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2,334,600 |
Reduction-responsive polypeptide nanomedicines significantly inhibit progression of orthotopic osteosarcoma.
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Osteosarcoma (OS) is the most common malignant bone tumor with high metastasis and mortality. Neoadjuvant chemotherapy is an effective therapeutic regimen, but the clinical application is limited by the unsatisfactory efficacies and considerable side effects. In this study, the reduction-responsive polypeptide micelles based on methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (mPEG<sub>113</sub>-b-PBMLC<sub>4</sub>, P4M, and mPEG<sub>113</sub>-b-PBMLC<sub>9</sub>, P9M) were developed to control the delivery of doxorubicin (DOX) in OS therapy. Compared to free DOX, P4M/DOX and P9M/DOX exhibited 2.6 and 3.5 times increase in the area under the curve of pharmacokinetics, 1.6 and 2.0 times increase in tumor accumulation, and 1.6 and 1.7 times decrease of the distribution in the heart. Moreover, the selective accumulation of micelles, especially P9M/DOX, in tumors induced stronger antitumor effects on both primary and lung metastatic OSs with less systematic toxicity. These micelles with smart responsiveness to intracellular microenvironments are highly promising for the targeted delivery of clinical chemotherapeutic drugs in cancer therapy.
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2,334,601 |
Socio-demographic and maternal predictors of adherence to 24-hour movement guidelines in Singaporean children.
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Integrated 24-Hour Movement Guidelines provide specific recommendations on screen viewing (SV), moderate-to-vigorous physical activity (MVPA) and sleep to improve health of children and youth. However, few studies have examined whether these guidelines are met in young children, particularly in Asia. We evaluated adherence to integrated and individual guidelines and its predictors in 5.5-year-old Singaporean children.</AbstractText>Growing Up in Singapore towards Healthy Outcomes (GUSTO) is a mother-offspring birth cohort study. At age 5.5 years, child SV was reported by parents. Movement behaviours (MBs) were measured continuously using wrist-worn accelerometers over 7 consecutive days and nights. For accelerometer data including ≥3 days with ≥16 h/day we estimated mean (±SD) daily MVPA, SV and nighttime sleep duration across the week. Adherence to integrated (Canadian/Australian) guidelines was defined as meeting all individual guidelines: ≥60 min of MVPA/day, ≤2 h of screen time/day, and 9-11 h of sleep/night. Socio-demographic and maternal predictors collected at pregnancy enrolment and at 26-28 weeks' gestation were examined by multivariable logistic regression.</AbstractText>Of 864 children followed up age 5.5 years, 547 (63.3%) had both valid ActiGraph and questionnaire data (51.7% boys and 58.3% Chinese ethnicity). Children averaged 101.9 (± 88.7) min/day SV, 67.3 (± 23.7) min/day MVPA and 480.6 (± 57.2) min/night sleep. Few children met integrated guidelines. Specifically, the proportions of children who met none, SV, MVPA, sleep and integrated guidelines were 11.2, 70.2, 59.6, 13.7 and 5.5%, respectively. Multivariable analysis showed that maternal activity and television (TV) viewing were associated with meeting integrated guidelines (insufficiently vs. highly active (OR [95% CI]): 0.11 [0.01, 0.95]; 2-3 vs. ≥ 3 h TV: 3.52 [1.02, 12.22]). Examining higher adherence to individual guidelines, Chinese ethnicity, younger maternal age and lower maternal TV and sleep time were associated with greater SV; male sex, Malay ethnicity, higher birth order and higher maternal activity level were associated with greater MVPA; and older maternal age was associated with adherence to sleep guideline.</AbstractText>Beyond individual behaviours, consideration of the full spectrum of MBs may be important to improve children's health. However, few Singaporean children adhere to integrated 24-h movement guidelines. Maternal behaviours as early as during pregnancy could be important targets for future interventions aiming to promote these MBs in children.</AbstractText>
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2,334,602 |
Leading progress in heart regeneration and repair.
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Ischemic heart disease is one of the leading causes of mortality. Myocardial infarction causes loss of cardiomyocytes in the injury area accompanied by formation of a fibrotic scar. This initiates a cascade of events including further loss of myocyte, increased fibrosis, and pathological cardiac hypertrophy, eventually leading to the heart failure. Cardiomyocytes in mammals have limited regenerative potential due to post mitotic nature of cardiomyocytes. Recently, multiple studies have provided substantial insights in to the molecular pathways governing this block in adult cardiomyocyte proliferation, and successfully employed that understanding to achieve cardiac regeneration. These strategies include directly reprograming the cardiomyocytes or manipulating the cardiac interstitium to repair the injured heart. In this review, we discuss the recent advances made in the field in the past two years.
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2,334,603 |
An online intervention for improving stroke survivors' health-related quality of life: study protocol for a randomised controlled trial.
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Recurrent stroke is a major contributor to stroke-related disability and costs. Improving health-risk behaviours and mental health has the potential to significantly improve recovery, enhance health-related quality of life (HRQoL), independent living, and lower the risk of recurrent stroke. The primary aim will be to test the effectiveness of an online intervention to improve HRQoL among stroke survivors at 6 months' follow-up. Programme effectiveness on four health behaviours, anxiety and depression, cost-effectiveness, and impact on other hospital admissions will also be assessed.</AbstractText><AbstractText Label="METHODS/DESIGN" NlmCategory="METHODS">An open-label randomised controlled trial is planned. A total of 530 adults will be recruited across one national and one regional stroke registry and block randomised to the intervention or minimal care control group. The intervention group will receive access to the online programme Prevent 2nd Stroke (P2S); the minimal care control group will receive an email with Internet addresses of generic health sites designed for the general population. The primary outcome, HRQoL, will be measured using the EuroQol-5D. A full analysis plan will compare between groups from baseline to follow-up.</AbstractText>A low-cost per user option to supplement current care, such as P2S, has the potential to increase HRQoL for stroke survivors, and reduce the risk of second stroke.</AbstractText>Australian and New Zealand Clinical Trials Registry, ID: ACTRN12617001205325p . Registered on 17 August 2017.</AbstractText>
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2,334,604 |
Neuro- and hepatic toxicological profile of (S)-2,4-diaminobutanoic acid in embryonic, adolescent and adult zebrafish.
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(S)-2,4-Diaminobutanoic acid (DABA) is a noncanonical amino acid often co-produced by cyanobacteria along with β-N-methylamino-l-alanine (BMAA) in algal blooms. Although BMAA is a well-established neurotoxin, the toxicity of DABA remains unclear. As part of our development of biocompatible materials, we wish to make use of DABA as both a building block and as the end-product of enzymatically induced depolymerization; however, if it is toxic at very low concentrations, this would not be possible. We examined the toxicity of DABA using both in vivo embryonic and adult zebrafish models. At higher sublethal concentrations (700 μm), the fish demonstrated early signs of cardiotoxicity. Adolescent zebrafish were able to tolerate a higher concentration. Post-mortem histological analysis of juvenile zebrafish showed no liver or brain abnormalities associated with hepato- or neurotoxicity. Combined, these results show that DABA exhibits no overt toxicity at concentrations (100-300 μm) within an order of magnitude of those envisioned for its application. This study further highlights the low cost and ease of using zebrafish as an early-stage toxicological screening tool.
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2,334,605 |
Being Healthy, Being Sick, Being Responsible: Attitudes towards Responsibility for Health in a Public Healthcare System.
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Lifestyle-induced diseases are becoming a burden on healthcare, actualizing the discussion on health responsibilities. Using data from the National Association for Heart and Lung Diseases (LHL)'s 2015 Health Survey (<i>N</i> = 2689), this study examined the public's attitudes towards personal and social health responsibility in a Norwegian population. The questionnaires covered self-reported health and lifestyle, attitudes towards personal responsibility and the authorities' responsibility for promoting health, resource-prioritisation and socio-demographic characteristics. Block-wise multiple linear regression assessed the association between attitudes towards health responsibilities and individual lifestyle, political orientation and health condition. We found a moderate support for social responsibility across political views. Respondents reporting unhealthier eating habits, smokers and physically inactive were less supportive of health promotion policies (including information, health incentives, prevention and regulations). The idea that individuals are responsible for taking care of their health was widely accepted as an abstract ideal. Yet, only a third of the respondents agreed with introducing higher co-payments for treatment of 'self-inflicted' conditions and levels of support were patterned by health-related behaviour and left-right political orientation. Our study suggests that a significant support for social responsibility does not exclude a strong support for personal health responsibility. However, conditional access to healthcare based on personal lifestyle is still controversial.
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2,334,606 |
Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016.
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To generate estimates of the global prevalence and incidence of urogenital infection with chlamydia, gonorrhoea, trichomoniasis and syphilis in women and men, aged 15-49 years, in 2016.</AbstractText>For chlamydia, gonorrhoea and trichomoniasis, we systematically searched for studies conducted between 2009 and 2016 reporting prevalence. We also consulted regional experts. To generate estimates, we used Bayesian meta-analysis. For syphilis, we aggregated the national estimates generated by using Spectrum-STI.</AbstractText>For chlamydia, gonorrhoea and/or trichomoniasis, 130 studies were eligible. For syphilis, the Spectrum-STI database contained 978 data points for the same period. The 2016 global prevalence estimates in women were: chlamydia 3.8% (95% uncertainty interval, UI: 3.3-4.5); gonorrhoea 0.9% (95% UI: 0.7-1.1); trichomoniasis 5.3% (95% UI:4.0-7.2); and syphilis 0.5% (95% UI: 0.4-0.6). In men prevalence estimates were: chlamydia 2.7% (95% UI: 1.9-3.7); gonorrhoea 0.7% (95% UI: 0.5-1.1); trichomoniasis 0.6% (95% UI: 0.4-0.9); and syphilis 0.5% (95% UI: 0.4-0.6). Total estimated incident cases were 376.4 million: 127.2 million (95% UI: 95.1-165.9 million) chlamydia cases; 86.9 million (95% UI: 58.6-123.4 million) gonorrhoea cases; 156.0 million (95% UI: 103.4-231.2 million) trichomoniasis cases; and 6.3 million (95% UI: 5.5-7.1 million) syphilis cases.</AbstractText>Global estimates of prevalence and incidence of these four curable sexually transmitted infections remain high. The study highlights the need to expand data collection efforts at country level and provides an initial baseline for monitoring progress of the World Health Organization global health sector strategy on sexually transmitted infections 2016-202</i>1.</AbstractText>
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2,334,607 |
Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors.
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The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments.</AbstractText>The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed.</AbstractText>Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7-1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04-0·17; p=0·0003) in men and 0·06 units per year (0·01-0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21-0·25) in men and 0·14 units per year (0·12-0·15) in women (both p<0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15-1·22] in men and 1·10 [1·06-1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval -0·84 g/L [95% CI -0·99 to -0·70] in men and -0·45 g/L [-0·59 to -0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval -6·5% [95% CI -7·6 to -5·5] in men and -5·3% [-6·5 to -4·2] in women; all p<0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p>0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p<0·0001).</AbstractText>During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores.</AbstractText>NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation.</AbstractText>Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
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2,334,608 |
Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease.
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Bardoxolone methyl attenuates inflammation by inducing nuclear factor erythroid-derived 2-related factor 2 and suppressing nuclear factor κB. The Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes (BEACON) trial was a phase 3 placebo-controlled, randomized, double-blind, parallel-group, international, multicenter trial in 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease. BEACON was terminated because of safety concerns, largely related to a significant increase in early heart failure events in patients randomized to bardoxolone methyl. Bardoxolone methyl resulted in increased estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. Herein, we present post hoc analyses characterizing the relation between the urine albumin-to-creatinine ratio and eGFR. The urine albumin-to-creatinine ratio and eGFR were assessed every four weeks through Week 12, followed by assessments every eight weeks thereafter, and 4 weeks after the last dose of bardoxolone methyl was administered. The initial increases in urine albumin-to-creatinine ratio observed in patients randomized to bardoxolone methyl were attenuated after six months. Multivariable regression analysis identified baseline eGFR and eGFR over time as the dominant factors associated with change in the urine albumin-to-creatinine ratio. Relative to placebo, bardoxolone methyl resulted in a significant decrease in albuminuria when indexed to eGFR (least-squared means: -0.035 [95% confidence interval -0.031 to -0.039]). Thus, among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl, changes in albuminuria are directly related to changes in eGFR, challenging the conventional construct that increases in albuminuria universally reflect kidney injury and denote harm.
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2,334,609 |
Autonomic reactivity during reading of a somatic distress script in patients with somatic symptom disorder.
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The relationship between resting-state heart rate variability (HRV) and somatic symptom disorder (SSD) has been explored in several studies. We planned to examine HRV during the performance of psychological tasks, and assumed that it could be applied for the diagnosis of SSD.</AbstractText>Fifty-three patients with SSD and 52 healthy controls were recruited. Demographic and psychological data were collected. Subjects' HRV was measured over five 5-minute blocks during which they viewed different scripts (resting state; health anxiety; somatic distress; depression; neutral topic). After each block they completed a self-assessment manikin. Generalized estimated equation analysis was used to analyze the impact of mental scripts, SSD and sex on physiological and psychological indicators.</AbstractText>In men there was a script*SSD interaction concerning high-frequency power (HF) involving the neutral script; SSD men showed significantly higher HF than healthy men when viewing neutral script. In women there were script*SSD interactions with respect to low-frequency power (LF) and HF involving the somatic distress script and a script*SSD interaction with respect to LF and emotional valence involving the neutral script; SSD women revealed significantly lower LF and HF than healthy women when viewing somatic distress script, they also showed significantly lower LF and higher valence than healthy ones during neutral script. The somatic distress script*SSD interaction still influenced LF and HF in women after adjusting for potential confounders.</AbstractText>In women cue-specific HRV is a better method of differentiating people with SSD from healthy individuals than resting-state HRV.</AbstractText>The Research Ethics Committee of National Taiwan University Hospital approved this study (approval number: 201410050RINB).</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,610 |
Three-dimensional bioprinting human cardiac tissue chips of using a painting needle method.
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Three-dimensional (3D) printers are attracting attention as a method for arranging and building cells in three dimensions. Bioprinting technology has potential in tissue engineering for the fabrication of scaffolds, cells, and tissues. However, these various printing technologies have limitations with respect to print resolution and due to the characteristics of bioink such as viscosity. We report a method for constructing of 3D tissues with a "microscopic painting device using a painting needle method" that, when used with the layer-by-layer (LbL) cell coating technique, replaces conventional methods. This method is a technique of attaching the high viscosity bioink to the painting needle tip and arranging it on a substrate, and can construct 3D tissues without damage to cells. Cell viability is the same before and after painting. We used this biofabrication device to construct 3D cardiac tissue (LbL-3D Heart) using human-induced pluripotent stem cell-derived cardiomyocytes. The constructed LbL-3D Heart chips had multiple layers with a thickness of 60 µm, a diameter of 1.1 mm, and showed synchronous beating (50-60 beats per min). The aforementioned device and method of 3D tissue construction can be applied to various kinds of tissue models and would be a useful tool for pharmaceutical applications.
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2,334,611 |
mRNA-Sequencing Identifies Liver as a Potential Target Organ for Triphenyl Phosphate in Embryonic Zebrafish.
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Triphenyl phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer in the United States. Using zebrafish as a model, the overall objective of this study was to identify potential organs that might be targeted by TPHP during embryonic development. Based on mRNA-sequencing, TPHP exposure from 24 to 30 h post fertilization (hpf) and 24 to 48 hpf significantly affected the abundance of 305 and 274 transcripts, respectively, relative to vehicle (0.1% DMSO) controls. In addition to minor effects on cardiotoxicity- and nephrotoxicity-related pathways, ingenuity pathway analysis (IPA) of significantly affected transcripts within 30- and 48-hpf embryos revealed that hepatotoxicity-related pathways were strongly affected following exposure to TPHP-alone. Moreover, although pretreatment with fenretinide (a retinoic acid receptor agonist) mitigated TPHP-induced pericardial edema and liver enlargement at 72 and 128 hpf, respectively, IPA revealed that fenretinide was unable to block TPHP-induced effects on cardiotoxicity-, nephrotoxicity-, and hepatotoxicity-related pathways at 48 hpf, suggesting that TPHP-induced effects on the transcriptome were not associated with toxicity later in development. In addition, based on Oil Red O staining, we found that exposure to TPHP nearly abolished neutral lipids from the embryonic head and trunk and, based on metabolomics, significantly decreased the total abundance of metabolites-including betaine, a known osmoprotectant-at 48 and 72 hpf. Overall, our data suggest that, in addition to the heart, TPHP exposure during early development results in adverse effects on the liver, lipid utilization, and osmoregulation within embryonic zebrafish.
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2,334,612 |
Postprandial Head-drops: Insight into Systemic Effects of Ocular Timolol Preparation in Elderly.
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Timolol is a nonselective beta-adrenergic antagonist with no intrinsic sympathomimetic activity. Conditions like intraocular hypertension (IOH) and primary open angle glaucoma (POAG) warrant the use of a topical ocular preparation of timolol. It works to effectively lower the intraocular pressure (IOP) in patients with glaucoma but due to its unique pharmacodynamics, it also poses some very striking systemic side-effects. These include heart block, arrhythmias, and syncopal episodes. Herein, we present a challenging case of a previously known healthy elderly 67-year-old female, known case of POAG, who presented to the clinic with a very peculiar complaint, i.e. episodes of her head dropping down on to the table multiple times after she was done eating her food. This led to a cascade of diagnostic tests being employed encompassing cardiovascular, endocrinal, neurological, and gastrointestinal systems; all of which came out to be negative. Finally, after a very thorough literature review, it was established that timolol was the true culprit. The cessation of the drug immediately resulted in lasting relief.
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2,334,613 |
The efficacy of addition of dexmedetomidine to intrathecal bupivacaine in lower abdominal surgery under spinal anesthesia.
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Spinal anesthesia is the common choice for anesthesia in lower abdomen surgery and intrathecal adjutants have gained popularity with the aim of prolonging the duration of block, quality of block and post operation pain control. The purpose of this study was to evaluate the effects of adding dexmedetomidine to hyperbaric bupivacaine in lower abdominal surgery under spinal anesthesia. The main outcomes were considered pain score, duration of analgesia, hemodynamic changes and adverse side effects like nausea and vomiting.</AbstractText>This double-blind randomized clinical trial was conducted on one hundred patients between 18 to 65 years old scheduled for lower abdominal surgery. Fifty patients were randomly allocated to receive either 12.5mg hyperbaric bupivacaine (2.5cc) plus 5µgr dexmedetomidine (0.5cc) intrathecally while fifty patients received either 12.5mg hyperbaric bupivacaine (2.5cc) and 0.5cc Saline 0.9% intrathecally.</AbstractText>Vital sign parameters like heart rate, blood pressure and oxygen saturation levels were registered in the normal range in both groups. The average duration of the onset of pain (230±86 min) in bupivacaine group was significantly (p≤0.000) less than dexmedetomidine group (495±138 minutes). The severity of pain at all times in dexmedetomidine group was significantly (p<0.05) less than bupivacaine group. The severity of shivering and the number of patients who needed treatment for nausea and vomiting in dexmedetomedine group has been less in comparison to bupivacaine.</AbstractText>We concluded that intrathecal dexmedetomidine increases the duration of analgesia and reduces postoperative pain without changes in the hemodynamic parameters and adverse side effects. It can be considered as an appropriate adjuvant to intrathecal local anesthetics for lower limb surgeries.</AbstractText>
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2,334,614 |
Biometric measurements of Santa Inês meat sheep reared on Brachiaria brizantha pastures in Northeast Brazil.
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This study was undertaken to examine biometric measurements during the growth phase of male and female Santa Inês sheep reared in Brachiaria brizantha pastures in northeastern Brazil. The experiment involved 24 castrated males and 24 females at an initial age of 90 days, with an average body weight of 19.04 ± 0.96 kg. Treatments consisted of the effect of four cultivars (Marandu, Xaraés, Piatã and Paiaguás) and two sexes. Six animals were used per treatment, in a randomized-block experimental design. The following characteristics were evaluated: abdominal circumference (AC), body condition score (BCS), body length (BL), body weight (BW), body capacity 1 (BC1), body capacity 2 (BC2), chest width (CW), heart girth (HG), leg circumference (LC), leg length (LL), rump height (RH), rump width (RW) and withers height (WH). Data were subjected to descriptive analysis, Pearson's correlation, ANOVA and Tukey's, Kruskal Wallis and Mann-Whitney tests. Univariate and multiple regressions were applied to estimate BW with a maximum error level of 5%. Significant differences were observed for the biometric measurements between sexes and cultivars (p<0.05). Body weight was highly correlated (>70%) with AC, WH, CG, RW, BC1 and BC2. The male sheep grazed on cultivars Piatã showed the best values for BW (40.43 kg), HG, RW, WH, LL, LC (102.46; 20.8; 65.23; 60.44; 42.54 cm respectively) and BC1 (4.25 kg/cm). Females grazed on cultivar Marandu had higher values for RW, CW, LL (17.26; 20.1; 75.98 cm respectively), BC1 (6.03 kg/cm) and BC2 (0.422 kg/cm). The equations that best estimated live weight were BC1 and HG. In male and female Santa Inês sheep, biometric parameters grow differently depending on the cultivar where they are grazed during the growth phase. Cultivars Marandu and Piatã are the most recommended for sheep production, as they provided the best performance and body development in those animals.
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2,334,615 |
Prevalence of and covariates associated with the oculocardiac reflex occurring in dogs during enucleation.
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To determine the prevalence of and covariates associated with the oculocardiac reflex (OCR) occurring in dogs during enucleations.</AbstractText>145 dogs that underwent enucleation at 2 veterinary teaching hospitals between January 2010 and June 2015.</AbstractText>Information was collected from the medical records of included dogs regarding age and body weight at hospital admission, breed (for classification of brachycephalic status), and whether they had received anticholinergic drugs or a retrobulbar nerve block (RNB) prior to enucleation. An OCR was considered to have occurred if there was a sudden decrease of ≥ 30% in heart rate from the baseline value (mean heart rate prior to the sudden decrease) during surgery in the absence of intraoperative administration of opioids or α2</sub>-adrenoceptor agonists. Associations were explored between the collected data and the prevalence of OCR by means of binomial logistic regression.</AbstractText>4.8% (7/145) of dogs had an OCR noted during enucleation. Dogs that received a preoperative RNB (n = 82) had significantly lower odds of an OCR being observed than dogs that received no preoperative RNB (OR, 0.12). No association with OCR was identified for age or brachycephalic conformation or for preoperative administration of anticholinergic drugs.</AbstractText>These findings suggested that preoperative administration of an RNB, but not preoperative administration of anticholinergic drugs, was associated with a lower prevalence of OCR in dogs during enucleations.</AbstractText>
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2,334,616 |
Pain Control in the Cardiothoracic Surgery Patient.
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Opioid analgesics are the historical mainstay for postoperative cardiothoracic surgery pain relief. Although opioids are efficacious, they are linked with adverse effects, including sedation and respiratory depression. Emerging research is helping clinicians move toward evidence-based, opioid-sparing management strategies, including peripheral nerve blocks and multimodal analgesia. Good communication is essential to understanding patients' perceptions of pain and attitudes toward different pain-relief methods. Preoperatively educating patients and families on expected nociception and treatment options decreases postprocedural pain. Discussing use of nonopioid analgesics for mild pain and instructions on tapering opioid medications at discharge may prevent future misuse.
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2,334,617 |
Linear periodization of strength training in blocks attenuates hypertension and diastolic dysfunction with normalization of myocardial collagen content in spontaneously hypertensive rats.
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This study evaluated the effects of a linear block strength training programme on the parameters of cardiac remodelling in spontaneously hypertensive rats. Thirty-nine rats were equally distributed in four groups: normotensive sedentary, normotensive trained, hypertensive sedentary and hypertensive trained. The strength training protocol was organized in three mesocycles of 4 weeks, with an increase in the training load organized in a linear fashion for each block, considering the weight established in the maximum loaded load test. The following parameters were evaluated: ventricular function assessed by echocardiogram, caudal blood pressure, ventricular haemodynamics and cardiac masses. Two-way analysis of variance was used to determine the differences between the group and time.</AbstractText>After 12 weeks of training, the hypertensive trained group presented the following results: increased muscle strength, reduced blood pressure, reduced heart rate, isovolumetric relaxation time and total collagen content, with increased cardiac function, without promoting changes in the mass and nuclear volume of cardiomyocytes. Also, blood pressure reduction seems to be associated with both muscle strength adjustments and total load progress.</AbstractText>The findings of this study showed that the training programme carried out attenuated systemic arterial pressure and preserved the ventricular function of spontaneously hypertensive rats without cardiac mass change.</AbstractText>
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2,334,618 |
Hierarchical Motion Estimation With Bayesian Regularization in Cardiac Elastography: Simulation and In Vivo Validation.
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Cardiac elastography (CE) is an ultrasound-based technique utilizing radio-frequency (RF) signals for assessing global and regional myocardial function. In this work, a complete strain estimation pipeline for incorporating a Bayesian regularization-based hierarchical block-matching algorithm, with Lagrangian motion description and myocardial polar strain estimation is presented. The proposed regularization approach is validated using finite-element analysis (FEA) simulations of a canine cardiac deformation model that is incorporated into an ultrasound simulation program. Interframe displacements are initially estimated using a hierarchical motion estimation framework. Incremental displacements are then accumulated under a Lagrangian description of cardiac motion from end-diastole (ED) to end-systole (ES). In-plane Lagrangian finite strain tensors are then derived from the accumulated displacements. Cartesian to cardiac coordinate transformation is utilized to calculate radial and longitudinal strains for ease of interpretation. Benefits of regularization are demonstrated by comparing the same hierarchical block-matching algorithm with and without regularization. Application of Bayesian regularization in the canine FEA model provided improved ES radial and longitudinal strain estimation with statistically significant ( ) error reduction of 48.88% and 50.16%, respectively. Bayesian regularization also improved the quality of temporal radial and longitudinal strain curves with error reductions of 78.38% and 86.67% ( ), respectively. Qualitative and quantitative improvements were also visualized for in vivo results on a healthy murine model after Bayesian regularization. Radial strain elastographic signal-to-noise ratio (SNR<sub>e</sub>) increased from 3.83 to 4.76 dB, while longitudinal strain SNR<sub>e</sub> increased from 2.29 to 4.58 dB with regularization.
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2,334,619 |
A flexible and parallelizable approach to genome-wide polygenic risk scores.
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The heritability of most complex traits is driven by variants throughout the genome. Consequently, polygenic risk scores, which combine information on multiple variants genome-wide, have demonstrated improved accuracy in genetic risk prediction. We present a new two-step approach to constructing genome-wide polygenic risk scores from meta-GWAS summary statistics. Local linkage disequilibrium (LD) is adjusted for in Step 1, followed by, uniquely, long-range LD in Step 2. Our algorithm is highly parallelizable since block-wise analyses in Step 1 can be distributed across a high-performance computing cluster, and flexible, since sparsity and heritability are estimated within each block. Inference is obtained through a formal Bayesian variable selection framework, meaning final risk predictions are averaged over competing models. We compared our method to two alternative approaches: LDPred and lassosum using all seven traits in the Welcome Trust Case Control Consortium as well as meta-GWAS summaries for type 1 diabetes (T1D), coronary artery disease, and schizophrenia. Performance was generally similar across methods, although our framework provided more accurate predictions for T1D, for which there are multiple heterogeneous signals in regions of both short- and long-range LD. With sufficient compute resources, our method also allows the fastest runtimes.
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2,334,620 |
Maternal feeding practices and children's food intake during an ad libitum buffet meal: Results from the GUSTO cohort.
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Parents' feeding practices have been shown to be associated with children's food intake and weight status, but little is known about feeding practices in Asian countries. This study used behavioral observation to explore the feeding practices of 201 mothers of 4.5 year-old children in Singapore during an ad libitum buffet lunch. Feeding practices were coded from videos, focusing on behaviors used to prompt the child to eat more food (autonomy-supportive and coercive-controlling prompts to eat, suggesting items from buffet), those to reduce intake (restriction, questioning food choice), and those related to eating rate (hurrying or slowing child eating). Child outcome measures included energy consumed, variety of food items selected, and BMI. Maternal restriction and trying to slow child eating rate were associated with higher energy consumed by the child (r = 0.19 and 0.13, respectively; p < 0.05). Maternal autonomy-supportive prompts and restriction were associated with a greater variety of items selected by children (r = 0.19 and 0.15, respectively; p < 0.05). The frequency of maternal feeding practice use differed across ethnic groups, with Malay mothers using the most prompts to eat (p < 0.05), Chinese mothers most likely to question a child's food choice (p < 0.01), and Indian mothers the last likely to tell the child to eat faster (p < 0.001). There were no differences between ethnic groups for other feeding practices. No associations were found between feeding practices and child BMI. It is possible that feeding practices related to restriction and slowing child eating are adopted in response to children who consume larger portions, although longitudinal or intervention studies are needed to confirm the direction of this relationship and create local recommendations.
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2,334,621 |
Keeping upbeat to prevent the heartbreak of anti-Ro/SSA pregnancy.
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Linked Comment: Ultrasound Obstet Gynecol 2019; 54: 87-95.
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2,334,622 |
The role of low-level vagus nerve stimulation in cardiac therapy.
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<b>Introduction:</b> Cardiovascular diseases are accompanied by autonomic nervous system (ANS) imbalance which is characterized by decreased vagal tone. Preclinical and clinical studies have revealed that increasing vagal activity via vagus nerve stimulation (VNS) could protect the heart. Based on these studies, VNS has emerged as a potential non-pharmaceutical treatment strategy. Although it's still difficult to find the optimal stimulus parameters, however, in arrhythmia model, it is reported that low-level VNS (LL-VNS) exacts paradoxical effects from the high-level VNS. Thus, the concept of LL-VNS is introduced. <b>Areas covered:</b> Animal and human studies have discussed the safety and efficacy of VNS and LL-VNS, and this review will discuss the research data in cardiovascular diseases, including atrial arrhythmia, ventricular arrhythmia, ischemia/reperfusion injury, heart failure, and hypertension. <b>Expert opinion:</b> In this regard, various clinical studies have been performed to verify the safety and efficacy of VNS. It is shown that VNS is well-tolerated and safe, but the results of its efficacy are conflicting, which may well block the translational process of VNS. The appearance of LL-VNS brings new idea and inspiration, suggesting an important role of subthreshold stimulation. A better understanding of the LL-VNS will contribute to translational research of VNS.
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2,334,623 |
Role of baseline 12‑lead ECG in predicting syncope caused by arrhythmia in patients investigated using an implantable loop recorder.
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To evaluate the role of baseline 12‑lead ECG in predicting the syncope mechanism during continuous monitoring using an implantable loop recorder (ILR).</AbstractText>Consecutive patients with syncope implanted with an ILR were enrolled. Baseline 12‑lead ECG were related to ECG diagnosis derived from ILR tracings recorded at the time of syncope recurrence.</AbstractText>In total 300 patients with a mean age of 66 ± 16 years were included, 49% (146/300) received an ILR-guided diagnosis during follow-up. Patients with abnormal baseline ECG more frequently received an ILR-guided diagnosis compared to those with normal baseline ECG 59% vs. 44%, p</i> = 0.018. For a diagnosis of arrhythmic syncope, the corresponding frequencies were 45% vs. 26%, p</i> = 0.001.Patients with bifascicular block significantly more common received an ILR-guided diagnosis 76% (25/33) compared to those with normal baseline ECG 44% (90/205), p</i> ≪ 0.001. In this subgroup, 96% (24/25) were diagnosed with arrhythmic syncope, 23 of which were due to bradyarrhythmia. Bifascicular block occurred almost exclusively among those ≥60 years (31/33). After logistic regression the adjusted OR for arrhythmic syncope was significant for bifascicular block 5.5 (95%CI 2.3-13.2), p</i> ≪ 0.001. PPV for bifascicular block in predicting arrhythmic syncope was 73% and NPV 73%.</AbstractText>A baseline 12‑lead ECG with bifascicular block was a strong predictor for syncope during follow-up, most often due to bradyarrhythmia caused by intermittent complete heart block. No other ECG findings were associated with the ILR outcome. We find it reasonable to consider permanent pacing instead of an ILR for patients with bifascicular block and unexplained syncope.</AbstractText>
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2,334,624 |
Comparison of IV granisetron and IV palonosetron on hemodynamics and sensory and motor block after spinal anesthesia with hyperbaric bupivacaine in patients undergoing abdominal hysterectomy.
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The present study evaluated the effects of two 5-HT3 serotonin receptor antagonists; granisetron and palonosetron on hemodynamics, sensory, and motor blockade induced by intrathecal bupivacaine in patients undergoing abdominal hysterectomy.</AbstractText>In total, 126 female patients (ASA I and II physical status) undergoing abdominal hysterectomy under spinal anesthesia with intrathecal bupivacaine were randomly divided into three groups out of which 40 patients in each group were evaluated for final outcome. Group G received intravenous 1 mg granisetron, group P received intravenous palonosetron 0.075 mg, and group C received intravenous normal saline. Study drug was given 5 min before the spinal anesthesia. Systolic, diastolic and mean arterial blood pressure, heart rate, sensory and motor blockade were assessed.</AbstractText>The systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate showed no significant differences among the three groups. Time to reach peak sensory block and modified Bromage 3 motor block, time to two segmental regression of sensory block, and motor regression to modified Bromage score of 0 were not statistically different among the three groups. Although statistically significant early regression of sensory block to segment S1 was seen in group G as compared to group P and group C, it was of no clinical significance. The incidence of nausea and vomiting was significantly lower in group G and P.</AbstractText>Intravenous administration of granisetron and palonosetron before intrathecal bupivacaine does not attenuate the hemodynamic changes in patients undergoing abdominal hysterectomy. Further, both 5-HT3 receptors antagonists do not have clinically significant effects on the spinal blockade produced by hyperbaric bupivacaine.</AbstractText>
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2,334,625 |
Nivolumab-induced myocarditis complicated by complete atrioventricular block in a patient with metastatic non-small cell lung cancer.<ELocationID EIdType="pii" ValidYN="Y">e229963</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1136/bcr-2019-229963</ELocationID><Abstract><AbstractText>We report a case of a 74-year-old man who developed myocarditis complicated by atrioventricular (AV) block following two doses of nivolumab for the treatment of non-small cell lung cancer. A diagnosis of drug-induced acute myocarditis with complete AV block was considered on the basis of elevated troponin, new onset left ventricular (LV) systolic dysfunction, absence of acute myocardial infarction and some findings suggestive of myocarditis on cardiac magnetic resonance. The patient was commenced on glucocorticoids, perindopril and carvedilol. AV block and LV dysfunction persisted despite 2 weeks of treatment. He ultimately became hypotensive which prompted an implantation of a cardiac resynchronisation therapy pacemaker. Follow-up echocardiogram at 6 weeks showed resolution of LV systolic dysfunction. However, he continued to have AV block.</AbstractText><CopyrightInformation>© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Jin Lin</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Division of Medicine, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mugwagwa</LastName><ForeName>Augustine Nyasha</ForeName><Initials>AN</Initials><AffiliationInfo><Affiliation>Division of Medicine, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Adelaide School of Medicine, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cieslik</LastName><ForeName>Luke</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Medicine, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joshi</LastName><ForeName>Rohit</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>University of Adelaide School of Medicine, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Oncology, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>BMJ Case Rep</MedlineTA><NlmUniqueID>101526291</NlmUniqueID><ISSNLinking>1757-790X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000074322">Antineoplastic Agents, Immunological</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014336">Troponin</NameOfSubstance></Chemical><Chemical><RegistryNumber>31YO63LBSN</RegistryNumber><NameOfSubstance UI="D000077594">Nivolumab</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000074322" MajorTopicYN="N">Antineoplastic Agents, Immunological</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002289" MajorTopicYN="N">Carcinoma, Non-Small-Cell Lung</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009205" MajorTopicYN="N">Myocarditis</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077594" MajorTopicYN="N">Nivolumab</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="N">Pacemaker, Artificial</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014336" MajorTopicYN="N">Troponin</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">arrhythmias</Keyword><Keyword MajorTopicYN="N">drugs and medicines</Keyword><Keyword MajorTopicYN="N">lung cancer (oncology)</Keyword></KeywordList><CoiStatement>Competing interests: None declared.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>1</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31300602</ArticleId><ArticleId IdType="pmc">PMC6626443</ArticleId><ArticleId IdType="doi">10.1136/bcr-2019-229963</ArticleId><ArticleId IdType="pii">12/7/e229963</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Wang C, Thudium KB, Han M, et al. . 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https://amhonline-amh-net-au.salus.idm.oclc.org/chapters/immunomodulators-antineoplastics/non-cytotoxic-antineoplastics/antineoplastic-antibodies/nivolumab (Accessed 17 Dec 2018).</Citation></Reference><Reference><Citation>Cooper LT. Myocarditis. N Engl J Med 2009;360:1526–38. 10.1056/NEJMra0800028</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJMra0800028</ArticleId><ArticleId IdType="pmc">PMC5814110</ArticleId><ArticleId IdType="pubmed">19357408</ArticleId></ArticleIdList></Reference><Reference><Citation>Friedrich MG, Sechtem U, Schulz-Menger J, et al. . Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol 2009;53:1475–87. 10.1016/j.jacc.2009.02.007</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jacc.2009.02.007</ArticleId><ArticleId IdType="pmc">PMC2743893</ArticleId><ArticleId IdType="pubmed">19389557</ArticleId></ArticleIdList></Reference><Reference><Citation>Bloomer T, Alexander M, Lenihan D, et al. . Myocarditis and rhabdomyolysis incidence with immune checkpoint inhibitors. J Am Coll Cardiol 2017;69:943 10.1016/S0735-1097(17)34332-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0735-1097(17)34332-2</ArticleId></ArticleIdList></Reference><Reference><Citation>Gibson R, Delaune J, Szady A, et al. . Suspected autoimmune myocarditis and cardiac conduction abnormalities with nivolumab therapy for non-small cell lung cancer. BMJ Case Rep 2016;2016:bcr2016216228 10.1136/bcr-2016-216228</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/bcr-2016-216228</ArticleId><ArticleId IdType="pmc">PMC4964148</ArticleId><ArticleId IdType="pubmed">27440853</ArticleId></ArticleIdList></Reference><Reference><Citation>Johnson DB, Balko JM, Compton ML, et al. . Fulminant myocarditis with combination immune checkpoint blockade. 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J Am Coll Cardiol 2018;2018:25701.</Citation><ArticleIdList><ArticleId IdType="pubmed">30412709</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31300595</PMID><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1532-8651</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Jul</Month><Day>11</Day></PubDate></JournalIssue><Title>Regional anesthesia and pain medicine</Title><ISOAbbreviation>Reg Anesth Pain Med</ISOAbbreviation></Journal>Randomized comparison between perineural dexamethasone and dexmedetomidine for ultrasound-guided infraclavicular block.
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We report a case of a 74-year-old man who developed myocarditis complicated by atrioventricular (AV) block following two doses of nivolumab for the treatment of non-small cell lung cancer. A diagnosis of drug-induced acute myocarditis with complete AV block was considered on the basis of elevated troponin, new onset left ventricular (LV) systolic dysfunction, absence of acute myocardial infarction and some findings suggestive of myocarditis on cardiac magnetic resonance. The patient was commenced on glucocorticoids, perindopril and carvedilol. AV block and LV dysfunction persisted despite 2 weeks of treatment. He ultimately became hypotensive which prompted an implantation of a cardiac resynchronisation therapy pacemaker. Follow-up echocardiogram at 6 weeks showed resolution of LV systolic dysfunction. However, he continued to have AV block.<CopyrightInformation>© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Jin Lin</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Division of Medicine, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mugwagwa</LastName><ForeName>Augustine Nyasha</ForeName><Initials>AN</Initials><AffiliationInfo><Affiliation>Division of Medicine, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>University of Adelaide School of Medicine, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cieslik</LastName><ForeName>Luke</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Medicine, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joshi</LastName><ForeName>Rohit</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>University of Adelaide School of Medicine, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Oncology, Lyell McEwin Hospital, Elizabeth Vale, South Australia, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>BMJ Case Rep</MedlineTA><NlmUniqueID>101526291</NlmUniqueID><ISSNLinking>1757-790X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000074322">Antineoplastic Agents, Immunological</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014336">Troponin</NameOfSubstance></Chemical><Chemical><RegistryNumber>31YO63LBSN</RegistryNumber><NameOfSubstance UI="D000077594">Nivolumab</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000074322" MajorTopicYN="N">Antineoplastic Agents, Immunological</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054537" MajorTopicYN="N">Atrioventricular Block</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002289" MajorTopicYN="N">Carcinoma, Non-Small-Cell Lung</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009205" MajorTopicYN="N">Myocarditis</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077594" MajorTopicYN="N">Nivolumab</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration & dosage</QualifierName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010138" MajorTopicYN="N">Pacemaker, Artificial</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014336" MajorTopicYN="N">Troponin</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">arrhythmias</Keyword><Keyword MajorTopicYN="N">drugs and medicines</Keyword><Keyword MajorTopicYN="N">lung cancer (oncology)</Keyword></KeywordList><CoiStatement>Competing interests: None declared.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>1</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31300602</ArticleId><ArticleId IdType="pmc">PMC6626443</ArticleId><ArticleId IdType="doi">10.1136/bcr-2019-229963</ArticleId><ArticleId IdType="pii">12/7/e229963</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Wang C, Thudium KB, Han M, et al. . In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res 2014;2:846–56. 10.1158/2326-6066.CIR-14-0040</Citation><ArticleIdList><ArticleId IdType="doi">10.1158/2326-6066.CIR-14-0040</ArticleId><ArticleId IdType="pubmed">24872026</ArticleId></ArticleIdList></Reference><Reference><Citation>Robert C, Long GV, Brady B, et al. . Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 2015;372:320–30. 10.1056/NEJMoa1412082</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJMoa1412082</ArticleId><ArticleId IdType="pubmed">25399552</ArticleId></ArticleIdList></Reference><Reference><Citation>Borghaei H, Paz-Ares L, Horn L, et al. . Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. 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Australian Product Information OPDIVO ® (Nivolumab) Warning: Immune-related adverse reactions with OPDIVO AND YERVOY (Ipilimumab) Combination Therapy. https://www.tga.gov.au/sites/default/files/auspar-nivolumab-180806-pi.pdf (Accessed 20 Nov 2018).</Citation></Reference><Reference><Citation>
Nivolumab - Australian Medicines Handbook. Aust Med Handb
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https://amhonline-amh-net-au.salus.idm.oclc.org/chapters/immunomodulators-antineoplastics/non-cytotoxic-antineoplastics/antineoplastic-antibodies/nivolumab (Accessed 17 Dec 2018).</Citation></Reference><Reference><Citation>Cooper LT. Myocarditis. N Engl J Med 2009;360:1526–38. 10.1056/NEJMra0800028</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJMra0800028</ArticleId><ArticleId IdType="pmc">PMC5814110</ArticleId><ArticleId IdType="pubmed">19357408</ArticleId></ArticleIdList></Reference><Reference><Citation>Friedrich MG, Sechtem U, Schulz-Menger J, et al. . Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol 2009;53:1475–87. 10.1016/j.jacc.2009.02.007</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.jacc.2009.02.007</ArticleId><ArticleId IdType="pmc">PMC2743893</ArticleId><ArticleId IdType="pubmed">19389557</ArticleId></ArticleIdList></Reference><Reference><Citation>Bloomer T, Alexander M, Lenihan D, et al. . Myocarditis and rhabdomyolysis incidence with immune checkpoint inhibitors. J Am Coll Cardiol 2017;69:943 10.1016/S0735-1097(17)34332-2</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0735-1097(17)34332-2</ArticleId></ArticleIdList></Reference><Reference><Citation>Gibson R, Delaune J, Szady A, et al. . Suspected autoimmune myocarditis and cardiac conduction abnormalities with nivolumab therapy for non-small cell lung cancer. BMJ Case Rep 2016;2016:bcr2016216228 10.1136/bcr-2016-216228</Citation><ArticleIdList><ArticleId IdType="doi">10.1136/bcr-2016-216228</ArticleId><ArticleId IdType="pmc">PMC4964148</ArticleId><ArticleId IdType="pubmed">27440853</ArticleId></ArticleIdList></Reference><Reference><Citation>Johnson DB, Balko JM, Compton ML, et al. . Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 2016;375:1749–55. 10.1056/NEJMoa1609214</Citation><ArticleIdList><ArticleId IdType="doi">10.1056/NEJMoa1609214</ArticleId><ArticleId IdType="pmc">PMC5247797</ArticleId><ArticleId IdType="pubmed">27806233</ArticleId></ArticleIdList></Reference><Reference><Citation>Mehta A, Gupta A, Hannallah F, et al. . Myocarditis as an immune-related adverse event with ipilimumab/nivolumab combination therapy for metastatic melanoma. Melanoma Res 2016;26:319–20. 10.1097/CMR.0000000000000251</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/CMR.0000000000000251</ArticleId><ArticleId IdType="pubmed">27110676</ArticleId></ArticleIdList></Reference><Reference><Citation>Behling J, Kaes J, Münzel T, et al. . New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Melanoma Res 2017;27:155–8. 10.1097/CMR.0000000000000314</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/CMR.0000000000000314</ArticleId><ArticleId IdType="pubmed">27977496</ArticleId></ArticleIdList></Reference><Reference><Citation>Matson DR, Accola MA, Rehrauer WM, et al. . Fatal Myocarditis Following Treatment with the PD-1 Inhibitor Nivolumab. J Forensic Sci 2018;63:954–7. 10.1111/1556-4029.13633</Citation><ArticleIdList><ArticleId IdType="doi">10.1111/1556-4029.13633</ArticleId><ArticleId IdType="pubmed">28833116</ArticleId></ArticleIdList></Reference><Reference><Citation>Velez MG, Suero-Abreu G, Duma N, et al. . Immune-related myocarditis and conduction abnormalities secondary to combination immunotherapy treatment with ipilimumab/nivolumab in a patient with merkel cell carcinoma. J Am Coll Cardiol 2018;71:A2617 10.1016/S0735-1097(18)33158-9</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/S0735-1097(18)33158-9</ArticleId></ArticleIdList></Reference><Reference><Citation>Frigeri M, Meyer P, Banfi C, et al. . Immune checkpoint inhibitor-associated myocarditis: A new challenge for cardiologists. Can J Cardiol 2018;34:92.e1–92.e3. 10.1016/j.cjca.2017.09.025</Citation><ArticleIdList><ArticleId IdType="doi">10.1016/j.cjca.2017.09.025</ArticleId><ArticleId IdType="pubmed">29275889</ArticleId></ArticleIdList></Reference><Reference><Citation>Kusumoto FM, Schoenfeld MH, Barrett C, et al. . ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay. J Am Coll Cardiol 2018;2018:25701.</Citation><ArticleIdList><ArticleId IdType="pubmed">30412709</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31300595</PMID><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1532-8651</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Jul</Month><Day>11</Day></PubDate></JournalIssue><Title>Regional anesthesia and pain medicine</Title><ISOAbbreviation>Reg Anesth Pain Med</ISOAbbreviation></Journal><ArticleTitle>Randomized comparison between perineural dexamethasone and dexmedetomidine for ultrasound-guided infraclavicular block.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">rapm-2019-100680</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1136/rapm-2019-100680</ELocationID><Abstract><AbstractText Label="BACKGROUND">This randomized trial compared perineural dexamethasone (5 mg) and dexmedetomidine (100 µg) for ultrasound-guided infraclavicular brachial plexus block. We hypothesized that both adjuvants would result in similar durations of motor block and therefore designed the study as an equivalence trial (equivalence margin=3.0 hours).<AbstractText Label="METHODS">One hundred and twenty patients undergoing upper limb surgery with ultrasound-guided infraclavicular block (using 35 mL of lidocaine 1%-bupivacaine 0.25% with epinephrine 5 µg/mL) were randomly allocated to receive perineural dexamethasone (5 mg) or dexmedetomidine (100 µg). Patients and operators were blinded to the nature of the perineural adjuvant. After the performance of the block, a blinded observer assessed the success rate (defined as a minimal sensorimotor composite score of 14 out of 16 points at 30 min) as well as the incidence of surgical anesthesia (defined as the ability to complete surgery without local infiltration, supplemental blocks, intravenous opioids, or general anesthesia). Heart rate and blood pressure were recorded before the block as well as during the first 2 hours after its performance. Furthermore, the level of sedation (using the Ramsay Sedation Scale) was recorded in the postanesthesia care unit. Postoperatively, the blinded observer contacted patients with successful blocks to inquire about the duration of motor block, sensory block, and postoperative analgesia.<AbstractText Label="RESULTS">No intergroup differences were observed in terms of success rate and surgical anesthesia. Compared with dexmedetomidine, dexamethasone provided longer durations of motor block (17.4 (4.0) vs 14.3 (3.0) hours; p<0.001; 95% CI 1.7 to 4.5), sensory block (19.0 (4.0) vs 15.0 (3.2) hours; p<0.001; 95% CI 2.6 to 5.4), and analgesia (22.2 (3.6) vs 16.9 (3.9) hours; p<0.001; 95% CI 3.7 to 6.9). Dexmedetomidine resulted in lower heart rate and blood pressure after the performance of the block, as well as an increased level of sedation postoperatively.<AbstractText Label="CONCLUSION">Compared with dexmedetomidine (100 µg), dexamethasone (5 mg) results in longer sensorimotor block and analgesic durations, as well as a decreased level of patient sedation. Further studies are required to compare dexamethasone and dexmedetomidine using different doses, local anesthetic agents, and approaches to the brachial plexus.<AbstractText Label="TRIAL REGISTRATION NUMBER">NCT03610893.
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Increasing serotonin bioavailability in preweaned dairy calves impacts hematology, growth, and behavior.
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Peripheral serotonin has been shown to regulate important physiological functions such as energy homeostasis and immunity, particularly in rodent and humans, but its role is poorly understood in livestock species. Herein, we tested the safety and effectiveness of increasing serotonin bioavailability in preweaned dairy calves by oral supplementation of a serotonin precursor (5-hydroxytryptophan, 5-HTP) or a serotonin reuptake inhibitor (fluoxetine, FLX). Bull Holstein calves (21 ± 2 d old; N = 24) were fed milk replacer (8 L/d) supplemented with either saline as control (CON, 8 mL/d, n = 8), FLX (40 mg/d, approx. 0.8 mg/kg; n = 8), or 5-HTP (90 mg/d, approx. 1.8 mg/kg; n = 8) for 10 consecutive days in a complete randomized block design. Heart rate (HR), respiration rate, rectal temperature, and health scores were recorded daily. Hip height and body weight were measured at d 1, 5, and 10 relative to initiation of supplementation. Blood samples were collected once before the supplementation period (d 1), during the 10-d supplementation period (daily), and during a 14-d withdrawal period (d 2, 3, 4, 7, and 14 relative to initiation of withdrawal). Cerebrospinal fluid and muscle tissue were collected from a subset of calves (n = 12) that were euthanized after the 10-d supplementation or 14-d withdrawal period. Whole blood serotonin concentrations increased in 5-HTP calves and decreased in FLX calves compared with CON (P < 0.001), indicating that serotonin bioavailability was increased in both groups. Whole blood serotonin concentrations of 5-HTP and FLX calves returned to CON levels after 7 d of withdrawal. All calves grew and were considered healthy throughout the study. In fact, calves fed 5-HTP had higher average daily gain compared with CON (0.87 vs 0.66 ± 0.12 kg/d, P = 0.05). Calves fed FLX had lower HR (P = 0.02) and greater red blood cells and hemoglobin counts on d 10 of supplementation compared with CON (P < 0.01). After the 14-d withdrawal period, FLX was not detected in circulation of FLX calves, but was still present in the muscle tissue. Our results demonstrate that manipulation of the serotonin pathway by supplementing FLX or 5-HTP is a feasible and safe approach in preweaned dairy calves; however, it takes more than 14 d for FLX to be completely withdrawn from the body.
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2,334,627 |
Automated Quantitative Stress Perfusion in a Clinical Routine.
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Cardiovascular magnetic resonance (CMR) perfusion imaging is a robust noninvasive technique to evaluate ischemia in patients with coronary artery disease (CAD). Although qualitative and semiquantitative methods have shown that CMR has high accuracy in diagnosing flow-obstructing lesions in CAD, quantitative ischemic burden is an important variable used in clinical practice for treatment decisions. Quantitative CMR perfusion techniques have evolved significantly, with accuracy comparable with both PET and microsphere evaluation. Routine clinical use of these quantitative techniques has been facilitated by the introduction of automated methods that accelerate the work flow and rapidly generate pixel-based myocardial blood flow maps.
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2,334,628 |
T2* Mapping Techniques: Iron Overload Assessment and Other Potential Clinical Applications.
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T2* mapping techniques has evolved significantly since their introduction in the early 2000s and a significant amount of evidence has been gathered to support their clinical routine use for iron overload assessment. This article focuses on the most important aspects of how to perform T2* imaging, from acquisition, to postprocessing, to analyzing the data with clinical concentration. Newer techniques have made T2* mapping more robust and accurate, allowing a broader use of this technique for noncontrast ischemia imaging based on blood oxygen levels, in addition to evaluation of intramyocardial hemorrhage and microvascular obstruction.
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2,334,629 |
Dissecting the role of the gut microbiota and diet on visceral fat mass accumulation.
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Both gut microbiota and diet have been shown to impact visceral fat mass (VFM), a major risk factor for cardiometabolic disease, but their relative contribution has not been well characterised. We aimed to estimate and separate the effect of gut microbiota composition from that of nutrient intake on VFM in 1760 older female twins. Through pairwise association analyses, we identified 93 operational taxonomic units (OTUs) and 10 nutrients independently linked to VFM (FDR < 5%). Conditional analyses revealed that the majority (87%) of the 93 VFM-associated OTUs remained significantly associated with VFM irrespective of nutrient intake correction. In contrast, we observed that the effect of fibre, magnesium, biotin and vitamin E on VFM was partially mediated by OTUs. Moreover, we estimated that OTUs were more accurate predictors of VFM than nutrients and accounted for a larger percentage of its variance. Our results suggest that while the role of certain nutrients on VFM appears to depend on gut microbiota composition, specific gut microbes may affect host adiposity regardless of dietary intake. The findings imply that the gut microbiota may have a greater contribution towards shaping host VFM than diet alone. Thus, microbial-based therapy should be prioritised for VFM reduction in overweight and obese subjects.
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2,334,630 |
The Crystalloid Co-Load: Clinically as Effective as Colloid Preload for Preventing Hypotension from Spinal Anaesthesia for Caesarean Delivery.
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Colloid preloading diminishes post-spinal hypotension. However, whether colloid preloading is superior to crystalloid co-loading is uncertain. In this retrospective study, we compared the effects of a colloid preload versus a crystalloid co-load on vasopressor requirements and maternal haemodynamics among women undergoing elective caesarean delivery (CD) with spinal anaesthesia.</AbstractText>We extracted data from the medical records of 160 healthy women who underwent elective CD with spinal anaesthesia at an academic obstetric centre before and after an institutional fluid-loading protocol change. Patients received a 500 mL 6% hydroxyethyl starch preload or a 1000 mL crystalloid co-load. The primary outcome was the total phenylephrine dose administered from spinal block placement to delivery.</AbstractText>Our cohort comprised 79 women in the colloid group and 77 women in the crystalloid group. The mean phenylephrine use was significantly lower in the colloid group than in the crystalloid group (489±403 μg vs. 647±464 μg, respectively, p=0.02). The maximal drop in systolic blood pressure was greater in the colloid group than in the crystalloid group (36±20 mmHg vs. 29±16 mmHg, respectively, p=0.02). There were no clinically significant differences between the groups in heart rate, blood loss, temperature and Apgar scores.</AbstractText>Vasopressor use was lower in colloid preloading than in crystalloid co-loading. However, differences in all outcome measures were minimal and likely clinically insignificant, suggesting that both fluid-loading techniques are appropriate to use for the prevention of spinal hypotension in women undergoing CD.</AbstractText>
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2,334,631 |
Independent associations of blood pressure and body mass index with interatrial block: a cross-sectional study in general Chinese population.
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This current study was performed to characterise the independent associations of obesity and hypertension with interatrial block (IAB) after adjusting for cardiovascular risk factors, echocardiographic left atrial diameter (LAD) and left ventricular mass index (LVMI) in a large general Chinese population.</AbstractText>A cross-sectional study.</AbstractText>A total of 11 956 permanent residents (≥35 years of age) from Liaoning Province in China were included in this study. Following the completion of a questionnaire, the enrolled participants were subjected to physical examinations, laboratory analyses, ECG and echocardiogram. Linear and logistic regression analyses were performed to evaluate the associations of hypertension and obesity with IAB.</AbstractText>IAB was defined as a prolongation of the P wave duration ≥120 ms on a digital 12-lead ECG.</AbstractText>The prevalence of IAB in hypertensive individuals was higher than the normotensive in both men (9.5 vs 5.9%; p<0.001) and women (6.6 vs 3.6%; p<0.001). In addition, the prevalence of IAB exhibited a sharp increase with advancing body mass index (BMI) in both men (from 4.9% to 13.0%) and women (from 3.5% to 6.9%) (ps- for trend <0.001). Multiple relevant clinical covariates, echocardiographic LAD and LVMI were adjusted in the multivariate linear and logistic regression analyses. The results revealed that systolic blood pressure, diastolic blood pressure and BMI were all independently associated with P wave duration (β=0.02, 0.09 and 0.25, respectively; all ps <0.005). Furthermore, hypertension was found to be independently associated with IAB (OR=1.27; p=0.018), while both overweight and obesity exhibited higher odds of IAB (OR=1.42 and 1.67, respectively; ps <0.005), compared with BMI <24.0 kg/m2</sup>.</AbstractText>The key findings of this study highlighted that hypertension and overweight/obesity were independently and significantly associated with IAB in general Chinese population.</AbstractText>© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation>
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2,334,632 |
[Efficacy of erector spinae block versus retrolaminar block for postoperative analgesia following posterior lumbar surgery].
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To compare the effect of erector spinae plane block and retrolaminar block for relieving acute pain after posterior lumbar surgery.</AbstractText>Eighty-nine patients undergoing selective posterior lumbar surgery under general anesthesia in our hospital between January and December, 2018, were recruited. Of these patients, 30 received total intravenous general anesthesia to serve as the control group, 28 received total intravenous general anesthesia (TIVA) combined with erector spinae plane block (ESPB), and 31 had TIVA combined with retrolaminar block (RLB). All the patients received patient-controlled intravenous analgesia (PCIA) for postoperative analgesia, and their heart rate, blood pressure, and pulse oximetry were routinely monitored during the anesthesia. VAS scores were evaluated before and at 2, 8, 12, 24, and 48 h after the surgery. Sufentanil consumption during the operation and PCIA were also recorded. The postoperative complications such as nausea and vomiting, urinary retention, itching and respiratory depression within 48 h after the surgery were also recorded.</AbstractText>At 2, 8 and 12 h postoperatively, VAS scores in the ESPB group and RLB group were significantly lower than those in the control group; the scores were significantly lower in RLB group than in ESPB group (P</i> &lt; 0.05). Compared with that in the control group, sufentanil consumption during the operation and PCIA were significantly decreased in both ESPB and RLB groups, particularly in the latter group (P</i> &lt; 0.05). Two patients experienced nausea and vomiting and 1 patient complained of pruritus in control group; 1 patient had over sedation and 1 had urinary retention in ESPB group; 1 patient had urinary retention in RLB group.</AbstractText>Ultrasound-guided RLB has better analgesic effect than ESPB for management of perioperative pain following posterior lumbar surgery.</AbstractText>
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2,334,633 |
Effect of different doses of intrathecal dexmedetomidine on hemodynamic parameters and block characteristics after ropivacaine spinal anesthesia in lower-limb orthopedic surgery: a randomized clinical trial.
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The study aims to compare the efficacy of different doses of intrathecal dexmedetomidine on hemodynamic parameters and block characteristics after ropivacaine spinal anesthesia in lower-limb orthopedic surgery. In a double-blind trial, 90 patients undergoing spinal anesthesia for lower-limb orthopedic surgery were included and then randomly assigned to three groups; dexmedetomidine 5 μg/kg, dexmedetomidine 10 μg/kg and placebo. Blood pressure, heart rate, and oxygen saturation were recorded in the three groups at the first 15 minutes and then every 15 to 180 minutes at recovery by a resident anesthesiologist, as well as sensory-motor block onset. The visual analog scale scores for the assessment of pain were recorded at recovery, and 2, 4, 6, and 12 hours postoperatively and the data were analyzed by Stata software. The onset and time to achieve sensory block to ≥ T8 were faster in the 10 μg/kg dexmedetomidine group than the other groups (P = 0.001). The Bromage score was higher in the 10 μg/kg dexmedetomidine group (P = 0.0001) with lower pain score as compared with the 5 μg/kg dexmedetomidine and placebo groups (P = 0.0001). Therefore, an increase in dexmedetomidine hastens the onset of sensory-motor block but not causes side effects. This study was approved by the Ethical Committee of Arak University of Medical Sciences in 2017 (Ethical Code: IR.ARAKMU.REC.1396.37), and the trail was registered and approved by the Iranian Registry of Clinical Trials in 2017 (IRCT No. IRCT2017070614056N12).
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2,334,634 |
TXNIP/Redd1 signalling and excessive autophagy: a novel mechanism of myocardial ischaemia/reperfusion injury in mice.
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Either insufficient or excessive autophagy causes cellular death and contributes to myocardial ischaemia/reperfusion (I/R) injury. However, mechanisms controlling the 'right-level' of autophagy in the heart remains unidentified. Thioredoxin-interacting protein (TXNIP) is a pro-oxidative molecule knowing to contribute to I/R injury. However, whether and how TXNIP may further inhibit suppressed autophagy or promote excessive cardiac autophagy in I/R heart has not been previously investigated.</AbstractText>Wild type or gene-manipulated adult male mice were subjected to myocardial I/R. TXNIP was increased in myocardium during I/R. Cardiac-specific TXNIP overexpression increased cardiomyocytes apoptosis and cardiac dysfunction, whereas cardiac-specific TXNIP knock-out significantly mitigated I/R-induced apoptosis and improved cardiac function. Importantly, TXNIP overexpression significantly promoted cardiac autophagy and TXNIP knock-out significantly inhibited cardiac autophagy. In vitro studies demonstrated that TXNIP increased autophagosome formation but inhibited autophagosome clearance during myocardial reperfusion. Atg5 siRNA significantly decreased hypoxia/reoxygenation induced apoptosis in cardiomyocytes with TXNIP overexpression. Mechanistically, TXNIP suppressed autophagosome clearance via increasing reactive oxygen species (ROS) level. However, TXNIP-increased autophagosome formation was not mediated by ROS as a ROS scavenger failed to block increased autophagosome formation in TXNIP overexpression heart. Finally, TXNIP directly interacted and stabilized Redd1 (an autophagy regulator), resulting in mTOR inhibition and autophagy activation. Redd1 knock-down significantly reduced autophagy formation and ameliorated I/R injury in TXNIP overexpression hearts.</AbstractText>Our results demonstrated that increased TXNIP-Redd1 expression is a novel signalling pathway that contributes to I/R injury by exaggerating excessive autophagy during reperfusion. These observations advance our understanding of the mechanisms of myocardial I/R injury.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: [email protected].</CopyrightInformation>
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2,334,635 |
A comprehensive, multiscale framework for evaluation of arrhythmias arising from cell therapy in the whole post-myocardial infarcted heart.
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Direct remuscularization approaches to cell-based heart repair seek to restore ventricular contractility following myocardial infarction (MI) by introducing new cardiomyocytes (CMs) to replace lost or injured ones. However, despite promising improvements in cardiac function, high incidences of ventricular arrhythmias have been observed in animal models of MI injected with pluripotent stem cell-derived cardiomyocytes (PSC-CMs). The mechanisms of arrhythmogenesis remain unclear. Here, we present a comprehensive framework for computational modeling of direct remuscularization approaches to cell therapy. Our multiscale 3D whole-heart modeling framework integrates realistic representations of cell delivery and transdifferentiation therapy modalities as well as representation of spatial distributions of engrafted cells, enabling simulation of clinical therapy and the prediction of emergent electrophysiological behavior and arrhythmogenensis. We employ this framework to explore how varying parameters of cell delivery and transdifferentiation could result in three mechanisms of arrhythmogenesis: focal ectopy, heart block, and reentry.
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2,334,636 |
Anemic Disease of the Newborn With Little Increase in Hemolysis and Erythropoiesis Due to Maternal Anti-Jr<sup>a</sup>: A Case Study and Review of the Literature.
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The severity of the hemolytic disease of the fetus and newborn (HDFN) due to Jr<sup>a</sup> mismatch ranges from no symptoms to severe anemia that requires intrauterine and exchange transfusions. We encountered a newborn, born to a healthy mother having anti-Jr<sup>a</sup> at 38 weeks of pregnancy, who had moderate anemia, a positive direct antiglobulin test (DAT) result, no increased erythropoiesis, and no jaundice at birth. Flow cytometry revealed that the Jr<sup>a</sup> antigen of red cells in the infant was nearly negative at birth, biphasic at 5 weeks, and lowly expressed at 7 months of life. We searched online for previous case reports on HDFN due to Jr<sup>a</sup> incompatibility. Among 63 reported cases, excluding 25 cases, 38 were included with the present case for analysis. Of 39 newborns, 10 developed clear anemia (hemoglobin <10.0 g/dL), and 1 died, 5 developed hydrops fetalis, 4 needed intrauterine transfusion and/or exchange transfusion, and 3 received red cell transfusion after birth; overlaps were included. Among 29 neonates with no anemia, 8 needed interventions including phototherapy and γ-globulin infusion, and the remaining 21 received conservative supports only. The maternal anti-Jr<sup>a</sup> titer, ranging between 4 and 2048, did not correlate with the severity of anemia, levels of bilirubin, or any interventions required. The DAT of red cells was positive in 29 of 36 fetuses/newborns tested, whereas it was often negative among anemic neonates (4 of 9) (P < .05). Hematopoiesis did not increase effectively, as indicated by reticulocyte ratios between 1.7% and 22.3%, even with the increase in reticulocytes in anemic neonates compared with nonanemic neonates (P < .05). Total bilirubin levels ranged broadly between 0.2 and 14.3 mg/dL but were generally low. The maternal anti-Jr<sup>a</sup> titer and IgG3 subclass did not correlate with the morbidity of the newborns. Being identical/compatible between mothers and their infants may possibly enhance infants' morbidity, as a weak tendency was observed (P = .053). Maternal anti-Jr<sup>a</sup> may suppress erythropoiesis in fetuses via a mechanism different from the established HDFN, such as anti-D, as evidenced by the lower reticulocyte count and small increase in bilirubin in neonates. As the anti-Jr<sup>a</sup> titer, IgG subclass, and DAT were not correlated with the severity, the mechanism of anti-Jr<sup>a</sup>-induced HDFN remains to be elucidated.
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2,334,637 |
An improved synthesis of a cyclopropene-based molecule for the fabrication of bioengineered tissues via copper-free click chemistry.
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Since its introduction in the field of biological imaging, the use of copper-free click chemistry has been extended to produce improved materials for vascular surgery, ophthalmology, environmental, and automotive applications. This wide applicability suggests that larger quantities of the chemical reagents for copper-free click chemistry will be required in the future. However, the large-scale synthesis of such chemicals has been barely investigated. A possible reason is the shortage of reliable synthetic protocols to obtain large quantities of these building blocks. We therefore present in this paper an improved synthetic protocol to obtain a cyclopropene-based carbonate, a key building block for the well-known copper-free click chemistry.</AbstractText>Our protocol builds upon an already available method to obtain a cyclopropene-based carbonate. When scaled up, several parameters of this method were changed in order to obtain an improved yield. First, the use of lower temperatures and slower addition rates of the chemicals avoided the formation of detrimental hotspots in the reaction system. Second, the use of less hygroscopic solvents minimized the decomposition of the cyclopropene carbonate. Finally, chromatographic purifications were minimized and improved by using deactivated silica.</AbstractText>We obtained the compound (2-methylcycloprop-2-en-1-yl)methyl (4-nitrophenyl) carbonate, a key building block for copper-free click chemistry, in an unprecedented 60% overall yield on a six-gram scale.</AbstractText>Our improved synthetic protocol demonstrates the potential of large-scale production of improved materials using click chemistry, with potential future applications in the fields of molecular imaging, vascular surgery, ophthalmology, and theranostics.</AbstractText>
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2,334,638 |
A normal sodium diet preserves serum sodium levels during treatment of acute decompensated heart failure: A prospective, blind and randomized trial.
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We tested the hypothesis that a normal sodium diet could be associated with preservation of serum sodium during treatment of acute decompensated heart failure (ADHF).</AbstractText>Forty-four patients hospitalized for ADHF were blindly randomized by using block method to a low sodium diet (LS: 3 g/day of dietary sodium chloride; n = 22, 59.5 ± 11.9 y.o., 50% males. LVEF = 30.0 ± 13.6%); and a normal sodium diet (NS: 7 g/day; n = 22, 56.4 ± 10.3 y.o., 68% males; LVEF = 27.8 ± 11.7%), and both groups were submitted to fluid restriction of 1.000 mL/day. At the 7th day of intervention 16 patients of LS group and 15 patients of NS group were assessed for difference in serum sodium. Both groups had equivalent decongestion, reflected by similar percent reduction of body weight (LS: -5.0 ± 4.7% vs NS: -4.5 ± 5.2%. p = 0.41). Reduction of the N terminal fragment of type B natriuretic peptide (NT-proBNP) was significant only in the NS (-1497.0 [-18843.0 - 1191.0]. p = 0.04). The LS group showed lower levels of serum sodium (135.4 ± 3.5 mmol/L) compared to the NS group (137.5 ± 1.9 mmol/L; p = 0.04). Four cases of hyponatremia were observed only in the LS group (22%). The NS group exhibited higher mean blood pressure values (79.4 ± 2.4 mmHg vs 75.5 ± 3.0 mmHg. p = 0.03), and lower heart rate (73.2 ± 1.6 bpm vs 75.5 ± 2.1 bpm. p = 0.02).</AbstractText>These results suggest that a normal sodium diet, when compared to a low sodium diet, is associated with similar degrees of decongestion, but with higher levels of natremia, blood pressure and lower neurohormonal activation during ADHF treatment.</AbstractText>clinicaltrials.gov Identifier no. NCT03722069.</AbstractText>Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,639 |
A novel diversity method for smartphone camera-based heart rhythm signals in the presence of motion and noise artifacts.
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The advent of smartphones has advanced the use of embedded sensors to acquire various physiological information. For example, smartphone camera sensors and accelerometers can provide heart rhythm signals to the subjects, while microphones can give respiratory signals. However, the acquired smartphone-based physiological signals are more vulnerable to motion and noise artifacts (MNAs) compared to using medical devices, since subjects need to hold the smartphone with proper contact to the smartphone camera and lens stably and tightly for a duration of time without any movement in the hand or finger. This results in more MNA than traditional methods, such as placing a finger inside a tightly enclosed pulse oximeter to get PPG signals, which provides stable contact between the sensor and the subject's finger. Moreover, a smartphone lens does not block ambient light in an effective way, while pulse oximeters are designed to block the ambient light effectively. In this paper, we propose a novel diversity method for smartphone signals that reduces the effect of MNAs during heart rhythm signal detection by 1) acquiring two heterogeneous signals from a color intensity signal and a fingertip movement signal, and 2) selecting the less MNA-corrupted signal of the two signals. The proposed method has advantages in that 1) diversity gain can be obtained from the two heterogeneous signals when one signal is clean while the other signal is corrupted, and 2) acquisition of the two heterogeneous signals does not double the acquisition procedure but maintains a single acquisition procedure, since two heterogeneous signals can be obtained from a single smartphone camera recording. In our diversity method, we propose to choose the better signal based on the signal quality indices (SQIs), i.e., standard deviation of instantaneous heart rate (STD-HR), root mean square of the successive differences of peak-to-peak time intervals (RMSSD-T), and standard deviation of peak values (STD-PV). As a performance metric evaluating the proposed diversity method, the ratio of usable period is considered. Experimental results show that our diversity method increases the usable period 19.53% and 6.25% compared to the color intensity or the fingertip movement signals only, respectively.
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2,334,640 |
Hepatic ferroptosis plays an important role as the trigger for initiating inflammation in nonalcoholic steatohepatitis.
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Nonalcoholic steatohepatitis (NASH) is a metabolic liver disease that progresses from simple steatosis to the disease state of inflammation and fibrosis. Previous studies suggest that apoptosis and necroptosis may contribute to the pathogenesis of NASH, based on several murine models. However, the mechanisms underlying the transition of simple steatosis to steatohepatitis remain unclear, because it is difficult to identify when and where such cell deaths begin to occur in the pathophysiological process of NASH. In the present study, our aim is to investigate which type of cell death plays a role as the trigger for initiating inflammation in fatty liver. By establishing a simple method of discriminating between apoptosis and necrosis in the liver, we found that necrosis occurred prior to apoptosis at the onset of steatohepatitis in the choline-deficient, ethionine-supplemented (CDE) diet model. To further investigate what type of necrosis is involved in the initial necrotic cell death, we examined the effect of necroptosis and ferroptosis inhibition by administering inhibitors to wild-type mice in the CDE diet model. In addition, necroptosis was evaluated using mixed lineage kinase domain-like protein (MLKL) knockout mice, which is lacking in a terminal executor of necroptosis. Consequently, necroptosis inhibition failed to block the onset of necrotic cell death, while ferroptosis inhibition protected hepatocytes from necrotic death almost completely, and suppressed the subsequent infiltration of immune cells and inflammatory reaction. Furthermore, the amount of oxidized phosphatidylethanolamine, which is involved in ferroptosis pathway, was increased in the liver sample of the CDE diet-fed mice. These findings suggest that hepatic ferroptosis plays an important role as the trigger for initiating inflammation in steatohepatitis and may be a therapeutic target for preventing the onset of steatohepatitis.
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2,334,641 |
Telemonitoring-supported exercise training, metabolic syndrome severity, and work ability in company employees: a randomised controlled trial.
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Metabolic syndrome is a predisposing factor for cardiovascular and metabolic disease, but also has socioeconomic relevance by affecting the health and productivity of workers. We tested the effect of regular telemonitoring-supported physical activity on metabolic syndrome severity and work ability in company employees.</AbstractText>This was a prospective, randomised, parallel-group, and assessor-blind study done in workers in the main Volkswagen factory (Wolfsburg, Germany). Volunteers with diagnosed metabolic syndrome according to American Heart Association/National Heart, Lung, and Blood Institute criteria were randomly assigned (1:1) to a 6-month lifestyle intervention focusing on regular exercise (exercise group), or to a waiting-list control group, using a computer-based assignment list with variable block length. Participants in the exercise group received individual recommendations for exercise at face-to-face meetings and via a smartphone application, with the aim of doing 150 min physical activity per week. Activities were supervised and adapted using activity-monitor data, which were transferred to a central database. Participants in the control group continued their current lifestyle and were informed about the possibility to receive the supervised intervention after study completion. The primary outcome was the change in metabolic syndrome severity (metabolic syndrome Z score) after 6 months in the intention-to treat population. This trial is registered with ClinicalTrials.gov, number NCT03293264, and is closed to new participants.</AbstractText>543 individuals were screened between Oct 10, 2017, and Feb 27, 2018, of whom 314 (mean age 48 years [SD 8]) were randomly assigned to receive the intervention (n=160; exercise group) or to a waiting list (n=154; control group). The mean metabolic syndrome Z score for the exercise group was significantly reduced after the 6-month intervention period (0·93 [SD 0·63] before and 0·63 [0·64] after the intervention) compared with the control group (0·95 [0·55] and 0·90 [0·61]; difference between groups -0·26 [95% CI -0·35 to -0·16], p<0·0001). We documented 11 adverse events in the exercise group, with only one event (a twisted ankle) regarded as directly caused by the intervention.</AbstractText>A 6-month exercise-focused intervention using telemonitoring systems reduced metabolic syndrome severity. This form of intervention shows significant potential to reduce disease risk, while also improving mental health, work ability, and productivity-related outcomes for employees at high risk for cardiovascular and metabolic disease.</AbstractText>Audi BKK health insurance and the German Research Foundation through the Cluster of Excellence REBIRTH.</AbstractText>Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.</CopyrightInformation>
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2,334,642 |
Unilateral Epidural Blockade for Lower Limb Fracture Surgery: Parasagittal Epidural Versus Midline Epidural Anesthesia.
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To compare the efficacy of parasagittal interlaminar (PIL) and midline interlaminar (MIL) approaches for epidural block in patients with lower limb orthopedic surgery.</AbstractText>This double-blind randomized clinical trial was performed on 40 patients undergoing tibial shaft fracture surgery. In PIL group, an 18-gauge, 3.5 inch, Tuohy needle was placed at the level of L2-3 or L3-4 intervertebral spaces and pushed forward in a posteroanterior (PA) direction vertical to the body surface. After determining the most lateral place for needle arrival in an anteroposterior (AP) view, needle was pushed forward into the epidural space. For the MIL group, needle was pushed forward from the midline interspinous space with the same method. After confirmation of needle position, 1 mL of contrast was injected to confirm the epidural space distribution and then 15 ml lidocaine 2% was injected. The sensory and motor block level, onset, duration, heart rate (HR), mean arterial pressure (MAP), and arterial oxygen saturation (SPO2), and success rate were recorded.</AbstractText>Mean patients' baseline characteristics showed no statistically significant difference between the two groups.p</i>>0.05). Outcome measures were statistically different and significantly higher in PIL group (p-values for sensory block level <0.001, motor block level <0.001, duration of sensory block: <0.001 and duration of motor block <0.001 and success rate: <0.001). Hemodynamic variables didn't show statistically significant difference between the two groups (p-values for Systolic pressure: 0.997, diastolic pressure:0.579, MAP:0.585, HR:0.710).</AbstractText>Epidural anesthesia with parasagittal interlaminar approach provide deep motor block, high sensory level block, and hemodynamic stability.</AbstractText>IRCT2017041615515N2.</AbstractText>
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2,334,643 |
Comparative Evaluation of Dexamethasone and Dexmedetomidine as Adjuvants for Bupivacaine in Ultrasound-Guided Infraorbital Nerve Block for Cleft Lip Repair: A Prospective, Randomized, Double-Blind Study.
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To compare dexamethasone (DA) to dexmedetomidine (DE) as adjuvants for bupivacaine during infraorbital nerve block (IONB) in a randomized clinical trial.</AbstractText>One hundred patients were randomized into two equal groups. By the guidance of ultrasound, the IONB was performed bilaterally in all patients, using 1 mL of the solution on each side. In DA group, 1 mL of 0.5% bupivacaine was added to 0.1 mg.kg-1 DA and diluted to 2 mL in DE group; 1 mL of 0.5% bupivacaine was added to 0.5 μg.kg-1</sup> DE and diluted to 2 mL. The primary outcome was time to first rescue analgesic. The secondary outcomes included face legs activity cry consolability (FLACC) score rating during the first 24 h, hemodynamic variables, the incidence of postoperative vomiting, sedation score, and parent satisfaction.</AbstractText>During the first 24 h postoperatively, the DE group showed a significantly lower FLACC score and a longer time to first analgesic request compared to DA group. Sedation and parent satisfaction scores were significantly higher while heart rate and mean blood pressure were significantly lower in DE group compared to DA group. There were no differences in other secondary outcomes.</AbstractText>The use of DE as an adjuvant to bupivacaine in IONB for cleft lip repair resulted in lower pain score and more prolonged duration of analgesia compared to DA.</AbstractText>
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2,334,644 |
Effect of Local Anesthesia and General Anesthesia Using I-gel Laryngeal Mask Airway in Diabetic Patients Undergoing Cataract Surgery: Comparative Study.
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Cataract surgery is one of the most commonly performed ophthalmic procedures. On choosing the appropriate method of anesthesia for diabetic patients with cataract whether regional or general, one should consider a technique that is associated with less stress response, minimal effect on hemodynamic and essentially associated with a good intraoperative glycemic control. This is yet to be determined.</AbstractText>The aim of this study is to evaluate the use of I-gel as an alternative to local anesthesia (LA) in diabetic patients undergoing cataract surgery.</AbstractText>This study was conducted on 60 controlled insulin-dependent diabetic patients undergoing cataract surgery. They were randomized to receive either LA by sub-Tenon's block (LA group n</i> = 30) or general anesthesia (GA) using I-gel (GA group n</i> = 30). Mean arterial blood pressure (MBP) and heart rate were monitored. Furthermore, blood glucose level and plasma cortisol level were measured at basal level, after induction of anesthesia or local block, after nuclear extraction, at the end of surgery, and 30, 60, 120, and 240 min postoperative.</AbstractText>There was no significant difference in either blood glucose or cortisol levels in both groups. Blood glucose level increased with induction of anesthesia in both groups. The use of I-gel was not associated with increase heart rate or MBP compared to the LA group.</AbstractText>Both local and GA using I-gel are relatively safe without marked changes in hemodynamics, blood glucose, or cortisol level in insulin-dependent diabetic patients.</AbstractText>
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2,334,645 |
Caudal block with analgosedation - a superior anaesthesia technique for lower abdominal surgery in paediatric population.
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Aim To compare intraoperative hemodynamic and respiratory stability and postoperative emergence delirium between two anaesthesia regimens in children (caudal block with intravenous continuous analgosedation versus general endotracheal anaesthesia) and intensity of postoperative pain and quality of postoperative analgesia. Method Forty children aged 2-6 years who underwent lower abdominal surgery were randomized depending on performed anaesthesia into two groups: caudal block with analgosedation (group CB) and general endotracheal anaesthesia (group GA). Intraoperative hemodynamic and respiratory stability were evaluated measuring systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate (HR) and arterial oxygen saturation (SaO2) in preinduction (t0), at the moment of surgical incision (t1), 10 minutes after surgical incision (t2) and at the time of skin suturing (t3). Postoperative emergence delirium was evaluated using Paediatric Anaesthesia Emergence Delirium score (PAED). Postoperative pain was evaluated by Children's and Infants' Postoperative Pain score (CHIPPS). Both scores were recorded every 5 minutes during first half hour postoperatively, additionally after 60 minutes postoperatively for CHIPPS score. Results SBP, DBP and MAP were lower at t1 (p<0.0001), t2 (p<0.05) and t3 (p<0.001) in the group CB. HR was lower at all studied time points (p<0.005) in the group CB. SaO2 was lower in the CB group but comparable with the GA group. PAED and CHIPPS scores were lower at 5, 10, 15, 20 and 25 minutes postoperatively (p<0.001) in the CB group. Conclusion Caudal block with analgosedation provides better control of intraoperative hemodynamic conditions, postoperative emergence delirium and postoperative pain than general endotracheal anaesthesia.
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2,334,646 |
Freezing in response to social threat: a replication.
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Freezing is an adaptive defensive response to a stressful event. Recent research suggests that freezing not only occurs in response to physical threats but also in response to social threats (e.g., angry faces; Roelofs et al. in Psychol Sci 21:1575-1581, 2010). Given the practical and theoretical importance of this finding, the current study aimed to replicate and extend it. Following the original study, we measured heart rate while participants viewed emotional faces (angry, happy, neutral). Extending the original study, we included a baseline measure and performed additional, more fine-grained analyses. Our results support the hypothesis that participants show physiological signs of freezing when looking at angry faces. Importantly, we also find this effect when comparing heart rate in the angry block to baseline levels. Interestingly, the heart rate effects are explained by deceleration in the first 30 s of the 1-min angry block, but not in the second 30 s. Like Roelofs et al., we find evidence that the effects are modulated by state anxiety, but our effects are only marginal and we do not replicate the negative correlation between heart rate and state anxiety in the angry block. In general, we thus find evidence for physiological signs of freezing in response to social threat. We discuss implications and venues for future research.
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2,334,647 |
Can Epidural Dexamethasone Reduce Patient-Controlled Epidural Consumption of Fentanyl and Levobupivacaine in Laboring Women? A Double-Blind, Randomized, Placebo-Controlled Trial.
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The efficacy of a single bolus dose of epidural dexamethasone added to levobupivacaine-fentanyl combination for labor analgesia has not been studied. In this randomized double-blind controlled trial, we assessed the effect of epidural dexamethasone in reducing the hourly average consumption of epidural levobupivacaine-fentanyl combination in laboring parturients and to study its effect on pain score, maternal satisfaction, maternal and neonatal outcome.</AbstractText>Sixty adult ASA I-II single-gestation full-term primigravid laboring parturients with cervical dilation ≤ 5 cm were randomly assigned to two equal-sized groups. Combined spinal-epidural block was performed in all the parturients. After placing the epidural catheter in epidural space, 8 mg of preservative-free dexamethasone was administered to the dexamethasone group, and 0.9% saline to the placebo group. All parturients received continuous background infusion of 5 ml of 0.1% levobupivacaine with 2 μg/ml of fentanyl with the provision of patient-controlled bolus of 5 ml of 0.1% levobupivacaine with 2 μg/ml of fentanyl (lockout interval 15 min). The primary outcome measure was the hourly total consumption of levobupivacaine-fentanyl mixture. The secondary outcome measures were maternal satisfaction, pain score, maternal hemodynamic parameters, fetal heart rate, duration of second stage of labor, mode of delivery, Apgar scores and adverse effects.</AbstractText>Hourly drug consumption and hourly bolus requirement were significantly lower in the dexamethasone group than placebo group (6.97 ml ± 1.22 vs. 8.40 ml ± 2.59 and 0.41 ± 0.26 vs. 0.72 ± 0.55, respectively, P</i> = 0.008 for both). There were no significant differences in other outcome measures.</AbstractText>Epidural dexamethasone significantly decreased average hourly drug consumption and the number of boluses in laboring parturients, thus providing epidural drug dose-sparing effect.</AbstractText>
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2,334,648 |
Advanced Imaging in Cardiac Sarcoidosis.
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Sarcoidosis is a chronic disease of unknown etiology characterized by the presence of noncaseating granulomas. Cardiac involvement in sarcoidosis may lead to adverse outcomes such as advanced heart block, arrhythmias, cardiomyopathy, or death. Cardiac sarcoidosis can occur in patients with established sarcoidosis, or it can be the sole manifestation of the disease. Traditional diagnostic techniques, including echocardiography, have poor sensitivity for diagnosing cardiac sarcoidosis. The accumulating evidence supports the essential role of advanced cardiac imaging modalities such as MRI and PET in diagnosis, risk stratification, and management of patients with cardiac sarcoidosis. The current review highlights important theoretic and practical aspects of using cardiac imaging tools in the evaluation of patients with suspected or established cardiac sarcoidosis.
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2,334,649 |
Urotensin-#receptor antagonist SB-706375 protected isolated rat heart from ischaemia-reperfusion injury by attenuating myocardial necrosis via RhoA/ROCK/RIP3 signalling pathway.
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SB-706375 is a selective receptor antagonist of human urotensin-II (hU-II), which can block the aorta contraction induced by hU-II in rats. The effect of SB-706375 on myocardial ischaemia-reperfusion (I/R) injury is unclear. The major objective of this study was to investigate whether SB-706375 has a protective effect on myocardial I/R injury in rats and explore its possible mechanisms. Isolated hearts of Adult Sprague-Dawley were perfused in a Langendorff apparatus, and haemodynamic parameters, lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), cardiac troponin I (cTnI), RhoA, and the protein expressions of U-II receptor (UTR), receptor-interacting protein 3 (RIP3), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and Rho-associated coiled-coil-containing protein kinase 2 (ROCK2) were assessed. We found that SB-706375 (1 × 10<sup>-6</sup> and 1 × 10<sup>-5</sup> mol/L) significantly inhibited the changes of haemodynamic parameters and reduced LDH and CK-MB activities and also cTnI level in the coronary effluents in the heart subjected to myocardial I/R injury. Further experiments studies showed that SB-706375 obviously prevented myocardial I/R increased RhoA activity and UTR, RIP3, ROCK1, and ROCK2 protein expressions. ROCK inhibition abolished the improving effect of SB-706375 on myocardial I/R-induced haemodynamic change in the isolated perfused rat heart. These findings suggested that SB-706375 provides cardio-protection against I/R injury in isolated rats by blocking UTR-RhoA/ROCK-RIP3 pathway.
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2,334,650 |
DOES THE ANESTHESIA TECHNIQUE AFFECT ARTERIAL PRESSURE AND REGIONAL CEREBRAL OXYGEN SATURATION DURING SHOULDER ARTHROSCOPY IN THE BEACH CHAIR POSITION?
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- This study aimed to investigate the impact of posture and anesthesia techniques on blood pressure changes, heart rate and regional cerebral oxygen saturation during shoulder arthroscopy in the beach chair position (BCP). Sixty patients were included in this prospective cohort study: 30 patients mechanically ventilated and subjected to general anesthesia (GA) and 30 patients subjected to interscalene block (ISB) without mechanical ventilation. Noninvasive blood pressure, heart rate (HR), peripheral blood oxygen saturation and regional oxygen saturation of the brain were measured in twelve predefined points during perioperative period. The GA group patients had significantly lower mean arterial pressure and heart rate values compared to patients in ISB group during BCP (p<0.001). There was a significant difference in regional cerebral saturation between the groups measured only in points of induction and emergence from anesthesia in favor of GA group when receiving 100% oxygen (p<0.001). Changes in the mean arterial pressure and regional cerebral oxygen saturation for both brain hemispheres correlated only at the 10<sup>th</sup> minute after setting up BCP in GA patients (right, p=0.004 and left, p=0.003). This correlation did not exist in the ISB group patients at any of the points measured. Cerebral desaturation events recorded in both groups were not statistically significantly different. Results of this study demonstrated that GA preserved regional cerebral oxygenation in a safe range during BCP despite changes in the arterial blood pressure and heart rate in comparison to ISB.
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2,334,651 |
Paravertebral Block Versus Intercostal Nerve Block in Non-Intubated Uniportal Video-Assisted Thoracoscopic Surgery: A Randomised Controlled Trial.
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Non-intubated uniportal video-assisted thoracoscopic surgery (VATS) has been reported to be safe and feasible for patients with various thoracic diseases, including those who have respiratory dysfunction. This study examined the anaesthetic and analgesic sparing effects of either paravertebral block or intercostal nerve block on the non-intubated technique with spontaneous ventilation in patients under general anaesthesia (GA) using a supraglottic airway device. The primary aim was to compare the anaesthetic sparing effect of paravertebral block versus intercostal nerve block in non-intubated GA with airway support via a supraglottic airway device during VATS surgery. The secondary aim was to compare the recovery characters and postoperative outcomes of the patients.</AbstractText>The study included 105 patients with American Society of Anesthesiologists (ASA) physical status II-III who had video-assisted thoracoscopy without endotracheal intubation and using a laryngeal airway. The patients were divided into three groups; each group consisted of 35 patients. Group I (35 patients): control group received only GA. Group 2 (35 patients): received a single-shot paravertebral block before induction of the GA. Group 3 (35 patients): received thoracoscopic intercostal block infiltration after induction of anaesthesia from the third to the eighth intercostal nerve block, in addition to intrathoracic vagal block. Heart rate, mean arterial pressure (MAP), and oxygen saturation were recorded before induction of GA (T0), after induction of GA (T1), 20 minutes later (T2), and before the end of the surgical procedure (T3).</AbstractText>Heart rate was significantly lower in Groups 2 and 3 compared with Group 1, and lower in Group 2 compared with Group 3. The MAP was significantly lower in Groups 2 and 3 compared with Group 1, and there was no significant difference between Groups 2 and 3. Oxygen saturation was significantly higher in Group 2 and in Group 3 compared with Group 1 and there was no significance difference between Groups 2 and 3. Expiratory fraction of sevoflurane (Ef sevo) was significantly lower in Groups 2 and 3 compared with Group 1, with no difference between Group 2 and 3. Groups 2 and 3 had lower fentanyl requirements, time to spontaneous eye movement, time to spontaneous arm movement, time to purposeful movement, and time to laryngeal mask removal than Group 1.</AbstractText>Regional anaesthesia by either preoperative paravertebral block or thoracoscopic intercostal nerve block with ipsilateral vagal block provided an anaesthetic sparing effect, guided by lower Ef sevo concentration, with comparable bi-spectral index in patients undergoing uniportal thoracoscopic surgery.</AbstractText>Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.</CopyrightInformation>
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2,334,652 |
The effects of slow loaded breathing training on exercise blood pressure in isolated systolic hypertension.
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Slow loaded breathing training has been shown to reduce resting blood pressure (BP) in isolated systolic hypertension (ISH), but it is not known whether this also reduces their exaggerated BP responses to exercise.</AbstractText>The study was a randomized controlled trial with block allocation stratified by sex. Twenty ISH patients (68 ± 5 yrs, 11 males) were randomized with one group undertaking 8-weeks training with slow loaded breathing (SLB: 25% maximum inspiratory pressure, 6 breaths per minute, 60 breaths every day) or deep breathing control (CON), with 8 weeks follow-up. Outcome measures were home BP and heart rate (HR) with laboratory measures of BP and HR responses to static handgrip and dynamic arm cranking exercise. Data were compared with a two-week run-in baseline.</AbstractText>Home systolic BP fell by 22 mmHg (20-23; mean, 95% CI), diastolic BP by 9 mmHg (7-11), and HR by 12 bpm (9-15; all p < .001) as a result of SLB training. Systolic BP at the end of 2-min isometric handgrip was 189 ± 10 mmHg (mean, SD) before training and 157 ± 6 mmHg following SLB training. After 4-min arm exercise, systolic BP, measured at the ankle, was reduced from 243 ± 8 mmHg during the run-in period to 170 ± 15 mmHg after SLB training with no change for CON. The reduction in exercise BP, in both types of exercise, was partly due to a reduction in resting BP and to a smaller increase above resting. Systolic and pulse pressures remained below run-in values 8 weeks after the end of SLB training, and BP response to handgrip exercise remained below run-in values at 4 weeks after SLB training.</AbstractText>SLB not only reduces resting BP in ISH but also the responses to both static and dynamic exercise, potentially reducing the negative aspect of exercise for cardiovascular health.</AbstractText>Copyright © 2019 John Wiley & Sons, Ltd.</CopyrightInformation>
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2,334,653 |
[Effects of an Acupoint Intervention on Improving Fatigue and Heart Rate Variability in Head and Neck Cancer Patients Receiving Concurrent Chemoradiotherapy].
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Fatigue is the most common symptom in head and neck cancer patients who receive concurrent chemoradiotherapy (CCRT). However, evidence of the effects of acupoint interventions on fatigue and heart rate variability in these patients is unclear.</AbstractText>To evaluate the effect of an acupoint intervention on fatigue and heart rate variability in head and neck cancer patients receiving CCRT.</AbstractText>This randomized controlled trail applied repeated measures, and used permuted block randomization to randomly assign the participants into the acupoint and control groups. Participants in both groups received usual care. In addition, participants in the acupoint group received transcutaneous electrical acupoint stimulation and auricular acupressure for a period of six weeks. Data were collected using the brief fatigue inventory and a heart rate variability device at baseline and during the 1st, 2nd, 3rd, and 6th weeks of the study.</AbstractText>The generalized estimating equation analysis found a significant group-by-time interaction for fatigue on the 6th week of acupoint stimulation (p = .036). No significant differences in group-by-time interaction were found for the standard deviation of normal to normal intervals (SDNN), low frequency (LF), high frequency (HF), or LF/HF ratio (p > .05).</AbstractText><AbstractText Label="CONCLUSIONS / IMPLICATIONS FOR PRACTICE" NlmCategory="CONCLUSIONS">This study supports the accessibility and feasibility of the acupoint intervention. No adverse effects were observed. The six-week transcutaneous electrical acupoint stimulation and auricular acupressure may be used to improve fatigue in head and neck cancer patients currently receiving CCRT.</AbstractText>
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2,334,654 |
Adiponectin suppresses amyloid-β oligomer (AβO)-induced inflammatory response of microglia via AdipoR1-AMPK-NF-κB signaling pathway.
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Microglia-mediated neuroinflammation is important in Alzheimer's disease (AD) pathogenesis. Extracellular deposition of β-amyloid (Aβ), a major pathological hallmark of AD, can induce microglia activation. Adiponectin (APN), an adipocyte-derived adipokine, exerts anti-inflammatory effects in the periphery and brain. Chronic APN deficiency leads to cognitive impairment and AD-like pathologies in aged mice. Here, we aim to study the role of APN in regulating microglia-mediated neuroinflammation in AD.</AbstractText>Inflammatory response of cultured microglia (BV2 cells) to AβO and effects of APN were studied by measuring levels of proinflammatory cytokines (tumor necrosis factor α [TNFα] and interleukin-1β [IL-1β]) in cultured medium before and after exposure to AβO, with and without APN pretreatment. Adiponectin receptor 1 (AdipoR1) and receptor 2 (AdipoR2) were targeted by small interference RNA. To study the neuroprotective effect of APN, cultured HT-22 hippocampal cells were treated with conditioned medium of AβO-exposed BV2 cells or were co-cultured with BV2 cells in transwells. The cytotoxicity of HT-22 hippocampal cells was assessed by MTT reduction. We generated APN-deficient AD mice (APN-/-</sup>5xFAD) by crossing APN-knockout mice with 5xFAD mice to determine the effects of APN deficiency on microglia-mediated neuroinflammation in AD.</AbstractText>AdipoR1 and AdipoR2 were expressed in BV2 cells and microglia of mice. Pretreatment with APN for 2 h suppressed TNFα and IL-1β release induced by AβO in BV2 cells. Additionally, APN rescued the decrease of AMPK phosphorylation and suppressed nuclear translocation of nuclear factor kappa B (NF-κB) induced by AβO. Compound C, an inhibitor of AMPK, abolished these effects of APN. Knockdown of AdipoR1, but not AdipoR2 in BV2 cells, inhibited the ability of APN to suppress proinflammatory cytokine release induced by AβO. Moreover, pretreatment with APN inhibited the cytotoxicity of HT-22 cells co-cultured with AβO-exposed BV2 cells. Lastly, APN deficiency exacerbated microglia activation in 9-month-old APN-/-</sup>5xFAD mice associated with upregulation of TNFα and IL-1β in the cortex and hippocampus.</AbstractText>Our findings demonstrate that APN inhibits inflammatory response of microglia to AβO via AdipoR1-AMPK-NF-κB signaling, and APN deficiency aggravates microglia activation and neuroinflammation in AD mice. APN may be a novel therapeutic agent for inhibiting neuroinflammation in AD.</AbstractText>
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2,334,655 |
The effects of music on anxiety and pain in patients during carotid endarterectomy under regional anesthesia: A randomized controlled trial.
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Music can be used as an alternative method to decrease anxiety in awake patients during surgical procedures. The aim of this study was to test the hypothesis that listening to music during carotid endarterectomy (CEA) under regional anesthesia decreases the patient's anxiety and pain.</AbstractText>A multicenter, prospective, randomized controlled trial.</AbstractText>Patients undergoing carotid endarterectomy under cervical plexus block.</AbstractText>Patients scheduled for carotid endarterectomy under cervical plexus block were randomized into two groups: Music Group and Control Group.</AbstractText>The primary endpoint of this study was the difference in intraoperative anxiety in patients with or without music during CEA under regional anesthesia, and the secondary endpoints were intraoperative and postoperative pain, use of additional local anesthetics, use of intravenous analgesics, patient and surgeon satisfaction and complications. Anxiety was assessed using State Trait Anxiety Inventory (STAI) and numeric rating scale (NRS). Visual analog scale (VAS) was used for pain assessment.</AbstractText>The postoperative STAI scores were similar in both groups (p = 0.839). The NRS scores measured immediately after the end of the surgery were statistically higher in Music Group (p = 0.001). The intraoperative anxiety statistically increased in Music Group, when the scores of the intraoperative responses to the questions of "are you relaxed?" and "are you calm?" were compared. (p = 0.0001 and p = 0.0001, respectively). There were no statistical differences in terms of the amount of intraoperative and postoperative analgesic used (p = 0.801, p = 0.773, respectively). The intraoperative VAS scores, postoperative VAS scores, patient and surgeon satisfaction scores were similar in both groups (p = 0.586, p = 0.185, p = 0.302 and p = 0.599, respectively). Systolic, diastolic and mean arterial blood pressure and heart rate were no different between Music Group and Control Group at any of all time points during the intraoperative period. Surgical side and contralateral side cerebral rSO2 values are similar in both groups (p = 0.438, p = 0.397, respectively).</AbstractText>Music use in CEA under regional anesthesia increased intraoperative patient anxiety, and had no effect on intraoperative and postoperative pain or patient satisfaction.</AbstractText>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,656 |
Birth month associates with risk of coronary artery disease and its complications: A propensity score matched analysis.
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Birth month and climate affect lifetime disease risk, while the underlying mechanisms remain largely elusive. It is vital to investigate the risks of coronary artery disease (CAD) and its complications in patients born in different months.</AbstractText>A total of 12,263 patient medical records were reviewed from the BioBank of First Affiliated Hospital of Xinxiang Medical University, with 4729 records from patients with CAD (CAD group) and 7534 records from control patients without CAD (control group). Two groups of patients were matched by the propensity score matched method. Birth months were compared between two groups of patients. The relationships between birth month and the numbers of CAD and its complications were also investigated. Interestingly, we also explore the relationship between the birth seasons and the numbers of CAD and its complications.</AbstractText>Compared to control, CAD group had greater CAD risks for patients born in November (OR 1.390, 95% CI 1.090-1.772), December (OR 1.358, 95% CI 1.067-1.730), and February (OR 1.332, 95% CI 1.043-1.700) compared to those born in May. Compared to patients born in December, patients born in January to March and May to September had greater risk of heart failure (P<0.05). There was no difference in the incidence of myocardial infarction, conduction block, and atrial fibrillation across birth months (P>0.05). In terms of birth season, patients born in winter have greater CAD risk than those born in spring (OR 1.247, 95% CI 1.075-1.447). And there was no difference in the incidence of CAD complications across with birth seasons (P>0.05).</AbstractText>There was a correlation between birth month and CAD. People born in November, December, and February had greater CAD risk, and people born in winter had greater CAD risk. Among CAD patients, those born in January to March and May to September had the greater risk of heart failure.</AbstractText>Copyright © 2019. Published by Elsevier España, S.L.U.</CopyrightInformation>
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Ultrasound-guided continuous serratus anterior plane block: dexmedetomidine as an adjunctive analgesic with levobupivacaine for post-thoracotomy pain. A prospective randomized controlled study.
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<b>Purpose:</b> The study aimed to evaluate the analgesic efficiency of dexmedetomidine (DEX) when added to levobupivacaine in continuous ultrasound-guided serratus anterior plane block (SAPB) performed at the end of major thoracic surgery. <b>Methods:</b> This randomized, double-blind trial included 50 adults undergoing thoracic surgery. Continuous SAPB was performed at the end of surgery. Patients were randomized into two groups. Group L (n=25) received levobupivacaine only while Group DL (n=25) received a mixture of levobupivacaine and DEX. All patients received intravenous (IV) paracetamol every 8 hrs. Morphine IV was given according to VAS score of pain as a 5 mg loading dose. The primary outcome measure was postoperative pain intensity. Secondary outcome measures were postoperative morphine consumption and adverse effects. <b>Results:</b> Analgesia was satisfactory in the two groups up to 24 hrs. VAS score was significantly lower in group DL compared to group L between 6 and 24 hrs postoperatively. Total morphine consumption was significantly lower in group DL compared to group L (<i>p</i><0.001). Up to 12 hrs postoperatively, sedation score was significantly lower in group DL compared to group L. Afterwards, all patients were fully alert. All values of mean arterial pressure and heart rate were within the clinically accepted ranges. There were no recorded cases of hypotension or bradycardia in the whole studied group. <b>Conclusions:</b> Continuous SAPB with levobupivacaine plus DEX seems to be a promising analgesic alternative following thoracotomy. Combined with IV paracetamol, this approach provided adequate analgesia and proper sedation. <b>Trial registration:</b> ISRCTN registry; study ID: ISRCTN35517318.
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2,334,658 |
Influence of Cholesterol and Bilayer Curvature on the Interaction of PPO-PEO Block Copolymers with Liposomes.
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Interactions of nonionic poly(ethylene oxide)- b-poly(propylene oxide) (PEO-PPO) block copolymers, known as Pluronics or poloxamers, with cell membranes have been widely studied for a host of biomedical applications. Herein, we report how cholesterol within phosphatidylcholine (POPC) lipid bilayer liposomes and bilayer curvature affects the binding of several PPO-PEO-PPO triblocks with varying PPO content and a tPPO-PEO diblock, where t refers to a tert-butyl end group. Pulsed-field-gradient NMR was employed to quantify the extent of copolymer associated with liposomes prepared with cholesterol concentrations ranging from 0 to 30 mol % relative to the total content of POPC and cholesterol and vesicle extrusion radii of 25, 50, or 100 nm. The fraction of polymer bound to the liposomes was extracted from NMR data on the basis of the very different mobilities of the bound and free polymers in aqueous solution. Cholesterol concentration was manipulated by varying the molar percentage of this sterol in the POPC bilayer preparation. The membrane curvature was varied by adjusting the liposome size through a conventional pore extrusion technique. Although the PPO content significantly influences the overall amount of block copolymer adsorbed to the liposome, we found that polymer binding decreases with increasing cholesterol concentration in a universal fashion, with the fraction of bound polymer dropping 10-fold between 0 and 30 mol % cholesterol relative to the total content of POPC and cholesterol. Increasing the bilayer curvature (decreasing the radius of the liposome) in the absence of cholesterol increases polymer binding between 2- and 4-fold over the range of liposome sizes studied. These results demonstrate that cholesterol plays a dominant role, and bilayer curvature has a less significant impact as the curvature decreases, on polymer-membrane association.
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2,334,659 |
RIANet: Recurrent interleaved attention network for cardiac MRI segmentation.
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Segmentation of anatomical structures of the heart from cardiac magnetic resonance images (MRI) has a significant impact on the quantitative analysis of the cardiac contractile function. Although deep convolutional neural networks (ConvNets) have achieved considerable success in medical imaging segmentation, it is still a challenging task for existing deep ConvNets to precisely and automatically segment multiple heart structures from cardiac MRI. This paper presents a novel recurrent interleaved attention network (RIANet) to comprehensively tackle this issue.</AbstractText>The proposed RIANet can efficiently reuse parameters to encode richer representative features via introducing a recurrent feedback structure, Clique Block, which incorporates both forward and backward connections between different layers with the same resolution. Further, we integrate a plug-and-play interleaved attention (IA) block to modulate the information passed to the decoding stage of RIANet by effectively fusing multi-level contextual information. In addition, we improve the discrimination capability of our RIANet through a deep supervision mechanism with weighted losses.</AbstractText>The performance of RIANet has been extensively validated in the segmentation contest of the ACDC 2017 challenge held in conjunction with MICCAI 2017, with mean Dice scores of 0.942 (left ventricular), 0.923 (right ventricular) and 0.910 (myocardium) for cardiac MRI segmentation. Besides, we visualize intermediate features of our RIANet using guided backpropagation, which can intuitively depict the effects of our proposed components in feature representation.</AbstractText>Experimental results demonstrate that our RIANet have achieved competitive segmentation results with fewer parameters compared with the state-of-the-art approaches, corroborating the effectiveness and robustness of our proposed RIANet.</AbstractText>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,660 |
Nivolumab Clearance Is Stationary in Patients With Resected Melanoma on Adjuvant Therapy: Implications of Disease Status on Time-Varying Clearance.
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Nivolumab clearance (CL) in patients with advanced melanoma (MEL) decreases over the treatment duration, with change in CL associated with improved disease status, measured by reduced tumor burden. Here, we characterize the pharmacokinetics of nivolumab administered as adjuvant therapy for patients with MEL (AdjMEL) whose tumors were removed by surgical resection. A population pharmacokinetic model was developed using data from 1,773 patients with AdjMEL, MEL, non-small cell lung cancer, and other solid tumors who received nivolumab over a dose range of 0.1-20 mg/kg every 2 weeks. In patients with AdjMEL, the geometric mean nivolumab CL of 6.0 mL/hour was 40% lower at baseline and did not vary with time and 20% lower at steady state compared with patients with MEL. Lower nivolumab CL in patients with AdjMEL and absence of time dependence support the hypothesis that changes in nivolumab CL in the metastatic setting are associated with disease status after treatment.
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2,334,661 |
Transitional care program to facilitate recovery following severe acute kidney injury.
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Patients with acute kidney injury needing prolonged renal replacement therapy (AKI-RRT) may benefit from a structured care process in form of an AKI transitional care program (ATCP), to facilitate RRT weaning and recovery.</AbstractText>We examined outcomes following ATCP implementation in adults with AKI-RRT from a tertiary institution (versus pre-ATCP controls), including mortality, cumulative hospital days, and renal function over one year; RRT and haemodialysis catheter days in initial 90 days.</AbstractText>We studied 89 patients with age 62 ( ± 15) years. 47% had septic AKI, 20% cardiorenal syndrome, and 29% had baseline eGFR < 30 mL/min/1.73 m2</sup>. Comparing 45 ATCP patients with 44 controls: 64% and 45% received continuous RRT (CRRT) (p = 0.07), with comparable rates of heart failure (24% versus 25%), ICU care (67% versus 70%), RRT successfully weaned (71% versus 75%), respectively; corresponding mortality rates were 24% and 32% (p = 0.44), hospital days of 205 (197-213) and 223 (215-232) per 1000 patient-days alive over one year (p = 0.002); with comparable RRT and catheter days. Serial serum creatinine in months following RRT cessation were comparable between either survivor-group. On multivariate analysis, heart failure or having received CRRT independently predicted mortality and longer hospital days (p < 0.05); ATCP was independently associated with reduced hospital days (p < 0.001). 17 ATCP patients and 14 controls required outpatient RRT weaning, with catheter days of 607 (568-648) and 683 (638-731) per 1000 patient-days in initial 90 days, respectively (p = 0.01).</AbstractText>Implementing a structured care pathway in patients with AKI-RRT may help reduce hospitalization, and reduce haemodialysis catheter days in the subgroup for outpatient RRT weaning.</AbstractText>
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2,334,662 |
Variable cellular decision-making behavior in a constant synthetic network topology.
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Modules of interacting components arranged in specific network topologies have evolved to perform a diverse array of cellular functions. For a network with a constant topological structure, its function within a cell may still be tuned by changing the number of instances of a particular component (e.g., gene copy number) or by modulating the intrinsic biochemical properties of a component (e.g., binding strength or catalytic efficiency). How such perturbations affect cellular response dynamics remains poorly understood. Here, we explored these effects in a common decision-making motif, cross-antagonism with autoregulation, by synthetically constructing this network in yeast.</AbstractText>We employed the engineering design strategy of reuse to build this topology with a single protein building block, TetR, creating necessary components through TetR mutations and fusion partners. We then studied the impact of several topology-preserving perturbations - strength of cross-antagonism, number of operator sites in a promoter, and gene dosage - on decision-making behavior. We found that reducing TetR repression strength, which hinders cross-antagonism, resulted in a loss of mutually exclusive cell responses. Unexpectedly, increasing the number of operator sites also impeded decision-making exclusivity, which may be a consequence of the averaging effect that arises when multiple transcriptional activators and repressors are accommodated at a given locus. Stochastic simulations of this topology revealed that, even for networks with high TetR repression strength and a low number of operator sites, increasing gene dosage can reduce exclusivity in response dynamics. We further demonstrated this result experimentally by quantifying gene copy numbers in selected yeast clones with differing phenotypic responses.</AbstractText>Our study illustrates how parameters that do not change the topological structure of a decision-making network can nonetheless exert significant influence on its response dynamics. These findings should further inform the study of native motifs, including the effects of topology-preserving mutations, and the robust engineering of synthetic networks.</AbstractText>
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2,334,663 |
Pregnancy outcomes in mixed connective tissue disease: a multicentre study.
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In this study we aimed to investigate foetal and maternal pregnancy outcomes from a large multicentre cohort of women diagnosed with MCTD and anti-U1RNP antibodies.</AbstractText>This multicentre retrospective cohort study describes the outcomes of 203 pregnancies in 94 consecutive women ever pregnant who fulfilled the established criteria for MCTD with confirmed U1RNP positivity.</AbstractText>The foetal outcomes in 203 pregnancies were as follows: 146 (71.9%) live births, 38 (18.7%) miscarriages (first trimester pregnancy loss of <12 weeks gestation), 18 (8.9%) stillbirths (pregnancy loss after 20 weeks gestation) and 11 (5.4%) cases with intrauterine growth restriction. Maternal pregnancy outcomes were as follows: 8 (3.9%) developed pre-eclampsia, 2 (0.9%) developed eclampsia, 31 (15.3%) developed gestational hypertension and 3 (1.5%) developed gestational diabetes. Women with MCTD and aPL and pulmonary or muscular involvement had worse foetal outcomes compared with those without. Moreover, we report a case of complete congenital heart block (0.45%) and a case of cutaneous neonatal lupus, both born to a mother with positive isolated anti-U1RNP and negative anti-Ro/SSA antibodies.</AbstractText>In our multicentre cohort, women with MCTD had a live birth rate of 72%. While the true frequency of heart block associated with anti-U1RNP remains to be determined, this study might raise the consideration of echocardiographic surveillance in this setting. Pregnancy counselling should be considered in women with MCTD.</AbstractText>© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: [email protected].</CopyrightInformation>
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2,334,664 |
Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Nonalcoholic Steatohepatitis.
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<AbstractText Label="BACKGROUND & AIMS">We studied the role of interleukin 11 (IL11) signaling in the pathogenesis of nonalcoholic steatohepatitis (NASH) using hepatic stellate cells (HSCs), hepatocytes, and mouse models of NASH.</AbstractText>We stimulated mouse and human fibroblasts, HSCs, or hepatocytes with IL11 and other cytokines and analyzed them by imaging, immunoblot, and functional assays and enzyme-linked immunosorbent assays. Mice were given injections of IL11. Mice with disruption of the interleukin 11 receptor subunit alpha1 gene (Il11ra1-/-</sup>) mice and Il11ra1+/+</sup> mice were fed a high-fat methionine- and choline-deficient diet (HFMCD) or a Western diet with liquid fructose (WDF) to induce steatohepatitis; control mice were fed normal chow. db/db mice were fed with methionine- and choline-deficient diet for 12 weeks and C57BL/6 NTac were fed with HFMCD for 10 weeks or WDF for 16 weeks. Some mice were given intraperitoneal injections of anti-IL11 (X203), anti-IL11RA (X209), or a control antibody at different timepoints on the diets. Livers and blood were collected; blood samples were analyzed by biochemistry and liver tissues were analyzed by histology, RNA sequencing, immunoblots, immunohistochemistry, hydroxyproline, and mass cytometry time of flight assays.</AbstractText>HSCs incubated with cytokines produced IL11, resulting in activation (phosphorylation) of ERK and expression of markers of fibrosis. Livers of mice given injections of IL11 became damaged, with increased markers of fibrosis, hepatocyte cell death and inflammation. Following the HFMCD or WDF, livers from Il11ra1-/-</sup> mice had reduced steatosis, fibrosis, expression of markers of inflammation and steatohepatitis, compared to and Il11ra1+/+</sup> mice on the same diets. Depending on the time of administration of anti-IL11 or anti-IL11RA antibodies to wild-type mice on the HFMCD or WDF, or to db/db mice on the methionine and choline-deficient diet, the antibodies prevented, stopped, or reversed development of fibrosis and steatosis. Blood samples from Il11ra1+/+</sup> mice fed the WDF and given injections of anti-IL11 or anti-IL11RA, as well as from Il11ra1-/-</sup> mice fed WDF, had lower serum levels of lipids and glucose than mice not injected with antibody or with disruption of Il11ra1.</AbstractText>Neutralizing antibodies that block IL11 signaling reduce fibrosis, steatosis, hepatocyte death, inflammation and hyperglycemia in mice with diet-induced steatohepatitis. These antibodies also improve the cardiometabolic profile of mice and might be developed for the treatment of NASH.</AbstractText>Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,665 |
Full-Fat Dairy Food Intake is Associated with a Lower Risk of Incident Diabetes Among American Indians with Low Total Dairy Food Intake.
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Diet plays a key role in development of diabetes, and there has been recent interest in better understanding the association of dairy food intake with diabetes.</AbstractText>This study examined the associations of full-fat and low-fat dairy food intake with incident diabetes among American Indians-a population with a high burden of diabetes.</AbstractText>The study included participants from the Strong Heart Family Study (SHFS), a family-based study of cardiovascular disease in American Indians, free of diabetes at baseline (2001-2003) (n = 1623). Participants were 14-86-y-old at baseline and 60.8% were female. Dairy food intake was assessed using a Block food frequency questionnaire. Incident diabetes was defined using American Diabetes Association criteria. Parametric survival models with a Weibull distribution were used to evaluate the associations of full-fat and low-fat dairy food intake with incident diabetes. Serving sizes were defined as 250 mL for milk and 42.5 g for cheese.</AbstractText>We identified 277 cases of diabetes during a mean follow-up of 11 y. Reported intake of dairy foods was low [median full-fat dairy food intake: 0.11 serving/1000 kcal; median low-fat dairy food intake: 0.03 serving/1000 kcal]. Participants who reported the highest full-fat dairy food intake had a lower risk of diabetes compared to those who reported the lowest full-fat food dairy intake [HR (95% CI): 0.79 (0.59, 1.06); P-trend = 0.03, comparing extreme tertiles, after adjustment for age, sex, site, physical activity, education, smoking, diet quality, and low-fat dairy food intake]. Low-fat dairy food intake was not associated with diabetes.</AbstractText>American Indians who participated in the SHFS reported low dairy food intake. Participants who reported higher full-fat dairy food intake had a lower risk of diabetes than participants who reported lower intake. These findings may be of interest to populations with low dairy food intake.</AbstractText>Copyright © American Society for Nutrition 2019.</CopyrightInformation>
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2,334,666 |
Soluble klotho regulates TRPC6 calcium signaling <i>via</i> lipid rafts, independent of the FGFR-FGF23 pathway.
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Soluble klotho (sKlotho), the shed ectodomain of α-klotho, protects the heart by down-regulating transient receptor potential canonical isoform 6 (TRPC6)-mediated calcium signaling. Binding to α2-3-sialyllactose moiety of gangliosides in lipid rafts and inhibition of raft-dependent signaling underlies the mechanism. A recent 3-Å X-ray structure of sKlotho in complex with fibroblast growth factor receptor (FGFR) and fibroblast growth factor 23 (FGF23) indicates that its β6α6 loop might block access to the proposed binding site for α2-3-sialyllactose. It was concluded that sKlotho only functions in complex with FGFR and FGF23 and that sKlotho's pleiotropic effects all depend on FGF23. Here, we report that sKlotho can inhibit TRPC6 channels expressed in cells lacking endogenous FGFRs. Structural modeling and molecular docking show that a repositioned β6α6 loop allows sKlotho to bind α2-3-sialyllactose. Molecular dynamic simulations further show the α2-3-sialyllactose-bound sKlotho complex to be stable. Domains mimicking sKlotho's sialic acid-recognizing activity inhibit TRPC6. The results strongly support the hypothesis that sKlotho can exert effects independent of FGF23 and FGFR.-Wright, J. D., An, S.-W., Xie, J., Lim, C., Huang, C.-L. Soluble klotho regulates TRPC6 calcium signaling <i>via</i> lipid rafts, independent of the FGFR-FGF23 pathway.
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2,334,667 |
Main Group Chemistry at the Interface with Molecular Magnetism.
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Innovative synthetic coordination and, increasingly, organometallic chemistry are at the heart of advances in molecular magnetism. Smart ligand design is essential for implementing controlled modifications to the electronic structure and magnetic properties of transition metal and f-element compounds, and many important recent developments use nontraditional ligands based on low-coordinate main group elements to drive the field forward. This review charts progress in molecular magnetism from the perspective of ligands in which the donor atoms range from low-coordinate 2p elements-particularly carbon but also boron and nitrogen-to the heavier p-block elements such as phosphorus, arsenic, antimony, and even bismuth. Emphasis is placed on the role played by novel main group ligands in addressing magnetic anisotropy of transition metal and f-element compounds, which underpins the development of single-molecule magnets (SMMs), a family of magnetic materials that can retain magnetization in the absence of a magnetic field below a blocking temperature. Nontraditional p-block donor atoms, with their relatively diffuse valence orbitals and more diverse bonding characteristics, also introduce scope for tuning the spin-orbit coupling properties and metal-ligand covalency in molecular magnets, which has implications in areas such as magnetic exchange coupling and spin crossover phenomena. The chemistry encompasses transition metals, lanthanides, and actinides and describes recently discovered molecular magnets that can be regarded, currently, as defining the state of the art. This review identifies that main group chemistry at the interface molecular magnetism is an area with huge potential to deliver new types of molecular magnets with previously unseen properties and applications.
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2,334,668 |
Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload.
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Phosphodiesterase type 3 (PDE3) inhibitors block the cAMP hydrolyzing activity of both PDE3 isoforms, PDE3A and PDE3B, which have distinct roles in the heart. Although PDE3 inhibitors improve cardiac function in heart disease patients, they also increase mortality. Nevertheless, PDE3 inhibitors can provide benefit to non-ischemic heart disease patients and are used extensively to treat heart failure in dogs. Since the isoform-dependence of the complex cardiac actions of PDE3 inhibition in diseased hearts remains unknown, we assessed the effects of PDE3 inhibitors as well as gene ablation of PDE3A or PDEB in mice following the induction of non-ischemic heart disease by pressure-overload with transverse-aortic constriction (TAC). As expected, after 6 weeks of TAC, mice exhibited left ventricular contractile dysfunction, dilation, hypertrophy and interstitial fibrosis, in association with increased macrophage numbers, activation of p38 MAPK and elevated PDE3 activity. Chronic PDE3 inhibition with milrinone (MIL), at doses that did not affect either cardiac contractility or arterial blood pressure, profoundly attenuated the adverse ventricular remodeling, reduced macrophage number and diminished p38-MAPK activation induced by TAC. Surprisingly, whole-body ablation of PDE3A, but not PDE3B, provided similar protection against TAC-induced adverse ventricular remodeling, and the addition of MIL to mice lacking PDE3A provided no further protection. Our results support the conclusion that PDE3A plays an important role in adverse cardiac remodeling induced by chronic pressure overload in mice, although the underlying biochemical mechanisms remain to be fully elucidated. The implications of this conclusion on the clinical use of PDE3 inhibitors are discussed.
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2,334,669 |
Choice of surgical tactics at the stage of preoperative preparation of patients with biliary sepsis.
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Introduction: There is a problem of choosing the optimal method for eliminating choledocholithiasis in accordance with one The lack of satisfactory results from the use of existing methods of surgical correction explains the constant interest of specialists to this problem, requires the improvement of the commonly accepted and the search for new approaches to the treatment of this concomitant disease. The aim: To substantiate the use of individual assessment at the stage of preoperative preparation for the purposeful differential tactic of surgical treatment of the biliary sepsis.</AbstractText>Materials and methods: The basis of our research was the results of the analysis of treatment of 112 patients with biliary sepsis who were on treatment from 2010 to 2017 in the surgical clinic № 2. An assessment of systemic inflammation performed according to the recommended criteria of the Chicago Interventional Conference on Intensive Care (USA, 1992). The systemic inflammatory response syndrome (SIRS) was determined in the presence of 2 or more symptoms: 1) t body> 38 ° C or <36 ° C, 2) heart rate> 90 / min; 3) breathing frequency> 20 / min; 4) white blood cell count> 12 × 109 / l or <4 × 109 / l; or> 10% immature forms (SOFA score 4, 27 ± 0.6 points).</AbstractText>Results: Based on the received pre-operative score, we proposed to optimize the differentiated selection of individualized surgical tactics, taking into account the available baseline conditions, to radically eliminate the cause of biliary sepsis and evaluate the measures of initial conservative therapy. In the course of work, anamnestic unit, clinical unit, laboratory-instrumental block used. The initial severity of the condition of each particular patient is calculate according to the received sum of points for each information block, which allows at the stage of preoperative preparation to standardize all patients in accordance with their score.</AbstractText>Conclusion: Thus, the ball assessment of the severity of the condition of patients allows us to determine not only the optimal tactics, the size and type of surgical correction, but also to determine the effectiveness of the selected composition of preoperative preparation and postoperative treatment, carrying out its dynamic assessment.</AbstractText>
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2,334,670 |
The effects of ultrasound-guided serratus plane block, in combination with general anesthesia, on intraoperative opioid consumption, emergence time, and hemodynamic stability during video-assisted thoracoscopic lobectomy: A randomized prospective study.
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Thoracotomy is one of the most painful surgeries; therefore, video-assisted thoracoscopic surgery (VATS) was developed to reduce the surgical stress of thoracotomy. Although VATS results in reduced postoperative pain compared with thoracotomy, it is still painful. Serratus plane block (SPB) is a novel technique that provides lateral chest wall analgesia by blocking the lateral branch of the intercostal nerve.</AbstractText>We conducted a prospective study in 50 patients, aged 20 to 75 years, undergoing three-port VATS lobectomy. Group G (n = 25) received conventional general anesthesia and Group S (n = 25) received SPB before induction of general anesthesia. In Group S, 20 ml of 0.375% ropivacaine was injected between the serratus anterior and latissimus dorsi muscles. During surgery, anesthesia was maintained by adjusting the propofol dose to maintain a bispectral index of 40 to 60 and the remifentanil dose to maintain blood pressure and heart rate within 70 to 130% of baseline.</AbstractText>Intraoperative remifentanil consumption was significantly lower in Group S compared to that in Group G (519.9 μg vs 1047.7 μg, P < .001). Moreover, emergence time was significantly shorter in Group S compared to Group G (10.8 minutes vs 14.9 minutes, P = .01). However, there were no significant differences in systolic blood pressure and heart rate (HR) between the groups at each time point. The doses of rescue drugs for the control of blood pressure and HR were not significantly different between the 2 groups.</AbstractText>Ultrasound-guided SPB could be a safe and effective regional anesthesia technique for VATS.</AbstractText>
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2,334,671 |
Relationships among stress, emotional intelligence, cognitive intelligence, and cytokines.
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The brain has multiple functions, and its structures are very closely related to one another. Thus, the brain areas associated with stress, emotion, and intelligence are closely connected. The purpose of this study was to investigate the multiple associations between stress and emotional intelligence (EI), between EI and intelligence quotient (IQ), between cytokines and stress, and between cytokines and IQ. We measured the stress, EI, cognitive intelligence using IQ, and cytokine levels of 70 healthy subjects. We also analyzed the association of cytokines with IQ according to hemispheric dominance using the brain preference indicator (BPI). We found significant negative correlations between stress and the components of EI, such as emotional awareness and expression, emotional thinking, and emotional regulation. High levels of anger, which is a component of stress, were significantly related to poor emotional regulation. Additionally, emotional application was positively correlated with full-scale IQ scores and scores on the vocabulary, picture arrangement, and block design subtests of the IQ test. High IL-10 levels were significantly associated with low stress levels only in the right-brain-dominant group. High IL-10 and IFN-gamma levels have been associated with high scores of arithmetic intelligence. TNF-alpha and IL-6 were negatively associated with vocabulary scores and full-scale IQ, but IL-10 and IFN-gamma were positively associated with scores on the arithmetic subtest in left-brain-dominant subjects. On the other hand, IL-10 showed positive correlations with scores for vocabulary and for vocabulary and arithmetic in right-brain-dominant subjects. Furthermore, we found significant linear regression models which can show integrative associations and contribution on emotional and cognitive intelligence. Thus, we demonstrated that cytokines, stress, and emotional and cognitive intelligence are closely connected one another related to brain structure and functions. Also, the pro-inflammatory cytokines TNF-alpha and IL-6 had negative effects, whereas the anti-inflammatory cytokines (e.g., IL-10 and IFN-gamma) showed beneficial effects, on stress levels, and multiple dimensions of emotional and cognitive intelligence. Additionally, these relationships among cytokines, stress, and emotional and cognitive intelligence differed depending on right and left hemispheric dominance.
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2,334,672 |
Predicting Academic Performance of Students Using a Hybrid Data Mining Approach.
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Data mining offers strong techniques for different sectors involving education. In the education field the research is developing rapidly increasing due to huge number of student's information which can be used to invent valuable pattern pertaining learning behavior of students. The institutions of education can utilize educational data mining to examine the performance of students which can support the institution in recognizing the student's performance. In data mining classification is a familiar technique that has been implemented widely to find the performance of students. In this study a new prediction algorithm for evaluating student's performance in academia has been developed based on both classification and clustering techniques and been ested on a real time basis with student dataset of various academic disciplines of higher educational institutions in Kerala, India. The result proves that the hybrid algorithm combining clustering and classification approaches yields results that are far superior in terms of achieving accuracy in prediction of academic performance of the students.
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2,334,673 |
Continuous surgical multi-level extrapleural block for video-assisted thoracoscopic surgery: a retrospective study assessing its efficacy as pain relief following lobectomy and wedge resection.
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<b>Background:</b> Video-assisted thoracoscopic surgery (VATS) causes less postoperative pain than thoracotomy; however, adequate analgesia remains vital. As part of a multi-modal postoperative analgesia, a continuous surgeon-placed extrapleural block catheter is an option. The aim of this retrospective study was to evaluate the analgesic efficacy of a continuous extrapleural block as part of a multimodal analgesic regimen after VATS in general, and VATS lobectomy and wedge resection in particular. <b>Methods:</b> Case records for patients having undergone VATS surgery and been provided a multi-level continuous extrapleural block with an elastomeric pump infusing levobupivacaine 2.7 mg/ml at a rate of 5 ml/h during 2015 and 2016 were reviewed. Pain (Numeric Rating Scale) at rest and mobilisation as well as opioid requirement (daily, postoperative days 0-3, as well as accumulated) were analysed.    <b>Results:</b> In all, 454 records were reviewed: 150 wedge resections, 264 lobectomies and 40 miscellaneous cases. At rest, pain was mild median NRS rated 3-3-1-1 for postoperative day (POD) 0 to 3, during movement, pain was rated moderate during POD 0 and 1 and mild the remaining days (median NRS 4-4-3-3 for POD 0-3). The proportion of patients exhibiting mild pain at rest increased from 55% on POD 0 to 81 % on POD 3. The percentage of patients experiencing severe pain at rest decreased from 15% to 6%. Median oxycodone consumption was 10 mg per day for POD 1-3. Pain after VATS wedge resection was significantly lower at POD 1 and 3 compared to pain after VATS lobectomy. <b>Conclusion:</b> We found a continuous surgeon-placed extrapleural catheter block to be a valuable and seemingly safe addition to our multimodal procedure specific analgesia after VATS. Whether the efficacy of the block can be improved by increasing local anaesthetic and/or adding adjuncts warrants further investigation.
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2,334,674 |
Effects of Thoracic Paravertebral Block on Nociceptive Levels After Skin Incision During Video-Assisted Thoracoscopic Surgery.
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BACKGROUND Regional anesthesia provides excellent analgesic effects after surgery. However, the effects of regional anesthesia on nociceptive levels during surgery under general anesthesia have not been quantitatively evaluated. To reveal the effects of thoracic paravertebral block (PVB) on nociceptive levels after skin incision during general anesthesia, we performed a retrospective cohort study in patients without serious preoperative conditions or comorbidities undergoing elective video-assisted thoracoscopic surgery (VATS). Nociceptive levels during general anesthesia were calculated using our previously determined Nociceptive Response (NR) equation, which utilizes common hemodynamic parameters. MATERIAL AND METHODS Data on 77 adult patients who underwent VATS from May 2018 to August 2018 were retrospectively obtained from our institutional database. We then performed propensity score matching between patients who received thoracic PVB (PVB group: n=29) and those who did not (Control group: n=48). The averaged values of systolic blood pressure (SBP), heart rate (HR), perfusion index (PI), bispectral index (BIS), and NR from 10 to 5 minutes before skin incision (T0), 5 to 10 minutes (T1), 10 to 15 minutes (T2), 15 to 20 minutes (T3), and 20 to 25 minutes after skin incision (T4), were calculated. RESULTS Twenty-four propensity score-matched patients in each group were analyzed. Mean NR values at T1 and T2 in the PVB group were significantly lower than those in the Control group. SBP, HR, PI, and BIS, however, showed no significant differences between the 2 groups, except for SBP at T2. CONCLUSIONS Thoracic PVB prevented an increase in NR values, which quantitatively represent nociceptive levels under general anesthesia, in patients undergoing VATS.
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2,334,675 |
Inhibition of miR-495 Improves Both Vascular Remodeling and Angiogenesis in Pulmonary Hypertension.
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Pulmonary hypertension (PH) is a chronic progressing vascular disease characterized by pulmonary arteriole remodeling and loss of pulmonary microvasculature. The aim of this study was to investigate a potential role for the miR-495 in PH pathogenesis and to explore its therapeutic potential in PH.</AbstractText>Male C57BL/6J mice were injected with SU5416 weekly during 3 weeks of exposure to 10% oxygen to cause PH. We first tested the effects of adeno-associated virus 9 (AAV9) delivery which was specifically designed to block miR-495 in the lungs of the PH model. Then, the biological function of miR-495 was analyzed in cultured pulmonary arterial endothelial cells (PAECs) under hypoxic condition.</AbstractText>The inhibition of miR-495 improves hemodynamics and vascular remodeling in PH. At the same time, these effects were associated with increases in angiogenic transcription factor VEZF1 and marked upregulation of other angiogenic genes such as Angpt-1 and IGF1. In vitro, cultured mouse PAECs were transfected with miR-495 inhibitor or miR-495 mimics. Both the flow cytometry results and CCK8 assay showed that miR-495 inhibitor increased the percentage of cells in the G2/M+S phase, and the wound healing assays indicated that the migration capacity of PAECs transfected with miR-495 inhibitor was increased compared to the inhibitor-NC cells.</AbstractText>Our results indicate that AAV9-TuD-miR-495 delivery improves hemodynamic and pulmonary vascular structural changes in PH mice.</AbstractText>© 2019 S. Karger AG, Basel.</CopyrightInformation>
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2,334,676 |
General anesthesia for patient with Fahr's syndrome: A case report.
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Fahr's syndrome (FS) is a rare neurological and psychiatric disorder characterized by bilateral brain calcifications when a secondary cause of the calcification is found.</AbstractText>A 53-year-old female patient diagnosed with FS for laminectomy because of ossification of posterior longitudinal ligament. She had a history of generalized tonic-clonic (GTC) seizure and medication with anticonvulsant drugs. She had gait disturbance, spasticity, bradykinesia, and diffuse calcifications in the basal ganglia, thalamus, cerebellum, and cerebral hemispheres on the brain computed tomography. On the preoperative examination, the serum and ionized calcium (Ca) were decreased to 3.7 and 2.22 mg/dL. Hypomagnesemia is combined with hypocalcemia. Furthermore, the level of parathyroid hormone was decreased to 2.18 pg/mL.</AbstractText>Due to the radiologic findings and laboratory test results, she was diagnosed with FS with primary hypoparathyroidism.</AbstractText>The Ca and magnesium (Mg) had been corrected before surgery but the electrolytes revealed low level at the intraoperative period. The 300 mg of calcium chloride was administered at 2 times and 1200 mg of it were infused for 1 hour during intraoperative periods. In addition, total 4 g of Mg sulfate intravenously administered. We used rocuronium as a neuromuscular block and checked neuromuscular function by train-of-four monitoring.</AbstractText>Residual neuromuscular blockade was reversed with pyridostigmine and her muscle power completely recovered. The patient was extubated successfully and no unpredictable events occurred. On the day following transfer, serum electrolytes remained low, and although Ca was continuously supplied, serum Ca did not recover to a normal level. The patient was medicated with anticonvulsant drugs but experienced GTC seizure 2 weeks after surgery.</AbstractText>We presume that the pathophysiology of FS was related to primary hypoparathyroidism and hypomagnesemia. FS raises concerns associated with neuromuscular problems, spasticity, and seizure, and concerns of hypotension, heart failure, cardiac arrhythmia, and cerebrovascular attack during perioperative periods, among anesthesiologists because of hypocalcemia and vessel calcification. During the perioperative period, Ca levels should be closely monitored, and titrated Ca replacement therapy is recommended. The simultaneous correction of hypomagnesemia is of considerable importance when correcting hypocalcemia.</AbstractText>
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2,334,677 |
How Well Do Seniors Estimate Distance to Food? The Accuracy of Older Adults' Reported Proximity to Local Grocery Stores.
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(1) Background: Findings from observational studies of relations between neighborhood environments and health outcomes underscore the importance of both objective and perceived experiences of those environments. A clearer understanding of the factors associated with discrepancies between these two assessment approaches is needed to tailor public health interventions to specific populations. This study examined how individual and neighborhood characteristics affect perceptions of supermarket distance, particularly when perceptions do not match objective measures. (2) Methods: Participants were older adults (<i>n</i> = 880) participating in the Senior Neighborhood Quality of Life Study in the Seattle/King County, WA or Baltimore/Washington, DC regions. Two main analyses were conducted. The primary outcome for Analysis I was participants' geographic information systems (GIS)-based objective network distance to the closest supermarket. Generalized linear mixed models with block group-level random effects were used to assess associations between objective supermarket distance and individual/neighborhood characteristics. The primary outcome for Analysis II was a categorical "accuracy" variable, based on participants' perceived distance to the nearest supermarket/grocery store relative to the objective distance, assuming a walking speed of 1.0 m/s. Multivariate log-linear models fit neural networks were used to assess influential covariates. (3) Results: Several significant associations with objective distance to the nearest supermarket were observed, including a negative relationship with body mass index (BMI) (95% CI = -45.56, -0.23), having walked to the supermarket in the last 30 days (-174.86, -59.42), living in a high-walkability neighborhood, and residing in Seattle/King County (-707.69, -353.22). In terms of participants' distance accuracy, 29% were classified as accurate, 33.9% were "Underestimators", 24.0% "Overestimators", and 13.2% responded "Don't Know". Compared to Accurate participants, Overestimators were significantly less likely to have walked to the supermarket in the last 30 days, and lived objectively closer to a supermarket; Underestimators perceived significantly higher pedestrian safety and lived objectively further from a supermarket; and Don't Know were more likely to be women, older, not living independently, and not having recently walked to the supermarket. (4) Conclusions: Both modifiable and nonmodifiable factors influence the accuracy of older adults' perceptions of their proximity to the nearest supermarket. Recent experience in walking to the closest supermarket, along with personal safety, represent potentially modifiable perceived environmental factors that were related to older adults' accuracy of perceptions of their neighborhood food environment.
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2,334,678 |
Classification of Clinical Isolates of <i>Klebsiella pneumoniae</i> Based on Their <i>in vitro</i> Biofilm Forming Capabilities and Elucidation of the Biofilm Matrix Chemistry With Special Reference to the Protein Content.
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<i>Klebsiella pneumoniae</i> is a human pathogen, capable of forming biofilms on abiotic and biotic surfaces. The limitations of the therapeutic options against <i>Klebsiella pneumoniae</i> is actually due to its innate capabilities to form biofilm and harboring determinants of multidrug resistance. We utilized a newer approach for classification of biofilm producing <i>Klebsiella pneumoniae</i> isolates and subsequently we evaluated the chemistry of its slime, more accurately its biofilm. We extracted and determined the amount of polysaccharides and proteins from representative bacterial biofilms. The spatial distribution of sugars and proteins were then investigated in the biofilm matrix using confocal laser scanning microscopy (CLSM). Thereafter, the extracted matrix components were subjected to sophisticated analysis incorporating Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, one-dimensional gel-based electrophoresis (SDS-PAGE), high performance liquid chromatography (HPLC), and MALDI MS/MS analysis. Besides, the quantification of its total proteins, total sugars, uronates, total acetyl content was also done. Results suggest sugars are not the only/major constituent of its biofilms. The proteins were harvested and subjected to SDS-PAGE which revealed various common and unique protein bands. The common band was excised and analyzed by HPLC. MALDI MS/MS results of this common protein band indicated the presence of different proteins within the biofilm. The 55 different proteins were identified including both cytosolic and membrane proteins. About 22 proteins were related to protein synthesis and processing while 15 proteins were identified related to virulence. Similarly, proteins related to energy and metabolism were 8 and those related to capsule and cell wall synthesis were 4. These results will improve our understanding of <i>Klebsiella</i> biofilm composition and will further help us design better strategies for controlling its biofilm such as techniques focused on weakening/targeting certain portions of the slime which is the most common building block of the biofilm matrix.
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2,334,679 |
Postoperative analgesia with ropivacaine and dexmedetomidine for ultrasound-guided fascia iliaca compartment block after arthroscopic knee surgery.
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The objective of this study is to evaluate the postoperative analgesic effect of a combination of ropivacaine and dexmedetomidine for ultrasound-guided fascia iliaca compartment block (FICB) after knee arthroscopy.</AbstractText>Forty patients scheduled for knee arthroscopy were randomized to receive either 30 ml of 0.25% ropivacaine alone (Group A, n</i> = 20) or combined with dexmedetomidine 1 μg/kg (Group B, n</i> = 20). Pain intensity was evaluated using the visual analogue scale (VAS), at rest and during activity at 4, 6, 8, 12, and 24 h after surgery. Level of consciousness was evaluated using the Ramsay sedation score. Time to first analgesic request after surgery, the dose of analgesic used in the first 24 h after surgery, variation of heart rate, and adverse reactions were also recorded.</AbstractText>VAS scores at 6 and 12 h after surgery were significantly lower in Group B compared to Group A (P</i> < 0.05). No significant difference was observed in the Ramsay sedation score or time to first analgesic request after surgery (P</i> > 0.05). The total dose of analgesic used in the first 24 h after surgery was higher in Group A than in Group B. The incidence of bradycardia was higher in Group B compared to Group A. No adverse reactions were observed in either group.</AbstractText>FICB with a combination of ropivacaine and dexmedetomidine resulted in significant reduction of VAS scores with lower postoperative analgesic requirement after arthroscopic knee surgery. No adverse reactions or complications were noted except for lower heart rate in Group B patients.</AbstractText>
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2,334,680 |
Evaluation of the effect and safety of dexmedetomidine as an additive to local anesthesia in peribulbar block for vitreoretinal surgery.
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We conducted a prospective, randomized study to evaluate the efficacy of dexmedetomidine as an additive to peribulbar block for vitreoretinal surgery in terms of onset time of block, hemodynamic stability profile, patient comfort, and surgeon satisfaction.</AbstractText>One hundred patients of American Society of Anesthesiologists grade 1 and 2 scheduled for vitreoretinal surgery were randomly assigned into two groups: control group (n = 50) received lignocaine bupivacaine block, and Dex group (n = 50) received lignocaine bupivacaine plus 20 μg dexmedetomidine peribulbar block. Information regarding time for onset of block, hemodynamic data, visual analog scale for pain, sedation levels, total duration of surgery, and surgeon satisfaction levels were collected.</AbstractText>All the demographic characteristics including age, gender, American Society of Anesthesiologists grade, onset of anesthesia, and duration of surgery were comparable in both groups. At the baseline, there was no statistically significant difference in heart rate, mean arterial pressure, diastolic blood pressure, and respiratory rate between the two groups, with a difference noted in systolic blood pressure at the baseline. There was significant difference noted in the systolic blood pressure and mean arterial pressure at different time intervals with a decreasing trend as time progressed. The mean sedation score was significantly higher in the Dex group than that in the control group. The surgeon satisfaction was higher in the Dex group than that in the control group.</AbstractText>Dexmedetomidine is a useful and safe drug in combination with lignocaine bupivacaine in peribulbar for vitreoretinal surgery as it maintains hemodynamic stability and provides sedation, which enables full cooperation and potentially better operating conditions.</AbstractText>
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2,334,681 |
A genome-wide association study implicates <i>NR2F2</i> in lymphangioleiomyomatosis pathogenesis.
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Lymphangioleiomyomatosis (LAM) occurs either associated with tuberous sclerosis complex (TSC) or as sporadic disease (S-LAM). Risk factors for development of S-LAM are unknown. We hypothesised that DNA sequence variants outside of TSC2</i>/TSC1</i> might be associated with susceptibility for S-LAM and performed a genome-wide association study (GWAS).</AbstractText>Genotyped and imputed data on 5 426 936 single nucleotide polymorphisms (SNPs) in 426 S-LAM subjects were compared, using conditional logistic regression, with similar data from 852 females from COPDGene in a matched case-control design. For replication studies, genotypes for 196 non-Hispanic White female S-LAM subjects were compared with three different sets of controls. RNA sequencing and immunohistochemistry analyses were also performed.</AbstractText>Two noncoding genotyped SNPs met genome-wide significance: rs4544201 and rs2006950 (p=4.2×10-8</sup> and 6.1×10-9</sup>, respectively), which are in the same 35 kb linkage disequilibrium block on chromosome 15q26.2. This association was replicated in an independent cohort. NR2F2</i> (nuclear receptor subfamily 2 group F member 2), a nuclear receptor and transcription factor, was the only nearby protein-coding gene. NR2F2</i> expression was higher by RNA sequencing in one abdominal LAM tumour and four kidney angiomyolipomas, a LAM-related tumour, compared with all cancers from The Cancer Genome Atlas. Immunohistochemistry showed strong nuclear expression in both LAM and angiomyolipoma tumours.</AbstractText>SNPs on chromosome 15q26.2 are associated with S-LAM, and chromatin and expression data suggest that this association may occur through effects on NR2F2</i> expression, which potentially plays an important role in S-LAM development.</AbstractText>The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2019.</CopyrightInformation>
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2,334,682 |
Impact of treatment planning using a structure block function on the target and organ doses related to patient movement in cervical esophageal cancer: A phantom study.
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Helical tomotherapy (HT) can restrict beamlets passing through the virtual contour on computed tomography (CT) image in dose optimization, reducing the dose to organs at risk (OARs). Beamlet restriction limits the incident beamlet angles; thus, the proper planning target volume (PTV) margin may differ from that of the standard treatment plan without beamlet restriction, depending on the patient's movement during dose delivery. Dose distribution changes resulting from patient movement have not been described for treatment plans with beamlet restriction. This study quantified changes in dose distribution to the target and OARs when beamlet restriction is applied to cervical esophageal cancer treatment plan using HT by systematically shifting a phantom. Treatment plans for cervical esophageal cancers with and without beamlet restriction modes [directional block (DB) and nonblock (NB), respectively] were designed for CT images of the RANDO phantom. The PTV margin for the DB mode was set to be the same as that for the NB mode (5 mm). The CT image was intentionally shifted by ±1, ±2, and ±3 voxels in the left-right, anterior-posterior, and superior-inferior directions, and the dose distribution was recalculated for each position using the fluence for the NB or DB mode. When the phantom shift was within the same PTV margin as the NB mode, changes in doses to the targets, lungs, heart, and spinal cord in the DB mode were small as those in the NB mode. In conclusion, the virtual contour shape used in this study would provide safe delivery even with patient movement within the same PTV margin as for the NB mode.
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2,334,683 |
Effects of Aerobic Exercise on Vibration Perception Threshold in Type 2 Diabetic Peripheral Neuropathy Population Using 3-sites Method: Single-blind Randomized Controlled Trial.
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The purpose of this study was to examine the effects of 8 wk of moderate intensity aerobic exercise on vibration perception threshold (VPT) in type 2 diabetic peripheral neuropathy (DPN).</AbstractText>Single blind parallel group randomized controlled trial was done in a tertiary center. Stratified block randomization was used for selecting participants. A total of 87 individuals participated in the study. After final randomization, there were only 47 individuals in the control group and 37 in the study group. The exercise group training was carried out in the range of 40% to 60% of heart rate reserve as an adjunct to this rating of perceived exertion (scale ranging from 6 to 20) before, during, and postexercise. For the control group, standard medical care, education for foot care, and diet (same as the experimental group) were given. Both the groups were assessed at baseline and wk 8.</AbstractText>On comparison of results for control and study group using repeated measures of analysis of variance for VPT measures for 3 sites (great toe, medial malleoli, first metatarsal phalanx), there was a significant difference between the 2 groups (df1, df2 = 1,63; F = 8.56; P < .001) for both lower limbs.</AbstractText>Aerobic exercises have an augmentative effect on vibratory sensations of the peripheral nerves, which implicates an attenuating effect on DPN in type 2 diabetes.</AbstractText>
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2,334,684 |
New mineralocorticoid receptor antagonists: update on their use in chronic kidney disease and heart failure.
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Aldosterone is a mineralocorticoid hormone with a well-known effect on the renal tubule leading to water retention and potassium reabsorption. Other major effects of the hormone include the induction of proinflammatory activity that leads to progressive fibrotic damage of the target organs, heart and kidney. Blocking the aldosterone receptor therefore represents an important pharmacological strategy to avoid the clinical conditions deriving from heart failure (CHF) and chronic kidney disease (CKD). However, steroidal mineralocorticoid receptor antagonists (MRA) have a low safety profile, especially in CKD patients due to the high incidence of hyperkalemia. A new generation of nonsteroidal MRA has recently been developed to obtain a selective receptor block avoiding side-effects like hyperkalemia and thereby making the drugs suitable for administration to CKD patients. This review summarizes the results of published preclinical and clinical studies on the nonsteroidal MRA, apararenone esaxerenone and finerenone. The trials showed a better safety profile with maintained drug efficacy compared with steroidal MRA. For this reason, nonsteroidal MRA represent an interesting new therapeutic approach for the prevention of CHF and CKD progression. Some basic research findings also yielded interesting results in acute clinical settings such as myocardial infarction and acute kidney injury.
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2,334,685 |
Prevalence and Significance of Interatrial Block in Takotsubo Syndrome (from the RETAKO Registry).
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Interatrial block (IAB) represents a conduction delay between right and left atria and is associated with an increased risk of atrial fibrillation and stroke. IAB has not been previously assessed in patients with Takotsubo syndrome (TS). Our aim was to describe the prevalence and prognostic significance of IAB in patients with TS. Data come from the Spanish National prospective registry of patients with definitive TS diagnosis. IAB was defined as a P-wave ≥120 ms and was considered partial when the P-wave was positive in inferior leads and advanced when it was biphasic (+/-). A total of 246 patients were included, normal P-wave was found in 151 (61%), partial IAB in 58 (24%), atrial fibrillation in 18 (7%), advanced IAB in 13 (5%), and 6 (2%) were pacemaker dependent. During a mean follow up of 12 months the composite of all-cause mortality and hospital readmission was significantly higher in patients with advanced IAB (31%) or atrial fibrillation (33%) than in the rest of the cohort (pacemaker stimulation 17%, normal P-wave 13%, partial IAB 12%), p < 0.01. The data regarding P wave characteristics were an independent predictor of the composite end point all-cause death and hospital readmission. IAB has a high prevalence in patients with TS. Advanced IAB and atrial fibrillation are associated with a poor prognosis.
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2,334,686 |
Defining the hemodynamic response of hypertensive and normotensive subjects through serial timed blood pressure readings in the clinic.
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Every third patient in the clinic is misdiagnosed due to white-coat phenomenon, necessitating needless and costly treatment. We aimed to study the hemodynamic response of the physician's visit on hypertensive and normotensive patients by investigating the trend of blood pressure (BP) before, during and 15 min after the physician-patient encounter.</AbstractText>A descriptive, cross-sectional study was conducted over a period of 8 months in the cardiology clinics at the Aga Khan University Hospital, Karachi. Both hypertensive and normotensive patients, aged ≥18 years, were recruited. Pregnant females or those with a history of volume loss were excluded. BP readings were taken using an automated, validated device (Omron-HEM7221-E) at three points: pre-clinic BP by the assessment nurse, in-clinic BP by the attending physician and post-clinic BP 15-min after the physician-patient encounter by a research assistant. Independent samples t-test was used to calculate the statistical difference between hypertensive and normotensive BP values.</AbstractText>Of 180 participants, 71% (n</i> = 128) were hypertensive and 57% (n</i> = 103) of all were males. The mean age of the participants was 57 ± 15 years. The mean and standard deviation(±SD) systolic BP (SBP) taken pre-clinic, in-clinic and 15-min post-clinic for hypertensive population was 128.7 ± 20 mmHg, 137.1 ± 21 mmHg and 127.9 ± 19 mmHg. The mean and standard deviation(±SD) SBP taken pre-clinic, in-clinic and 15 min post-clinic for normotensive population was 112 ± 16 mmHg, 115.8 ± 20 mmHg and 111.8 ± 15 mmHg. The hypertensive SBP values showed statistically significant difference from the normotensive values (difference in pre-clinic SBP: 16.7 mmHg, p</i>-value < 0.001; in-clinic SBP: 21.3 mmHg, p-value < 0.001; and 15 min post-clinic: 16.1 mmHg, p-value < 0.001).</AbstractText>Hypertensive and normotensive patients display congruent hemodynamics upon visiting the physician, the alert response being accentuated amongst the hypertensive group. In-clinic BP readings are higher for both hypertensive and normotensive patients making them unreliable for screening and management of hypertension amongst both the groups.</AbstractText>
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2,334,687 |
The effect of fluconazole on oral methadone in dogs.
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To determine the effects of fluconazole on oral methadone pharmacokinetics and central effects mediated by opioid receptors in dogs.</AbstractText>Prospective, incomplete block.</AbstractText>A total of 12 healthy Beagle dogs.</AbstractText>Dogs were randomly allocated into two groups of six dogs. In total, four treatments (two treatments/group) were administered including: oral methadone (1 mg kg-1</sup>); oral fluconazole (5 mg kg-1</sup>) every 12 hours starting 24 hours prior to oral methadone (1 mg kg-1</sup>); oral fluconazole (2.5 mg kg-1</sup>) every 12 hours starting 24 hours prior to oral methadone (1 mg kg-1</sup>); and oral fluconazole (5 mg kg-1</sup>) every 24 hours starting 12 hours prior to oral methadone (1 mg kg-1</sup>). At least 28 days were implemented as a washout period between fluconazole treatments. Rectal temperature (RT), heart rate (HR), respiratory rate (fR</sub>), sedation scores and blood samples were obtained for 24 hours after methadone administration. Plasma drug concentrations were measured with liquid chromatography/mass spectrometry.</AbstractText>Significantly higher maximum plasma methadone concentration (mean, 25-46 ng mL-1</sup>) occurred in all fluconazole-administered treatments than in methadone alone (1.5 ng mL-1</sup>). The mean 12 hour methadone plasma concentration in fluconazole treatments was 11-20 ng mL-1</sup>. Significantly decreased RT and variable sedation occurred in all fluconazole treatments, but no changes occurred with methadone alone. There were no differences in HR or fR</sub> among treatments.</AbstractText>Fluconazole significantly increases the extent and duration of oral methadone exposure in dogs resulting in significant central opioid effects.</AbstractText>Copyright © 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,688 |
The CNS theory of osteoarthritis: Opportunities beyond the joint.
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Osteoarthritis (OA) is a leading cause of global disability that affects more than half of the population over 65. It is not a single disease but a progressive, inflammatory- and immune-altering multi-disease that affects the whole joint. OA has many risk factors including age, obesity, gender, lifestyle, joint morphology, metabolic dysfunction and genetic disposition. A major stumbling block in treating clinical OA has been the inability to detect its early onset and disease progression. This gap in understanding may arise from our failure to recognize that the OA patient exhibits a vulnerability to dysregulation of central feedback circuits that control sympathetic tone, inflammation, circadian rhythms (central and peripheral clocks), gut microbiome, metabolic redox and whole joint pathology. Early detection of OA and slowing its progression may come from discoveries outside the joint targeting these potentially modifiable upstream targets. We argue that future treatments may benefit from moving from a knee-centric viewpoint to a more systems-based, whole-body approach. The challenge, however, will be to better characterize these key circuits and apply this knowledge to develop new therapies and interventions.
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2,334,689 |
TRPM4 channel and cancer.
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The TRPM4 channel has been extensively studied in cerebral diseases such as stroke, head injury and multiple sclerosis. In the heart, gain-of-function mutations of TRPM4 are a cause of familial cardiac block. Recently, evidence has emerged to support the role of TRPM4 in certain types of cancer, such as prostate cancer and large B cell lymphoma. The expression of TRPM4 could mediate certain behaviors of cancer cells such as migration and invasion. However, the mechanisms are largely unknown. As a nonselective monovalent cation channel, TRPM4 upregulation and activation enhance sodium entry, which leads to depolarization of the membrane potential. The membrane potential is critical in regulating calcium influx, and a disturbed calcium homeostasis is always associated with cancer cell behaviors. Research on TRPM4 channels in cancer is at a very early stage. In this review, we summarize the expression of TRPM4 in various cancers as well as our current understanding of TRPM4 in cancer. The potential mechanisms of the TRPM4 channel in regulating calcium homeostasis in cancer cells are further discussed in detail. Targeting the TRPM4 channel can be a novel way of managing cancer metastasis via disrupting calcium signaling pathways.
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2,334,690 |
Iron status and risk factors of iron deficiency among pregnant women in Singapore: a cross-sectional study.
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Iron deficiency is the most prevalent nutrient deficiency and the most common cause of anaemia worldwide. Because of the increased iron requirements during pregnancy, iron deficiency can lead to maternal anaemia and reduced newborn iron stores. We examined the proportion and risk factors of iron deficiency among pregnant women in a developed Asian country.</AbstractText>Within a prospective cohort in Singapore, 985 Asian women were assessed for iron status at 26-28 weeks' gestation, with plasma ferritin and soluble transferrin receptor (sTfR) measurements. Iron status was determined according to plasma ferritin concentrations at ≥30 μg/L (iron sufficiency), 15 to < 30 μg/L (modest iron depletion) and < 15 μg/L (severe iron depletion). Multivariable ordinal logistic regression was used to analyze risk factors for modest and severe iron depletion.</AbstractText>The median (25-75th percentile) plasma ferritin concentration was 24.2 (19.9-30.6) μg/L. Overall, 660 (67.0%) and 67 (6.8%) women had modest and severe iron depletion, respectively. Higher plasma sTfR was observed in women with severe iron depletion than among those with iron sufficiency (median 17.6 versus 15.5 nmol/L; p < 0.001). Age < 25 years (odds ratio 2.36; 95% confidence interval 1.15-4.84), Malay (2.05; 1.30-3.24) and Indian (1.98; 1.14-3.44) ethnicities (versus Chinese), university qualification (1.64; 1.13-2.38), multiparity (1.73; 1.23-2.44) and lack of iron-containing supplementation (3.37; 1.25-8.53) were associated with increased odds of modest and severe iron depletion.</AbstractText>Nearly three-quarters of Singaporean women were iron deficient in the early third trimester of pregnancy. These results suggest universal screening and supplementation of at-risk pregnancies may be evaluated as a preventive strategy.</AbstractText>NCT01174875 . Registered 1 July 2010 (retrospectively registered).</AbstractText>
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2,334,691 |
Video-Assisted Thoracic Surgery (VATS) Talc Pleurodesis Versus Pleurectomy for Primary Spontaneous Pneumothorax: A Large Single-Centre Study with No Conversion.
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Primary spontaneous pneumothorax (PSP) is a relatively common clinical entity with high incidence in the young population. Video-Assisted Thoracic Surgery (VATS) bullectomy and chemical or mechanical pleurodesis are two primary modalities of treatment. There has been much debate on the ideal mode of pleurodesis, but the literature on surgical outcomes comparing VATS pleurectomy with talc pleurodesis has been inconclusive.</AbstractText>We performed a single-centre 5-year observational retrospective study of 202 patients who underwent VATS bullectomy with talc pleurodesis or parietal pleurectomy.</AbstractText>There were no significant differences in the demographics, pre-operative and intra-operative characteristics in both groups. Recurrence of pneumothorax, chest tube duration and hospital stay were similar in both groups. However, talc pleurodesis had a shorter operative time compared to pleurectomy.</AbstractText>Our study demonstrated comparable outcomes between talc pleurodesis and pleurectomy following VATS bullectomy for patients with PSP.</AbstractText>
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2,334,692 |
Multi-organ failure induced by Nivolumab in the context of allo-stem cell transplantation.
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Immune checkpoint inhibitors have radically changed the landscape of anti-tumor therapies in several malignancies. However the adverse events associated with immune checkpoint blockade in combination with other treatments remains to be thoroughly documented. Here we report the case of a 33-year-old male with classical Hodgkin lymphoma who was successfully treated for lymphoma but experienced serious and eventually fatal multisystem organ failure following nivolumab administration and allogeneic stem cell transplantation.</AbstractText>The patient was diagnosed with stage IIIa nodular sclerosing Hodgkin lymphoma. Originally treated by chemotherapy and autologous stem cell transplantation, he subsequently received two allogeneic stem cell transplants from matched and haplo-identical siblings upon successive disease recurrences. Nivolumab treatment was administered prior to the second allograft, after which complete remission of lymphoma was achieved (year 10), as evidenced by clinical and radiographic examination. However within the next 3 months, the patient went on to develop a constellation of symptoms affecting multiple organs, including acute pneumonia with no evidence of bacterial infection, widespread cutaneous eruptions on trunk and lower limbs, mucosal ulcerations, myositis, diarrhea and colitis. Further complications included hepatic cytolysis, acute renal failure, pancreatitis, as well as complete heart block. Some of these injuries being suggestive of graft-versus-host disease, the patient was administered immunosuppressive therapy (mycophenolate, steroids and polyvalent immunoglobulins), but died shortly afterwards. Tissue biopsies revealed extensive lymphocytic infiltration (mostly CD3 + T cells) in skin, liver, and most peculiarly in muscles, including the myocardium. Massive lymphoid-histiocytic infiltration of muscle fibers was accompanied by acute necrotizing myositis and endomysial inflammation.</AbstractText>Multi-organ failure represents a rare but potentially fatal outcome of immune checkpoint blockade in patients receiving allogeneic stem cell grafts. Nivolumab may induce atypical immune-mediated tissue inflammation and damage, such as the extensive muscular polymyositis described here in a patient with Hodgkin lymphoma. Nivolumab might also worsen GVHD symptoms in the context of allogeneic stem cell transplantation. Irrespective of the actual pathological mechanisms, clinicians should be alerted to these fatal drug-related toxicities.</AbstractText>
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2,334,693 |
Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma.
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Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MS<sup>E</sup>. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma.
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2,334,694 |
Systemic Lupus Erythematosus and Pregnancy: A Brief Review.
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Systemic lupus erythematosus is a chronic multisystemic autoimmune disease that predominantly affects young women of childbearing age group. There is a complex immunologic interplay during pregnancy in patients with systemic lupus erythematosus. The pregnancy has direct impact on the disease where an increased rate of flares is noted, and lupus leads to increased risk of hypertensive diseases of pregnancy, preterm birth as well as miscarriages, particularly those with antiphospholipid antibodies. Neonates born to patients with lupus are at increased risk of neonatal lupus as well as heart block if born to patients with positive SSA/SSB. Despite the increased risk of morbidity, recent data suggest improved outcomes in pregnant patients with lupus. A multidisciplinary approach with careful monitoring of pregnancy and lupus could reduce adverse outcomes in these patients. This requires careful pregnancy planning, defining the clinical and serologic involvement of lupus, careful monitoring the patient for adverse pregnancy outcome as well as lupus flares and comprehensive understanding of the drugs that can be safely used in pregnancy. Fetuses should be carefully monitored for heart and neonates for neonatal lupus. Hydroxychloroquine, azathioprine and corticosteroids can be used during pregnancy and may reduce the risk of adverse outcomes. Similarly, appropriate therapy needs to be instituted for hypertensive diseases in pregnancy. Anticoagulant therapy may be necessary for patients with antiphospholipid syndrome.
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2,334,695 |
A checklist manifesto: Can a checklist of common diagnoses improve accuracy in ECG interpretation?
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To determine whether a checklist of possible etiologies for syncope provided alongside ECGs helps Emergency Medicine (EM) residents identify ECG patterns more accurately than with ECGs alone.</AbstractText>We developed a test of ten ECGs with syncope-related pathology from ECG Wave-Maven. We reviewed the literature and used expert consensus to develop a checklist of syncope-related pathologies commonly seen and diagnosed on ECGs. We randomized residents from three New York EM residency programs to interpret ECGs with or without a checklist embedded into the test.</AbstractText>We randomized 165 residents and received completed tests from 100 (60%). Of those who responded, 39% were interns, 23% PGY2s, and 38% were PGY3s or PGY4s. We found no significant difference in overall test scores between those who read ECGs with a checklist and those who read ECGs alone. In post-hoc analysis, residents given a checklist of syncoperelated etiologies were significantly more likely to recognize Brugada (96% vs. 78%, p = 0.007), long QT (86% vs. 68%, p = 0.03) and heart block (100% vs 78%, p = 0.003) as compared to those without a checklist. Those with a checklist were more likely to overread normal ECGs (72% vs 35%, p = 0.0001) compared to those without a checklist, finding pathology where there was none.</AbstractText>Using a checklist with common syncope-related pathology when interpreting an ECG for a patient with clinical scenario of syncope may improve residents' ability to recognize some clinically important pathologies; however it could lead to increased interpretation and suspicion of pathology that is not present.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,696 |
Heart and Lung Transplants from HCV-Infected Donors to Uninfected Recipients.
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Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection.</AbstractText>We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation.</AbstractText>A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.</AbstractText>In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).</AbstractText>Copyright © 2019 Massachusetts Medical Society.</CopyrightInformation>
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2,334,697 |
Joint consensus on anesthesia in urologic and gynecologic robotic surgery: specific issues in management from a task force of the SIAARTI, SIGO, and SIU.
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Proper management of patients undergoing robotic-assisted urologic and gynecologic surgery must consider a series of peculiarities in the procedures for anesthesiology, critical care medicine, respiratory care, and pain management. Although the indications for robotic-assisted urogynecologic surgeries have increased in recent years, specific guidance documents are still lacking.</AbstractText>A multidisciplinary group including anesthesiologists, gynecologists, urologists, and a clinical epidemiologist systematically reviewed the relevant literature and provided a set of recommendations and unmet needs on peculiar aspects of anesthesia in this field.</AbstractText>Nine core contents were identified, according to their requirements in urogynecologic robotic-assisted surgery: patient position, pneumoperitoneum and ventilation strategies, hemodynamic variations and fluid therapy, neuromuscular block, renal surgery and prevention of acute kidney injury, monitoring the Department of anesthesia, postoperative delirium and cognitive dysfunction, prevention of postoperative nausea and vomiting, and pain management in endometriosis.</AbstractText>This consensus document provides guidance for the management of urologic and gynecologic patients scheduled for robotic-assisted surgery. Moreover, the identified unmet needs highlight the requirement for further prospective randomized studies.</AbstractText>
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2,334,698 |
Premature MicroRNA-1 Expression Causes Hypoplasia of the Cardiac Ventricular Conduction System.
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Mammalian cardiac Purkinje fibers (PFs) are specified from ventricular trabecular myocardium during mid-gestation and undergo limited proliferation before assuming their final form. MicroRNA-1 (miR-1), a negative regulator of proliferation, is normally expressed in the heart at low levels during the period of PF specification and outgrowth, but expression rises steeply after birth, when myocardial proliferation slows and postnatal cardiac maturation and growth commence. Here, we test whether premature up-regulation and overexpression of miR-1 during the period of PF morphogenesis influences PF development and function. Using a mouse model in which miR-1 is expressed under the control of the Myh6 promoter, we demonstrate that premature miR-1 expression leads to PF hypoplasia that persists into adulthood, and miR-1 TG mice exhibit delayed conduction through the ventricular myocardium beginning at neonatal stages. In addition, miR-1 transgenic embryos showed reduced proliferation within the trabecular myocardium and embryonic ventricular conduction system (VCS), a source of progenitor cells for the PF. This repression of proliferation may be mediated by direct translational inhibition by miR-1 of the cyclin dependent kinase Cdk6, a key regulator of embryonic myocardial proliferation. Our results suggest that altering the timing of miR-1 expression can regulate PF development, findings which have implications for our understanding of conduction system development and disease in humans.
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2,334,699 |
Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: A randomised controlled trial.
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Prophylactic vasopressors are fundamental during caesarean delivery under spinal anaesthesia. The aim of this work is to compare the efficacy and safety of phenylephrine and norepinephrine when used in variable infusion rate during caesarean delivery.</AbstractText>A randomised, double-blinded, controlled trial was conducted including mothers scheduled for elective caesarean delivery under spinal anaesthesia. Participants were allocated to two groups norepinephrine group (n = 60), and phenylephrine group (n = 63). Participants received prophylactic vasopressors after spinal block at rate started at 0.05 mcg/kg/min and 0.75 mcg/kg/min respectively. The rate of vasopressor infusion was manually adjusted according to maternal systolic blood pressure. Both groups were compared according to incidence of post-spinal hypotension (the primary outcome), incidence of bradycardia, incidence of reactive hypertension, systolic blood pressure, heart rate, rescue vasopressor consumption, number of physician interventions, and neonatal outcomes.</AbstractText>One hundred and twenty-three mothers were available for final analysis. Both groups were comparable in the incidence of post-spinal hypotension (32% versus 30%, P = 0.8). The number of physician intervention was lower in norepinephrine group. The incidence of bradycardia and the incidence of reactive hypertension were potentially lower in norepinephrine group without reaching statistical significance, (13% vs. 21%, P = 0.3) and (12% vs. 24%, P = 0.1). Rescue vasopressor consumption, and neonatal outcomes were comparable between both groups.</AbstractText>When given in a manually adjusted infusion, norepinephrine effectively maintained maternal SBP during caesarean delivery under spinal anaesthesia with lower number of physician interventions, and likely less incidence of reactive hypertension and bradycardia compared to phenylephrine.</AbstractText>Copyright © 2019 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.</CopyrightInformation>
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