Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma.

BACKGROUND The C-509T polymorphism of TGF-beta(1) gene has been associated with asthma and atopy in white populations. OBJECTIVE We investigated the association between asthma and previously identified polymorphisms at C-509T and T869C of the TGF-beta(1) gene among 250 Chinese patients with asthma and 308 healthy controls in Hong Kong. METHODS Genotyping was performed on peripheral blood genomic DNA by using PCR-RFLP. RESULTS There were no differences in the frequencies of genotypes and alleles between patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium (P < .01). Among atopic subjects, significant differences were found in genotype and allele frequencies for T869C polymorphism between patients and controls (P = .014 and P = .019, respectively), and individuals bearing the CC genotype were associated with increased risk for the development of asthma (odds ratio, 2.58; 95% CI, 1.17-5.66; P = .018) after adjusting for age, sex, and smoking status. Individuals with asthma bearing the CT genotype of the C-509T polymorphism had significantly increased risk for severe airflow obstruction compared with individuals who had mild obstruction (odds ratio, 4.00; 95% CI, 1.06-15.08; P = .035). CONCLUSION Our results indicate that the polymorphisms at C-509T and T869C of the TGF-beta(1) gene are associated with asthma susceptibility in atopic subjects of the Hong Kong Chinese population, and the C-509T polymorphism may play a role in the pathogenesis of airflow obstruction.
Critically Ill Children During the 2009–2010 Influenza Pandemic in the United States

BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had ≥1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1–20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors.
Osteogenic and chondrogenic potential of biomembrane cells from the PMMA‐segmental defect rat model

A layer of cells (the “biomembrane”) has been identified in large segmental defects between bone and surgically placed methacrylate spacers or antibiotic‐impregnated cement beads. We hypothesize that this contains a pluripotent stem cell population with potential valuable applications in orthopedic tissue engineering. Objectives using biomembranes harvested from rat segmental defects were to: (1) Culture biomembrane cells in specialized media to direct progenitor cells along bone or cartilage cell differentiation lineages; (2) evaluate harvested biomembranes for mesenchymal stem cell markers, and (3) define relevant gene expression patterns in harvested biomembranes using microarray analysis. Culture in osteogenic media produced mineralized nodules; culture in chondrogenic media produced masses containing chondroitin sulfate/sulfated proteoglycans. Molecular analysis of biomembrane cells versus control periosteum showed significant upregulation of key genes functioning in mesenchymal stem cell differentiation, development, maintenance, and proliferation. Results identified significant upregulation of WNT receptor signaling pathway genes and significant upregulation of BMP signaling pathway genes. Findings confirm that the biomembrane has a pluripotent stem cell population. The ability to heal large bone defects is clinically challenging, and novel tissue engineering uses of the biomembrane hold great promise in treating non‐unions, open fractures with large bone loss and/or infections, and defects associated with tumor resection. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1198–1212, 2012
The effect of budesonide (Rhinocort) in the treatment of small and medium-sized nasal polyps.

The objectives of this study were to determine if the size of nasal polyps could be assessed in a reproducible way and to study the effect of budesonide in patients suffering from eosinophilic nasal polyposis with small and medium sized polyps. Ninety-one patients entered the study. Budesonide 200 micrograms b.i. d. (aerosol or aqua) and placebo (aerosol or aqua) were compared in a 3-month double-blind, multi-centre, randomized study. Efficacy was measured by an assessment of polyp size, nasal peak-flow index and the patient's assessment of nasal symptoms. The conclusions were that the size of polyps could be assessed in a reproducible way, and that budesonide delivered either as a water-based suspension or as an aerosol is effective in the treatment of patients with small and medium sized polyps.
Suicidal behavior and attitudes among medical students in the United Arab Emirates.

BACKGROUND Few studies have investigated suicidal behavior and attitudes of medical students. We are not aware of any previous reports emerging from the Arab world. AIMS To investigate suicidal behavior and attitudes among medical students in the United Arab Emirates (UAE). METHOD The prevalence of suicidal ideation and attempts as well as attitudes toward suicide and reactions to a hypothetical suicidal friend were assessed using a self-report survey. Furthermore, the survey included the self-assessment of the current mood and religiosity, and socio-demographic information. RESULTS A group of 115 medical students (mean age 20.7 years, 59.1% female) participated in the survey. The prevalence of lifetime suicidal ideation was 17.5% and of suicide attempts 1.8%. In general, students showed very low acceptability of suicide, strong beliefs in the punishment after death, and highly endorsed communicating problems with parents. Moreover, high acceptance of and support for a suicidal friend were found. Sadness was associated with higher acceptability of suicide and fewer beliefs in punishment after death. Religiosity was associated with less acceptability of suicide, seeing suicide in context of mental illness, communicating problems with parents, and greater support for a suicidal friend. CONCLUSIONS The prevalence of suicidal ideation and attempts among medical students in the UAE was in the lower range in international comparison. Negative attitudes toward suicide were accompanied by a strong support for a suicidal friend, and both were related to religiosity.
Treating pressure ulcers with clostridial collagenase ointment: Results from the US Wound Registry

We assessed the clinical effectiveness of clostridial collagenase ointment (CCO) as an adjunct to selective debridement compared with selective debridement alone for the management of stage IV pressure ulcers (PU) in the hospital outpatient department setting. Outcome data were derived from retrospective de‐identified electronic medical records from 2007 to 2013 using the US Wound Registry. A propensity score method was used to adjust for selection bias and to test for treatment effect between PU treated with CCO plus selective debridement vs. selective debridement alone. A total of 337 CCO and 336 non‐CCO stage IV PU were identified. The proportion of wounds closed at any time (e.g., at 1 or 2 years) was two times greater for stage IV PU treated with CCO compared with those not treated with CCO. Kaplan–Meier analysis showed that time to wound closure at 1 year was significantly faster for PU treated with CCO vs. PU not treated with CCO. Among those with five or more CCO applications or selective debridement treatments, significantly more CCO‐treated PU were closed at 1 or 2 years than non–CCO‐treated PU. CCO as an adjunct to selective debridement improved clinical outcomes and provided faster rates of closure of stage IV PU relative to selective debridement alone.
NMDA receptors and PSD‐95 are found in attachment plaques in cerebellar granular layer glomeruli

N‐methyl‐d‐aspartate (NMDA) receptors mediate long‐term changes in excitatory synapses in response to glutamate release. In the cerebellar granular layer, most glutamatergic synapses are formed between mossy terminals and granule cell dendrites, which together with some other components, make up complex glomerular structures. Glomeruli contain numerous attachment plaques (or puncta adherentia), which are sites of adhesion between cells. These structures are found mainly between granule cell dendrites, and probably help maintain the integrity of glomeruli. Attachment plaques contain adhesive proteins such as cadherins. In this study, we show that NMDA receptors are common at these attachment plaques, in addition to being found at synapses. We used four different antibodies to the NMDA receptor subunit, NR1, and another to NR2A/B. In contrast, labelling for an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) glutamate receptor antibody was seen only in a few attachment plaques, although AMPA receptors were seen frequently at glomerular synapses. We also show that substantial levels of the NMDA receptor‐associated protein, PSD‐95, are found in both synapses and attachment plaques. One way that NMDA receptors mediate changes in synapses is through effects on synaptic cadherins, which change their adhesive properties in response to NMDA receptor activation and consequently may alter synaptic function. The presence of NMDA receptors in attachment plaques suggests that these receptors mediate changes in the adhesive properties of these plaques, similar to this function in synapses.
Hippocampus-dependent and -independent theta-networks of active maintenance

Recent studies in humans and animals raise the possibility that actively maintaining a detailed memory of a scene within working memory may require the hippocampus, a brain structure better known for its role in long-term memory. We show that the hippocampus is behaviorally and functionally critical for configural-relational (CR) maintenance by orchestrating the synchrony of occipital and temporal brain regions in the theta-frequency range. Using magnetoencephalography in healthy adults and patients with bilateral hippocampal sclerosis, we distinguish this hippocampus-dependent theta-network from one that is independent of the hippocampus and used for non-CR scene maintenance. This non-CR theta-network involved frontal and parietal brain regions. We also show that the functional and topographical dissociation between these two networks cannot be accounted for by perceptual difficulty or the amount of information to be maintained (“load”). Also, we confirm in healthy adults that active maintenance of the CR arrangement of objects within a scene is impaired by task-interference during the delay in a manner akin to working-memory maintenance processes. Together, these findings demand reconsideration of the classical functional-anatomical distinctions between long- and short-term memory.
Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

OBJECTIVE--To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN--One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING--Outpatient clinics of five hospitals. SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE--Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS--For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS--Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.
The Role of Protein Phosphatase 2A Catalytic Subunit Cα in Embryogenesis: Evidence from Sequence Analysis and Localization Studies

Abstract Protein phosphatase 2A (PP2A) constitutes one of the major families of protein serine/threonine phosphatases found in all eukaryotic cells. PP2A holoenzymes are composed of a catalytic subunit complexed with a structural regulatory subunit of 65 kDa. These core subunits associate with regulatory subunits of various sizes to form different heterotrimers which have been purified and evaluated with regard to substrate specificity. In fully differentiated tissues PP2A expression levels are highest in the brain, however, relatively little is known about expression in the developing embryo. In order to determine the composition of PP2A catalytic subunits in the mouse, cDNAs were cloned and the genomic organization of PP2A Cα was determined. By a gene targeting approach in the mouse, we have previously shown that the absence of the major catalytic subunit of PP2A, Cα, resulted in embryonic lethality around embryonic day E6.5. No mesoderm was formed which implied that PP2A plays a crucial role in gastrulation. Here, we extended our studies and analyzed wildtype embryos for Cα expression at subsequent stages of development. After gastrulation is completed, we find high expression of Cα restricted to the neural folds, which suggests that PP2A plays an additional pivotal role in neurulation.
Anxiety during the performance of colonoscopies: modification using music therapy

Background and study aims Colonoscopies are usually performed using pharmacological sedation. This process entails certain risks. In the search for alternative methods, some studies have analysed the effect music can have on patients during the procedure when used as a complement to sedation. We present a prospective, randomized study in which we assess the anxiolytic action music has when it is administered during a single colonoscopy. Patients and methods We included 118 patients who were scheduled for ambulatory colonoscopies. They were randomly assigned to the control group (n = 55) and the experimental group (n = 63). We determined their levels of anxiety using the State-Trait Anxiety Inventory Test (STAI) form, which they filled in before and after the examination. Patients listened to music through personal headphones. Results The score on the STAI form before the examination was 25.25 ± 10.49 and 28.16 ± 11.43 in the control and experimental groups, respectively (P > 0.05). The decrease of the score on the STAI scale after the colonoscopy in the control and experimental groups was 6.27 (95% confidence interval, 3.26–9.28) and 11.35 (95% confidence interval, 8.64–14.05), respectively (P < 0.01). Conclusions Listening to music during ambulatory colonoscopies decreases the level of anxiety that is inherent to the process without other anxiolytic methods.
Low molecular weight heparin in unstable coronary artery disease

Since the recognition that any thrombosis overlying a ruptured atherosclerotic plaque is a central component of the pathogenesis of unstable coronary artery disease (CAD), a number of antithrombotic treatment strategies have been investigated in randomised clinical trials. Aspirin reduces the occurrence of symptomatic and silent ischaemia, myocardial infarction (MI) and death in patients with unstable CAD, both in the acute phase and during continued long-term treatment and is now considered routine therapy. The addition of unfractionated heparin infusion further reduces cardiac events during the treatment period, but is not associated with any sustained benefits during long-term follow-up. Low molecular weight heparins (LMWHs) are completely absorbed by the sc. route. A predictable anticoagulant effect is maintained by sc. injections every 12 - 24 h without laboratory monitoring. The FRISC trial demonstrated that, in conjunction with aspirin, the LMWH dalteparin reduced death and MI by more than 50% in the acute phase. Four similar trials have directly compared LMWH with unfractionated heparin and demonstrated at least the same efficacy in the acute phase, treated between three and eight days. The LMWH enoxaparin was more effective at reducing death or MI than unfractionated heparin infusion during the three days of treatment, an effect which lasted up to 12 months. Prolonged out-patient treatment beyond the acute phase has been evaluated in four trials. It was demonstrated, in two of these trials, that continuing twice-daily injections of dalteparin further reduced the risk of death, MI and need for revascularisation at least during the initial six weeks of treatment. This effect was confined, however, to patients with signs of myocardial damage, i.e., elevation of troponin, at admission. During prolonged out-patient treatment, there is an increased risk of severe bleeding due to the combination of LMWH with aspirin. Based on successful results, the LMWHs, having the convenience of treatment and the option for continuation in an out-patient setting, should replace unfractionated heparin as the routine treatment in unstable CAD. If an early invasive procedure is considered, the LMWH therapy should be continued until the intervention as a ‘bridge-to-revascularisation’. New antiplatelet agents are also emerging as additional useful tools for treating these patients, thus it is urgent to evaluate the comibination of these new therapies with the LMWHs.
Impaired mitochondrial respiration and decreased fatigue resistance followed by severe muscle weakness in skeletal muscle of mitochondrial DNA mutator mice

• Defective mitochondrial function has been shown to cause muscle weakness and exercise intolerance. • We used a mouse model of premature ageing with defective proofreading of mitochondrial DNA (mtDNA): the mtDNA mutator mouse. • Muscles of young (3–5 months) mtDNA mutator mice showed reduced endurance, which was caused by decreased mitochondrial ATP production accompanied by decreased levels of factors stimulating mitochondrial biogenesis. • The dominant defect in muscles of old (11 months) mtDNA mutator mice was severe weakness, which was caused by decreased intracellular Ca2+ stores. • These results underline two important aspects of mitochondria‐to‐nucleus signalling in skeletal muscle: (1) it fails to respond adequately to decreased mitochondrial ATP production in sedentary animals; and (2) it can induce decreased intracellular Ca2+ stores and hence muscle weakness. • These results have implication for normal ageing and suggest that the decreased mitochondrial function induced by a sedentary lifestyle may predispose to muscle weakness later in life.
The Dale E. McFarlin memorial lecture: The immunology of the multiple sclerosis lesion

This review surveys the structural terrain of the multiple sclerosis (MS) lesion from the standpoint of its immunologic responsiveness. Similarities in lymphocyte trafficking patterns are noted between MS and its laboratory model, experimental allergic encephalomyelitis (EAE), and in both conditions, the inflammatory response is selective for the central nervous system (CNS). While adhesion molecules abound during the genesis of the MS lesion, none has yet been found that is unusual to this condition and, indeed, many occur in other neurodegenerative states in which inflammation is not a component of the lesion. Cytokines are effective regulators of lymphocyte traffic and adhesion events and most can be located in MS lesions. Of these, tumor necrosis factor‐α (TNF‐α) occurs in abundance. Together with its known affinity to effect myelin and oligodendrocyte destruction and to up‐regulate adhesion molecule expression, the presence of TNF‐α renders it an important player in lesion pathogenesis. Demyelination is described as a rapid lytic event, perhaps involving cytokines and immunoglobulin, and structural similarities are common in the patterns seen in MS and EAE. Oligodendrocytes survive the initial stages of lesion formation. Moreover, they are now known to proliferate and elaborate new myelin at the same time as myelin is being degraded. This paradoxical reparatory scenario is apparently a transient event although rims of remyelination persist about the margins of chronic lesions. The speculation is reiterated that the demise of the oligodendrocyte in MS may occur late in lesion formation and may be in part related to the expression of heat shock proteins (specifically, members of the hsp 60 family), potent stimulators of T‐cell receptor‐γδ T cells that have been claimed to have cytolytic activity and that have been located in chronic active MS lesions. In sum, while no single immune system molecule can be assigned as unusual to the CNS in MS, and while there appears to be nothing unique about the manner in which the CNS responds to the inflammation, the true uniqueness of the situation in MS is probably related to the many, normally sequestered, specific antigens within the myelin sheath and the biology of the myelinating cell, the oligodendrocyte.