Utilizing genotyping-by-sequencing to elucidate Neotropical army ant evolution

The articulation of science and humanism has been from the outset one of the keystones of our programmatic initiative on person centered medicine. This involves the notion that the scientific method is what gives science its foundations and at the same time represents one of the principal strategies and tools to understand, formulate and intervene in crucial and paramount human concerns and activities such as health. A scientific approach to health and health care, from the perspective of person centered medicine, involves not only attending to organs and diseases (preferential topics in much of contemporary medicine), but more broadly to the whole field of human health, including ill health and positive health, within which organs and diseases are inscribed. (aut.ref.

Regional Prevalence of Short Stature in Saudi School-Age Children and Adolescents

Objective. To assess the magnitude of regional difference in prevalence of short stature in Saudi children and adolescents. Subjects and Methods. A representative sample from three different regions of the Kingdom of Saudi Arabia (KSA) (North, Southwest, and Center) was used to calculate the prevalence of short stature (standard deviation score less than −2) in children 5 to 17 years of age. Results. There were 9018 children and adolescents from 5 to 17 years of age (3366, 2825, and 2827 in the Northern, Southwestern and Central regions, resp.) and 51% were boys. In both school-age children and adolescents, there was a significantly higher prevalence of short stature in the Southwestern than in the Northern or the Central region (P < 0.0001). Conclusion. The finding of significant regional variation between regions helps in planning priorities for research and preventive measures

Students’ perception towards behavioral intention of audio and video teaching styles : an acceptance study

Recently audio and video material has been used significantly in various online platforms. The audio-video materials enhance the teaching and learning process by facilitating the transformation of the data and providing a richer interactive environment, hence gaining wide intention within the educational realm. However, empirical studies have not examined the acceptance of the audio and video material depending on a conceptual model where acceptance is the key factor. The present study attempts to overcome this gap in the literature review by investigating the effects of media richness, speed and vividness, perceived concentration, perceived ease of use, perceived usefulness on the acceptance of audio-video material. What distinguishes the current study is the fact that content richness is considered as a mediator that affects all other factors in the conceptual model. The data is collected by distributing the online survey to college students. The results provide mostly insight and support for students’ intention to use audio-visual resources in a conceptual model. The technology characteristics of speed and vividness as well as TAM constructs were significant predictors of technology acceptance. However, it is concluded that the external factor of the perceived concentration has no impact on the students’ perception and intention to use audio-visual resources. In the recommendation, some theoretical and practical implications are stated along with the focus on technology designers, change managers, and users

A UK wide cohort study describing management and outcomes for infants with surgical Necrotising Enterocolitis

The Royal College of Surgeons have proposed using outcomes from necrotising enterocolitis (NEC) surgery for revalidation of neonatal surgeons. The aim of this study was therefore to calculate the number of infants in the UK/Ireland with surgical NEC and describe outcomes that could be used for national benchmarking and counselling of parents. A prospective nationwide cohort study of every infant requiring surgical intervention for NEC in the UK was conducted between 01/03/13 and 28/02/14. Primary outcome was mortality at 28-days. Secondary outcomes included discharge, post-operative complication, and TPN requirement. 236 infants were included, 43(18%) of whom died, and eight(3%) of whom were discharged prior to 28-days post decision to intervene surgically. Sixty infants who underwent laparotomy (27%) experienced a complication, and 67(35%) of those who were alive at 28 days were parenteral nutrition free. Following multi-variable modelling, presence of a non-cardiac congenital anomaly (aOR 5.17, 95% CI 1.9-14.1), abdominal wall erythema or discolouration at presentation (aOR 2.51, 95% CI 1.23-5.1), diagnosis of single intestinal perforation at laparotomy (aOR 3.1 95% CI 1.05-9.3), and necessity to perform a clip and drop procedure (aOR 30, 95% CI 3.9-237) were associated with increased 28-day mortality. These results can be used for national benchmarking and counselling of parents

Hyperosmotic Stress Induces a Specific Pattern for Stress Granule Formation in Human-Induced Pluripotent Stem Cells

Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2α phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Alterations in the Interleukin-1/Interleukin-1 Receptor Antagonist Balance Modulate Cardiac Remodeling following Myocardial Infarction in the Mouse

Background Healing after acute myocardial infarction (AMI) is characterized by an intense inflammatory response and increased Interleukin-1 (IL-1) tissue activity. Genetically engineered mice lacking the IL-1 receptor (IL-1R1-/-, not responsive to IL-1) or the IL-1 receptor antagonist (IL-1Ra, enhanced response to IL-1) have an altered IL-1/IL-1Ra balance that we hypothesize modulates infarct healing and cardiac remodeling after AMI. Methods IL-1R1-/- and IL-1Ra-/- male mice and their correspondent wild-types (WT) were subjected to permanent coronary artery ligation or sham surgery. Infarct size (trichrome scar size), apoptotic cell death (TUNEL) and left ventricular (LV) dimensions and function (echocardiography) were measured prior to and 7 days after surgery. Results When compared with the corresponding WT, IL-1R1-/- mice had significantly smaller infarcts (−25%), less cardiomyocyte apoptosis (−50%), and reduced LV enlargement (LV end-diastolic diameter increase [LVEDD], −20%) and dysfunction (LV ejection fraction [LVEF] decrease, −50%), whereas IL-1Ra-/- mice had significantly larger infarcts (+75%), more apoptosis (5-fold increase), and more severe LV enlargement (LVEDD increase,+30%) and dysfunction (LVEF decrease, +70%)(all P values \u3c0.05). Conclusions An imbalance in IL-1/IL-1Ra signaling at the IL-1R1 level modulates the severity of cardiac remodeling after AMI in the mouse, with reduced IL-1R1 signaling providing protection and unopposed IL-1R1 signaling providing harm

A role for domain I of the hepatitis C virus NS5A protein in virus assembly

The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome replication and assembly. NS5A comprises three domains, of these domain I is believed to be involved exclusively in genome replication. In contrast, domains II and III are required for the production of infectious virus particles and are largely dispensable for genome replication. Domain I is highly conserved between HCV and related hepaciviruses, and is highly structured, exhibiting different dimeric conformations. To investigate the functions of domain I in more detail, we conducted a mutagenic study of 12 absolutely conserved and surface-exposed residues within the context of a JFH-1-derived sub-genomic replicon and infectious virus. Whilst most of these abrogated genome replication, three mutants (P35A, V67A and P145A) retained the ability to replicate but showed defects in virus assembly. P35A exhibited a modest reduction in infectivity, however V67A and P145A produced no infectious virus. Using a combination of density gradient fractionation, biochemical analysis and high resolution confocal microscopy we demonstrate that V67A and P145A disrupted the localisation of NS5A to lipid droplets. In addition, the localisation and size of lipid droplets in cells infected with these two mutants were perturbed compared to wildtype HCV. Biophysical analysis revealed that V67A and P145A abrogated the ability of purified domain I to dimerize and resulted in an increased affinity of binding to HCV 3’UTR RNA. Taken together, we propose that domain I of NS5A plays multiple roles in assembly, binding nascent genomic RNA and transporting it to lipid droplets where it is transferred to Core. Domain I also contributes to a change in lipid droplet morphology, increasing their size. This study reveals novel functions of NS5A domain I in assembly of infectious HCV and provides new perspectives on the virus lifecycle