A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

A Turning Point for Paediatric Developmental Services in Oman : Establishment of a national autism screening programme

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A case of probable esomeprazole-induced transient liver injury in a pregnant woman with hyperemesis.

We report a case of 22-year-old primigravida presented to Women's Hospital - Hamad Medical Corporation emergency with severe epigastric pain, nausea, and vomiting. On admission, she was dehydrated with remarkably worsening symptoms. Laboratory findings revealed significantly elevated liver enzymes with unknown etiology. Her past medical history showed an admission for nausea and vomiting 3 weeks previously and she was discharged on antiemetics, and esomeprazole for the first time. Due to the predominantly elevated liver enzymes, the clinical pharmacist discussed the possibility of esomeprazole-induced adverse effects and suggested to suspend esomeprazole based on the evidence from literature review. The liver enzymes showed a substantial improvement within days after the discontinuation of the drug; however, a rechallenge was not done since it could have adversely affected the mother or the fetus. Using the Naranjo Adverse Drug Reaction Probability scales, the adverse reaction due to esomeprazole was classified as 'probably'

Revisiting the Prevalence of Autism Spectrum Disorder among Omani Children: A multicentre study

Objectives: This study aimed to provide an updated estimate of the prevalence of autism spectrum disorder (ASD) among Omani children. Methods: This retrospective descriptive study was conducted from December 2011 to December 2018. Data were retrieved from the three main autism diagnostic centres in Oman: Sultan Qaboos University Hospital, Royal Hospital and Al-Massarah Hospital. The ASD diagnosis was made by experienced clinicians based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The overall population prevalence estimates per 10,000 children aged 0–14 years old in Oman were calculated using the denominator of the mid-period population data. Results: A total of 1,705 ASD cases were identified with the majority of cases being male (78.1%). The overall prevalence rate of ASD was estimated at 20.35 per 10,000 children (95% confidence interval: 19.39–21.32) between 2012–2018. Boys were found to have a 3.4-fold higher prevalence of ASD than girls (31.23/10,000 versus 9.07/10,000). Regionally, the majority of cases were found in the capital, Muscat, where the highest prevalence was 36.51 cases per 10,000 children. Conclusion: The prevalence of ASD among Omani children is 15-fold higher than estimates from 2011. This increase can be attributed to improvements in diagnostic services, increased awareness of ASD, better screening programmes and changes in diagnostic criteria. In addition, this increase in prevalence suggests a need for a registry of developmental disabilities and more extensive diagnostic and rehabilitation services in Oman.Keywords: Autism Spectrum Disorder; Epidemiology; Prevalence; Oman

Successful Treatment of Novel H1N1 Influenza related Fulminant Myocarditis with Extracorporeal Life Support

The prevalence of myocardial involvement in influenza infection ranges from 0% to 12%. The 2009 pH1N1 influenza virus, formerly known as swine flu, first appeared in Mexico and the United States of America in March and April 2009 and has swept the globe with unprecedented speed. We report a case of fulminant myocarditis associated with this virus treated successfully using extra-corporal membrane oxygenator

DECK: Distance and environment-dependent, coarse-grained, knowledge-based potentials for protein-protein docking

<p>Abstract</p> <p>Background</p> <p>Computational approaches to protein-protein docking typically include scoring aimed at improving the rank of the near-native structure relative to the false-positive matches. Knowledge-based potentials improve modeling of protein complexes by taking advantage of the rapidly increasing amount of experimentally derived information on protein-protein association. An essential element of knowledge-based potentials is defining the reference state for an optimal description of the residue-residue (or atom-atom) pairs in the non-interaction state.</p> <p>Results</p> <p>The study presents a new Distance- and Environment-dependent, Coarse-grained, Knowledge-based (DECK) potential for scoring of protein-protein docking predictions. Training sets of protein-protein matches were generated based on bound and unbound forms of proteins taken from the D<smcaps>OCKGROUND</smcaps> resource. Each residue was represented by a pseudo-atom in the geometric center of the side chain. To capture the long-range and the multi-body interactions, residues in different secondary structure elements at protein-protein interfaces were considered as different residue types. Five reference states for the potentials were defined and tested. The optimal reference state was selected and the cutoff effect on the distance-dependent potentials investigated. The potentials were validated on the docking decoys sets, showing better performance than the existing potentials used in scoring of protein-protein docking results.</p> <p>Conclusions</p> <p>A novel residue-based statistical potential for protein-protein docking was developed and validated on docking decoy sets. The results show that the scoring function DECK can successfully identify near-native protein-protein matches and thus is useful in protein docking. In addition to the practical application of the potentials, the study provides insights into the relative utility of the reference states, the scope of the distance dependence, and the coarse-graining of the potentials.</p

Sustainable environmental geotechnics practices for a green economy

The revitalisation of the global economy after the Covid-19 era presents environmental geotechnics with the opportunity to reinforce the need for a change in paradigm towards a green, circular economy and to promote aggressively the use and development of sustainable technologies and management practices. This paper aims to assist in this effort by concentrating on several thematic areas where sustainability solutions and future improvements are sought. These include the re-entry of construction and demolition of wastes, excavated materials, industrial wastes and marine sediments into the production cycle and the reuse of existing foundations. Despite the recent trend in advanced countries towards recycling and waste-to-energy thermal treatment, landfills still constitute the most common municipal solid waste management practice, especially in low-and-middle-income countries, and technological solutions to improve their environmental footprint are hereby presented. At the same time, remediation solutions are required to address the multitude of contaminated sites worldwide. Advanced developments that incorporate environmental, economic and social dimensions are expounded by the authors, together with sustainable ground improvement solutions for infrastructure projects conducted in soft and weak soils. The topic of thermo-active geostructures concludes this paper, where, apart from their infrastructure utility, these structures have the potential to contribute to the renewable energy source.Published versionThe second author would like to acknowledge the support of the Office of the Associate Provost for Research and Academic Development at Abu Dhabi University, UAE through grant19300540

A Rationale for Schistosomiasis Control in Elementary Schools of the Rainforest Zone of Pernambuco, Brazil

In 2001, a World Health Assembly resolution urged member states to ensure treatment against schistosomiasis and soil-transmitted helminthiasis in endemic areas with the goal of attaining a minimum target of at least 75% of all school-aged children by 2010. In the highly endemic Rainforest Zone of Pernambuco (ZMP), northeast Brazil, the Schistosomiasis Control Program has registered a cumulative coverage of only 20% of the population at risk, which jeopardizes the accomplishment of the minimum target for that area. Demographic and parasitological data from a representative municipality of the ZMP provide evidence that the current, community-based approach to control can be complemented with school-based actions. In the most troubled municipalities, individual diagnosis and treatment could be focused on school-aged children rather than whole populations without compromising the principles of the primary health care system. Local health and education teams should be encouraged to include school-based interventions to scale up coverage and achieve a rapid impact on infection