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Gastroparesis is a debilitating disease of insufficient gastric emptying and visceral hypersensitivity characterized by nausea, vomiting, early satiety, and bloating. Gastric emptying scintigraphy (GES), in combination with typical symptoms and normal esophagogastroduodenoscopy findings, is used to diagnose the disease. Gastric per-oral endoscopic pyloromyotomy (G-POEM) has emerged as a novel technique for treating gastroparesis, with up to an 80% success rate. This procedure involves myotomy of the distal stomach. We hypothesize that responders to this therapy are characterized by more distal dysmotility than nonresponders, as defined by GES retention patterns. Methods: We used regional gastric emptying measurements from diagnostic GES to determine the proximal or distal predominance of disease for each patient. We then compared treatment response and symptoms in each patient to total gastric half-emptying time (T((1/2))), proximal gastric T((1/2)), and a ratio comparing the 2 values. Results: In total, 47 patients underwent G-POEM during the study period. A significant difference (P < 0.01) was found in proximal-to-total T((1/2)) ratio between responders and nonresponders. A significant difference between pre- and postprocedural proximal-to-total T((1/2)) ratios was identified for each patient. No correlations were identified between motility patterns and symptoms or in motility patterns among the different etiologies of the disease. Conclusion: Proximal-to-total T((1/2)) ratio may represent an important patient selection factor for G-POEM versus other treatment modalities going forward. Local retention patterns in GES may not inform the symptom profile in gastroparesis. | Gastroparesis |
Standardized management of oncology patients necessarily includes screening for nutritional risk. Weight loss of > 5 kg within 3 months and diminished food intake are warning signals even in overweight patients. In case oral nutrition is neither adequate nor feasible even by fortification or oral nutritional supplements, the implantation of a percutaneous endoscopic gastrostomy (PEG) or fine needle catheter jejunostomy (FNCJ) offers enteral access for long-term nutritional support. Although the indications derive from fulfilling caloric needs, endoscopic or operative measures are not considered to be an urgent or even emergency measure. The endoscopist or surgeon should be fully aware and informed of the indications and make a personal assessment of the situation. The implantation of a feeding tube requires informed consent of the patient or legal surrogates. The review summarizes recent indications, technical problems and complications. | Jejunostomy |
Marine organisms are the excellent sources for biologically active compounds. Cnidarian venoms are potentially valuable materials used for biomedical research and drug development. The present work was carried out to analyse haemolytic, analgesic and CNS depressant activity of sea anemone Heteractis aurora. In haemolytic assay, among the five different RBC blood cells, the chicken blood exhibited maximum hemolytic activity of 64 Hemolytic Unit (HU). The maximum Analgesic Ratio (AR) of 5 recorded at 15 and 30 min interval and minimum was recorded after 45, 60 and 120 min time intervals. In jumping response activity, the maximum of 5 AR recorded at 15, 30 & 45 min and minimum was recorded at 90 & 120 min time intervals. The maximum decrease of depressant activity of 45.07% was determined in CNS depressant activity. Anti-inflammatory activity showed significant inhibition by crude extract of Heteractis aurora. | Nematocyst |
Mangroves are salt-tolerant forest ecosystem that extends between tropical and subtropical intertidal regions of the world. Mangroves are biochemically unique vegetation that produce wide array of natural products with immense medicinal potential. These plants are the most valuable resources and provide economic and ecological benefits to the coastal people. Natural products from these plants are of great interest as they provide innumerable direct and indirect benefits to human beings for the discovery of novel antimicrobial and other bioactive compounds. They possess active metabolites with some novel chemical structures that belong to diverse chemical classes such as alkaloids, phenol, steroids, terpenoids and tannins. Several mangrove species have been used in traditional medicine or have few applications as insecticide and pesticide. To date, several mangroves, and their associated species and solvent extracts are screened for antimicrobial activity along with the presence of potent bioactive compounds. The present article emphasizes and creates awareness about the potential mangrove plants and their associates as a source of biologically active compounds with potent antimicrobial properties. This paper also elaborates the mechanisms of action and various methods for screening of antimicrobial compounds. | Avicennia |
The psbA2 gene exhibits light-dependent and rhythmic expression in a unicellular cyanobacterium, Microcystis aeruginosa (Synechocystis) K-81. To further understand the psbA2 expression, biological analyses were performed in homologous and heterologous cyanobacterial cells. The results of the experiments using the K-81 cells revealed that (i) the light-dependent expression appeared on transcriptional and/or post-transcriptional level(s) under light/dark cycles, (ii) circadian-rhythmic transcripts were also observed under the control of an endogenous clock. To assess whether light-dependent and rhythmic psbA2 expression occurs in heterologous cyanobacterium, Synechococcus sp. strain PCC 7942, the K-81 psbA2 5'-upstream region of which the promoter and its around sequences share with those of PCC 7942 psbAII, was fused to the bacterial lacZ reporter gene, introduced into the genome of PCC 7942 and the psbA2 transcripts were directly investigated by primer extension. The K-81 psbA2 specific transcripts were also light-dependent and rhythmic in PCC 7942, strongly demonstrating that a common regulatory mechanism exists per se for the psbA2 expression in both strains. Furthermore, psbA2 expression in the recombinant PCC 7942 strain, AG400 in which the region from -404 to +111 of psbA2 is fused to lacZ, exhibited clear rhythmicity, while very little or no rhythmicity was observed in AG429 (-38 to +14, the only promoter region), suggesting that the region(s) around the promoter was essentially required for clear rhythmic expression." | Photosynthetic Reaction Center Complex Proteins |
BACKGROUND: Levamisole is used as a steroid-sparing drug for the treatment of frequently relapsing or steroid-dependent idiopathic nephrotic syndrome in children. As part of a large multicentre randomized controlled trial with levamisole, pharmacokinetic and pharmacodynamic parameters of levamisole in children with idiopathic nephrotic syndrome were investigated, as well as the feasibility of using saliva as an alternative and patient-friendly matrix for determining levamisole concentrations. In this study, the authors presented the development and validation of a highly sensitive method for determining levamisole in plasma and saliva using liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: In 100 muL samples, proteins were precipitated with 750 muL acetonitrile/methanol 420:80 (v/v) with levamisole-D5 as an internal standard. Calibration standards were prepared over a range of 0.1 ng/mL-50 ng/mL. To determine ultrafiltration efficiency, the ultrafiltrate was obtained by centrifuging blank plasma samples over the filter. Both filtered and nonfiltered samples were analyzed. RESULTS: For plasma, accuracy and within-run and between-run imprecision were between 95.0% and 100% and <14.5%, respectively, and for saliva, between 100.9% and 107.5%, and <13.3%. No significant matrix effects were observed. Samples were stable at benchtop for 24 hours and -80 degrees C, for at least 14 months (stability experiments ongoing). The ultrafiltration efficiency of unbound concentrations in plasma was lower than 85% (58.9%) but stable, and, therefore, the observed concentration should be corrected. CONCLUSIONS: Based on observations, the developed measure can determine levamisole concentrations in participant saliva samples. | Levamisole |
OBJECTIVE: Endovascular popliteal artery aneurysm (PAA) repair has acceptable outcomes compared with open repair for elective therapy. Endovascular repair for urgent PAA causing acute limb ischemia (ALI) has not been well-studied. This project compares outcomes of urgent endovascular and open repair of PAA with ALI. METHODS: The Vascular Quality Initiative database for peripheral vascular interventions (PVIs) and infrainguinal bypass were reviewed for PAAs with ALI from 2010 to 2021. Only patients entered as having symptoms of ALI in the PVI module and ALI as indication in the infrainguinal bypass module were included. In addition, patients undergoing elective treatment were excluded and the sample analyzed was restricted to patients undergoing urgent and emergent open and endovascular repair. Patient demographics and comorbidities as well as procedural details were compared between the two groups. Perioperative complications up to 30 days were compared as well as long-term outcomes including major amputation and mortality at 1 year. RESULTS: Urgent PAA repair for ALI constituted 10.5% (n = 571) of all PAAs. Most urgent repairs were open (80.6%; n = 460) with 19.4% (n = 111) endovascular. The proportion of endovascular repair significantly increased from 16.7% in 2010 to 85.7% in 2021. Patients undergoing endovascular repair were older (71.2 +/- 12.5 vs 68.0 +/- 11.8; P = .011) than patients undergoing open repair. They were also more likely to have coronary artery disease (32.4% vs 21.7%; P = .006). Open PAA repair was associated with more bleeding complications (20.8% vs 2.7%; P < .001), longer postoperative length of stay (8.1 +/- 9.3 days vs 4.9 +/- 5.6 days; P < .001), and less likelihood of discharge to home (64.9% vs 70.3%; P = .051). Perioperative major amputation rate was 7.5% with no difference between the two treatment strategies up to 1 year. However, patients receiving endovascular repair had higher inpatient (1.1% vs 0%; P < .001), 30-day (6.3% vs 0.4%; P < .001), and 1-year (16.5% vs 8.4%; P = .02) mortality. Multivariable regression analysis suggested that endovascular repair was possibly associated with increased 30-day mortality, but not 1-year mortality. CONCLUSIONS: Endovascular PAA has exponentially increased from 2010 to 2021. Endovascular repair is associated with decreased complications and hospital length of stay. The increased perioperative mortality seen in this group is likely due to selection bias. | Popliteal Artery Aneurysm |
OBJECTS: A lot has been published about neuroendoscopic procedures over the last decade. Most of these publications are about the effectiveness of endoscopic third ventriculostomy, the most frequently performed neuroendoscopic procedure. Little is published about the effectiveness of other, less frequently performed neuroendoscopic procedures. Over the years more reports about the complications of endoscopic procedures are published, but again most of these publications are about endoscopic third ventriculostomy and only a little is presented about the complications of all other neuroendoscopic procedures. Furthermore, most reports are about intraoperative and immediate postoperative complications; only a few reports evaluated the long-term complications of neuroendoscopic procedures. There are also a few publications that analyse the failures of neuroendoscopic procedures but a good definition of failure is not given. The reports mention, again, mainly endoscopic third ventriculostomy procedures, and are mostly directed at the short-term failure rates, defined as the need for a shunt to be placed. Less attention is paid to the effects of the endoscopic procedures in the longer term. Looking at longer terms emphasises the need for a better definition of failure. METHODS: To get more insight into the long-term complications and failures of neuroendoscopic procedures, we reviewed the literature and evaluated our own series of 485 different cranial endoscopic procedures. With the information gathered we tried to answer the questions mentioned above. CONCLUSIONS: Most of the complications of neuroendoscopic procedures are transient, either spontaneously or by medical intervention. Only a few permanent complications are known, in our series 1.6%, and most of them are not typically related to the endoscopic procedure itself but are due to the ventricular approach necessary for and the management of the endoscopy. Mortality rates are less than 1%. A uniform definition of failure cannot be given for all neuroendoscopic procedures, because the procedures are too heterogeneous and the indications are widespread. Failures are mainly diagnosed within a few months of the procedure but neurosurgeons must be aware of failure in the longer term, because if not diagnosed they can give rise to increased morbidity and probably mortality. | Ventriculostomy |
The sensitizing potential of three periodontal dressing materials was evaluated by the guinea pig maximization test. The results indicated a difference in the sensitization rate of the three materials. | Balsams |
A 52-year-old woman was found to have abnormal shadows in her chest radiograph in a health examination. At the age of 47 middle lobe syndrome had been pointed out and Mycobacterium intracellulare had been cultured from her sputum. Chest computed tomography scans showed a coin lesion and bronchiectasis in the middle lobe. On the other hand she suffered xerostomia and had a high level of serum anti-SS-A antibody. Further examination of her eyes and mouth gave her a diagnosis of primary Sjogren's syndrome (pSS). By video-assisted thoracoscopic surgery we resected the coin lesion which contained an abscess with acid-fast bacilli, identical to Mycobacterium intracellulare. The histopathology showed lymphocytic infiltration, caseous necrosis with Langhans' giant cells, and epithelioid granulomas. We finally made a diagnosis of pSS presenting with middle lobe syndrome (MLS) complicated by nontuberculous mycobacterial disease (NTM). We discuss the mechanism by which pSS could be complicated by NTM and MLS. Clinicians should pay attention to this possible relationship, especially among middle-aged and elderly women. | Middle Lobe Syndrome |
OBJECTIVE: To provide national estimates of the effect of out-of-pocket premiums and benefits on Medicare beneficiaries' choice among managed care health plans. DATA SOURCES/STUDY SETTING: The data represent the population of all Medicare+ Choice (M+C) plans offered to Medicare beneficiaries in the United States in 1999. STUDY DESIGN: The dependent variable is the log of the ratio of the market share of the jth health plan to the lowest cost plan in the beneficiary's county of residence. The explanatory variables are measures of premiums and benefits in the jth health plan relative to the premiums and benefits in the lowest cost plan. DATA COLLECTION METHODS: The data are from the 1999 Medicare Compare database, and M+C enrollment data from the Centers for Medicare and Medicaid Services (CMS). PRINCIPAL FINDINGS: A $10 increase in an M+C plan's out-of-pocket premium, relative to its competitors, is associated with a decrease of four percentage points in the jth plan's market share (i.e., from 25 to 21 percent), holding the premiums of competing plans constant. CONCLUSIONS: Although our price elasticity estimates are low, the market share losses associated with small changes in a health plan's premium, relative to its competitors, may be sufficient to discipline premiums in a competitive market. Bidding behavior by plans in the Medicare Competitive Pricing Demonstration supports this conclusion. | Medicare Part C |
BACKGROUND: In this paper we describe a novel method to achieve high yield bacterial expression of a small protein domain with considerable therapeutic potential; Domain I of Beta-2-glycoprotein I (beta2GPI). beta2GPI is intrinsic to the pathological progression of the Antiphospholipid Syndrome (APS). Patients develop autoantibodies targeting an epitope located on the N-terminal Domain I of beta2GPI rendering this domain of interest as a possible therapeutic. RESULTS: This new method of production of Domain I of beta2GPI has increased the production yield by ~20 fold compared to previous methods in E.coli. This largely scalable, partially automated method produces 50-75 mg of pure, folded, active Domain I of beta2GPI per litre of expression media. CONCLUSION: The application of this method may enable production of Domain I on sufficient scale to allow its use as a therapeutic. | beta 2-Glycoprotein I |
We examined previous reports of Lema praeusta (Fab.) (Coleoptera: Chrysomelidae) as a minor pest of turmeric, eggplant, bottle gourd and pumpkin leaves, but no feeding damage by larvae and adults of L. praeusta were recorded by us on these leaves. We observed feeding by the larvae and adults of L. praeusta on ten species of Commelinaceae plants in no-choice tests. The biology, fecundity and life table parameters of L. praeusta on two Commelinaceae weeds, Commelina benghalensis L. and Murdannia nudiflora (L.) Brenan were determined under laboratory conditions (27 +/- 1 degrees C, 65 +/- 5% RH and 12L:12D). Total larval development times of L. praeusta were 6.36 +/- 0.07 and 7.28 +/- 0.11 days (mean +/- SE) on C. benghalensis and M. nudiflora, respectively. Adult females lived 106.25 +/- 1.17 and 77.65 +/- 0.91 days (mean +/- SE) on C. benghalensis and M. nudiflora, respectively. Each female laid 272.95 +/- 2.39 and 224 +/- 1.74 eggs (mean +/- SE) during a lifetime on C. benghalensis and M. nudiflora, respectively. The net reproductive rate (Ro), intrinsic rate of increase (rm), generation time (Tc), doubling time (DT) and finite rate of increase (lambda) were 136.48, 0.14, 36.17, 5.10 and 1.41 on C. benghalensis, respectively, whereas Ro, rm, Tc, DT and lambda were 112, 0.20, 23.64, 3.47 and 1.51 on M. nudiflora, respectively, suggesting that L. praeusta could be a potential biocontrol agent against C. benghalensis and M. nudiflora in the fields of rice, maize, sorghum, soybean, mung bean, peanut and cotton. | Commelinaceae |
GSK2330672 is an inhibitor of the ileal bile acid transporter, designed to have minimal systemic exposure, and is under development as a potential therapeutic for pruritus associated with primary biliary cholangitis and other cholestatic liver diseases. A phase 1, double-blind, placebo-controlled, 4-period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic characteristics of GSK2330672 in healthy Japanese participants. Sixteen healthy male participants received single oral doses of GSK2330672 (10-180 mg) or placebo in each period. No serious adverse events and no adverse events leading to study discontinuation or withdrawal were reported. Drug-related adverse events reported included gastrointestinal symptoms (mostly diarrhea) and positive fecal occult blood tests, and were all mild and resolved without any interventions. GSK2330672 was undetectable in the majority of participants' plasma. Pharmacodynamic observations included a tendency for total serum bile acids to reduce and for serum 7alpha-hydroxy-4-cholesten-3-one, a key intermediate of bile acid synthesis, to increase with increasing doses of GSK2330672. In the context of recently published indications of potential efficacy for cholestatic pruritus in non-Japanese populations, these data support further evaluations of GSK2330672 in Japanese patients. | Methylamines |
A review is given of what is known about the functional significance of variation of the morphology of the human mandible and jaw muscles. First, the mandible is a lever transferring muscular forces to the teeth. The angle between corpus and ramus and the width of the ramus are particularly relevant in this respect as they determine the mechanical advantage of the lever system and the capacity for sagittal (open-close) movement. The stability of the mandible in asymmetric bites is especially affected by the ratio between the intermolar and intercondylar distances. The repertoire of bite forces that can be generated at any tooth and the loading pattern of the temporomandibular joint are strongly dependent on the relative size of the masseter, temporalis and medial pterygoid muscles. Second, executing its function as a lever, the mandible is subjected to shearing, bending and torsional forces. The bony parts harbouring the teeth, joints and muscle attachments serve to counter these forces; additional strength is needed in three areas i.e. in the symphysis, the condylar neck and in the transition area between corpus and ramus. In human populations there are clear-cut patterns of correlation between some facial skeletal traits, jaw joint morphology and strength and line of action of the jaw muscles. As a result, facial morphologies can be distinguished with marked differences in mechanical performance of their masticatory apparatus. It is suggested that they emerge as a result of diverging environmental influences during postnatal growth. | Mandible |
Investigations on how the central nervous system (CNS) effortlessly conducts complex hand movements have led to an extensive study of synergies or movement primitives. Of the different types of hand synergies, kinematic and muscle synergies have been widely studied in literature, but only a few studies have fused both. In this paper kinematic and muscle activities recorded from the activities of daily living were first fused and then dimensionally reduced through principal component analysis (PCA). By using these principal components or musculoskeletal synergies in a weighted linear combination, the recorded kinematics and muscle activities were reconstructed. The performance of these musculoskeletal synergies in reconstructing the movements was compared to the kinematic and muscle synergies reported previously in the literature by us and others. The results from these findings indicate that musculoskeletal synergies perform better than the synergies extracted without fusion. These newly demonstrated musculoskeletal synergies might improve neural control of robotics, prosthetics and exoskeletons. Clinical Relevance- In this paper, musculoskeletal synergies were extracted from the fusion of kinematic and muscle activities recorded from the activities of daily living. These newly demonstrated musculoskeletal synergies might enhance our understanding of neural control of robotics, prosthetics and exoskeletons. | Hand Strength |
A rapid and sensitive high-performance liquid chromatographic quantitation of meclocycline (I) in a cream formulation is described. The acidified methanolic extract of the sample was diluted with mobile phase and analyzed on a reverse-phase column by using a mobile phase consisting of EDTA buffer (pH 6.6)-tetrahydrofuran (85:15 v/v). The method gave linear, quantitative, and reproducible results with a detection limit of 0.4 ppm for meclocycline. | Oxytetracycline |
The conformational flexibility of linkage-specific polyubiquitin chains enables ubiquitylated proteins and their receptors to be involved in a variety of cellular processes. Linear or Met1-linked polyubiquitin chains, associated with nondegradational cellular signalling pathways, have been known to adopt multiple conformations from compact to extended conformations. However, the extent of such conformational flexibility remains open. Here, the crystal structure of linear Ub2 was determined in a more compact conformation than that of the previously known structure (PDB entry 3axc). The two structures differ significantly from each other, as shown by an r.m.s.d. between C(alpha) atoms of 3.1 A. The compactness of the linear Ub2 structure in comparison with PDB entry 3axc is supported by smaller values of the radius of gyration (Rg; 18 versus 18.9 A) and the maximum interatomic distance (Dmax; 55.5 versus 57.8 A). Extra intramolecular hydrogen bonds formed among polar residues between the distal and proximal ubiquitin moieties seem to contribute to stabilization of the compact conformation of linear Ub2. An ensemble of three semi-extended and extended conformations of linear Ub2 was also observed by small-angle X-ray scattering (SAXS) analysis in solution. In addition, the conformational heterogeneity in linear polyubiquitin chains is clearly manifested by SAXS analyses of linear Ub3 and Ub4: at least three distinct solution conformations are observed in each chain, with the linear Ub3 conformations being compact. The results expand the extent of conformational space of linear polyubiquitin chains and suggest that changes in the conformational ensemble may be pivotal in mediating multiple signalling pathways. | Polyubiquitin |
The prevalence and dissemination of antibiotic resistance genes (ARGs) have been globally gained increasing concerns. However, the fate and spread of ARGs in food waste (FW) and its large-scale biotreatment systems are seldomly understood. Here, we investigated the initial and biologically treated FW in two major FW treatment systems of aerobic fermentation (AF) and anaerobic co-digestion (AcoD) processes. The total relative abundances of integrons and ARGs significantly increased from initial FW to treated FW. Among targeted ARGs, ermB and strB were predominant ARGs, which accounted for 52.58-95.28% of total abundance across all samples. Mantel test indicated that integrons (intl1 and intl2) were positively and significantly correlated with detected ARGs (Mantel test, r = 0.24, p < 0.05), suggesting integrons display significant contributions on driving ARG alteration during FW treatment processes. RDA results indicated that bla(OXA), strB and bla(TEM) were more likely to be proliferated by potential host of Firmicutes (96.55-99.77%) in initial FW, while bla(CTX-M) and mefA were potentially enriched by Proteobacteria (17.12-49.82%) in AF system and ermB, sul1, aadA and tetQ were possibly enhanced by Bacteroidetes (27.43-43.71%) in AcoD system. Consideration of the higher enriched abundance of total ARGs (66.88 +/- 87.34 times) and the used inoculum sludge in AcoD-treated system, the resource utilization of anaerobically digested products should draw our more attentions. These findings would deepen our understanding of prevalence and proliferation of ARGs in FW treatment systems and serve as a foundation for guiding the application of biologically treated FW. | Integrons |
PURPOSE: To determine whether phosphodiesterase-5 inhibitor documentation is associated with biochemical relapse-free and overall survival of patients with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We undertook a retrospective cohort analysis of 3,100 patients with prostate cancer treated with radical prostatectomy between 2003 and 2015. The patients were categorized as a phosphodiesterase- 5- inhibitor user or non-user. The biochemical relapse-free and overall survival at 5-years and 10-years were determined. RESULTS: Of the patients, 1,372 reported phosphodiesterase-5 inhibitor documentation, and 1,728 did not. The biochemical recurrence-free survival for non-users at 5- and 10-years follow-up was 87.6% and 85.3%, respectively, and the overall survival at these time intervals was 97.9% and 94.5%. The biochemical recurrence-free survival for phosphodiesterase-5 inhibitor users was 94.3% and 93.2% at 5- and 10-years follow-up, respectively, and overall survival was 99.2% and 95.8% at these intervals. The hazard ratio for biochemical recurrence-free survival was 0.44 (CI 0.34-0.56) and for overall survival was 0.65 (CI 0.45-0.94). On the multivariate analysis, phosphodiesterase-5 inhibitor documentation was associated with a lower risk of biochemical recurrence and death when corrected for the other variables. Age at surgery and Gleason scores >8 was associated with a higher risk of death. Higher pathological stage, higher Gleason score, presence of lymph node metastases, and nonwhite race were associated with a higher risk of recurrence. CONCLUSION: This retrospective analysis revealed a significant association of postoperative phosphodiesterase-5 inhibitor documentation with biochemical recurrence-free- and overall survival in patients with localized prostate cancer treated with radical prostatectomy. Larger scale studies are warranted to investigate the clinical significance of this association." | Phosphodiesterase 5 Inhibitors |
Despite increasing interest in the claustrum (Cl) over the last decades, its function is still a puzzling problem. Among the experimental species of potential use in Cl research, the pig is considered an interesting model, because of the similarities of its brain with the corresponding cortical and subcortical human structures. The swine Cl presents a peculiar morphology, characterized by a wide posterior enlargement, ideal for physiological investigations. There is a wealth of data on general anatomy, cytoarchitecture, and chemo architecture of the Cl, but much less is known about the dendritic morphometry of its neurons. Dendritic length and branching pattern are key features to understand the organization of the microcircuitry, and thus the delineation of the structure-function relationships of the Cl. To this effect, we undertook (a) a quantitative study of the dendrites of the spiny neurons of the swine Cl, employing the Golgi staining; and (b) an immunohistochemical analysis to describe the distribution of the parvalbumin (PV)-immunoreactive interneurons throughout the same nucleus. Taken together, the results that we report here show that the dendritic architecture and the distribution of the PV expressing interneurons change when the Cl of this species changes its shape along the rostro-caudal axis, thus suggesting a potentially specific function for the large posterior puddle. Anat Rec, 302:1638-1646, 2019. (c) 2019 American Association for Anatomy. | Claustrum |
Currently, a small number of studies discuss augmentative and alternative (AAC) interventions in low- and middle-income countries (LMICs). The primary purpose of this scoping review was to summarize the current evidence base on communication-based interventions and partner training in LMICs, to explore and identify gaps in the AAC evidence base and guide future research. A total of 18 studies were identified. The results revealed many positive outcomes arising from AAC interventions, including increased communication, improved participation, increased knowledge about communication, and increased use of partner communication strategies, thus adding to the evidence base that AAC can be successfully implemented in LMICs. However, these studies did not broadly represent most LMICs and there were only a handful of indirect intervention studies training communication partners. To this end, there is an urgent need to expand the level of AAC intervention research conducted in LMICs in order to better serve individuals with complex communication needs living in these countries." | Communication Aids for Disabled |
Since the publication of a special issue on bruxism of the NTvT in July 2000, consensus has been reached on bruxism's definition as a repetitive masticatory muscle activity that is characterised by clenching and/or grinding while awake (awake bruxism) or during sleep (sleep bruxism). As yet, however, no consensus exists about the diagnosis of bruxism: sufficient evidence to establish the reliability and validity of the commonly used techniques (self-report, clinical examination, imaging, electromyography, polysomnography) has not yet been produced. Morphological factors are no longer considered important aetiological factors, while increasing evidence suggests aetiological roles for psychosocial, physiological, biological, and exogenous factors. This review paper is the first part of a diptych and is concerned with the definition, diagnostics, epidemiology and possible causes of this disorder. In the second part, that will be published in the next issue, associations of bruxism with other conditions will be discussed, along with its (purported) consequences and its management. | Habits |
A series of potential topoisomerase II-mediated anticancer 9-anilinoacridine derivatives, which are designed to avoid bio-oxidation and possessed long duration of drug action, is reviewed. Among these agents, 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) derivatives and their alkylcarbamates have been investigated and developed for potential clinical application. | Acridines |
The balance between MR- and GR-mediated effects is of paramount importance for the homeostatic control of stress responsiveness, adaptation and cognition in animals. If the MR/GR activation ratio is shifted, the control of glucocorticoids on neuronal excitability (Joels & de Kloet, 1994), neuroendocrine reactivity and behavior will change (de Kloet, 1991). In order to elucidate the underlying neural substrate of behavior, the different levels of biological organization must be brought into relation with each other. For instance, we have suggested that GRs are involved in the storage of information and MRs in the execution of behavior preceding information processing. It is nevertheless important to reemphasize that the biological significance of behavioral responses is due to the concerted action of various receptor systems. In addition, the results on the function of MRs and GRs show clearly that the coupling of one receptor with one function is too reductionistic to fully explain the biological relevance of such receptors. | Receptors, Mineralocorticoid |
Acyltransferases (ATs) are key determinants of building block specificity in polyketide biosynthesis. Despite the importance of protein-protein interactions between AT and acyl carrier protein (ACP) during the acyltransfer reaction, the mechanism of ACP recognition by AT is not understood in detail. Herein, we report the crystal structure of AT VinK, which transfers a dipeptide group between two ACPs, VinL and VinP1LdACP, in vicenistatin biosynthesis. The isolated VinK structure showed a unique substrate-binding pocket for the dipeptide group linked to ACP. To gain greater insight into the mechanism of ACP recognition, we attempted to crystallize the VinK-ACP complexes. Because transient enzyme-ACP complexes are difficult to crystallize, we developed a covalent cross-linking strategy using a bifunctional maleimide reagent to trap the VinK-ACP complexes, allowing the determination of the crystal structure of the VinK-VinL complex. In the complex structure, Arg-153, Met-206, and Arg-299 of VinK interact with the negatively charged helix II region of VinL. The VinK-VinL complex structure allows, to our knowledge, the first visualization of the interaction between AT and ACP and provides detailed mechanistic insights into ACP recognition by AT. | Acyl Carrier Protein |
Tenosynovitis with psammomatous calcification, described in 1983 by Gravanis and Gaffney, is a distinctive clinicopathologic variant of idiopathic calcifying tenosynovitis" or "calcific tendonitis." However, tenosynovitis with psammomatous calcification is poorly recognized by pathologists and for this reason has not been adopted widely as a distinct entity. We present the clinicopathologic features of 6 cases of tenosynovitis with psammomatous calcification. Cases involved the tendons, peritendinous soft tissues, and adjacent synovium of the distal extremities (3 fingers, 2 feet, and 1 carpal tendon) of women who ranged in age from 16 to 83 years (mean 48 y). The lesions presented a painful mass. A history of occupational or sports-related repetitive motion and/or persistent mild trauma was noted in all patients. No patient had a history of hyperphosphatemia. All lesions were treated by surgical excision and described clinically as variably cystic nodules composed of amorphous "cheese-like" debris. Histologically, the lesions were centered in the tendon or peritendinous soft tissue and composed of a mixed (myo) fibroblastic and histiocytic proliferation in association with a degenerating tendinous tissue, which was undergoing dystrophic calcification, with the formation of distinctive psammoma body-like spheroidal bodies. The clinical and morphologic characteristics of tenosynovitis with psammomatous calcification (distal location, absent hyperphosphatemia, and psammomatous calcifications) differ from those of typical idiopathic calcifying tenosynovitis/calcific tendinitis (proximal location and dystrophic tendinous calcification) and tumoral calcinosis (hyperphosphatemia and amorphous soft tissue calcification), and it should be recognized as a distinct clinicopathologic entity. Improved recognition of these unique features by pathologists should allow ready diagnosis of this unusual pseudotumor in most instances." | Tenosynovitis |
Ethanamizuril(N-4-[4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-phenoxy]-phenyl-acetamide, EZL) is a new anticoccidiosis compound and belongs to the class of triazines. In this study, the metabolism, distribution, and excretion of EZL were evaluated in chickens after administration of EZL at a single dosage. According to the relevant drug biotransformation rules, the exact molecular mass detection, the fragmentation characteristics, and the retention times, a total of five metabolites were identified in vivo in chickens, including two phase I metabolites and three phase II conjugated metabolites. The major metabolic pathways of EZL in chickens were deacetylation, hydroxylation, and glucuronidation. Regarding (14)C-tissue residues after administration, kidney was considered to be the target tissue, as (14)C-tissue residues could be detected at 240 h postdose. DeacetylEZL (M3) was the main metabolite, accounting for 68.65% and 25.62% of (14)C in kidney at 6 and 24 h, respectively. In heart, muscle, skin+fat, and lung tissues, EZL was the main radioactive substance accounting for 94.88%, 97.32%, 96.23%, and 91.3% of (14)C, respectively. In the liver, EZL and M3 were 20.76% and 54.65% of (14)C, respectively. In chicken tissues the ratio of M5 was too low to be quantitated and it was mainly detected in chicken fecal and bile samples. In chicken excreta, EZL, M3, and glucuronidation of EZL (M5) accounted for 7.02%, 12.33%, and 10.32% of the dose, respectively and were eliminated primarily. This study presents the first detection of EZL metabolites, which is helpful for further understanding of the metabolic mechanism and in vivo intermediate processes of EZL. The results of this study will be good bases for better understanding EZL's anticoccidiosis mechanism and will serve as a helpful reference for assessing the risks to animals and humans. | Coccidiostats |
Acoustic-resolution photoacoustic microscopy (AR-PAM) enables visualization of biological tissues at depths of several millimeters with superior optical absorption contrast. However, the lateral resolution and sensitivity of AR-PAM are generally lower than those of optical-resolution PAM (OR-PAM) owing to the intrinsic physical acoustic focusing mechanism. Here, we demonstrate a computational strategy with two generative adversarial networks (GANs) to perform semi/unsupervised reconstruction with high resolution and sensitivity in AR-PAM by maintaining its imaging capability at enhanced depths. The b-scan PAM images were prepared as paired (for semi-supervised conditional GAN) and unpaired (for unsupervised CycleGAN) groups for label-free reconstructed AR-PAM b-scan image generation and training. The semi/unsupervised GANs successfully improved resolution and sensitivity in a phantom and in vivo mouse ear test with ground truth. We also confirmed that GANs could enhance resolution and sensitivity of deep tissues without the ground truth. | Microscopy, Acoustic |
Abnormal respiration with episodic tachypnea-apnea can occur in several syndromes (particularly, the Rett, Joubert, Mohr and Dandy-Walker syndromes). These syndromes are briefly reviewed. In the Rett syndrome, in contrast to in most other genetically determined syndromes, the onset of breathing abnormalities does not occur in the neonatal period. | Orofaciodigital Syndromes |
Thirty years ago, Waclaw and myself were working on the same organism and had the same type of interest. Since that happy time, our trajectories have diverged so much that I am afraid any paper I might offer for his jubilee would seem completely strange and irrelevant to him and as well to his colleagues. For this reason, I decided rather to offer Waclaw, as a modest present, a product of my recent work which I consider, perhaps presumptuously, as an 'oeuvre d'art' (of course, this qualification is not supposed to apply to this paper as a whole, just to the figure). Please note above the expressions 'divergent trajectories' and 'strange'; we will meet them again below in a different context. | Bacteriophage lambda |
OBJECTIVES: Psoriasis and psoriatic arthritis (PsA) are associated with nail changes. Recent reports suggest that nail changes may be a part of the enthesitis of PsA and that they predict the onset of arthritis among patients with psoriasis, but they have not reported on subclasses of nail changes. However, earlier reports suggested that onycholysis is the nail change most strongly associated with PsA. If nail changes in PsA are a sign of enthesitis, they might be associated with small joint disease in general and the objective of this study was to test this hypothesis. METHODS: A total of 154 patients recruited through the Reykjavik Psoriatic Arthritis Study had a joint, skin, and nail evaluation. Associations with small joint disease were tested using univariate analysis, and confirmed in a multivariate model. RESULTS: Onycholysis had a strong association with small joint involvement [odds ratio (OR) 3.42, 95% confidence interval (CI) 1.41-8.92], while other types of nail changes did not. The number of swollen joints and shorter disease duration were also associated with small joint disease. CONCLUSIONS: Onycholysis is associated with small joint disease in PsA. Future studies of PsA should report the subtypes of nail changes. Longitudinal studies are needed to determine whether onycholysis predicts PsA. | Onycholysis |
Neutral ceramidase (NCDase) is considered to be a critical enzyme for controlling the turnover of ceramide, an important bioactive lipid, which determines cell's fate. All-trans retinoic acid (ATRA) has been reported to induce neuronal differentiation and cell-cycle arrest [Lopez-Carballo, Moreno, Masia, Perez, and Barettino (Activation of the phosphatidylinositol 3-kinase/Akt signalling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human neuroblastoma cells. J Biol Chem 2002:277:25297-304.)]. In this study, we observed that ATRA-induced cellular ceramide accumulation, cell-growth arrest and differentiation accompanied with down-regulation of NCDase in SH-SY5Y cells, without a decrease in sphingosine or sphingosine 1-phosphate. We examined whether the down-regulation of NCDase was involved in the increase in ceramide and cell differentiation. ATRA was found to down-regulate mRNA, protein and the enzyme activity of NCDase. Interestingly, GATA-2 was also decreased with ATRA treatment, and experiments using its expression vector and siRNA and chromatin immunoprecipitation assay demonstrated GATA-2 acted as transcription-factor of NCDase gene expression. By establishing stable transfectants with decreased NCDase expression and activity, we clarified the significance of NCDase down-regulation for ATRA-induced neuronal differentiation. Those sub-clones showed both increased cellular ceramide and reduced cell growth as well as neuronal differentiation phenotypes. These results demonstrate that down-regulation of NCDase through ATRA-induced GATA-2 decrease plays an important role in induction of ceramide accumulation and neuronal differentiation in SH-SY5Y cells. | Neutral Ceramidase |
BACKGROUND: Comprehensive data concerning the sexual behaviour of Italian adolescents are lacking; the planning of prevention programmes is therefore difficult. METHODS: The current study evaluates the knowledge of Italian adolescents about sexuality and their use of methods to prevent pregnancy and sexually transmitted infections. The age at first intercourse in the current sample was compared to that found in past samples to ascertain whether sex education was needed at an earlier age. The efficacy of one school-based sex education programme was analysed. RESULTS: Overall 630 students in three Italian cities were surveyed. Just over half the students were sexually active. Among these, the mean age at first intercourse was 15.6 years (SD +/- 1.3). The contraception most widely used was the condom although 'coitus interruptus', 'natural family planning' and 'no method' were also mentioned. The knowledge among students from Latina, after they had received sex education, was significantly better. CONCLUSION: Our data show a lower mean age at first intercourse than has been reported for earlier periods by other authors. School-based sexual education is effective in improving knowledge. Sexual health services for young people must be available and counselling services improved. | Contraception Behavior |
Pyroptosis is a regulated form of cell death that leads to inflammation and plays a role in many different diseases. Pyroptosis was initially defined by the dependence on caspase-1, a protease which is activated by innate immune signaling complexes called inflammasomes. Caspase-1 cleaves the protein gasdermin D, releasing the N-terminal pore-forming domain, which inserts into the plasma membrane. Recent studies have revealed that other gasdermin family members form plasma membrane pores, leading to lytic cell death, and the definition of pyroptosis was revised to gasdermin-dependent cell death. In this review, we discuss how the use of the term pyroptosis has changed over time, as well as currently understood molecular mechanisms leading to pyroptosis and functional consequences of this form of regulated cell death. | Gasdermins |
A great proportion of essential tremor (ET) patients have not so far been able to receive functional benefits from traditional therapies. In this regard, the use of functional electrical stimulation (FES) has been proposed for reducing tremor amplitude by stimulating muscles in antiphase with respect to the trembling motion. Although some studies have reported success in terms of tremor attenuation, drawbacks still exist that prevent the method from being used in real-life applications. In this article, we explore an alternative approach: a strategy based on the hypothesis that FES-induced constant muscle contraction may provide functional benefit for tremor patients. To evaluate the proposed strategy, experiments were conducted in which stimulation was intermittently turned on and off while the subjects performed a static motor task. The results of the proposed experimental protocol indicate that tremor attenuation using this strategy is feasible, as consistent tremor attenuation levels were obtained in eight out of 10 ET patients. Nonetheless, tremor reduction was not instantaneous for all successful trials, indicating that prior training with FES may improve the overall response. Furthermore, although simpler assistive devices may potentially be designed based on this technique, some experimental difficulties still exist, which suggests that further studies are necessary. | Essential Tremor |
Oxidant stress has been implicated as playing a role in the pathogenesis of cholestatic liver injury. The objective of this study was to determine whether the xanthine oxidase/xanthine dehydrogenase enzyme system was involved in this oxidant stress. Adult Sprague-Dawley rats were treated with the xanthine oxidase inhibitor, oxypurinol, and randomized to bile duct ligation or sham surgery; vehicle-treated, sham-operated rats served as controls. After 5 d of bile duct ligation, serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total and direct bilirubin concentrations were significantly elevated, and increased lipid peroxidation of hepatic mitochondria and microsomes was present. Treatment with oxypurinol reduced the aspartate aminotransferase, alanine aminotransferase, and bilirubin values by 26-47% but did not alter the increased lipid peroxidation of mitochondria and microsomes. Serum vitamin E:total lipids ratio was also reduced in both bile duct-ligated groups, consistent with oxidant injury. These data show that inhibition of xanthine oxidase reduces biochemical evidence of hepatocellular injury during bile duct ligation without affecting oxidant damage to intracellular hepatocyte organelles. Thus, in this model a component of cholestatic injury appears to have been caused by oxidant stress from a source outside of the hepatocyte. | Oxypurinol |
We describe a patient with dural arteriovenous fistulas of the cavernous sinus (CS-dAVFs) who developed an intracerebral haemorrhage (ICH) mimicking hypertensive putaminal haemorrhage. Drainage into the superior ophthalmic vein (SOV) and inferior petrosal sinus (IPS) was not demonstrated on cerebral angiography, and only cortical venous reflux into the Sylvian vein was observed. In cases of venous drainage concentrated on the Sylvian vein, CS-dAVFs could indicate ICH with radiological appearance resembling putaminal haemorrhage. | Putaminal Hemorrhage |
Rotenone effectively inhibits the in vitro formation of microtubules from tubulin containing or lacking microtubule-associated proteins. In both cases a concentration of rotenone equal to that of tubulin present completely blocks assembly. The inhibition can be reversed by the addition of dimethylsulfoxide or by removing rotenone with charcoal. | Rotenone |
The over-collection and habitat destruction of natural Dendrobium populations for their commercial medicinal value has led to these plants being under severe threat of extinction. In addition, many Dendrobium plants are similarly shaped and easily confused during the absence of flowering stages. In the present study, we examined the application of the ITS2 region in barcoding and phylogenetic analyses of Dendrobium species (Orchidaceae). For barcoding, ITS2 regions of 43 samples in Dendrobium were amplified. In combination with sequences from GenBank, the sequences were aligned using Clustal W and genetic distances were computed using MEGA V5.1. The success rate of PCR amplification and sequencing was 100%. There was a significant divergence between the inter- and intra-specific genetic distances of ITS2 regions, while the presence of a barcoding gap was obvious. Based on the BLAST1, nearest distance and TaxonGAP methods, our results showed that the ITS2 regions could successfully identify the species of most Dendrobium samples examined; Second, we used ITS2 as a DNA marker to infer phylogenetic relationships of 64 Dendrobium species. The results showed that cluster analysis using the ITS2 region mainly supported the relationship between the species of Dendrobium established by traditional morphological methods and many previous molecular analyses. To sum up, the ITS2 region can not only be used as an efficient barcode to identify Dendrobium species, but also has the potential to contribute to the phylogenetic analysis of the genus Dendrobium. | Dendrobium |
Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABA(A) and GABA(B) receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking. By immunofluorescence, we assessed that the proportion of Mo5 neurons positively stained for GABA(A)Rs was significantly higher after sleep deprivation (SD, ~65%) than sleep control (SC, ~32%) and that the luminance of the GABA(A)R fluorescence was significantly higher after SD than SC and sleep recovery (SR). Although, all Mo5 neurons were positively stained for GABA(B)Rs and AChM2Rs (100%) in all groups, the luminance of these receptors was significantly higher following SD as compared to SC and SR. We conclude that the density of GABA(A), GABA(B) and AChM2 receptors increases on Mo5 neurons during SD. The increase in these receptors would be associated with increased inhibition in the presence of GABA and ACh and thus a homeostatic down-scaling in the excitability of the Mo5 neurons after prolonged waking and resulting increased susceptibility to muscle hypotonia or atonia along with sleep. | Trigeminal Motor Nucleus |
Renal lithiasis is known for its high incidence and prevalence, but mainly for its morbidity and recurrence. Despite a good indication and appropriate surgical treatment, the essential problem, the origin of the formation of the stones, generally persists and it is not uncommon that patients suffer multiple treatments and discomfort secondary to ancillary measures normally used to prevent complications. It is widely known, for consistency, that a prophylactic treatment with general or, in a smaller group of patients, specific measures are appropriate to diminish recurrences. Nevertheless, prophylaxis is not usually used by many urologists and, on top of that, in the majority of those cases when it is taken into consideration, it is the patient who fails for inadequate treatment compliance. It is very important, in any of our conversations with the urinary lithiasis' patient in relation with the disease, that the urologist provides a proper and detailed information about all its features, from diagnosis to active treatment and possible complications and, of course in those cases where prophylaxis is going to be essential to avoid new unpleasant episodes of pain and associated surgical interventions, emphasizing that improving his/her quality of life depends, to a great extent, on the patient himself. In this article, considering the existing evidence and personal experience, we intend to detail those behaviors we should take into consideration to facilitate the patient both therapeutic decisions and a positive attitude towards his/her disease, with the aim to control it in the best possible way." | Treatment Adherence and Compliance |
The person with an ostomy may focus on the negative aspects of the stoma rather than its function to the detriment of self-image, acceptance of a new lifestyle, and ability to self-care. The purpose of this integrative literature review was to explore factors involved in the adaption process of persons with a gastrointestinal stoma with a focus on the role of nonspecialist professional nurses in the process. The authors searched the databases of the Virtual Health Library, the Latin American and Caribbean of Health Sciences Information System, the Scientific Electronic Library Online, the Spanish Bibliographic Index of Health Sciences, International Literature on Health Sciences (MEDLINE), and the Cochrane Library using the keywords ostomy, adaption, and nursing for full text articles in all languages published between 2008 and 2013. Of the 612 articles identified, 21 were not duplicates and met the inclusion criteria of availability of full text, published in the past 5 years, indexed, and covering the topic of stoma adaption; this literature was analyzed using Bardin's thematic analysis. Three categories emerged: experiences and adaption strategies employed by the person with a stoma, the role of the care provider, and education as a tool in healthcare. Persons with a stoma need time and support from caregivers, family, and friends to adjust to the changes and adapt to having a stoma. This includes the ability to overcome the stigma of appearance and activities involving social interaction. Caregivers and health professionals need to serve as information resources while encouraging care autonomy. The more informed the patient, the smoother the adaption process. The literature also suggests nursing education may affect caregiving. Further research to elucidate the adaption experienced by each person with an ostomy is needed to help the multidisciplinary team plan care appropriately. | Ostomy |
An experiment was carried out to examine the effect of boiling the carcass on the subsequent microsphere content of the skeleton. Intracardiac injections of radioactive microspheres were made in five rabbits and the animals killed humanely. The tibia and femur were then removed from one lower limb by dissection, and from the other after boiling it in a pressure cooker. The mean radioactivity in the bones was significantly less following boiling: 61% (SD 14) of the control tibia and 56% (SD 11) of the control femur. As a methodological check, the radioactivity in the bones of left and right legs was compared after both had been removed by boiling. In three animals, the mean activity (left compared with right) was 101% (SD 6) in the tibia and 100% (SD 3) in the femur. Boiling the carcass led to a substantial reduction in the microsphere content of the bones and cannot be recommended as a method of sample preparation for quantitative bone blood flow work. | Tin Radioisotopes |
The objective of this study was to determine the prevalence of angiostrongylosis in tawny frogmouths (Podargus strigoides) and brushtail possums (Trichosurus vulpecula) with signs of neurological disease, and to describe the clinicopathological features of angiostrongylosis in both species. Tawny frogmouths and brushtail possums with signs of neurological disease were sampled from the Sydney metropolitan area between October 1998 and June 2010. Samples from 100 tawny frogmouths and 31 brushtail possums from the Australian Registry of Wildlife Health (ARWH), the Wildlife Assistance and Information Foundation (WAIF) and Wildlife Health and Conservation Centre (WHCC), University of Sydney were examined. Histological examinations of the brain, spinal cord and other available tissues were used to characterize the disease responsible for each animal's clinical signs. Of the 100 tawny frogmouths with neurological disease examined, angiostrongylosis was considered responsible in 80 (80%), traumatic injury in 17 (17%), protozoal infection in 3 (3%) and other diseases in 2 (2%) and the cause of clinical signs was unknown in 10 (10%). Eleven tawny frogmouths presenting with neurological signs associated with head trauma had concurrent angiostrongylosis. Of the 31 brushtail possums, Wobbly Possum Syndrome (WPS) was diagnosed in 21 (68%), angiostrongylosis in 4 (13%) and other diseases in the remaining 6 (19%). Angiostrongylosis was overrepresented in hand reared juvenile possums. Cases of angiostrongylosis in tawny frogmouths followed a strong seasonal pattern peaking through late summer and autumn. The results confirm that Angiostrongylus cantonensis is endemic in Sydney, Australia and that tawny frogmouths could be important sentinels for this zoonotic parasite. | Phalangeridae |
The rapid growth of post-World War II psychology in the United States led to intradisciplinary tensions and opportunities. In this article, I examine these tensions and opportunities in the context of social change from the 1950s through the present, attending specifically to the broad impact of federal funding on psychology. I argue that as psychology became a resource-rich field, it was forced to move from a narrow, parochial stance to a position as a national-level professional player that had to deal with the challenges of mixing science and practice, as well as meeting the demands of non-White psychologists at the national level. The impetus to create a more inclusive psychology has grown in the last three decades of the 20th century and has helped create possibilities for greater richness in American psychology and movement toward a truly international role vis-a-vis emergent psychologies around the world. | Psychology |
Pathologists and pediatric hematologist/ oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided. | Histiocytes |
INTRODUCTION: Nurses in Kenya provide significant health care including immunization in government-run health facilities. Nurses' went on strike for 150 days in 2017. This study sought to determine the strike's effect on immunization services. METHODS: Data on number of fully immunized infants reported in 18 county referral hospitals was extracted from the Kenya Health Information System and analyzed for strike and similar non-strike months. A similar analysis was conducted for 14 faith-based health facilities that were not affected by the strike. RESULTS: A Mann-Whitney U Test revealed significant difference in the mean number of fully immunized infants during the strike period (Md= 111, n=18) and non-strike period (Md=289, n=18), U=37, z= -4.0, p= .000, r=.6. A decline of 56.9% was reported during the strike. Faith-based health facilities reported an increase of 251.6% during the strike periodConclusion. This nurses' strike may have adversely affected immunization services. | Strikes, Employee |
The petrosal ganglion (PG) provides sensory innervation to the carotid sinus and carotid body through the carotid (sinus) nerve (CN). Application of either acetylcholine (ACh) or adenosine 5'-triphosphate (ATP) to the PG superfused in vitro activates CN fibers. Dopamine (DA) modulates the effects of ACh. We have previously shown that DA when applied to the PG modulates the effects of ACh on carotid sinus nerve fibers. We currently report the effects of DA on the ATP-induced responses in the isolated PG in vitro. While DA had no effect on the basal activity recorded from the CN, it reduced ATP-induced responses in a dose-dependent manner, when preceding ATP applications by 30 s. Our results suggest that DA-a transmitter present in a group of PG neurons and in carotid body cells-may act as an inhibitory modulator of ATP-evoked responses in PG neurons. | Ganglia, Sensory |
A one-year influenza A virus (IAV) monitoring program was conducted in a live-bird market (LBM) in Thailand. Using one-step real-time RT-PCR (rRT-PCR), 2.39 % of live birds were found to be IAV positive. Twenty viruses could be identified as IAV subtype H7N6. Eight IAV-H7N6 viruses were subjected to whole-genome sequencing and genetic characterization. Phylogenetic analysis showed that the HA gene of Thai H7N6 is grouped with those of the H7 Eurasian viruses. The NA gene is closely related to those of the N6 Eurasian viruses. This is the first report of IAV subtype H7N6 in Thailand." | Influenza A Virus, H7N7 Subtype |
Emerging and re-emerging infections such as SARS (2003) and pandemic H1N1 (2009) have caused concern for public health researchers and policy makers due to the increased burden of these diseases on health care systems. This concern has prompted the use of mathematical models to evaluate strategies to control disease spread, making these models invaluable tools to identify optimal intervention strategies. A particularly important quantity in infectious disease epidemiology is the basic reproduction number, R0. Estimation of this quantity is crucial for effective control responses in the early phase of an epidemic. In our previous study, an approach for estimating the basic reproduction number in real time was developed. This approach uses case notification data and the structure of potential transmission contacts to accurately estimate R0 from the limited amount of information available at the early stage of an outbreak. Based on this approach, we extend the existing methodology; the most recent method features intra- and inter-age groups contact heterogeneity. Given the number of newly reported cases at the early stage of the outbreak, with parsimony assumptions on removal distribution and infectivity profile of the diseases, experiments to estimate real time R0 under different levels of intra- and inter-group contact heterogeneity using two age groups are presented. We show that the new method converges more quickly to the actual value of R0 than the previous one, in particular when there is high-level intra-group and inter-group contact heterogeneity. With the age specific contact patterns, number of newly reported cases, removal distribution, and information about the natural history of the 2009 pandemic influenza in Hong Kong, we also use the extended model to estimate R0 and age-specific R0. | Basic Reproduction Number |
Dermatan sulfate is a glycosaminoglycan that selectively inhibits the action of thrombin through interaction with heparin cofactor II. Unlike heparin it does not interact with other coagulation factors and is able to inhibit thrombin associated with clots. This property has made dermatan sulfate an attractive candidate as an antithrombotic drug. Previous studies have showed that dermatan sulfate derived from porcine/bovine intestinal mucosa/skin or marine invertebrates is capable of stimulating heparin cofactor II-mediated thrombin inhibition in vitro. This biological activity is reported for the first time in this study using dermatan sulfate derived from mammalian tissues other than intestinal mucosa or skin. Ten different bovine tissues including the aorta, diaphragm, eyes, large and small intestine, esophagus, skin, tendon, tongue, and tongue skin were used to prepare dermatan sulfate-enriched fractions by anion exchange chromatography and acetone precipitation. Heparin cofactor II/dermatan sulfate-mediated thrombin inhibition measured in vitro revealed activity comparable to or higher than the commercial standard with 2-fold differences observed between some tissues. Analysis of the extracted dermatan sulfate using fluorophore-assisted carbohydrate electrophoresis revealed significant differences in the relative percentage of all the mono-sulfated disaccharides, in particular the predominant mammalian disaccharide uronic acid-->N-acetyl-D-galactosamine-4-O-sulfate, confirming previous reports regarding variations in sulfation in dermatan sulfate from different tissues. Overall, these findings demonstrate that dermatan sulfate extracted from a range of bovine tissues exhibits in vitro antithrombin activity equivalent to or higher than that observed for porcine intestinal mucosa, identifying additional sources of dermatan sulfate as potential antithrombotic agents. | Dermatan Sulfate |
AIM: Aware that Down Syndrome patients present among their clinical characteristics impaired immunity, the aim of this study is to identify the statistically significant differences in inflammation-related gene expression by comparing Down Syndrome patients with Periodontal Disease (DS+PD+) with Down Syndrome patients without Periodontal Disease (DS+PD-), and their relationship with periodontitis as a chronic oral inflammatory clinical feature. MATERIALS AND METHODS: Case study and controls on eleven Down Syndrome patients (DS+PD+ vs. DS+PD-). RNA was extracted from peripheral blood using a Qiagen PAXgene Blood miRNA Kit when performing an oral examination. A search for candidate genes (92 selected) was undertaken on the total genes obtained using a Scientific GeneChip(R) Scanner 3000 (Thermo Fisher Scientific) and Clariom S solutions for human, mouse, and rat chips, with more than 20,000 genes annotated for measuring expression levels. RESULTS: Of the 92 inflammation-related genes taken initially, four genes showed a differential expression across both groups with a p value of <0.05 from the data obtained using RNA processing of the patient sample. Said genes were TNFSF13B (p = 0.0448), ITGB2 (p = 0.0033), ANXA3 (p = 0.0479), and ANXA5 (p = 0.016). CONCLUSIONS: There are differences in inflammation-related gene expression in Down Syndrome patients when comparing patients who present a state of chronic oral inflammation with patients with negative rates of periodontal disease. | Annexin A3 |
Lineage tracing can provide key insights into the development of tissues, such as the retina. Yet it is not possible to manipulate human cells during embryogenesis. The authors observed a distinct phenotype in female carriers of X-linked disorders, in particular, carriers of choroideremia caused by mutations in CHM, encoding Rab escort protein-1. The authors found that X chromosome inactivation provides a method for retinal lineage tracing in human patients. Live imaging of female carriers displays a developmental pattern that is different within the peripheral retina compared with the posterior retina and provides important insights into the development and migration of retinal cells. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e158-e162.]. | Choroideremia |
A sensitive and specific assay for measurement of adenine nucleotides and adenosine by paired-ion high-performance liquid chromatography is described. The 1,N6-ethenoderivatives of ATP (epsilon-ATP), ADP (epsilon-ADP), AMP (epsilon-AMP), and adenosine (epsilon-Ado), formed by reaction with chloroacetaldehyde at 37 degrees C, were separated under isocratic conditions in 20 min. These compounds are strongly fluorescent at an emission wavelength of 280 nm, rendering a lowest detection limit of 2-5 pmol per injection. The detector responded linearly over the measured ranges (5-100 pmol for epsilon-Ado and 5-4000 pmol for nucleotides). Specificity was confirmed enzymatically. alpha, beta-Methyleneadenosine 5'-diphosphate could be used as an internal standard for measurement of the nucleotides. Significant amounts of NADH appeared as a separate peak in hypoxic tissue. Recoveries from snap-frozen kidney were 88, 92, 76, and 63% for AMP, ADP, ATP, and adenosine, with SD for recovery of 1.0, 10.5, 8.3, and 5.6%, respectively. This method was successfully used to measure adenine nucleotides and adenosine in oxygenated and hypoxic perfused rat kidneys. | Adenine Nucleotides |
BACKGROUND: Progesterone binding to the surface of the amphibian oocyte initiates the meiotic divisions. Our previous studies with Rana pipiens oocytes indicate that progesterone binds to a plasma membrane site within the external loop between the M1 and M2 helices of the alpha-subunit of Na/K-ATPase, triggering a cascade of lipid second messengers and the release of the block at meiotic prophase. We have characterized this site, using a low affinity ouabain binding isoform of the alpha1-subunit. RESULTS: Preparations of isolated plasma membranes from Rana oocytes demonstrate that physiological levels of progesterone (or the non-metabolizable progestin R5020) successively activate phosphatidylethanolamine-N-methyltransferase (PE-NMT) and sphingomyelin synthase within seconds. Inhibition of PE-NMT blocks the progesterone induction of meiosis in intact oocytes, whereas its initial product, phosphatidylmonomethylethanolamine (PME), can itself initiate meiosis in the presence of the inhibitor. Published X-ray crystallographic data on Na/K-ATPase, computer-generated 3D projections, heptad repeat analysis and hydrophobic cluster analysis of the transmembrane helices predict that hydrophobic residues L, V, V, I, F and Y of helix M2 of the alpha1-subunit interact with F, L, G, L, L and F, respectively, of helix M3 of PE-NMT. CONCLUSION: We propose that progesterone binding to the first external loop of the alpha1-subunit facilitates specific helix-helix interactions between integral membrane proteins to up-regulate PE-NMT, and, that successive interactions between two or more integral plasma membrane proteins induce the signaling cascades which result in completion of the meiotic divisions." | Phosphatidyl-N-Methylethanolamine N-Methyltransferase |
MOTIVATION: Recently, various tools for detecting single nucleotide polymorphisms (SNPs) involved in epistasis have been developed. However, no studies evaluate the employed statistical epistasis models such as the chi2-test or quadratic regression independently of the tools that use them. Such an independent evaluation is crucial for developing improved epistasis detection tools, for it allows to decide if a tool's performance should be attributed to the epistasis model or to the optimization strategy run on top of it. RESULTS: We present a protocol for evaluating epistasis models independently of the tools they are used in and generalize existing models designed for dichotomous phenotypes to the categorical and quantitative case. In addition, we propose a new model which scores candidate SNP sets by computing maximum likelihood distributions for the observed phenotypes in the cells of their penetrance tables. Extensive experiments show that the proposed maximum likelihood model outperforms three widely used epistasis models in most cases. The experiments also provide valuable insights into the properties of existing models, for instance, that quadratic regression perform particularly well on instances with quantitative phenotypes. AVAILABILITY AND IMPLEMENTATION: The evaluation protocol and all compared models are implemented in C++ and are supported under Linux and macOS. They are available at https://github.com/baumbachlab/genepiseeker/, along with test datasets and scripts to reproduce the experiments. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. | Epistasis, Genetic |
Many studies have reported temporal changes in the relative importance of density-dependence and environmental stochasticity in affecting population growth rates, but they typically assume that the predominant factor limiting growth remains constant over long periods of time. Stochastic switches in limiting factors that persist for multiple time-steps have received little attention, but most wild populations may periodically experience such switches. Here, we consider the dynamics of three populations of individually marked bighorn sheep (Ovis canadensis) monitored for 24-28 years. Each population experienced one or two distinct cougar (Puma concolor) predation events leading to population declines. The onset and duration of predation events were stochastic and consistent with predation by specialist individuals. A realistic Markov chain model confirms that predation by specialist cougars can cause extinction of isolated populations. We suggest that such processes may be common. In such cases, predator-prey equilibria may only occur at large geographical and temporal scales, and are unlikely with increasing habitat fragmentation. | Puma |
Epilobium angustifolium L. (EA) has been used as a topical agent since ancient times. There has been an increasing interest in applying EA as a raw material used topically in recent years. However, in the literature, there are not many reports on the comprehensive application of this plant to skin care and treatment. EA contains many valuable secondary metabolites, which determine antioxidant, anti-inflammatory, anti-aging, and antiproliferative activity effects. One of the most important active compounds found in EA is oenothein B (OeB), which increases the level of ROS and protects cells from oxidative damage. OeB also influences wound healing and reduces inflammation by strongly inhibiting hyaluronidase enzymes and inhibiting COX-1 and COX-2 cyclooxygenases. Other compounds that play a key role in the context of application to the skin are flavonoids, which inhibit collagenase and hyaluronidase enzymes, showing anti-aging and anti-inflammatory properties. While terpenes in EA play an important role in fighting bacterial skin infections, causing, among other things cell membrane, permeability increase as well as the modification of the lipid profiles and the alteration of the adhesion of the pathogen to the animal cells. The available scientific information on the biological potential of natural compounds can be the basis for the wider use of EA in skin care and treatment. The aim of the article is to review the existing literature on the dermocosmetic use of E. angustifolium. | Onagraceae |
Osmolytes are a series of different kinds of small molecules that can maintain the correct conformation of protein by acting as molecular chaperons. In this study, the protective effects of four compatible osmolytes, i.e., proline, sucrose, DMSO and glycerol, were studied during arginine kinase (EC 2.7.3.3) unfolding and aggregation. The results showed that all the osmolytes applied in this study obviously prevented AK unfolding and inactivation that was due to a GdnHCl denaturant by reducing the inactivation rate constants (k(i)), increasing the transition free energy changes (DeltaDeltaG(i)) and increasing the value for the midpoint of denaturation (C(m)). Furthermore, the osmolytes remarkably prevented AK aggregation in a concentration-dependent manner during AK refolding. Our results strongly indicated that osmolytes were not only metabolism substrates, but they were also important compounds with significant physiological protective functions for proteins, especially in some extremely harsh environments. | Arginine Kinase |
BACKGROUND: Dopamine (DA) is hypothesized to modulate anxiety-like behavior, although the precise role of DA in anxiety behaviors and the complete anxiety network in the brain have yet to be elucidated. Recent data indicate that dopaminergic projections from the ventral tegmental area (VTA) innervate the interpeduncular nucleus (IPN), but how the IPN responds to DA and what role this circuit plays in anxiety-like behavior are unknown. METHODS: We expressed a genetically encoded G protein-coupled receptor activation-based DA sensor in mouse midbrain to detect DA in IPN slices using fluorescence imaging combined with pharmacology. Next, we selectively inhibited or activated VTA-->IPN DAergic inputs via optogenetics during anxiety-like behavior. We used a biophysical approach to characterize DA effects on neural IPN circuits. Site-directed pharmacology was used to test if DA receptors in the IPN can regulate anxiety-like behavior. RESULTS: DA was detected in mouse IPN slices. Silencing/activating VTA-->IPN DAergic inputs oppositely modulated anxiety-like behavior. Two neuronal populations in the ventral IPN (vIPN) responded to DA via D(1) receptors (D1Rs). vIPN neurons were controlled by a small population of D1R neurons in the caudal IPN that directly respond to VTA DAergic terminal stimulation and innervate the vIPN. IPN infusion of a D1R agonist and antagonist bidirectionally controlled anxiety-like behavior. CONCLUSIONS: VTA DA engages D1R-expressing neurons in the caudal IPN that innervate vIPN, thereby amplifying the VTA DA signal to modulate anxiety-like behavior. These data identify a DAergic circuit that mediates anxiety-like behavior through unique IPN microcircuitry. | Interpeduncular Nucleus |
BACKGROUND: Dexmethylphenidate is a single-isomer stimulant medication approved for the treatment of attention deficit hyperactivity disorder (ADHD). Single-isomer drugs have the potential for decreased undesired effects and improved therapeutic efficacy. Stimulant medications have been the mainstay treatments for ADHD for fifty years, and ability to reduce their adverse effects would be useful in promoting patient compliance with treatment. OBJECTIVE: To review the literature on the safety and efficacy of dexmethylphenidate. METHODS: MedLine, PubMed search of dexmethylphenidate research. RESULTS/CONCLUSIONS: Dexmethylphenidate is a safe and effective treatment for ADHD. Its overall safety and tolerability profile is similar to other members of the psychostimulant class." | Dexmethylphenidate Hydrochloride |
OBJECTIVE: We sought to investigate the effect of body mass index (BMI) on in vitro response to tocolytics. STUDY DESIGN: Myometrial biopsies were obtained at the time of scheduled cesarean deliveries from term nonlaboring women with BMI < or =29.9 (26.3 +/- 1.3; n = 7), 30-34.9 (31.8 +/- 1.2; n = 16), and > or = 35 (39.5 +/- 4.9; n = 9). Tissue strips were suspended in organ chambers for isometric tension recording. The effects of cumulative doses (10(-10) to 10(-5) mol/L) of nifedipine or indomethacin on spontaneous uterine contractility were determined. Areas under the contraction curve were compared using 1-way analysis of variance with Tukey post hoc test. RESULTS: Myometrial response to tocolytics did not differ between the BMI groups. Nifedipine, but not indomethacin, significantly inhibited myometrial contractility independent of BMI. CONCLUSION: BMI does not affect uterine response to tocolytics in isolated uterine tissue from term nonlaboring women. | Myometrium |
In this study the authors set out to determine whether postoperative hyperbaric oxygen (HBO) therapy increases the survival rate of the composite graft in the rat ear model. A composite graft (1 x 0.5 cm2) that included skin, subcutaneous tissue, and cartilage was created from the left ear, and was transferred onto the posterior auricular site of the right ear. The animals were divided into two groups: a control group (N = 10) and an experimental group receiving HBO (N = 10). The experimental group was given HBO immediately following reattachment for 4 hours, and then for 6 hours each day for 5 days (2 atm). The results showed the average ear flap survival area in the experimental group was 82%, and it was 26.5% in the control group (p < 0.01). Histology demonstrated the existence of neovascularization in the experimental group. We have concluded that postoperative HBO therapy increases the survival of the rat ear composite graft, and that the effect of this therapy is influenced by the magnitude (size and thickness) of the graft. | Ear |
Matrine and oxymatrine, major components of Sophora flavescens, were confirmed to have a protective effect on restraint and water immersion stress ulcer in mice. Oxymatrine inhibits the formation of some experimental gastric ulcer, pylorus ligation ulcer and indomethacin ulcer, which are considered to relate to acid secretion. Oxymatrine decreases acid secretion in Shay's rats and inhibits gastric motility induced by restraint and water immersion stress when administered intraduodenally. These results suggest that the protective effect of oxymatrine on stress ulcer is possibly due to a decrease of acid secretion and inhibition of gastric motility. In spite of its weak inhibition of gastric acid secretion, intravenous injection of matrine is rather effective for stress ulcer. Matrine exhibits the inhibition of writhing induced by acetic acid, prolongation of sleeping time induced by pentobarbital, hypothermia and inhibition of locomotor activity induced by methamphetamine. Matrine (i.v.) also inhibits gastric motility induced by restraint and water immersion stress. On the other hand, the administration of matrine exhibits clear contraction on the preparation of the fundus strip of rats at high concentration. The contractile response of the fundus strip to matrine is not inhibited by treatment with tetrodotoxin, and is not modified with atropine, while pretreatment of the fundus strip with antihistamine abolished or reduced the contractile response. It can therefore be assumed that the direct action of matrine on the stomach smooth muscle possibly contributes to the mechanism of the matrine induced inhibition of the spontaneous gastric motility and rise in the tone of stomach, and may play an important role in the protection of the restraint and water immersion stress ulcer formetion. | Matrines |
In this work, we build an electronic syrinx, i.e., a programmable electronic device capable of integrating biomechanical model equations for the avian vocal organ in order to synthesize song. This vocal prosthesis is controlled by the bird's neural instructions to respiratory and the syringeal motor systems, thus opening great potential for studying motor control and its modification by sensory feedback mechanisms. Furthermore, a well-functioning subject-controlled vocal prosthesis can lay the foundation for similar devices in humans and thus provide directly health-related data and procedures. | Sound Spectrography |
BACKGROUND: Exposure to pesticides via take-home can be an important pathway for farmworkers' families. OBJECTIVE: The aim of this review was to summarize and analyze the literature published during the last decade of exposure to pesticides via take-home pathway in farmworkers' families. METHODS: We conducted a systematic review to identify peer-reviewed articles of interest; only articles related to take-home pathway that included some sort of pesticide monitoring were considered for inclusion. Systematic reviews, literature reviews, and meta-analyses were excluded, resulting in a total of 39 articles elected for analysis. The articles were summarized based on the location of the study, population (sample size), pesticide analyzed, and type of sample. RESULTS: The majority of the reviewed studies were conducted in the U.S., but there seems to be an increase in literature on pesticide take-home pathway in developing countries. Most of the articles provided evidence that farmworkers' families are exposed to pesticides at higher levels than non-farmworkers' families. The levels may depend on several factors such as seasonality, parental occupation, cohabitation with a farmworker, behavior at work/home, age, and gender. Community-based interventions disrupting the take-home pathway seem to be effective at reducing pesticide exposure. DISCUSSION/CONCLUSION: The take-home pathway is an important contributor to overall residential exposures, but other pathways such as pesticide drift, indoor-residential applications, and dietary intake need to be considered. A more comprehensive exposure assessment approach is necessary to better understand exposures to pesticides. | Environmental Exposure |
The trigeminovagal reflex is a phenomenon that occurs rarely during maxillofacial surgery. Previously described as the oculocardiac reflex, this reflex can occur during ocular and periocular surgery. To be more anatomically precise, it was renamed the trigeminocardiac or trigeminovagal reflex, since stimulation of any part of the trigeminal nerve can elicit this reflex arc. We describe a case of asystole during mobilization of a maxilla following a Le Fort 1 osteotomy. | Reflex, Trigeminocardiac |
Deep vein thrombosis (DVT) causes high morbidity and mortality. Successful resolution of DVT-related thrombi is the key point in the treatment of DVT. Recently, endothelial progenitor cells (EPCs) which are multipotent progenitor cells mainly residing in human bone marrow have emerged as a promising therapeutic choice for DVT-related thrombus resolution. In this review, we discussed the mobilization and homing property of EPCs into the sites of thrombosis, mechanisms of EPCs in DVT-related thrombus resolution from the aspects of promoting endothelial regeneration, revascularization, vasoactive and angiogenic factor secretion, proteinase generation, thrombus propagation and recurrence prevention, and vein wall remodeling. In addition, we also provide suggestions on EPCs as a therapeutic choice for thrombus resolution. | Endothelial Progenitor Cells |
Insertion of an internal DNA fragment into the act1 gene, which encodes one of several sigma(54)-activator proteins in Myxococcus xanthus, produced a mutant defective in fruiting body development. While fruiting-body aggregation appears normal in the mutant, it fails to sporulate (<10(-6) the wild-type number of viable spores). The A and C intercellular signals, which are required for sporulation, are produced by the mutant. But, while it produces A-factor at levels as high as that of the wild type, the mutant produces much less C-signal than normal, as measured either by C-factor bioassay or by the total amount of C-factor protein detected with specific antibody. Expression of three C-factor-dependent reporters is altered in the mutant: the level of expression of Omega4414 is about 15% of normal, and Omega4459 and Omega4403 have alterations in their time course. Finally, the methylation of FrzCD protein is below normal in the mutant. It is proposed that Act1 protein responds to C-signal reception by increasing the expression of the csgA gene. This C-signal-dependent increase constitutes a positive feedback in the wild type. The act1 mutant, unable to raise the level of csgA expression, carries out only those developmental steps for which a low level of C-signaling is adequate. | RNA Polymerase Sigma 54 |
Premarital counseling is required for couples wishing to be married in China. The counseling primarily provides information about contraception. We evaluated adding premarital HIV/AIDS counseling and voluntary HIV testing to the standard counseling. The test was offered free to one group and at the standard cost to the other. The proportion of those accepting HIV testing among all participants receiving premarital counseling was used as a measure of acceptability. Sixteen percent of participants not charged chose to accept testing versus 1.4% of those charged ( p < .001). Lack of HIV/AIDS knowledge and charging for the test were correlated with refusal. Over 5% of participants admitted to premarital sex, most with their fiancee, and a significantly higher portion was female. Only 22% used condoms. Study participants were randomized for 1-year follow-up. Only four participants reported extramarital sexual activity during that year. Acceptance of HIV testing was disappointingly low. Implementing strategies to reduce stigmatization and increase knowledge of HIV/AIDS, in addition to not charging for testing, may increase the acceptance of HIV testing. | HIV Testing |
New high-flux synchrotron radiation circular dichroism (SRCD) beamlines are providing important information for structural biology, but can potentially cause denaturation of the protein samples under investigation. This effect has been studied at the new CD1 dedicated SRCD beamline at ISA in Denmark, where radiation-induced thermal damage effects were observed, depending not only on the radiation flux but also on the focal spot size of the light. Comparisons with similar studies at other SRCD facilities worldwide has lead to the estimation of a flux density threshold under which SRCD beamlines should be operated when samples are to be exposed to low-wavelength vacuum ultraviolet radiation for extended periods of time. | Protein Denaturation |
Reactions of chloro(alkoxycarbonyl)methylenetriphenylphosphoranes with protected D-ribofuranoses resulted in the exclusive formation of C-beta-D-ribofuranosyl glycosides, which were converted to some C-nucleosides, such as showdomycin and pyrido-[1,2-a]pyrimidine C-nucleosides. | Showdomycin |
Six bioactive alkaloids, aristolactam B(1), piperolactam A(2), aristolactam A(3), norcepharadione B(4), cepharadione B(5) and splendidine(6) were isolated by bioactivity-guided fractionation of a methanolic extract of the aerial part of Houttuynia cordata. Several of them exhibited significant cytotoxicity against five human tumor cell lines (A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT-15) in vitro. | Houttuynia |
The presence of maternal DNA or even maternal cells within the offspring (microchimerism) has been reported for many fetal tissues, including the liver, heart, and spleen. Microchimerism is believed to be involved in the pathogenesis of autoimmune diseases; however, the cellular origin of this phenomenon remains unknown. Here, we determined whether differentiated T lymphocytes could transmigrate through the immunosuppressive environment of the placenta to reach the fetus. In vitro-differentiated effector/memory Th1 and Th17 cells from OVA(3)(2)(3)(-)(3)(3)(9)-specific TCR(tg) T cells of OT-II mice were adoptively transferred (i.v.) into the tail veins of pregnant Ly5.1 mice at d15 and d19 of gestation. Mice were then sacrificed 40 h after adoptive cell transfer. Using radioactive labeling of T cells with sodium chromate [Cr(5)(1)] prior to adoptive transfer, we observed that homing of pro-inflammatory Th cells was equally efficient in both pregnant and non-pregnant mice. Transmigration of Th1- and Th17-like cells through the highly immunosuppressive environment of the placenta into the fetus was significantly enhanced in experimental mice compared to control mice (P < 0.0001). In addition, a substantial amount of effector Th cells accumulated in the placenta. Finally, we found that treatment with Pertussis Toxin resulted in a 3-fold increase in the transmigration of effector Th17 cells into the fetus (P < 0.0001). When pro-inflammatory Th1-or Th17-like cells were injected into syngeneic mothers, almost all of the fetuses analyzed exhibited radioactivity, suggesting that transmigration of effector T cells occurs frequently. Our results suggest the possibility of novel roles for these maternal effector cells in the pathogenesis or reduction of disease. | Transcellular Cell Migration |
Rupture of the cranial cruciate ligament is the most common cause of stifle lameness in the adult dog. An understanding of the pathogenesis of cranial cruciate ligament rupture and the resulting degenerative joint disease is crucial in establishing an accurate diagnosis and implementing appropriate treatment. Early diagnosis of the cruciate-deficient stifle with appropriate therapeutic intervention may minimize degenerative joint disease but does not prevent it in all cases. Rehabilitation of the surgically corrected cruciate-deficient stifle may influence the success of the surgical outcome. | Joint Diseases |
AIMS: Nonhuman primates have been used to investigate pathogenic mechanisms and evaluate immune responses following Chlamydia trachomatis inoculation. This study aimed to systemically profile antibody responses to C. trachomatis infection in nonhuman primates. MATERIALS AND METHODS: Sera were obtained from 4 pig-tailed and 8 long-tailed macaques which were intravaginally or ocularly infected with live C. trachomatis organisms, and analyzed by C. trachomatis proteome array of antigens. KEY FINDINGS: The sera from 12 macaques recognized total 172 C. trachomatis antigens. While 84 antigens were recognized by pig-tailed macaques intravaginally infected with serovar D strain, 125 antigens were recognized by long-tailed macaques ocularly infected with serovar A, and 37 antigens were recognized by both. Ocular inoculation with virulent A2497 strain induced antibodies to more antigens. Among the antigens uniquely recognized by A2497 strain infected macaques, outer membrane complex B antigen (OmcB) induced robust antibody response. Although macaques infected by less virulent A/HAR-13 strain failed to develop antibodies to OmcB, reinfection by A2497 strain induced high levels of antibodies to OmcB. SIGNIFICANCE: Proteome array has revealed a correlation of chlamydial infection invasiveness with chlamydial antigen immunogenicity, and identified antibody responses to OmcB potentially as biomarkers for invasive infection with C. trachomatis. | Reproductive Tract Infections |
This study aims to estimate the prevalence of serositis and identify risk factors for serositis in a large cohort of systemic lupus erythematosus (SLE) patients. A cross-sectional study was conducted based on the medical records of patients hospitalized with SLE at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital. Patients were diagnosed with serositis when they presented with symptoms and signs of pleuritis or/and pericarditis. We explored factors associated with the generation and quantity of serositis by using binary and ordinal logistic regression analysis. Among the 1668 lupus patients, 298 have serositis. Active lupus disease, fever (>/=38 degrees C) and high D-dimer were all significantly associated with the generation and quantity of serositis. Male gender was independent significant risk factor for pleuritis but not for pericarditis, while low complement C4 and high erythrocyte sedimentation rate (ESR) were risk factors for pericarditis rather than for pleuritis. The possible prevalence of serositis in patients with SLE was 17.9%. The significant associations of active lupus disease, fever (>/=38 degrees C) and high D-dimer with serositis suggest that higher disease activity and hypercoagulability may both contribute to the generation and development of serositis in SLE. The risk factors for pleuritis and pericarditis in SLE are similar but not identical. | Serositis |
The authors describe the electroclinical and evolutive aspects of 4 cases (including 2 brothers) of myoclonic epileptic encephalopathy beginning between 2 days and 10 weeks of life. From the onset of myoclonic jerks, polymorphous fits (partial seizures, tonic seizures) and multifocal electrical abnormalities are associated. Repeated spasms and 'suppression-burst' patterns appear later. The neurological status deteriorates progressively, leading within a few months to decerebration posture with opisthotonus. In spite of thorough neuroradiological, biochemical, cytological to metabolic investigations, etiology remains unknown. However, the electroclinical and evolutive patterns are similar to that of metabolic diseases, especially non-ketotic hyperglycemia. The authors discuss the relations between their observations and those in the literature and the nosological problems of this particular epileptic encephalopathy of infancy. | Decerebrate State |
INTRODUCTION: The clinical criteria for brain death consist of the demonstration of the absence of any clinical sign of encephalic activity. Confirmatory testing is usually not required for the diagnosis of brain death, except in some special situations that the Spanish law details. In these situations demonstrating cerebral circulatory arrest (CCA) by cerebral flow studies is necessary to support the diagnosis of brain death. OBJECTIVE: To review the use of transcranial Doppler ultrasonography (TCD) for confirming brain death and to establish uniform criteria for the routine use of TCD as a confirmatory test. METHODS: Based on literature analysis, the authors developed the guidelines for performance and interpretation of TCD in clinically brain-dead patients, in order to confirm the diagnosis. The active members of the Spanish Neurosonology Society (SONES) reviewed an initial draft, until a consensus was reached. RESULTS: In a clinically brain-dead patient, specific intracranial flow patterns indicating CCA can be visualized by TCD. The specific flow patterns are the presence of reverberating flow and/or systolic spikes, and should be detected in both middle cerebral arteries and also in the basilar artery. We recommend to repeat the examination within 30 minutes to confirm the findings. CONCLUSIONS: TCD is a useful method detecting CCA and therefore can be used to confirm brain death in a clinically brain-dead patient. The presence of reverberating flow, systolic spikes or absence of flow in the basilar and both middle cerebral arteries observed in two examinations is highly specific for the prediction of CCA and brain death in all patients." | Ultrasonography, Doppler, Transcranial |
Prednimustine is an ester of chlorambucil and prednisolone. The drug has had some activity in experimental as well as in human tumors, including breast cancer. The objective of the current study is to compare the clinical effectiveness and toxicity of prednimustine with its components of chlorambucil plus prednisolone, and to compare the clinical effectiveness and toxicity of a continuous treatment with an intermittent one. Two hundred and one patients with advanced breast cancer were randomized to the following treatments: I: prednimustine continuously; 40 mg/m2 d; II: prednimustine intermittently, 160 mg/m2 d 1 to 5, repeated every three weeks; and III: chlorambucil 8 mg/m2 d plus prednisolone 8 mg/m2 d, both given continuously. All treatments were given orally. One hundred and ninety five patients were evaluable for assessment of response to the treatments. The response rates were 21% in both of the prednimustine-treated groups, whereas only 11% of the patients treated with chlorambucil and prednisolone responded. The duration of remission with continuous prednimustine was longer than with the other two treatment groups, but not significantly so. One hundred and ninety five patients were evaluable for assessment of hematologic toxicity. No differences were observed between the two prednimustine-treated groups, whereas the group treated with chlorambucil plus prednisolone experienced a significantly higher degree of leukopenia and/or thrombopenia. Subjective toxicities, nausea, vomiting and psychical symptoms were only moderate in the three treatment groups, but significantly more pronounced in the group treated with intermittent prednimustine. Because of these promising results, prednimustine should be compared to other alkylating agents in patients with advanced breast cancer in randomized trials. | Prednimustine |
BACKGROUND: Ponticulus posticus (PP) occurs frequently and may cause symptom series, including vertebrobasilar insufficiency, migraine, hearing loss, and Barre-Lieou syndrome. However, few studies to date have described surgical treatment of PP. We report a rare case of a patient who suffered from torticollis, facial asymmetry, localized pain, and Barre-Lieou syndrome in connection with PP. We also review the pertinent literature, focusing on surgical treatment for symptoms due to PP. CASE PRESENTATION: A 23-year-old male presented with the chief complaint of continuous significant dizziness to the point of losing consciousness while rotating his head to the right. Plain radiographs and computed tomography (CT) scans of the cervical spine showed a capital ES, Cyrillic1 anomaly with the formation of complete PP on the left (dominant) side, with acute-angled, capital ES, Cyrillic-shaped kinking of the vertebral artery. Resection of PP via the posterior midline was performed successfully. The patient had satisfactory postoperative relief from localized pain and Barre-Lieou syndrome, but there were no obvious changes in the torticollis and facial asymmetry observed during the 3-month follow-up period. CONCLUSIONS: This case is a rare presentation of torticollis, facial asymmetry, localized pain, and Barre-Lieou syndrome in connection with one-sided complete PP. This tetrad indicates that PP may affect the patient earlier than expected. In such situations, early diagnosis and timely surgical treatment may significantly improve patients' quality of life and avoid the development of torticollis and face asymmetry." | Posterior Cervical Sympathetic Syndrome |
Acetabularia rhodopsin II (ARII or Ace2), an outward light-driven algal proton pump found in the giant unicellular marine alga Acetabularia acetabulum, has a unique property in the cytoplasmic (CP) side of its channel. The X-ray crystal structure of ARII in a dark state suggested the formation of an interhelical hydrogen bond between C218(ARII) and D92(ARII), an internal proton donor to the Schiff base (Wada et al., 2011). In this report, we investigated the photocycles of two mutants at position C218(ARII): C218A(ARII) which disrupts the interaction with D92(ARII), and C218S(ARII) which potentially forms a stronger hydrogen bond. Both mutants exhibited slower photocycles compared to the wild-type pump. Together with several kinetic changes of the photoproducts in the first half of the photocycle, these replacements led to specific retardation of the N-to-O transition in the second half of the photocycle. In addition, measurements of the flash-induced proton uptake and release using a pH-sensitive indium-tin oxide electrode revealed a concomitant delay in the proton uptake. These observations strongly suggest the importance of a native weak hydrogen bond between C218(ARII) and D92(ARII) for proper proton translocation in the CP channel during N-decay. A putative role for the D92(ARII)-C218(ARII) interhelical hydrogen bond in the function of ARII is discussed. | Acetabularia |
Antidepressant drugs of the SSRI family are used as a third-line treatment for neuropathic pain. In contrast MAOi antidepressants, that also increase extracellular serotonin bioavailability have little or no effects on this condition. In addition to their action of the serotonin transporter, some SSRI have been shown to inhibit voltage gated sodium channels. Here we investigated the potential inhibition of SSRIs and MAOi antidepressants on Nav1.7 or Nav1.8, which are expressed in sensory neurons and play an important role in pain sensation. We used the whole-cell patch-clamp technique on HEK293 cells expressing either Nav1.7 or Nav1.8, and evaluated the effects of the SSRIs fluoxetine, paroxetine, and citalopram as well as one MAOi antidepressants on the electrophysiological properties of the Na(+) channels. Paroxetine exhibited the greatest affinity for Na(+) channels. In ascending order of affinity for Nav1.7 were paroxetine (IC50=10 microM), followed by fluoxetine (IC50=66 microM), then citalopram (IC50=174 microM). In ascending order of affinity for Nav1.8 were paroxetine (IC50=9 microM), followed by fluoxetine (IC50=49 microM), then citalopram (IC50=100 microM). Paroxetine and fluoxetine accelerated the onset of slow-inactivation and delayed the time-course of recovery from inactivation for both channels. Paroxetine and fluoxetine also had a prominent effect on the frequency-dependent inhibition, with a greater effect on Nav1.7. In contrast to SSRIs, MAOi did not affect Na(+) channels currents. These results suggest that, in certain conditions, the analgesic effect of SSRIs may in part be due to their interactions with Na(+) channels." | NAV1.8 Voltage-Gated Sodium Channel |
New analogs of amino acid-conjugated bile acids were synthesized in which the amide bond was reversed from its normal configuration. These structural isomers of the beta-alanyl conjugates of cholic acid and ursodeoxycholic acid were synthesized by reaction of succinic anhydride with the 24-nor-23-amine derivatives of cholic acid and ursodeoxycholic acid. The chemical and physical properties of these reverse amide conjugated bile acid analogs were compared with those of the normal glycine and beta-alanine conjugates. The reverse amide analogs comigrated with their isomeric beta-alanine conjugates during thin-layer chromatography using a variety of solvent systems. However, the isomeric pairs could be resolved by reversed-phase high performance liquid chromatography, with the reverse amides having greater retention times compared to the beta-alanine conjugates. Critical micelle concentrations, solubility of undissociated forms, and acid dissociation constants were similar for the isomeric pairs. Significant differences in melting points were observed, however, While the isomeric pairs showed no significant differences in sensitivity to base hydrolysis, the reverse amides were not hydrolyzed by the cholylglycine hydrolase from Clostridium perfringens, even after long incubation periods. | Bile Acids and Salts |
During sexual maturation, pituitary gonadotropins stimulate the gonads to produce increasing amounts of biologically active steroids and yet gonadotropin release does not become suppressed until concentrations of sex hormones, LH and FSH, in peripheral circulation stabilizes at a higher adult level. There is a substantial amount of evidence that in many mammals, this transition from prepubertal to adult level of activity of the pituitary-gonadal axis is associated with a reduction in the sensitivity of the hypothalamic-adenohypophyseal system to negative feedback of gonadal steroids. In the female, these changes are accompanied by the appearance of positive estrogen feedback on gonadotropin release. In seasonal breeders, annual transitions between the periods of gonadal activity and quiescence are associated with corresponding shifts in the sensitivity to steroid feedback. Peripheral levels of pituitary prolactin (PRL) typically increase during sexual maturation and exhibit large seasonal fluctuations in response to changes in photoperiod and ambient temperature. We propose that PRL is one of the factors which regulate the sensitivity of gonadotropin release to gonadal steroid feedback. In hyperprolactinemic women, responsiveness to negative estrogen feedback increases, while LH response to positive estrogen feedback is reduced or absent. In hyperprolactinemic men, both LH and testosterone levels are reduced, implying increased sensitivity of LH release to negative testosterone feedback. In the male rat, both physiological amounts of PRL and experimentally-induced hyperprolactinemia increase the ability of exogenous testosterone to suppress LH and FSH release. Different regulatory mechanisms appear to operate in the seasonally breeding male golden hamster, in which short photoperiod causes concomitant suppression of PRL, LH, FSH and testosterone release. In this species, pharmacologic suppression of PRL release leads to increased responsiveness of plasma gonadotropin levels to negative feedback effects of testosterone, while PRL-secreting ectopic pituitary transplants exert an opposite effect. We have examined some of the suspected mechanisms of PRL modulation of testosterone feedback in male golden hamsters. In immature animals, the amount of cytoplasmic androgen receptors in the anterior pituitary was decreased by mild hyperprolactinemia and increased by treatment with bromocriptine, an inhibitor of PRL release. Bromocriptine increased pituitary androgen binding also in adult hamsters. These findings would imply that PRL modulates the responsiveness to negative steroid feedback at the pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS)" | Hypothalamo-Hypophyseal System |
The Qing dynasty, the last feudal dynasty of Chinese history, the social formation of which had changed many times as well as the hygienic law formation changed accordingly. The legislative principles of consulting the hygienic law system of the Han and the Jin dynasty, the hygienic law with thoughts of concentration of authority and the rules of rites, the customary law with supplementary functions, the colonial nature of late hygienic law constituted the characteristics of hygienic law system of the Qing dynasty, which had certain reference values to current construction of hygienic law system. | Hygiene |
Transhumanism is a technoprogressive" socio-political and intellectual movement that advocates for the use of technology in order to transform the human organism radically, with the ultimate goal of becoming "posthuman." To this end, transhumanists focus on and encourage the use of new and emerging technologies, such as genetic engineering and brain-machine interfaces. In support of their vision for humanity, and as a way of reassuring those "bioconservatives" who may balk at the radical nature of that vision, transhumanists claim common ground with a number of esteemed thinkers and traditions, from the ancient philosophy of Plato and Aristotle to the postmodern philosophy of Nietzsche. It is crucially important to give proper scholarly attention to transhumanism now, not only because of its recent and ongoing rise as a cultural and political force (and the concomitant potential ramifications for bioethical discourse and public policy), but because of the imminence of major breakthroughs in the kinds of technologies that transhumanism focuses on. Thus, the articles in this issue of The Journal of Medicine and Philosophy are either explicitly about transhumanism or are on topics, such as the ethics of germline engineering and criteria for personhood, that are directly relevant to the debate between transhumanists (and technoprogressives more broadly) and bioconservatives." | Genetic Enhancement |
Endometrial carcinoma is listed among the absolute contra-indications to hormone therapy. After all the existing opinions so far, hormone therapy after FIGO stage I or II endometrial cancer is still thought of as a possibility, and up to now the continuous combined oestrogen/progestogen replacement therapy would be recommended. However, until today, only observational studies have been put forward. Although no study has established an increased rate of recurrences or mortality, alternatives such as phytopreparations, tibolone, or, in, particular, psychotherapeutic drugs such as venlafaxine should be considered for the relief of climacteric complaints. Progestogen-only therapy also comes particularly into question. Indeed, the wider discussion about the gestagen effects regarding the risks of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches, gels) instead of continuous combined oestrogen/progestogen replacement therapy, and this also is now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinomas, such as hypertension, obesity, polycystic ovary syndrome, diabetes mellitus, etc. However, each form of hormone therapy should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives. | Contraindications |
Basic Violet 3, Basic Violet 1, and Basic Violet 4 are triphenylmethane dyes that function as direct (nonoxidative) hair colorants. No current uses or use concentrations in cosmetics are reported. The term Gentian Violet is used synonymously with Basic Violet 1 and Basic Violet 3, although the chemical structures of these 2 dyes are not the same. The Cosmetic Ingredient Review Expert Panel noted that Basic Violet 1, 3, and 4 contain quaternary ammonium ions, and therefore the rate of penetration across the epidermis is expected to be slow. The panel concluded that because of the carcinogenic potential of these dyes, insufficient data exist to support the safety of Basic Violet 1, 3, and 4 in cosmetic formulation. Dermal absorption data and a risk assessment are needed to complete this safety assessment. | Hair Dyes |
To evaluate the impact of parenteral iron administration on the survival and rate of hospitalization of US hemodialysis patients, a nonconcurrent cohort study of 10,169 hemodialysis patients in the United States in 1994 was conducted. The main outcome measures were patient survival and rate of hospitalization. After adjusting for 23 demographic and comorbidity characteristics among 5833 patients included in multivariable analysis, bills for <or=10 vials of iron over 6 mo showed no adverse effect on survival (adjusted relative risk [RR] = 0.93; 95% confidence interval [CI], 0.84 to 1.02; P = 0.14) when compared with none, but bills for >10 vials showed a statistically significant elevated rate of death (adjusted RR = 1.11; 95% CI, 1.00 to 1.24; P = 0.05). Bills for <or=10 vials of iron over 6 mo also showed no significant association with hospitalization (adjusted RR = 0.92; 95% CI, 0.83 to 1.03; P = 0.15), but bills for >10 vials showed statistically significant elevated risk (adjusted RR = 1.12; 95% CI, 1.01 to 1.25; P = 0.03). Prescribing iron in quantities of <or=10 vials over 6 mo had no association with an elevated risk of death or rate of hospitalization. More intensive dosing was associated with diminished survival and higher rates of hospitalization, even after extensive adjustment for baseline comorbidity. Although these potential risks may be offset by the known elevations in morbidity and mortality associated with anemia, these findings indicate that caution is warranted when prescribing >10 vials (1000 mg) of iron dextran over a period of 6 mo. | Iron-Dextran Complex |
L-p-Bromotetramisole is proposed as a new reagent for use in determining intestinal and (or) placental isoenzymes of alkaline phosphatase in human serum. Its main advantage over L-phenylalanine is its high discriminating potency at very low concentrations. For highest accuracy, the samples may even be titrated" with the inhibitor. Analytical recoveries of intestinal and placental isoenzymes in serum are complete, and results correlate well with those by other methods. At the appropriate concentrations, L-p-bromotetramisole gives nearly identical results on a variety of sera, irrespective of the buffer used. Within-day CV's were 6.1 and 2.1 for 20% and 60% of the resistant isoenzyme activity, respectively. The day-to-day CV was 3.45 for a sample containing 53.3% of the resistant isoenzyme (n=15). The well-known increase in placental isoenzyme activity with time of gestation could be confirmed on 612 sera from pregnant women. The activities of the intestinal isoenzyme in sera from healty blood donors (n = 126) and hospitalized patients (n = 135) agree with previous findings obtained by the other techniques." | Tetramisole |
Arynes are important and versatile intermediates in a variety of transformations. Commonly used solvents for aryne chemistry include acetonitrile and dichloromethane. Although rarely reported, the reactive nature of aryne intermediates makes them prone to side reactions, which sometimes involve solvent participation. Acetonitrile and dichloromethane are not always innocent solvents and can participate in aryne-based reactions. These results are presented in the context of ongoing mechanistic investigations of the triple aryne-tetrazine reaction. | Acetonitriles |
OBJECTIVE: To determine whether a device (Urologix Targis system) used for transurethral microwave treatment interferes with sensing, pacing, and arrhythmia detection by permanent pacemakers and implantable cardioverter-defibrillators (ICDs). METHODS: We tested 13 pacemakers in both bipolar and unipolar sensing configurations and 8 ICDs in vitro. Pacemakers and ICDs were programmed to their most sensitive settings. Energy outputs of the microwave device were typical of those used clinically. The probe of the microwave device was anchored 1.2 cm from the pacemaker or ICD being tested. RESULTS: No sensing, pacing, or arrhythmic interactions were noted with any ICD or any pacemaker programmed to the bipolar configuration. One pacemaker (Guidant Vigor 1230) showed intermittent tracking when programmed to the unipolar configuration. CONCLUSIONS: Most patients with permanent pacemakers or ICDs can safely undergo transurethral microwave therapy using the device tested. Pacemakers and ICDs should be programmed to the bipolar configuration (if available) during therapy. The pacemaker or ICD should be interrogated before and after therapy to determine whether programming changes occurred as a result of treatment. However, our findings suggest that this is unlikely. | Short-Wave Therapy |
Birt-Hogg-Dube (BHD) syndrome is an autosomal and predominantly inherited disorder. We report 3 cases of BHD syndrome. Case 1:A 24-year-old man was admitted to our hospital due to left-sided spontaneous pneumothorax. He had a previous drainage history of right-sided spontaneous pneumothorax. In operation, we resected the cyst at segment 8 of the left lung and covered the lung using polyglycolic acid( PGA) sheet. Case 2:A 47-year-old man was admitted to our hospital due to right-sided spontaneous pneumothorax. He had a previous surgical history of right-sided spontaneous pneumothorax and left-sided spontaneous pneumothorax. In operation, we resected the cyst at segment 8 of the right lung and covered the lung using fibrin glue-coated collagen fleece. Case 3:A 60-year-old man was admitted to our hospital due to left-sided spontaneous pneumothorax. He had 2 times of previous drainage history of left-sided spontaneous pneumothorax. In operation, we resected the cysts at lingular division of the lung and covered the lung using PGA sheet. On genetic analysis, all 3 cases were diagnosed with the BHD syndrome. | Birt-Hogg-Dube Syndrome |
Behavior of the green flagellate alga Chlamydomonas changes in response to a number of chemical stimuli. Specific sensitivity of the cells to different substances might appear only at certain stages of the life cycle. The heterogamous species C. allensworthii demonstrates chemotaxis of male gametes towards pheromones excreted by female gametes. In C. reinhardtii chemotaxis towards tryptone occurs only in gametes, whereas chemotaxis towards ammonium, on the contrary, only in vegetative cells. Chemotaxis to different chemical stimuli might involve different mechanisms of reception and signal transduction, elucidation of which has only recently begun. Indirect evidences show that the cells likely respond to tryptone with changes in the membrane electrical conductance. The recently completed project of sequencing the whole nuclear genome of C. reinhardtii provides the basis for future identification of molecular elements of the chemosensory cascade in this alga. | Chemotaxis |
Thiamine and thiamine mono-, pyro- and triphosphate were found at detectable levels in synaptosomes isolated from whole rat brain. Synaptosomes prepared from whole brain, cerebellum and medulla were also found to contain uridine and inosine mono- and diphosphatases as well as the thiamine pyrophosphate synthetizing and hydrolyzing enzymes, but no thiamine monophosphatase. By isoelectric focusing on thin layer polyacrylamide gel of Triton X-100 homogenates of synaptosomes, thiamine pyrophosphatase activity could be separated into 10 bands with different isoelectric points. The contents of thiamine compounds and enzymes in synaptosomes were generally lower than those found in neuronal cell bodies. | Thiamine Triphosphate |
OBJECTIVE: IDH1/2 mutations, intervening in epigenetic procedures, are frequently encountered in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Knowledge of the genetics, immunophenotypes, and mutational kinetics of IDH1/2-mutated AML can contribute to the understanding of AML clonal architecture and inform therapeutics and monitoring. METHODS: We retrospectively analyzed 50 IDH1/2-mutated AML/MDS-EB cases of our institution, to identify recurrent co-mutations, immunophenotypes, patterns of co-variance of IDH1/2 allele burdens with those of recurrent co-mutations, frequency of persistent IDH1/2 mutation as clonal hematopoiesis of indeterminate potential (CHIP) in remission and response to hypomethylating agents. RESULTS: Most frequently co-mutated genes were DNMT3A, SRSF2 and NPM1. Most cases with co-existent IDH1/2 and NPM1 mutations (11/13) showed an 'APL-like' immunophenotype (CD34-HLADR-). Allele burdens of mutated IDH1/2 were identical to mutated SRSF2 allele burdens at diagnosis and remission, but not always to mutated NPM1 allele burden in remission. We show persistence of significant mutIDH1/2 allele burden in approximately one-fourth of patients with deep remissions. IDH1/2 mutations were significantly more frequent among responders to first-line HMA-based regimens than among non-responders, in patients treated for myeloid neoplasms with excess blasts. CONCLUSIONS: IDH1/2 mutations are most frequently accompanied by DNMT3A, SRSF2 and NPM1 mutations. NPM1-IDH1/2 mutated AML has a mature phenotype possibly amenable to differentiation therapies. IDH1/2 and SRSF2 mutations probably arise at the same developmental stage of the disease, as their allele burdens covariate. IDH1/2 mutation represents CHIP in a substantial proportion of cases and is therefore no reliable residual disease marker. The preferential presence of IDH1/2 mutations among HMA-responders could inform therapeutic decisions if confirmed in larger series. | Genetic Profile |
Children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are at risk for low immunization coverage and other adverse health-related outcomes. Immunization-promoting strategies in WIC have been shown to produce dramatic improvements in immunization coverage. This evaluation of a local WIC initiative in Milwaukee is the first study to evaluate the impact of these strategies on improving the utilization of other clinical preventive services at the medical home. The use of more intensive immunization-promoting strategies in WIC may improve utilization of well child care visits and receipt of other clinical preventive services in the medical home. | Preventive Health Services |
Th17 cells are essential for protection against extracellular pathogens, but their aberrant activity can cause autoimmunity. Molecular mechanisms that dictate Th17 cell-differentiation have been extensively studied using mouse models. However, species-specific differences underscore the need to validate these findings in human. Here, we characterized the human-specific roles of three AP-1 transcription factors, FOSL1, FOSL2 and BATF, during early stages of Th17 differentiation. Our results demonstrate that FOSL1 and FOSL2 co-repress Th17 fate-specification, whereas BATF promotes the Th17 lineage. Strikingly, FOSL1 was found to play different roles in human and mouse. Genome-wide binding analysis indicated that FOSL1, FOSL2 and BATF share occupancy over regulatory regions of genes involved in Th17 lineage commitment. These AP-1 factors also share their protein interacting partners, which suggests mechanisms for their functional interplay. Our study further reveals that the genomic binding sites of FOSL1, FOSL2 and BATF harbour hundreds of autoimmune disease-linked SNPs. We show that many of these SNPs alter the ability of these transcription factors to bind DNA. Our findings thus provide critical insights into AP-1-mediated regulation of human Th17-fate and associated pathologies. | Fos-Related Antigen-2 |
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