Direct Immunosensor Design Based on the Electrochemical Reduction of 4-((4-Nitrophenyl) ethynyl) benzenethiol Monolayers

The synthesis and characterization of novel N-arylhydroxylamine-based molecular wires are described for use in the site-directed covalent immobilization of whole IgG antibodies onto gold electrode surfaces. The hydroxylamine, electrochemically generated in situ from reduction of the corresponding nitrobenzene, is stable under a wide range of solution conditions and reacts selectively with carbohydrate away from the antibody-binding site to allow the development of immunosensors with maximal activity. Cyclic voltammetric responses have shown a direct correlation between the structure and length of the molecular wire and its stability and concentration at the electrode surface

Evaluation of expressive writing for postpartum health: A randomized controlled trial

Pregnancy, birth and adjusting to a new baby is a potentially stressful time that can negatively affect the health of women. There is some evidence that expressive writing can have positive effects on psychological and physical health, particularly during stressful periods. The current study aimed to evaluate whether expressive writing would improve women’s postpartum health. A randomized controlled trial was conducted with three conditions: expressive writing (n=188), a control writing task (n=213), or normal care (n=163). Measures of psychological health, physical health and quality of life were measured at baseline (6-12 weeks postpartum), 1 month and 6 months later. Ratings of stress were taken before and after the expressive writing task. Intent-to-treat analyses showed no significant differences between women in the expressive writing, control writing and normal care groups on measures of physical health, anxiety, depression, mood or quality of life at 1 and 6 months. Uptake and adherence to the writing tasks was low. However, women in the expressive writing group rated their stress as significantly reduced after completing the task. Cost analysis suggest women who did expressive writing had the lowest costs in terms of healthcare service use and lowest cost per unit of improvement in quality of life. Results suggest expressive writing is not effective as a universal intervention for all women 6-12 weeks postpartum. Future research should examine expressive writing as a targeted intervention for women in high-risk groups, such as those with mild or moderate depression, and further examine cost-effectiveness

Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.

OBJECTIVE: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects. METHODS: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. RESULTS: Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. CONCLUSIONS: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently

Feasibility and acceptability of expressive writing with postpartum women: a randomised controlled trial

Abstract Background: Pregnancy, birth and adjusting to a new baby is a potentially stressful time that can negatively affect women’s mental and physical health. Expressive writing, where people write about a stressful event for at least 15 minutes on three consecutive days, has been associated with improved health in some groups but it is not clear whether it is feasible and acceptable for use with postpartum women. This study therefore examined the feasibility and acceptability of expressive writing for postpartum women as part of a randomised controlled trial (RCT). Methods: The Health After Birth Trial (HABiT) was an RCT evaluating expressive writing for postpartum women which included measures of feasibility and acceptability. At 6 to 12 weeks after birth 854 women were randomised to expressive writing, a control writing task or normal care, and outcome measures of health were measured at baseline, one month later and six months later. Feasibility was measured by recruitment, attrition, and adherence to the intervention. Quantitative and qualitative measures of acceptability of the materials and the task were completed six months after the intervention. Results: Recruitment was low (10.7% of those invited to participate) and the recruited sample was from a restricted sociodemographic range. Attrition was high, increased as the study progressed (35.8% at baseline, 57.5% at one month, and 68.1% at six months) and was higher in the writing groups than in the normal care group. Women complied with instructions to write expressively or not, but adherence to the instruction to write for 15 minutes per day for three days was low (Expressive writing: 29.3%; Control writing: 23.5%). Acceptability measures showed that women who wrote expressively rated the materials/task both more positively and more negatively than those in the control writing group, and qualitative comments revealed that women enjoyed the writing and/or found it helpful even when it was upsetting. Conclusions: The feasibility of offering expressive writing as a universal self-help intervention to all postpartum women 6 to 12 weeks after birth in the HABiT trial was low, but the expressive writing intervention was acceptable to the majority of women who completed it

Plant Species\u27 Origin Predicts Dominance and Response to Nutrient Enrichment and Herbivores in Global Grasslands

Exotic species dominate many communities; however the functional significance of species\u27 biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Response to Comments on "Productivity Is a Poor Predictor of Plant Species Richness"

Pan et al. claim that our results actually support a strong linear positive relationship between productivity and richness, whereas Fridley et al. contend that the data support a strong humped relationship. These responses illustrate how preoccupation with bivariate patterns distracts from a deeper understanding of the multivariate mechanisms that control these important ecosystem properties