2,190 research outputs found

    Can achievement at medical admission tests predict future performance in postgraduate clinical assessments? A UK-based national cohort study

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    OBJECTIVE: To determine whether scores on two undergraduate admissions tests (BioMedical Admissions Test (BMAT) and University Clinical Aptitude Test (UCAT)) predict performance on the postgraduate Membership of the Royal Colleges of Physicians (MRCP) examination, including the clinical examination Practical Assessment of Clinical Examination Skills (PACES). DESIGN: National cohort study. SETTING: Doctors who graduated medical school between 2006 and 2018. PARTICIPANTS: 3045 doctors who had sat BMAT, UCAT and the MRCP. PRIMARY OUTCOME MEASURES: Passing each section of the MRCP at the first attempt, including the clinical assessment PACES. RESULTS: Several BMAT and UCAT subtest scores displayed incremental predictive validity for performance on the first two (written) parts of the MRCP. Only aptitude and skills on BMAT (OR 1.34, 1.08 to 1.67, p=0.01) and verbal reasoning on UCAT (OR 1.34, 1.04 to 1.71, p=0.02) incrementally predicted passing PACES at the first attempt. CONCLUSIONS: Our results imply that the abilities assessed by aptitude and skills and verbal reasoning may be the most important cognitive attributes, of those routinely assessed at selection, for predicting future clinical performance. Selectors may wish to consider placing particular weight on scales assessing these attributes if they wish to select applicants likely to become more competent clinicians. These results are potentially relevant in an international context too, since many admission tests used globally, such as the Medical College Admission Test, assess similar abilities

    Spin dependent parton distributions and structure functions

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    Nuclear parton distributions and structure functions are determined in an effective chiral quark theory. We also discuss an extension of our model to fragmentation functions.Comment: To appear in the proceedings of the 20th European Conference on Few-Body Problems in Physics, Pisa, September 10-14, 200

    Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

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    Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

    In vivo antihyperglycaemic and antihyperlipidemic activities and chemical constituents of Solanum anomalum

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    Solanum anomalum is a plant used ethnomedically for the treatment of diabetes. The study was aimed to validate ethnomedical claims in rat model and identify the likely antidiabetic compounds. Leaf extract (70–210 mg/kg/day) and fractions (140 mg/kg/day) of S. anomalum were evaluated in hyperglycaemic rats induced using alloxan for effects on blood glucose, lipids and pancreas histology. Phytochemical characterisation of isolated compounds and their identification were performed using mass spectrometry and NMR spectroscopy. Bioinformatics tool was used to predict the possible protein targets of the identified bioactive compounds. The leaf extract/fractions on administration to diabetic rats caused significant lowering of fasting blood glucose of the diabetic rats during single dose study and on repeated administration of the extract. The hydroethanolic leaf extracts also enhanced glucose utilization capacity of the diabetic rats and caused significant lowering of glycosylated hemoglobin levels and elevation of insulin levels in the serum. Furthermore, triglycerides, LDL-cholesterol, and VLDL-cholesterol levels were lowered significantly, while HDL–cholesterol levels were also elevated in the treated diabetic rats. There was absence or few pathological signs in the treated hyperglycaemic rat pancreas compared to that present in the pancreas of control group. Diosgenin, 25(R)-diosgenin-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside, uracil, thymine, 1-octacosanol, and octacosane were isolated and identified. Protein phosphatases along with secreted proteins are predicted to be the major targets of diosgenin and the diosgenin glycoside. These results suggest that the leaf extract/fractions of S. anomalum possess antidiabetic and antihyperlipidemic properties, offer protection to the pancreas and stimulate insulin secretion, which can be attributable to the activities of its phytochemical constituents

    Intraspecfic variation in cold-temperature metabolic phenotypes of Arabidopsis lyrata ssp petraea

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    Atmospheric temperature is a key factor in determining the distribution of a plant species. Alongside this, plant populations growing at the margin of their range may exhibit traits that indicate genetic differentiation and adaptation to their local abiotic environment. We investigated whether geographically separated marginal populations of Arabidopsis lyrata ssp. petraea have distinct metabolic phenotypes associated with exposure to cold temperatures. Seeds of A. petraea were obtained from populations along a latitudinal gradient, namely Wales, Sweden and Iceland and grown in a controlled cabinet environment. Mannose, glucose, fructose, sucrose and raffinose concentrations were different between cold treatments and populations, especially in the Welsh population, but polyhydric alcohol concentrations were not. The free amino acid compositions were population specific, with fold differences in most amino acids, especially in the Icelandic populations, with gross changes in amino acids, particularly those associated with glutamine metabolism. Metabolic fingerprints and profiles were obtained. Principal component analysis (PCA) of metabolite fingerprints revealed metabolic characteristic phenotypes for each population and temperature. It is suggested that amino acids and carbohydrates were responsible for discriminating populations within the PCA. Metabolite fingerprinting and profiling has proved to be sufficiently sensitive to identify metabolic differences between plant populations at different atmospheric temperatures. These findings show that there is significant natural variation in cold metabolism among populations of A. l. petraea which may signify plant adaptation to local climates

    Can achievement at medical admission tests predict future performance in postgraduate clinical assessments? A UK-based national cohort study.

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    OBJECTIVE: To determine whether scores on two undergraduate admissions tests (BioMedical Admissions Test (BMAT) and University Clinical Aptitude Test (UCAT)) predict performance on the postgraduate Membership of the Royal Colleges of Physicians (MRCP) examination, including the clinical examination Practical Assessment of Clinical Examination Skills (PACES). DESIGN: National cohort study. SETTING: Doctors who graduated medical school between 2006 and 2018. PARTICIPANTS: 3045 doctors who had sat BMAT, UCAT and the MRCP. PRIMARY OUTCOME MEASURES: Passing each section of the MRCP at the first attempt, including the clinical assessment PACES. RESULTS: Several BMAT and UCAT subtest scores displayed incremental predictive validity for performance on the first two (written) parts of the MRCP. Only aptitude and skills on BMAT (OR 1.34, 1.08 to 1.67, p=0.01) and verbal reasoning on UCAT (OR 1.34, 1.04 to 1.71, p=0.02) incrementally predicted passing PACES at the first attempt. CONCLUSIONS: Our results imply that the abilities assessed by aptitude and skills and verbal reasoning may be the most important cognitive attributes, of those routinely assessed at selection, for predicting future clinical performance. Selectors may wish to consider placing particular weight on scales assessing these attributes if they wish to select applicants likely to become more competent clinicians. These results are potentially relevant in an international context too, since many admission tests used globally, such as the Medical College Admission Test, assess similar abilities

    Cost-effectiveness of monitoring glaucoma patients in shared care: an economic evaluation alongside a randomized controlled trial

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    Background. Population aging increases the number of glaucoma patients which leads to higher workloads of glaucoma specialists. If stable glaucoma patients were monitored by optometrists and ophthalmic technicians in a glaucoma follow-up unit (GFU) rather than by glaucoma specialists, the specialists' workload and waiting lists might be reduced. We compared costs and quality of care at the GFU with those of usual care by glaucoma specialists in the Rotterdam Eye Hospital (REH) in a 30-month randomized clinical trial. Because quality of care turned out to be similar, we focus here on the costs. Methods. Stable glaucoma patients were randomized between the GFU and the glaucoma specialist group. Costs per patient year were calculated from four perspectives: those of patients, the Rotterdam Eye Hospital (REH), Dutch healthcare system, and society. The outcome measures were: compliance to the protocol; patient satisfaction; stability according to the practitioner; mean difference in IOP; results of the examinations; and number of treatment changes. Results. Baseline characteristics (such as age, intraocular pressure and target pressure) were comparable between the GFU group (n = 410) and the glaucoma specialist group (n = 405). Despite a higher number of visits per year, mean hospital costs per patient year were lower in the GFU group (€139 vs. €161). Patients' time and travel costs were similar. Healthcare costs were significantly lower for the GFU group (€230 vs. €251), as were societal costs (€310 vs. €339) (p < 0.01). Bootstrap-, sensitivity- and scenario-analyses showed that the costs were robust when varying hospital policy and the duration of visits and tests. Conclusion. We conclude that this GFU is cost-effective and deserves to be considered for implementation in other hospitals

    A Single Amino Acid Mutation in SNAP-25 Induces Anxiety-Related Behavior in Mouse

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    Synaptosomal-associated protein of 25 kDa (SNAP-25) is a presynaptic protein essential for neurotransmitter release. Previously, we demonstrate that protein kinase C (PKC) phosphorylates Ser187 of SNAP-25, and enhances neurotransmitter release by recruiting secretory vesicles near to the plasma membrane. As PKC is abundant in the brain and SNAP-25 is essential for synaptic transmission, SNAP-25 phosphorylation is likely to play a crucial role in the central nervous system. We therefore generated a mutant mouse, substituting Ser187 of SNAP-25 with Ala using “knock-in” technology. The most striking effect of the mutation was observed in their behavior. The homozygous mutant mice froze readily in response to environmental change, and showed strong anxiety-related behavior in general activity and light and dark preference tests. In addition, the mutant mice sometimes exhibited spontaneously occurring convulsive seizures. Microdialysis measurements revealed that serotonin and dopamine release were markedly reduced in amygdala. These results clearly indicate that PKC-dependent SNAP-25 phosphorylation plays a critical role in the regulation of emotional behavior as well as the suppression of epileptic seizures, and the lack of enhancement of monoamine release is one of the possible mechanisms underlying these defects

    Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

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    The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability
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