Benzoate in bulk and tablet dosage forms.
Two simple, sensitive, accurate, precise and economical spectrophotometric methods have been developed and validated for the determination of rizatriptan benzoate (RZT) in pure form and pharmaceutical formulations. These methods were ::: based on the formation of charge transfer complex between RZT as n-electron donor and alizarin red S (ARS) or ::: quinalizarin (Quinz) as π-acceptor in methanol to form highly colored chromogens which showed an absorption ::: maximum at 532 and 574 nm using ARS and Quinz, respectively. The optimization of the reaction conditions such as the ::: type of solvent, reagent concentration and reaction time were investigated. Under the optimum conditions, Beer’s law is ::: obeyed in the concentration ranges 1.0-16 and 2.0-20 g mL-1 using ARS and Quinz, respectively with good correlation ::: coefficient (r2 ≥ 0.9996) and with a relative standard deviation (RSD% ≤ 1.16). The molar absorptivity, Sandell ::: sensitivity, detection and quantification limits were also calculated. The methods were successfully applied to the ::: determination of RZT in its pharmaceutical formulations and the validity assesses by applying the standard addition ::: technique. Results obtained by the proposed methods for the pure RZT and commercial tablets agreed well with those ::: obtained by the reported method.
Two simple, sensitive, accurate, precise and economical spectrophotometric methods have been developed and validated for the determination of rizatriptan benzoate (RZT) in pure form and pharmaceutical formulations. These methods were ::: based on the formation of charge transfer complex between RZT as n-electron donor and alizarin red S (ARS) or ::: quinalizarin (Quinz) as π-acceptor in methanol to form highly colored chromogens which showed an absorption ::: maximum at 532 and 574 nm using ARS and Quinz, respectively. The optimization of the reaction conditions such as the ::: type of solvent, reagent concentration and reaction time were investigated. Under the optimum conditions, Beer’s law is ::: obeyed in the concentration ranges 1.0-16 and 2.0-20 g mL-1 using ARS and Quinz, respectively with good correlation ::: coefficient (r2 ≥ 0.9996) and with a relative standard deviation (RSD% ≤ 1.16). The molar absorptivity, Sandell ::: sensitivity, detection and quantification limits were also calculated. The methods were successfully applied to the ::: determination of RZT in its pharmaceutical formulations and the validity assesses by applying the standard addition ::: technique. Results obtained by the proposed methods for the pure RZT and commercial tablets agreed well with those ::: obtained by the reported method.
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A novel and efficient device of solvent stir-bar microextraction (SSBME) system coupled with GC-FID detection was introduced for the pre-concentration and determination of malondialdehyde (MDA) in different biological matrices. In the proposed device, a piece of porous hollow fiber was located on a magnetic rotor by using a stainless steel-wire (as a mechanical support) and the whole device could stir with the magnetic rotor in sample solution cell. The device provided higher pre-concentration factor and better precision in comparison with conventional SBME due to the reproducible, stable and high contact area between the stirred sample and the hollow fiber. Organic solvent type, donor and acceptor phase pH, temperature, electrolyte concentration, agitation speed, extraction time, and sample volume as the effective factors on the SSBME efficiency, were examined and optimized. Pure tris-(2-ethylhexyl) phosphate (TEHP) was examined for the first time as supported liquid membrane (SLM) for the determination of MDA by SSBME method. In contrast to the conventional SLMs of SBME in the literature, the SLM of TEHP was highly stable in contact with biological fluids and provided the highest extraction efficiency. Under optimized extraction conditions, the method provided satisfactory linearity in the range 1-500 ng mL-1, low LODs (0.3-0.7 ng mL-1), good repeatability and reproducibility (RSD% (n = 5) < 4.5) with the pre-concentration factors higher than 130-fold. To verify the accuracy of the proposed method, the traditional spectrophotometric TBA (2-thiobarbituric acid) test was used as a reference method. Finally, the proposed method was successfully applied for the determination and quantification of MDA in biological fluids.
In this research, for the first time, a new strategy based on ion pair–based solvent bar liquid-phase microextraction (IP-SB-LPME) in combination with GC instrument was introduced for sensitive determination of malondialdehyde (MDA) in lipid-rich foods. In this three-phase process, a cationic surfactant was added initially into alkaline donor solution to form hydrophobic ion pair with the anionic analyte. Then, the ion pair formed was enriched into organic solvent immobilized in the pores of the HF and finally back extracted into an acidified acceptor phase in the lumen of the fiber. Significant parameters affecting the proposed method were optimized to obtain the maximum preconcentration factor. Under the optimized conditions, the method provided good linearity in the range of 3–600 μg L−1 in pure water, 65.0–6875.0 μg kg−1 in infant powder milk, and 52.5–6875.0 μg kg−1 in vegetable oils. Acceptable repeatability and reproducibility (CV < 4%) with preconcentration factors in the range of 82–100 times were obtained. Methodological validation was accomplished by using the conventional spectrophotometric TBA (2-thiobarbituric acid) test. Finally, this procedure was applied to monitor trace amounts of MDA in the lipid-rich foods with satisfactory results.
Physical training is known to induce oxidative stress in individuals subjected to intense exercise. In this study, we investigated plasma malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) activity of 25 young male footballers and a control group of similar age. Red blood cell (RBC) count, haemoglobin (Hb) and haematocrit (Hct) values, and copper (Cu) and zinc (Zn) levels were also examined. The maximal oxygen uptake of all subjects was determined in order to establish their functional capacity. The main finding of the present study was that plasma MDA levels, one of the most commonly used markers of lipid peroxidation, of this group of footballers aged under 21 decreased slightly when compared with those of the control group (p and SOD (r=0.42; p
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Three phase partitioning is a process in which mixing t -butanol with ammonium sulphate with a protein solution leads to the formation of three phases. Generally, the interfacial protein precipitate (formed between upper t -butanol rich and lower aqueous phase) can be easily dissolved back in aqueous buffers. In case of ovalbumin, this led to a precipitate which was insoluble in aqueous buffers. This precipitate when solubilized with 8 M urea and subjected to three phase partitioning under various conditions led to many refolded soluble conformational variants of ovalbumin. One of these showed trypsin inhibitory activity, had marginally higher β-sheet content and had higher surface hydrophobicity (both with respect to native ovalbumin). Scanning electron microscopy and Atomic force microscopy of this preparation showed a thread like structure characteristic of amyloid fibrils. The behaviour of ovalbumin during three phase partitioning makes it a valuable system for gaining further understanding of protein aggregation.
ABSTRACT In recent years, a big trend has been the development of rapid, green, efficient, economical, and scalable approaches for the separation and purification of bioactive molecules from natural sources, which can be used in food, cosmetics, and medicine. As a new nonchromatographic bioseparation technology, three-phase partitioning (TPP) is attracting the attention of a growing number of scientists and engineers. Although a number of studies have been published in the last 40 years regarding the extraction, separation, and purification of numerous bioactive molecules using TPP systems, a background review on TPP partitioning fundamentals and its applications is much needed. Therefore, the present review focuses in detail on the TPP separation process, including the definition of TPP, partitioning mechanisms, parameters for establishing the suitable condition to form precipitate such as concentration of ammonium sulfate, content of tert-butanol, pH and temperature, and the application for separation and purification of protein, enzyme, plant oil, polysaccharide, and other small molecule organic compounds. In addition, the possible directions of future developments in TPP technology are discussed. The review presents a good opportunity, as well as a challenge for scientists, to understand the detailed partitioning rule and to take better use of TPP for the production and separation of various bioactive molecules, which have been intensively applied in the food and medical fields.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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Heparin, heparan sulphate, and various derivatives thereof have been oxidised with periodate at pH 3.0 and 4° and at pH 7.0 and 37°. Whereas oxidation under the latter conditions destroys all of the nonsulphated uronic acids, treatment with periodate at low pH and temperature causes selective oxidation of uronic acid residues. The reactivity of uronic acid residues depends on the nature of neighbouring 2-amino-2-deoxyglucose residues. d -Glucuronic acid residues are susceptible to oxidation when flanked by N -acetylated amino sugars, but resistant when adjacent residues are either unsubstituted or N -sulphated. L -Iduronic acid residues in their natural environment (2-deoxy-2-sulphoamino- d -glucose) are resistant to oxidation, whereas removal of N -sulphate groups renders a portion of these residues periodate-sensitive. Oxidised uronic acid residues in heparin-related glycans may be cleaved by alkali, producing a series of oligosaccharide fragments. Thus, periodate oxidation-alkaline elimination provides an additional method for the controlled degradation of heparin.
The chapter will review early and more recent seminal contributions to the discovery and characterization of heparanase and non-anticoagulant heparins inhibiting its peculiar enzymatic activity. Indeed, heparanase displays a unique versatility in degrading heparan sulfate chains of several proteoglycans expressed in all mammalian cells. This endo-β-D-glucuronidase is overexpressed in cancer, inflammation, diabetes, atherosclerosis, nephropathies and other pathologies. Starting from known low- or non-anticoagulant heparins, the search for heparanase inhibitors evolved focusing on structure-activity relationship studies and taking advantage of new chemical-physical analytical methods which have allowed characterization and sequencing of polysaccharide chains. New methods to screen heparanase inhibitors and to evaluate their mechanism of action and in vivo activity in experimental models prompted their development. New non-anticoagulant heparin derivatives endowed with anti-heparanase activity are reported. Some leads are under clinical evaluation in the oncology field (e.g., acute myeloid leukemia, multiple myeloma, pancreatic carcinoma) and in other pathological conditions (e.g., sickle cell disease, malaria, labor arrest).
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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A quantitative bioanalytical method involving chemical derivatization, solid phase extraction (SPE) and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) was developed for the determination of 4-fluorobenzyl chloride (4FBCl) in human plasma. 4FBCl is a volatile and reactive molecule that is very unstable in human plasma. In order to stabilize 4FBCl in plasma samples prior to storage, 4-dimethylaminopyridine (DMAP) was added, forming a stable quaternary amine salt derivative. A three-step weak cation-exchange SPE procedure was then employed to remove excess DMAP. The plasma extracts were analyzed by HPLC/MS/MS using a TurboIonspray interface and multiple reaction monitoring. Unlike 4FBCl, the quaternary amine derivative shows excellent sensitivity in electrospray mass spectrometry. The method was validated over a concentration range of 0.5–500 ng/mL using 45 μL of plasma. The maximum within-run and between-run precision observed in a three-run validation for quality control (QC) samples was 12.5 and 7.6%, respectively. The maximum percentage bias observed at all QC sample concentrations was 11.9%. The method has proven to be robust and compatible with high-throughput bioanalysis. Copyright © 2005 John Wiley & Sons, Ltd.
This is the first of two reviews devoted to derivatization approaches for "soft" ionization mass spectrometry (FAB, MALDI, ESI, APCI) and deals, in particular, with small molecules. The principles of the main "soft" ionization mass spectrometric methods as well as the reasons for derivatizing small molecules are briefly described. Derivatization methods for modification of amines, carboxylic acids, amino acids, alcohols, carbonyl compounds, monosaccharides, thiols, unsaturated and aromatic compounds etc. to improve their ionizability and to enhance structure information content are discussed. The use of "fixed"-charge bearing derivatization reagents is especially emphasized. Chemical aspects of derivatization and "soft" ionization mass spectrometric properties of derivatives are considered.
We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero.
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A novel phosphate prodrug system for amines, amino acids, peptides, and peptide mimetics, which utilizes a fast hydroxy amide lactonization of a 3-(2‘-hydroxy-4‘,6‘-dimethylphenyl)-3,3-dimethylpropionic amide system, was developed. Prodrugs of five model amine/amino acids, including p-anisidine, GlyOMe, PheOMe, LysOMe, and Asp-α-OMe, were synthesized. The syntheses of these model phosphate prodrugs were accomplished by coupling the amine or the protected amino acids with 3-[2‘-(dibenzylphosphono)oxy-4‘,6‘-dimethylphenyl]-3,3-dimethylpropionic acid using coupling agents such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride and 1-(3-dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride, followed by hydrogenolysis. These phosphate prodrugs were evaluated as substrates for the human placental alkaline phosphatase (AP). The structural features of the amine/amino acids attached to the carboxylic acid group of the promoiety were not found to significantly affect the substrate activity for AP, as evidenced by th...
The purpose of this work is to review the published strategies for the productionof prodrugs of amines. The review is divided in two main groups of approaches: those thatrely on enzymatic activation and those that take advantage of physiological chemicalconditions for release of the drugs. A compilation of the most important approaches ispresented in the form of a table, where the main advantages and disadvantages of eachstrategy are also referred.
Colon cancer is the second most common cause of cancer deaths in the USA and Europe. Despite aggressive therapies, many tumors are resistant to current treatment protocols and epidemiological data suggest that diet is a major factor in the etiology of colon cancer. This study aimed to evaluate the antioxidant activity and the influence of 3,4-dihydroxyphenylacetic (3,4-DHPAA), p-coumaric (p-CoA), vanillic (VA) and ferulic (FA) acids on cell viability, cell cycle progression, and rate of apoptosis in human colon adenocarcinoma cells (HT-29). The results showed that all compounds tested reduce cell viability in human colon cancer cells. 3,4-DHPAA promoted the highest effect antiproliferative with an increase in the percentage of cells in G0/G1 phase, accompanied by a reduction of cells in G2/M phase. Cell cycle analysis of VA and FA showed a decrease in the proportion of cells in G0/G1 phase (10.0 µM and 100.0 µM). p-CoA and FA acids increased the percentage of apoptotic cells and non-apoptotic cells. 3,4-DHPAA seems to be the substance with the greatest potential for in vivo studies, opening thus a series of perspectives on the use of these compounds in the prevention and treatment of colon cancer.
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The terahertz region of the electromagnetic spectrum spans the frequency range between the infrared and the microwave. Traditionally the exploitation of this spectral region has been difficult owing to the lack of suitable source and detector. Over the last ten years or so, terahertz technology has advanced considerably with both terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) instruments now commercially available. This review outlines some of the recent pharmaceutical applications of terahertz pulsed spectroscopy and imaging. The following application areas are highlighted: (1) discrimination and quantification of polymorphs/hydrates, (2) analysis of solid form transformation dynamics, (3) quantitative characterisation of tablet coatings: off-line and on-line, (4) tablet coating and dissolution, (5) spectroscopic imaging and chemical mapping. This review does not attempt to offer an exhaustive assessment of all anticipated pharmaceutical applications; rather it is an attempt to raise the awareness of the emerging opportunities and usefulness offered by this exciting technology.
Absorption spectra of polycrystalline L-, D-, and DL-tartaric acid have been measured by terahertz time domain spectroscopy (THz-TDS). Different absorption bands are observed for DL-tartaric acid and its enantiomers (L- and D-tartaric acid). This result shows that the THz-TDS can be used for distinguishing between DL-tartaric acid and enantiomers (L- and D-tartaric acid). Moreover, partial least square (PLS) can be found to improve the quantitation of L-tartaric acid in L- and DL-tartaric acid mixture by THz-TDS.
Berzelius failed to make use of Faraday's electrochemical laws in his laborious determination of equivalent weights.
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trans-Methyl styryl ketone (MSK; trans-4-phenyl-3-buten-2-one) is a beta-unsaturated ketone that has a wide range of uses in industry, as well as consumer products. MSK does not appear to be overtly toxic in animal models, however, it has been shown to be mutagenic in several in vitro assays after S-9 activation. In this study experiments were conducted to characterize MSK absorption, distribution, metabolism, and elimination after iv, oral, and topical administration to female B6C3F1 mice. After iv administration, [14C]MSK (20 mg/kg; 120 microCi/kg) was rapidly cleared from the blood as evidenced by the following pharmacokinetic values (mean +/- SD): terminal disposition half-life (t1/2), 7.98 +/- 1.72 min; mean residence time, 5.6 +/- 1.7 min; steady-state apparent volume of distribution (Vss), 3.33 +/- 0.75 liters/kg; and systemic body clearance (CLs), 0.53 +/- 0.05 liters/min/kg. Within 48 hr, 92.4% of the dose was excreted in the urine and 3.5% in the feces. The major blood metabolites after iv administration were identified by GC-MS as the 4-phenyl-3-buten-2-ol (methyl styryl carbinol), 4-hydroxy-4-phenyl-2-butanone, and benzyl alcohol. After oral administration of [14C]MSK (200 mg/kg; 100 microCi/kg), 95% of the dosed radioactivity was recovered in the urine and 1.2% in the feces within 48 hr. Major urinary metabolites were identified by LC-MS/MS as N-phenylacetyl-l-glycine (35.1% of dose) and N-benzyl-L-glycine (19.1% of dose). Only a small amount of MSK was detected in the blood after oral administration ( approximately 0.73 microg/ml at 10 min), and [14C]-equivalents in the blood never exceeded 2.8% of the dose. Ater topical application of [14C]MSK (250 mg/kg; 50 microCi/kg), approximately 40% of the dose was absorbed and 84.5% of the absorbed dose was excreted into the urine (36% of the total dose). Urinary metabolites were similar to those described for oral administration. Importantly, [14C]-equivalents were not detected in the blood at any time after dermal administration. These results indicate that the rate of MSK clearance is equivalent to its rate of absorption, and tissue exposure to intact MSK is expected to be limited.
The metabolism of trans-[3-14C]cinnamaldehyde was investigated in male and female Fischer 344 rats and CD1 mice at doses of 2 and 250 mg/kg body weight given by ip injection and in males at 250 mg/kg by oral gavage. Some 94% of the administered dose was recovered in the excreta in 72 hr in both species with most (75–81%) present in the 0–24-hr urine. Less than 2% of the administered dose was found in the carcasses at 72 hr after dosing. Urinary metabolites were identified by their chromatographic characteristics. In both species the major urinary metabolite was hippuric acid accompanied by 3-hydroxy-3-phenylpropionic acid, benzoic acid and benzoyl glucuronide. The glycine conjugate of cinnamic acid was formed to a considerable extent only in the mouse. The oxidative metabolism of cinnamaldehyde essentially follows that of cinnamic acid, by β-oxidation analogous to that of fatty acids. Apart from the metabolites common to cinnamic acid and cinnamaldehyde, 7% of 0–24-hr urinary 14C was accounted for by two new metabolites in the rat and three in the mouse, which have been shown in other work to arise from a second pathway of cinnamaldehyde metabolism involving conjugation with glutathione. The excretion pattern and metabolic profile of cinnamaldehyde in rats and mice are not systematically affected by sex, dose size and route of administration. The data are discussed in terms of their relevance to the safety evaluation of trans-cinnamaldehyde, particularly the validity or otherwise of extrapolation of toxicity data from high to low dose.
We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero.
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Basic Principles, Characteristics, and Selection of Open Tubular Columns in Gas Chromatography (F. Onuska). Characteristics of Modern GC Instrumentation (C. Tashiro & R. Clement). Multidimensional Gas Chromatography: Techniques and Applications (W. Ligon). The Mass Spectrometer as a Gas Chromatographic Detector (E. Reiner & R. Clement). Qualitative and Quantitative Methods of Analysis for Gas Chromatography (R. St. Louis & H. Hill). Derivatization Techniques (V. Taguchi). Gas Chromatography Profiling in Biomedical Investigations (J. Rosenfeld). Fatty Acids, Fatty Acids Containing Lipids, and Their Gas Chromatographic Analysis (F. Muskiet & J. Van Doormaal). The Progress of Analytical Chemistry in Sport Drug Testing (A. Viau). Amino Acids (S. MacKenzie). GC--MS Analysis of Human Plasma (V. Taguchi). Gas Chromatography of Microorganisms (G. Eiceman, et al.). Applications of Gas Chromatography in Clinical and Forensic Toxicology (P. Beaumier & R. Leavitt). Gas Chromatography of Organometallic Compounds (G. Eiceman). Index.
A method for profiling arachidonic acid metabolites by radio gas chromatography (GC) is described. The incubation mixture of rabbit platelets with [14C]arachidonic acid was purified on a Sep-Pak C18 cartridge and derivatized with diazomethane,O-methylhydroxylamine and dimethylisopropylsilylimidazole. The recovery of total14C-radioactivity was 93.1±7.2%. Loss of radioactivity during derivatization was negligible. Baseline separations for [14C]arachidonic acid and its metabolites were obtained in a single run within 45 min by GC using a synchronized accumulating radioisotope detector (GC/SARD). The recovery of radioactivity from the GC column was virtually 100%. The chemical structures of the metabolites were confirmed by GC/mass spectrometry; peaks of arachidonic acid metabolites were assigned by comparison of the methylene unit values with those of radioactive peaks in GC/SARD analyses. The intra-assay coefficients of variation in GC/SARD analyses were less than 10%. The method was used to map the profile of arachidonic acid metabolites formed by rabbit platelets in the presence of indomethacin, baicalein or glutathione.
Blunt trauma abdomen rarely leads to gastrointestinal injury in children and isolated gastric rupture is even rarer presentation. We are reporting a case of isolated gastric rupture after fall from height in a three year old male child.
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In Streptomyces hydrogenans the uptake of basic amino acids occurs via several transport systems: 1. 1. One system (System b Arg ) is highly specific for arginine ( K m = 7.10−6 M ). l -Arginine influx is only inhibited by closely related analogs such as d -arginine, canavanine and arginine methyl ester, but not by lysine, ornithine, neutral and acidic amino acids. 2. 2. A second system (System b Arg/Lys ) transports both arginine ( K m = 0.6 · 10−6 M) and lysine ( K m = 0.9·10−6 M ). This system has a higher affinity for l -arginine than System b Arg . Cells grown in synthetic media containing 12 mM l -lysine or l -arginine show a much higher transport capacity than cells grown in complete media or synthetic media with NH 4 Cl as nitrogen donor. These differences in transport capacity strongly support the multi-component concept of basic amino acid transport in Streptomyces cells. System b Arg/Lys can be inhibited by analogs of arginine and lysine but not by neutral and acidic amino acids. 3. 3. At very high extracellular concentrations of lysine or arginine both amino acids are transported via a system primarily mediating the uptake of neutral amino acids (System n ). The capacity of this system is high but its affinity to basic amino acids is very low [ K m (arginine) = 0.7·10−3 M; K m (lysine) = 1.6·10−3 M]. This system shows exchange between neutral and basic amino acids.
The uptake of various amino acids into Streptomyces hydrogenans grown in chemostatically and turbidostatically controlled steady state cultures has been investigated. A close correlation between transport capacity and the growth rates of the cells was found. As shown by kinetic analysis, the increased transport is due to elevated maximum uptake rates, the apparent Michaelis constants remaining unchanged. Analysis of the unidirectional fluxes of cycloleucine revealed that not only the influx is raised as the growth rate is increased but also the efflux. Hence, the conclusion is drawn that the growth-rate dependent modulation of transport capacity is, at least, partially due to the variation of the concentration of active transport components. Since the cells were grown in the absence of external amino acids the results suggest that amino acid transport into S. hydrogenans is under control of endogenous effectors.
Autism is a developmental, cognitive disorder clinically characterized by impaired social interaction, communication and restricted behaviours. The present study was designed to explore whether an abnormality in transport of tyrosine and/or alanine is present in children with autism. Skin biopsies were obtained from 11 children with autism (9 boys and 2 girls) fulfilling the DSM-IV diagnostic criteria for autistic disorder and 11 healthy male control children. Transport of amino acids tyrosine and alanine across the cell membrane of cultured fibroblasts was studied by the cluster tray method. The maximal transport capacity, V(max) and the affinity constant of the amino acid binding sites, K(m), were determined. Significantly increased V(max) for alanine (p=0.014) and increased K(m) for tyrosine (p=0.007) were found in children with autism. The increased transport capacity of alanine across the cell membrane and decreased affinity for transport sites of tyrosine indicates the involvement of two major amino acid transport systems (L- and A-system) in children with autism. This may influence the transport of several other amino acids across the blood-brain-barrier. The significance of the findings has to be further explored.
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Porphyria cutanea tarda (PCT)-like photosensitivity eruptions have occurred in patients treated with naildixic acid, furosemide (Lasix), or tetracycline. An animal model for nalidixic acid photosensitivity was developed in young CF-1 female mice. The hair on the back was plucked from groups of animals that were injected i.p, each day with nalidixic acid or saline. The animals were exposed to black-lamp radiation for 12 h daily for 6 weeks, followed by a 2-week rest period, and then 4 more weeks of UV radiation exposure. The nalidixic acid-treated animals developed far greater gross and chronic inflammatory changes than the saline-treated animals; microscopically and ultrastructurally they showed blister formation beneath the basal lamina at the same level as that found in PCT. This model appears to be suitable for the study of PCT-like and other photosensitivity reactions.
Pseudoporphyria (PP) is characterized by skin fragility, blistering and scarring in sun-exposed skin areas without abnormalities in porphyrin metabolism. The phenylpropionic acid derivative group of nonsteroidal anti-inflammatory drugs, especially naproxen, is known to cause PP. Naproxen is currently one of the most prescribed drugs in the therapy of juvenile idiopathic arthritis (JIA). The prevalence of PP was determined in a 9-year retrospective study of children with JIA and associated diseases. In addition, we prospectively studied the incidence of PP in 196 patients (127 girls and 69 boys) with JIA and associated diseases treated with naproxen from July 2001 to March 2002. We compared these data with those from a matched control group with JIA and associated diseases not treated with naproxen in order to identify risk factors for development of PP. The incidence of PP in the group of children taking naproxen was 11.4%. PP was particularly frequent in children with the early-onset pauciarticular subtype of JIA (mean age 4.5 years). PP was associated with signs of disease activity, such as reduced haemoglobin (<11.75 g/dl), and increased leucocyte counts (>10,400/μl) and erythocyte sedimentation rate (>26 mm/hour). Comedications, especially chloroquine intake, appeared to be additional risk factors. The mean duration of naproxen therapy before the onset of PP was 18.1 months, and most children with PP developed their lesions within the first 2 years of naproxen treatment. JIA disease activity seems to be a confounding factor for PP. In particular, patients with early-onset pauciarticular JIA patients who have significant inflammation appear to be prone to developing PP upon treatment with naproxen.
The search for organic molecules at the surface of Mars is a top priority of the Mars Science Laboratory (NASA) and ExoMars 2020 (ESA) space missions. Their main goal is to search for past and/or present molecular compounds related to a potential prebiotic chemistry and/or a biological activity on the Red Planet. A key step to interpret their data is to characterize the preservation or the evolution of organic matter in the martian environmental conditions. Several laboratory experiments have been developed especially concerning the influence of ultraviolet (UV) radiation. However, the experimental UV sources do not perfectly reproduce the solar UV radiation reaching the surface of Mars. For this reason, the International Space Station (ISS) can be advantageously used to expose the same samples studied in the laboratory to UV radiation representative of martian conditions. Those laboratory simulations can be completed by experiments in low Earth orbit (LEO) outside the ISS. Our study was part of the Photochemistry on the Space Station experiment on board the EXPOSE-R2 facility that was kept outside the ISS from October 2014 to February 2016. Chrysene, adenine, and glycine, pure or deposited on an iron-rich amorphous mineral phase, were exposed to solar UV. The total duration of exposure to UV radiation is estimated to be in the 1250-1420 h range. Each sample was characterized prior to and after the flight by Fourier transform infrared (FTIR) spectroscopy. These measurements showed that all exposed samples were partially degraded. Their quantum efficiencies of photodecomposition were calculated in the 200-250 nm wavelength range. They range from 10-4 to 10-6 molecules·photon-1 for pure organic samples and from 10-2 to 10-5 molecules·photon-1 for organic samples shielded by the mineral phase. These results highlight that none of the tested organics are stable under LEO solar UV radiation conditions. The presence of an iron-rich mineral phase increases their degradation.
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Background and Objectives: The clinical use of cyclophosphamide-doxorubicin (CP-DOX) in breast cancer treatment may cause hepatotoxicity. This study assessed the protective effect of alpha-lipoic acid (ALA) against hepatotoxicity induced by CP-DOX in albino rats. Materials and Methods: Thirty-six adult male albino rats were randomized into six groups (A-F) of n = 6. Group A (control) was treated intraperitoneally (ip) with 0.3 mL of normal saline 8 hourly for 48h. Group B was treated with 10 mg/kg of ALA 8 hourly ip for 48 h. Group C was treated with a dose of CP-DOX (150/20 mg/kg) for 24 h. Group D was pre-treated with ALA 8 hourly for 48 h before treatment with a dose of CP-DOX ip for 24h. Group E was co-treated with a dose of CP-DOX and ALA ip 8 hourly for 48 h. Group F was treated with a dose of CP-DOX for 24 h before treatment with ALA ip 8 hourly for 48 h. After treatment, rats were euthanized; blood samples were collected and evaluated for serum liver function markers. Liver samples were evaluated for biochemical markers and histology. Results: Liver catalase, superoxide dismutase, glutathione (GSH), and GSH peroxidase levels were significantly (P < 0.001) decreased in CP-DOX-treated rats. Aminotransferases, alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase, total bilirubin, conjugated bilirubin, and malondialdehyde levels were significantly (P < 0.001) increased in CP-DOX-treated rats. The liver of CP-DOX-treated rats showed hepatocyte necrosis. However, CP-DOX-induced hepatotoxicity was significantly reversed in rats pre-treated (P < 0.001), co-treated (P < 0.01), and post-treated (P < 0.05) with ALA when compared to CP-DOX-treated rats. Conclusion: Pre-treatment with ALA produced the best protective effect against CP-DOX-induced hepatotoxicity.
Publisher Summary Catalase exerts a dual function: (1) decomposition of H 2 O 2 to give H 2 O and O 2 (catalytic activity) and (2) oxidation of H donors, for example, methanol, ethanol, formic acid, phenols, with the consumption of 1 mol of peroxide (peroxide activity). The kinetics of catalase does not obey the normal pattern. Measurements of enzyme activity at substrate saturation or determination of the K s is therefore impossible. In contrast to reactions proceeding at substrate saturation, the enzymic decomposition of H 2 O 2 is a first-order reaction, the rate of which is always proportional to the peroxide concentration present. Consequently, to avoid a rapid decrease in the initial rate of the reaction, the assay must be carried out with relatively low concentrations of H 2 O 2 (about 0.01 M). This chapter discusses the catalytic activity of catalase. The method of choice for biological material, however, is ultraviolet (UV) spectrophotometry. Titrimetric methods are suitable for comparative studies. For large series of measurements, there are either simple screening tests, which give a quick indication of the approximative catalase activity, or automated methods.
In the article the effect of proton exchange waveguide lithium niobate on domain kinetics. It is shown that PE planar waveguide on the side z-results change in the character of the domain walls on the side of the z +. It was determined that the qualitative difference in the samples with varying concentration of protons in the modified layer is not.
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A sensitive and specific and automated liquid chromatography–electrospray mass spectrometric (LC–ESI-MS) assay for the quantification of Cyclosporin A in human plasma was developed. Following a simple protein precipitation step, the supernatant was extracted on-line and directly injected into the system LC–ESI-MS. A relatively new type of monolithic column consisting of a silica rod with bimodal pore structure was used to achieve a retention time of 2.4 min with a very low backpressure at a flow rate of 1 ml/min. The assay was linear from 0.050 to 1.000 μg/ml. The mean recovery was 91%. The mean inter-day and intra-day precisions were 1.85% and 2.83%, respectively. The combination of the automated solid phase extraction and the low retention time achieved with this columns increase the throughput and decrease the time of analysis of each sample. This technology is useful in order to improve the efficiency of the bioanalytical studies.
A rapid and sensitive method for the determination of immunosuppressive drugs through surface-assisted laser desorption/ionization mass spectrometric detection (SALDI/MS) was developed. Colloidal Pd and α-cyano-4-hydroxycinnamic acid (CHCA) were used as the SALDI co-matrix. To eliminate interference and enhance the sensitivity, dispersive liquid-liquid microextraction (DLLME) was employed to extract the immunosuppressive drugs from the aqueous solutions. Under optimal extraction and detection conditions, calibration curves for cyclosporine and everolimus in aqueous solutions were linear over a concentration range from 0.01 to 1.20 μM. For sirolimus, the linear concentration range of the calibration curve was from 0.05 to 2.00 μM. The limits of detection (LODs) were calculated to be 3, 3, and 14 nM for cyclosporine, everolimus, and sirolimus, respectively. The enrichment factors of DLLME were calculated to be 108, 122, and 101 for cyclosporine, everolimus, and sirolimus, respectively. This novel method was successfully applied for the determination of immunosuppressive drugs in human urine and serum samples.
We prove that groups acting geometrically on delta-quasiconvex spaces contain no essential Baumslag-Solitar quotients as subgroups. This implies that they are translation discrete, meaning that the translation numbers of their nontorsion elements are bounded away from zero.
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Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has proved to be one of the best methods for identification and determination of the number of monomer units of simple polymers, including their end-groups. However, most man-made polymers are complex materials with numerous macromolecules (oligomers) of different chain lengths and different chemical compositions in one sample. Since MALDI MS primarily produces singly charged ions of each molecule in the sample, its mass spectra are easy to interpret and therefore useful for polymer characterization. Different oligomers of interesting polymers can be isolated in tandem mass spectrometry (MS/MS) for analysis of their monomer sequence to relate properties of the polymer to its molecular structure. Furthermore, the polymerization mechanism responsible for a given polymer can often be deduced from the oligomer structure. MALDI MS-based methods have been used for the determination of molar mass distributions of complex polymers. However, to obtain meaningful data, proper understanding of polymer complexity as well as good insight of MALDI MS instrumentation and sample preparation protocol is necessary. Since the introduction of MALDI, different types of mass analyzers have been used. Each type has its advantages while other mass analyzers are simply not suitable for MALDI or for the targeted mass range.
The development of soft ionization techniques, electrospray ionization (ESI) and matrixassisted laser desorption/ionization (MALDI), just over a decade ago made it possible to analyze polymers intact by mass spectrometry (MS). 1-4 Owing to its ability to determine absolute molar masses for individual oligomers of a polymer, MS has become one of the most powerful analytical techniques available to polymer scientists today. Both ESI and MALDI MS are very useful in analyzing polymers. The former is particularly suitable for biopolymers which are generally monodisperse (i.e all molecules in the sample have the same chain length and mass) and the latter allows easier analysis of synthetic polymers which are always obtained with varying degrees of polydispersity. Most commonly used with a time-of-flight (TOF) mass analyzer, MALDI MS is the workhorse 1-4 and can be used to (i) identify homopolymers, (ii) determine the number of monomer units, (iii) identify the end-groups, and (iv) analyze copolymers. MALDI TOF MS can also be coupled (off-line) with size exclusion chromatography in order to construct calibration curves for molar mass distribution analysis of novel polymers. The talk will cover above MS applications, important aspects of instrumentation with special emphasis on MALDI TOF MS, and sample preparation protocol. A brief discussion of recent developments in mass spectrometry of polymers will be given.
The development of soft ionization techniques, electrospray ionization (ESI) and matrixassisted laser desorption/ionization (MALDI), just over a decade ago made it possible to analyze polymers intact by mass spectrometry (MS). 1-4 Owing to its ability to determine absolute molar masses for individual oligomers of a polymer, MS has become one of the most powerful analytical techniques available to polymer scientists today. Both ESI and MALDI MS are very useful in analyzing polymers. The former is particularly suitable for biopolymers which are generally monodisperse (i.e all molecules in the sample have the same chain length and mass) and the latter allows easier analysis of synthetic polymers which are always obtained with varying degrees of polydispersity. Most commonly used with a time-of-flight (TOF) mass analyzer, MALDI MS is the workhorse 1-4 and can be used to (i) identify homopolymers, (ii) determine the number of monomer units, (iii) identify the end-groups, and (iv) analyze copolymers. MALDI TOF MS can also be coupled (off-line) with size exclusion chromatography in order to construct calibration curves for molar mass distribution analysis of novel polymers. The talk will cover above MS applications, important aspects of instrumentation with special emphasis on MALDI TOF MS, and sample preparation protocol. A brief discussion of recent developments in mass spectrometry of polymers will be given.
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Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzimido moiety, is a novel meal time glucose regulator used for the treatment of type II diabetes. This article examines published analytical methods for the determination of nateglinide in pharmaceuticals and biological samples. The techniques of assay include UV and visible-range spectrophotometry, high performance liquid chromatography (HPLC), high performance thin layer chromatography (HPTLC), micellar liquid chromatography (MLC), micellar electro kinetic chromatography (MEKC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, HPLC with UV-detection is the most widely used technique for the assay of drug both in pharmaceuticals and biological samples. This technique has been also used for studying drug dissolution, separation and determination of enantiomers, impurities and related substances. The assay of nateglinide in blood plasma and serum for studying pharmacokinetics and bioequivalence has principally been carried out with HPLC-UV and LC-MS/MS techniques.
The review presents analytical methods for determination of new oral drugs for the treatment of type 2 diabetes mellitus (T2DM), focusing on peroxisome proliferator-activated receptor gamma agonists (glitazones), dipeptidyl peptidase 4 inhibitors (gliptins) and sodium/glucose co-transporter 2 inhibitors (gliflozins). Drugs derived from prandial glucose regulators, such as glinides, are considered because they are present in some new therapeutic options. The review presents analytical procedures suitable for determination of the drugs in bulk substances, such as pharmaceuticals and biological samples, including HPLC-UV, HPLC/LC-MS, TLC/HPTLC, CE/CE-MS, spectrophotometric (UV/VIS), spectrofluorimetric and electrochemical methods, taken from the literature over the past ten years (2006-2016). Some new procedures for extraction, separation and detection of the drugs, including solid phase extraction with molecularly imprinted polymers (SPE-MIP), liquid phase microextraction using porous hollow fibers (HP-LPME), HILIC chromatography, micellar mobile phases, ion mobility spectrometry (IMS) and isotopically labeled internal standards, are discussed.
MLL1 regulates circadian promoters by depositing H3K4 trimethyl marks, whose levels are also modulated by the NAD+-dependent deacetylase SIRT1. SIRT1 is now shown to promote circadian deacetylation of MLL1, thus affecting MLL1's methyltransferase activity.
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The simultaneous separation of bovine whey proteins [alpha-lactalbumin and beta-lactoglobulin (A+B)] and soybean proteins was performed, for the first time, by capillary electrophoresis. Different experimental conditions were tested. The most suitable consisted of 0.050 M phosphate buffer (pH 8) with 1 M urea and 1.2 mg/ml methylhydroxyethylcellulose, UV detection at 280 nm, 15 kV applied voltage, and 30 degrees C temperature. Quantitation of bovine whey proteins in a commercial powdered soybean milk manufactured by adding bovine whey to its formulation was performed using the calibration method of the external standard. Direct injection of a solution of the powdered soybean milk only enabled quantitation of alpha-lactalbumin in the commercial sample. Detection of beta-lactoglobulin (A+B) required acid precipitation of the solution of the sample in order to concentrate bovine whey proteins in the supernatant prior to the analysis of this protein in the whey obtained. Since alpha-lactalbumin could also be quantitated from the injection of the whey, the simultaneous determination of alpha-lactalbumin and beta-lactoglobulin (A+B) was possible upon acid precipitation of the powdered soybean milk solution. Detection limits obtained were 14 microg/g sol. for alpha-lactalbumin and 52 microg/g sol. for beta-lactoglobulin (A+B) which represent protein concentrations about 60 microg/100 g sample for alpha-lactalbumin and 100 microg/100 g sample for beta-lactoglobulin (A+B).
Two analytical methods, capillary electrophoresis (CE) with UV detection and high-performance liquid chromatography (HPLC) with photodiode array detection, were developed for the determination of α-lactalbumin (α-Lac), β-lactoglobulin A (β-Lg A), and β-lactoglobulin B (β-Lg B) in whey protein powder, colostrum, raw milk, and infant formula. The CE analysis was performed in a bare fused silica capillary (57 cm × 50 μm, effective length 50 cm) with a separation buffer consisting of 0.5 mol L−1 boric acid, 0.025 mol L−1 hydroxypropyl-β-cyclodextrin, and 0.8 g L−1 poly(ethylene oxide) 4,000,000 at pH 9.10. The HPLC analysis was performed on a CAPCELL PAK C8 SG 300 (200 × 4.6 mm, 5-μm particles) column with a gradient mobile phase mixture consisting of acetonitrile and water containing trifluoroacetic acid. The CE method is suitable for the simultaneous determination of α-Lac, β-Lg A, and β-Lg B in whey powder, colostrum, and raw bovine milk, whereas the HPLC method can only be used for quantitative assays of β-Lg A and β-Lg B due to the co-elution of lactoferrin with α-Lac. Recoveries for both methods over the concentration range were between 90.7% and 116.8%. Whey protein powder had the highest content of the above three proteins. The contents of α-Lac in infant formula increased with the raise of age stage. Infant formula with the same age stage but different brands and countries had significant differences in the content of α-Lac.
ABSTRACTUNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system...
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Classification of seized methamphetamine by impurity profiling can provide very useful information on drug intelligence. In this report, the validity of inorganic impurity analysis in discriminating seized methamphetamine samples in Japan was investigated using inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS). Triplicate sampling was carried out on 17 methamphetamine samples seized in Japan. About 20 mg of methamphetamine was taken, and was dissolved in 20 ml of water. After the qualitative analysis, Ba, Sb, Pd, Sr, Br, Zn and Cu were determined by ICP-MS, and Na was determined by AAS. Among eight elements determined in this study, most cations showed large heterogeneity in their content. On the other hand, the contents of Na which is abundant in methamphetamine samples, showed relatively small intra-sample variation, and that of Br also showed good homogeneity. On the basis of the concentration of Br and Na, 17 seized methamphetamine samples were classified into five groups. Trace elements such as Tl, Hg, Au or Cs were qualitatively detected by ICP-MS. These elements can provide useful information to impurity profiling of seized methamphetamine, because these elements are characteristically present in each sample. Application of ICP-MS and AAS to the analysis of inorganic impurities can be helpful in giving additional information to the impurity profiling of seized methamphetamine by organic impurity analysis.
When underivatized methamphetamine hydrochloride (MA·HCl) in methanol is subjected to the instant gas chromatographic–mass spectrometric (GC–MS) profiling with old inlet liners at temperatures above 200 °C, appreciable amounts of N , N -dimethylamphetamine (DMA) and amphetamine (AP) are produced. The presence of these two artifacts is attributed to the N -demethylation and N -methylation reactions of MA as well as methyl group exchange with methanol. These artifacts are only produced in old injection port liners and at elevated temperatures. The formation of artifacts is proportional to concentration of MA·HCl. It is suggested that special cautions and measures be undertaken to prevent artifacts.
Background ::: Serum calcium (Ca) and inorganic phosphate (Pi) concentrations and calcium-phosphate product (CPP) levels are positively associated with worse outcomes in patients with chronic kidney disease, but there are few data for Pi or Ca and none for CPP in patients with chronic heart failure (CHF).
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A simple and rapid colorimetric method for determination of phytate in urine
Lowering of serum cholesterol and triglycerides and modulation of divalent cations by dietary phytate.
Validation study of a rapid colorimetric method for the determination of phytic acid and inorganic phosphorus from seeds
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Review of the biological properties and toxicity of usnic acid
Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model
Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells
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BIOCHEMICAL STUDIES ON ACID AND ALKALINE RIBONUCLEASE IN SERA OF WOMEN WITH DIFFERENT OVARIAN TUMORS
Purification and characterization of two ribonucleases from human erythrocytes: immunological and enzymological comparison with ribonucleases from human urine.
Adipose Lipolysis Unchanged by Preexercise Carbohydrate Regardless of Glycemic Index
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Determination of ochratoxin A in pork meat products: single laboratory validation method and preparation of homogeneous batch materials
OCHRATOXIN A DETERMINATION IN CURED HAM BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY FLUORESCENCE DETECTION AND ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY: A COMPARATIVE STUDY
Radar backscatter is not a 'direct measure' of forest biomass
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A Brief Review of the Anticancer Activity of α-Aminophosphonic Acid Derivatives and a Report on the in Vitro Activity of Some Dialkyl α-aryl- (or Heteroaryl)-α-(Diphenylmethylamino)Methanephosphonates
Evaluation of ecotoxicological impact of new pyrrole-derived aminophosphonates using selected bioassay battery
Meyrier ) 2 , 8-Dihydroxyadeninuria-induced progressive renal failure
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Retention of ionisable compounds on high-performance liquid chromatography. XV. Estimation of the pH variation of aqueous buffers with the change of the acetonitrile fraction of the mobile phase.
Electrospray Ionisation Efficiency Scales: Mobile Phase Effects and Transferability
On free nilpotent quotient groups
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Enantioselective liquid-liquid extractions of underivatized general amino acids with a chiral ketone extractant.
Modelling studies of enantioselective extraction of an amino acid derivative in slug flow capillary
[34] Screening of dietary carotenoids and carotenoid-rich fruit extracts for antioxidant activities applying 2,2′-azinobis(3-ethylenebenzothiazoline-6-sulfonic acid radical cation decolorization assay
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Effect of UV Irradiation and Temperature on Free Radical Properties in Dehydrocholic and Ursodeoxycholic Acids: An EPR Study
Electron Paramagnetic Resonance Examination of Free Radical Formation in Salicylic Acid and Urea Exposed to UV Irradiation
A Universal Optimal Consumption Rate for an Insider
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The differential form of the perturbed angular correlation is studied for a gas model. An expression for W ( θ , t ) is obtained, which is also valid for the case where the correlation time τ c is of the order of the time interval t between the two radiations. In the limits τ c → ∞ and τ c ⪡ t the known results are recovered. Some numerical results are given.
The technique of Perturbed Angular Correlations of γ-rays has been used to study the rotational correlation times in aqueous solution of the peptides: oxytocin, glycyltryptophan, cholecystokinin and the glycopeptide ristocetin. These peptides were labelled with excited 111mCd through the covalent coupling of the metal chelator diethylenetriaminepentaacetic acid (DTPA) to the primary amines-of the peptides. The experimental correlation times are in good accordance with calculations based on the molecular weight. This indicates that the 111mCd-DTPA is rigidly bound to the molecules. In the case of ristocetin, the correlation time was measured at 2°C, 25°C and 38°C. These experiments show the expected linear dependence on the viscosity divided by temperature. The feasibility of determining rotational correlation times for peptides without lysines and with correlation times in the ns region is thus demonstrated. Also, the correlation time of 111mCd-DTPA coupled to the lysines of bovine serum albumin was determined. The measured correlation time is about 5 times less than the calculated correlation time. This effect is assigned to local motion. In spite of this, experiments show that 111mCd-DTPA-bovine-serum-albumin is significantly immobilised by aggregation with immunoglobulins. The nuclear quadrupole interactions, necessary for determining the correlations times, were determined for 111mCd-DTPA-ristocetin and 111mCd-DTPA-bovine-serum-albumin by adding sucrose to a concentration of 63% and cooling to 2°C. This showed a small but significant difference between the two molecules. We interpret this as due to different conformations, possibly different coordination numbers.
Bayesian approach remained rather unsuccessful in treating nonparametric problems. This is primarily due to the difficulty in finding workable prior distribution on the parameter space , which in nonparametric problems is taken to be a set of probability distributions on a given sample space. Two Desirable Properties of a Prior 1. The support of the prior should be large. 2. Posterior distribution given a sample of observation should be manageable analytically. These properties are antagonistic : One may be obtained at the expense of other.
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