Candidates registered for reasonable adjustments underperform compared to other candidates in the national undergraduate Prescribing Safety Assessment: Retrospective cohort analysis (2014-2018).

AIMS: Candidates with disabilities are eligible for reasonable adjustments (RA) while undertaking the national Prescribing Safety Assessment (PSA). The PSA is a novel open-book, time-constrained, multiformat assessment that may pose challenges to candidates with dyslexia and other disabilities. METHODS: Retrospective cohort analysis of 36 140 UK candidates undertaking first-sitting of the PSA (2014-2018). RESULTS: Of the 36 140 candidates, 9.1% (3284) were registered for RA. The RA group had lower pass rates (absolute difference 1.94%, 95% confidence interval 1.01-2.87%; P < .001) and assessment scores (1.16 percentage marks, 95% confidence interval 0.83-1.48; P < .001) compared with the non-RA group. This absolute difference is small relative to overall variability. This difference persists after adjusting for confounding factors (medical school and paper), and was present for all 8 different question types. The attainment gap within each medical school is negatively correlated with the school's overall performance, both in terms of pass rate (P < .001) and scores (P = .01). The RA group were also less likely to perceive the PSA as an appropriate test, having easy to follow layout/presentation or clear/unambiguous questions, even after adjusting for candidate performance. CONCLUSION: This analysis identifies slight differences in academic performance of candidates requiring RA in a national undergraduate assessment. The study is limited by the unavailability of data on ethnicity, sex, age, diagnosis and time of diagnosis. While further research is required to determine the cause of the attainment gap, this study emphasises the need to maintain a careful review on the fairness and validity of all aspects of the assessment

Vac-and-fill: A micromoulding technique for fabricating microneedle arrays with vacuum-activated, hands-free mould-filling

We report a simple and reproducible micromoulding technique that dynamically fills microneedle moulds with a liquid formulation, using a plastic syringe, triggered by the application of vacuum (‘vac-and-fill’). As pressure around the syringe drops, air inside the syringe pushes the plunger to uncover an opening in the syringe and fill the microneedle mould without manual intervention, therefore removing inter-operator variability. The technique was validated by monitoring the plunger movement and pressure at which the mould would be filled over 10 vacuum cycles for various liquid formulation of varying viscosity (water, glycerol, 20% polyvinylpyrrolidone (PVP) solution or 40% PVP solution). Additionally, the impact of re-using the disposable syringes on plunger movement, and thus the fill pressure, was investigated using a 20% PVP solution. The fill pressure was consistent at 300–450 mbar. It produced well-formed and mechanically robust PVP, poly(methylvinylether/maleic anhydride) and hydroxyethylcellulose microneedles from liquid formulations. This simple and inexpensive technique of micromoulding eliminated the air entrapment and bubble formation, which prevent reproducible microneedle formation, in the resultant microneedle arrays. It provides a cost-effective alternative to the conventional micromoulding techniques, where the application of vacuum (‘fill-and-vac’) or centrifugation following mould-filling may be unsuitable, ineffective or have poor reproducibility

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Evaluation of the nasal mucociliary transport rate by rhinoscintigraphy before and after surgery in patients with deviated nasal septum

In this study, we have investigated the effect of nasal septal deviation (NSD) on nasal mucociliary activity and how does a septoplasty operation affecs the nasal mucociliary transport rate in the first and third months during the post-operative period. Twenty-two patients who were diagnosed with NSD and 22 healthy controls were studied using rhinoscintigraphy with Tc-99m-macroaggregated albumin (Tc-99m-MAA). On each case, the nasal mucociliary transport rate (NMTR) was measured pre-operatively only on five cases, on the first and third months of post-operative period. The NMTRs of patients with a deviated septum were significantly lower than the NMTRs of the healthy controls on both the convex and concave sides. Significant improvement was observed in the first post-operative month. On the concave and convex sides, the average postop third month post-operative NMTR value was higher than the first month post-operative NMTR values. It was concluded that the septoplasty operation improves reduced NMTRs after surgery. The effect of nasal surgery on nasal mucociliary activity may be more accurately evaluated in the third month than the first month of post-operative period

The Use of Orthologous Sequences to Predict the Impact of Amino Acid Substitutions on Protein Function

Computational predictions of the functional impact of genetic variation play a critical role in human genetics research. For nonsynonymous coding variants, most prediction algorithms make use of patterns of amino acid substitutions observed among homologous proteins at a given site. In particular, substitutions observed in orthologous proteins from other species are often assumed to be tolerated in the human protein as well. We examined this assumption by evaluating a panel of nonsynonymous mutants of a prototypical human enzyme, methylenetetrahydrofolate reductase (MTHFR), in a yeast cell-based functional assay. As expected, substitutions in human MTHFR at sites that are well-conserved across distant orthologs result in an impaired enzyme, while substitutions present in recently diverged sequences (including a 9-site mutant that “resurrects” the human-macaque ancestor) result in a functional enzyme. We also interrogated 30 sites with varying degrees of conservation by creating substitutions in the human enzyme that are accepted in at least one ortholog of MTHFR. Quite surprisingly, most of these substitutions were deleterious to the human enzyme. The results suggest that selective constraints vary between phylogenetic lineages such that inclusion of distant orthologs to infer selective pressures on the human enzyme may be misleading. We propose that homologous proteins are best used to reconstruct ancestral sequences and infer amino acid conservation among only direct lineal ancestors of a particular protein. We show that such an “ancestral site preservation” measure outperforms other prediction methods, not only in our selected set for MTHFR, but also in an exhaustive set of E. coli LacI mutants

African-American crack abusers and drug treatment initiation: barriers and effects of a pretreatment intervention

BACKGROUND: Individual and sociocultural factors may pose significant barriers for drug abusers seeking treatment, particularly for African-American crack cocaine abusers. However, there is evidence that pretreatment interventions may reduce treatment initiation barriers. This study examined the effects of a pretreatment intervention designed to enhance treatment motivation, decrease crack use, and prepare crack abusers for treatment entry. METHODS: Using street outreach, 443 African-American crack users were recruited in North Carolina and randomly assigned to either the pretreatment intervention or control group. RESULTS: At 3-month follow-up, both groups significantly reduced their crack use but the intervention group participants were more likely to have initiated treatment. CONCLUSION: The intervention helped motivate change but structural barriers to treatment remained keeping actual admissions low. Policy makers may be interested in these pretreatment sites as an alternative to treatment for short term outcomes

Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

BACKGROUND: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). METHODS: We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). RESULTS: The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. CONCLUSION: Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen

Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer

Background: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis