Evaluation of the first year of the Oxpal Medlink: A web-based partnership designed to address specific challenges facing medical education in the occupied Palestinian territories

Objectives: To (1) evaluate educational needs of clinical students at Al-Quds University Medical School in the West Bank; (2) address these needs where possible using synchronous distance learning, with clinicians in Oxford providing case-based tutorials to undergraduates in the West Bank via an online platform (WizIQ) and (3) assess the impact of this education. Design: Review of online OxPal Medlink database for tutorials held between March 2012 and April 2013. Needs assessment and evaluation of student and tutor experiences through online questionnaires, focus groups and semi-structured interviews. Setting: Oxford University Hospitals, Oxford, UK, and Al-Quds University Medical School, Abu Dies, Palestine. Participants: Doctors at Oxford University Hospitals and fourth-, fifth- and sixth-year medical students and faculty members at Al-Quds Medical School. Main outcome measures Number of tutorials, student participation, student-rated satisfaction and qualitative feedback from tutors and students. Results: Students demonstrated strong theoretical knowledge but struggled to apply this in presentation-based scenarios. Between March 2012 and April 2013, 90 tutorials were delivered to 60 students. Feedback: >95% respondents rated tutorials as ‘Excellent’ or ‘Good’ and ‘Very’ or ‘Fairly’ relevant to their future practice in Palestine. Students reported the programme had modified their approach to patients but requested better synchronization with concurrent attachments and clarification of learning outcomes. Conclusions: OxPal Medlink is a novel, web-based distance-learning partnership designed to overcome some of the challenges to local medical education in the occupied Palestinian territories. Evaluation of the first year indicates teaching is relevant to local practice and of high quality. This approach may have the potential to strengthen local capacity for medical education

Engineered spider silk-based 2D and 3D materials prevent microbial infestation

Biofilm formation, especially of antimicrobiotic-resistant microbial strains, are a major problem in health care. Therefore, there is great interest in developing advanced materials that are selectively inhibiting microbial adhesion to surfaces, but at the same time promoting mammalian cell growth. In nature, some spider silks have evolved to repel microbes, a feature that could be used in biomaterials. To unravel how microbe repellence can be achieved in engineered spider silk, different recombinant spider silk proteins based on the consensus sequences of Araneus diadematus dragline silk proteins (fibroin 3 and 4) were processed into 2D-patterned films and 3D-hydrogels. Strikingly, protein structure characteristics on the nanoscale are the basis for the detected microbe-repellence. Designed spider silk materials promoted mammalian cell attachment and proliferation while inhibiting microbial infestation, demonstrating the great potential of these engineered spider silk-based materials as bio-selective microbial-resistant coatings in biomedical as well as technical applications

Clinical profile of high-risk febrile neutropenia in a tertiary care hospital

BackgroundInfection in the immunocompromised host has been a reason of concern in the clinical setting and a topic of debate for decades. In this study, the aim was to analyse the clinical profile of high-risk febrile neutropenic patients.AimsTo study the clinical profile of high risk febrile neutropenia patients with the objective of identifying the most common associated malignancy, most common associated pathogen, the source of infection, to correlate the treatment and management with that of the Infectious Diseases Society of America (IDSA) 2010 guidelines and to assess the clinical outcome.MethodsA cross-sectional time bound study was carried out and a total of 80 episodes of high-risk febrile neutropenia were recorded among patients with malignancies from September 2011 to July 2013 with each episode being taken as a new case.ResultsNon-Hodgkin’s lymphoma (30 per cent) was the most common malignancy associated, commonest source of infection was due to central venous catheters, the commonest pathogens were gram negative (52 per cent) the treatment and management of each episode of high risk febrile neutropenia correlated with that of IDSA 2010 guidelines and the mortality rate was 13.75 per cent.ConclusionFebrile neutropenia is one of the major complications and cause of mortality in patients with malignancy and hence understanding its entire spectrum can help us reduce morbidity and mortality

A New Species of Boubou (Malaconotidae: Laniarius) from the Albertine Rift

We describe Laniarius willardi, a new species of boubou shrike (Malaconotidae) from the Albertine Rift of Africa. The most conspicuous, distinguishing morphological feature of the species is a gray to blue-gray iris. This and external morphometric data indicate that L. willardi is diagnosable from other black or sooty boubous. Further, L. willardi is genetically diagnosable, and its closest relative is the Mountain Sooty Boubou (L. poensis camerunensis) from Cameroon. The Crimson-breasted Bush-shrike (L. atrococcineus) and the Lowland Sooty Boubou (L. leucorhynchus) are together the sister clade to L. willardi—L.p. camerunensis. Laniarius willardi and the geographically codistributed L. p. holomelas differ by 11.5% in uncorrected sequence divergence, and elevational data taken from museum specimens suggest the possibility of elevational segregation of the species at ∼2,000 m, withL. willardi occurring at lower elevations. Our broad sampling of black and sooty boubou taxa indicate that (1) races of Mountain Sooty Boubou (L. poensis) do not form a monophyletic clade; (2) L. p. camerunensismay represent multiple, nonsister lineages; and (3) at least one race of Fülleborn\u27s Black Boubou (L. fuelleborni usambaricus) is genetically distinct from other races of that species

Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial

AbstractRegular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133+2.0 microarrays and tested effects of 60-day aspirin supplementation (325mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) – accession number GSE71571 – was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9])

<i>De Novo</i> and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects

Congenital heart disease (CHD) has a complex genetic etiology, and recent studies suggest that high penetrance de novo mutations may account for only a small fraction of disease. In a multi-institutional cohort surveyed by exome sequencing, combining analysis of 987 individuals (discovery cohort of 59 affected trios and 59 control trios, and a replication cohort of 100 affected singletons and 533 unaffected singletons) we observe variation at novel and known loci related to a specific cardiac malformation the atrioventricular septal defect (AVSD). In a primary analysis, by combining developmental coexpression networks with inheritance modeling, we identify a de novo mutation in the DNA binding domain of NR1D2 (p.R175W). We show that p.R175W changes the transcriptional activity of Nr1d2 using an in vitro transactivation model in HUVEC cells. Finally, we demonstrate previously unrecognized cardiovascular malformations in the Nr1d2tm1-Dgen knockout mouse. In secondary analyses we map genetic variation to protein-interaction networks suggesting a role for two collagen genes in AVSD, which we corroborate by burden testing in a second replication cohort of 100 AVSDs and 533 controls (p = 8.37e-08). Finally, we apply a rare-disease inheritance model to identify variation in genes previously associated with CHD (ZFPM2, NSD1, NOTCH1, VCAN, and MYH6), cardiac malformations in mouse models (ADAM17, CHRD, IFT140, PTPRJ, RYR1 and ATE1), and hypomorphic alleles of genes causing syndromic CHD (EHMT1, SRCAP, BBS2, NOTCH2, and KMT2D) in 14 of 59 trios, greatly exceeding variation in control trios without CHD (p = 9.60e-06). In total, 32% of trios carried at least one putatively disease-associated variant across 19 loci,suggesting that inherited and de novo variation across a heterogeneous group of loci may contribute to disease risk

Neutrophils induce paracrine telomere dysfunction and senescence in ROS‐dependent manner

Cellular senescence is characterized by an irreversible cell cycle arrest as well as a pro-inflammatory phenotype, thought to contribute to aging and age-related diseases. Neutrophils have essential roles in inflammatory responses; however, in certain contexts their abundance is associated with a number of age-related diseases, including liver disease. The relationship between neutrophils and cellular senescence is not well understood. Here, we show that telomeres in non-immune cells are highly susceptible to oxidative damage caused by neighboring neutrophils. Neutrophils cause telomere dysfunction both in vitro and ex vivo in a ROS-dependent manner. In a mouse model of acute liver injury, depletion of neutrophils reduces telomere dysfunction and senescence. Finally, we show that senescent cells mediate the recruitment of neutrophils to the aged liver and propose that this may be a mechanism by which senescence spreads to surrounding cells. Our results suggest that interventions that counteract neutrophil-induced senescence may be beneficial during aging and age-related disease

Challenges in the implementation of the NeoOBS study, a global pragmatic observational cohort study, to investigate the aetiology and management of neonatal sepsis in the hospital setting

Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network