Dual inhibition of IGF1R and ER enhances response to trastuzumab in HER2 positive breast cancer cells.

Although HER2 targeted therapies have improved prognosis for HER2 positive breast cancer, HER2 positive cancers which co-express ER have poorer response rates to standard HER2 targeted therapies, combined with chemotherapy, than HER2 positive/ER negative breast cancer. Administration of hormone therapy concurrently with chemotherapy and HER2 targeted therapy is generally not recommended. Using publically available gene expression datasets we found that high expression of IGF1R is associated with shorter disease-free survival in patients whose tumors are ER positive and HER2 positive.

Trihydroborates and Dihydroboranes Bearing a Pentacoordinated Phosphorus Atom: Double Ring Expansion To Balance the Coordination States.

The first trihydroborate bearing a pentacoordinated phosphorus atom was synthesized as a new P-B bonded compound. Hydride abstraction of the trihydroborate gave an intermediary dihydroborane, which showed hydroboration reactivity and was trapped with pyridine whilst maintaining the P-B bond. The dihydroborane underwent a rearrangement, which involved a double ring expansion to compensate for the unbalanced coordination states of the phosphorus and boron atoms, to give a new fused bicyclic phosphine-boronate.

Remifentanil for Sedation of Children With Traumatic Brain Injury.

Objective: To determine whether remifentanil would provide adequate sedation while allowing frequent and reproducible neurologic assessments in children admitted to the pediatric intensive care unit (PICU) with traumatic brain injury (TBI) during mechanical ventilation.

Design: Retrospective review.

Setting: Tertiary care PICU.

The state of the art and future opportunities for using longitudinal n-of-1 methods in health behaviour research: a systematic literature overview.

n-of-1 studies test hypotheses within individuals based on repeated measurement of variables within the individual over time. Intra-individual effects may differ from those found in between-participant studies. Using examples from a systematic review of n-of-1 studies in health behaviour research, this article provides a state of the art overview of the use of n-of-1 methods, organised according to key methodological considerations related to n-of-1 design and analysis, and describes future challenges and opportunities.

Health-related quality-of-life and receipt of women-centered HIV care among women living with HIV in Canada.

We measured health-related quality of life (HRQOL) using the SF-12 among women living with HIV (WLWH) in Canada between August 2013 and May 2015. We investigated differences by perceived receipt of women-centered HIV care (WCHC), assessed using an evidence-based definition with a 5-point Likert item: "Overall, I think that the care I have received from my HIV clinic in the last year has been women-centered" (dichotomized into agree vs. disagree/neutral).

Whole-exome sequencing of individuals from an isolated population implicates rare risk variants in bipolar disorder.

Bipolar disorder affects about 1% of the world's population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance.

Concurrent iron and zinc deficiencies in lactating mothers and their children 6-23 months of age in two agro-ecological zones of rural Ethiopia.

Purpose: The aim of this study is to examine the co-occurrences of low serum ferritin and zinc and anaemia among mothers and their children in two agro-ecological zones of rural Ethiopia.

Methods: Data were collected from 162 lactating mothers and their breast fed children aged 6-23 months. The data were collected via a structured interview, anthropometric measurements, and blood tests for zinc, ferritin and anaemia.

The synthesis and structure of a dianionic species with a bond between pentacoordinated tin atoms: bonding properties of the tin-tin bond.

The first dianionic compound bearing a bond between two pentacoordinated tin atoms, a distannate, was synthesized in a stable form by using two sets of an electron-withdrawing C,O-bidentate ligand on each tin atom. The structure of the distannate was determined by NMR spectroscopy and X-ray crystallographic analysis. The Sn-Sn bond of the distannate was shown to be a single bond featuring high s-character.

Genetic variation in the miR-708 gene and its binding targets in bipolar disorder.

Objective: rs12576775 was found to be associated with bipolar disorder (BD) in a genome-wide association study (GWAS). The GWAS signal implicates genes for the microRNAs miR-708 and miR-5579 and the first exon of the Odd Oz/ten-m homolog 4 gene (ODZ4). In the present study, miR-708, its surrounding region, and its targets were analyzed for potential BD-associated functional variants.

Variations between post- and pre-harvest seasons in stunting, wasting, and Infant and Young Child Feeding (IYCF) practices among children 6-23 months of age in lowland and midland agro-ecological zones of rural Ethiopia.

Introduction: Food availability and access are strongly affected by seasonality in Ethiopia. However, there are little data on seasonal variation in Infant and Young Child Feeding (IYCF) practices and malnutrition among 6-23 months old children in different agro-ecological zones of rural Ethiopia.

Methods: Socio-demographic, anthropometry and IYCF indicators were assessed in post- and pre-harvest seasons among children aged 6-23 months of age randomly selected from rural villages of lowland and midland agro-ecological zones.

Anemia and undernutrition among children aged 6-23 months in two agroecological zones of rural Ethiopia.

Background: Child malnutrition during the first 1,000 days, commencing at conception, can have lifetime consequences. This study assesses the prevalence of anemia and undernutrition among children aged 6-23 months in midland and lowland agroecological zones of rural Ethiopia.

Methods: Cross-sectional data examining sociodemographic, anthropometry, hemoglobin levels, and meal frequency indicators were collected from 216 children aged 6-23 months and their mothers randomly selected from eight rural kebele (villages).

Rapporteur summaries of plenary, symposia, and oral sessions from the XXIIIrd World Congress of Psychiatric Genetics Meeting in Toronto, Canada, 16-20 October 2015.

The XXIIIrd World Congress of Psychiatric Genetics meeting, sponsored by the International Society of Psychiatric Genetics, was held in Toronto, ON, Canada, on 16-20 October 2015. Approximately 700 participants attended to discuss the latest state-of-the-art findings in this rapidly advancing and evolving field. The following report was written by trainee travel awardees.

Investigation of the genotoxic potential of the marine biotoxins azaspiracid 1-3.

Azaspiracids (AZAs) are the most recently discovered group of biotoxins and are the cause of azaspiracid shellfish poisoning (AZP) in humans. To date over thirty analogues have been identified. However, toxicological studies of AZAs are limited due to the lack of availability of toxins and toxin standards.

Establishing the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS): Operationalizing Community-based Research in a Large National Quantitative Study.

Background: Community-based research has gained increasing recognition in health research over the last two decades. Such participatory research approaches are lauded for their ability to anchor research in lived experiences, ensuring cultural appropriateness, accessing local knowledge, reaching marginalized communities, building capacity, and facilitating research-to-action. While having these positive attributes, the community-based health research literature is predominantly composed of small projects, using qualitative methods, and set within geographically limited communities.

Demonstrating the financial impact of clinical libraries: a systematic review.

Objective: The purpose of this review is to evaluate the tools used to measure the financial value of libraries in a clinical setting.

Methods: Searches were carried out on ten databases for the years 2003-2013, with a final search before completion to identify any recent papers.

Results: Eleven papers met the final inclusion criteria.

Integrating Evidence From Systematic Reviews, Qualitative Research, and Expert Knowledge Using Co-Design Techniques to Develop a Web-Based Intervention for People in the Retirement Transition.

Background: Integrating stakeholder involvement in complex health intervention design maximizes acceptability and potential effectiveness. However, there is little methodological guidance about how to integrate evidence systematically from various sources in this process. Scientific evidence derived from different approaches can be difficult to integrate and the problem is compounded when attempting to include diverse, subjective input from stakeholders.

Pilot Randomised Controlled Trial of a Web-Based Intervention to Promote Healthy Eating, Physical Activity and Meaningful Social Connections Compared with Usual Care Control in People of Retirement Age Recruited from Workplaces.

Background: Lifestyle interventions delivered during the retirement transition might promote healthier ageing. We report a pilot randomised controlled trial (RCT) of a web-based platform (Living, Eating, Activity and Planning through retirement; LEAP) promoting healthy eating (based on a Mediterranean diet (MD)), physical activity (PA) and meaningful social roles.

Methods: A single blinded, two-arm RCT with individual allocation.

Recent Advances in X-ray Cone-beam Computed Laminography.

X-ray computed tomography is an established volume imaging technique used routinely in medical diagnosis, industrial non-destructive testing, and a wide range of scientific fields. Traditionally, computed tomography uses scanning geometries with a single axis of rotation together with reconstruction algorithms specifically designed for this setup. Recently there has however been increasing interest in more complex scanning geometries.

CACNA1C hypermethylation is associated with bipolar disorder.

The CACNA1C gene, encoding a subunit of the L-type voltage-gated calcium channel is one of the best-supported susceptibility genes for bipolar disorder (BD). Genome-wide association studies have identified a cluster of non-coding single-nucleotide polymorphisms (SNPs) in intron 3 to be highly associated with BD and schizophrenia. The mechanism by which these SNPs confer risk of BD appears to be through an altered regulation of CACNA1C expression.

Nanoparticle Surface Affinity as a Predictor of Trophic Transfer.

Nanoscale materials, whether natural, engineered, or incidental, are increasingly acknowledged as important components in large, environmental systems with potential implications for environmental impact and human health. Mathematical models are a useful tool for handling the rapidly increasing complexity and diversity of these materials and their exposure routes. Presented here is a mathematical model of trophic transfer driven by nanomaterial surface affinity for environmental and biological surfaces, developed in tandem with an experimental functional assay for determining these surface affinities.

Hypomethylation of FAM63B in bipolar disorder patients.

Bipolar disorder (BD) and schizophrenia (SZ) are known to share common genetic and psychosocial risk factors. A recent epigenome-wide association study performed on blood samples from SZ patients found significant hypomethylation of FAM63B in exon 9. Here, we used iPLEX-based methylation analysis to investigate two CpG sites in FAM63B in blood samples from 459 BD cases and 268 controls.

Drug breakthrough offers hope to arthritis sufferers: qualitative analysis of medical research in UK newspapers.

Background: Newspaper stories can impact behaviours, particularly in relation to research participation. It is therefore important to understand the narratives presented and ways in which these are received. Some work to date assumes journalism transmits existing medical knowledge to a passive audience.

Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against Plasmodium falciparum: design, synthesis and biological evaluation.

Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one. The orchestration of this process critically relies upon numerous organised phospho-signaling cascades, which are mediated by a number of central kinases.