Genetic background modulates behavioral impairments in R6/2 mice and suggests a role for dominant genetic modifiers in Huntington’s disease pathogenesis

Variability and modification of the symptoms of Huntington’s disease (HD) are commonly observed in both patient populations and animal models of the disease. Utilizing a stable line of the R6/2 HD mouse model, the present study investigated the role of genetic background in the onset and severity of HD symptoms in a transgenic mouse. R6/2 congenic C57BL/6J and C57BL/6J × DBA/2J F1 (B6D2F1) mice were evaluated for survival and a number of behavioral phenotypes. This study reports that the presence of the DBA/2J allele results in amelioration or exacerbation of several HD-like phenotypes characteristic of the R6/2 mouse model and indicates the presence of dominant genetic modifiers of HD symptoms. This study is the first step in identifying genes that confer natural genetic variation and modify the HD symptoms. This identification may lead to novel targets for treatment and help elucidate the molecular mechanisms of HD pathogenesis

From theory to practice: improving the impact of health services research

BACKGROUND: While significant strides have been made in health research, the incorporation of research evidence into healthcare decision-making has been marginal. The purpose of this paper is to provide an overview of how the utility of health services research can be improved through the use of theory. Integrating theory into health services research can improve research methodology and encourage stronger collaboration with decision-makers. DISCUSSION: Recognizing the importance of theory calls for new expectations in the practice of health services research. These include: the formation of interdisciplinary research teams; broadening the training for those who will practice health services research; and supportive organizational conditions that promote collaboration between researchers and decision makers. Further, funding bodies can provide a significant role in guiding and supporting the use of theory in the practice of health services research. SUMMARY: Institutions and researchers should incorporate the use of theory if health services research is to fulfill its potential for improving the delivery of health care

Some peace of mind: assessing a pilot intervention to promote mental health among widows of injecting drug users in north-east India

<p>Abstract</p> <p>Background</p> <p>HIV prevalence in north-east India is high and injecting drug use (IDU) is common. Due to HIV-related deaths there are increasing numbers of IDU widows, many of whom are HIV infected, and experiencing poor health, social isolation, discrimination and poverty, all factors likely to be compromising their mental health. There is increasing recognition of the links between HIV and mental health.</p> <p>Methods</p> <p>The aim of this study was to pilot a peer-facilitated, participatory action group (PAG) process and assess the impact of the intervention on the mental health of participants. The intervention consisted of 10 PAG meetings involving 74 IDU widows. Changes in quality of life (WHOQOL-BREF), mental health (GHQ12) and somatic symptoms were assessed. The value of the intervention from the perspective of the participants was captured using a qualitative evaluation method (Most Significant Change).</p> <p>Results</p> <p>Participants' quality of life, mental health and experience of somatic symptoms improved significantly over the course of the intervention, and the women told stories reflecting a range of 'significant changes'.</p> <p>Conclusion</p> <p>This pilot intervention study demonstrated that a participatory approach to mental health promotion can have a positive impact on the lives of vulnerable women, and the potential to contribute to HIV prevention. Further investigation is warranted.</p

Smaller classes promote equitable student participation in STEM

Under embargo until: 2020-07-24As science, technology, engineering, and mathematics (STEM) classrooms in higher education transition from lecturing to active learning, the frequency of student interactions in class increases. Previous research documents a gender bias in participation, with women participating less than would be expected on the basis of their numeric proportions. In the present study, we asked which attributes of the learning environment contribute to decreased female participation: the abundance of in-class interactions, the diversity of interactions, the proportion of women in class, the instructor's gender, the class size, and whether the course targeted lower division (first and second year) or upper division (third or fourth year) students. We calculated likelihood ratios of female participation from over 5300 student–instructor interactions observed across multiple institutions. We falsified several alternative hypotheses and demonstrate that increasing class size has the largest negative effect. We also found that when the instructors used a diverse range of teaching strategies, the women were more likely to participate after small-group discussions.acceptedVersio

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Integrating Palliative Care Into the Care of Neurocritically Ill Patients: A Report From the Improving Palliative Care in the ICU Project Advisory Board and the Center to Advance Palliative Care.

OBJECTIVES: To describe unique features of neurocritical illness that are relevant to provision of high-quality palliative care; to discuss key prognostic aids and their limitations for neurocritical illnesses; to review challenges and strategies for establishing realistic goals of care for patients in the neuro-ICU; and to describe elements of best practice concerning symptom management, limitation of life support, and organ donation for the neurocritically ill. DATA SOURCES: A search of PubMed and MEDLINE was conducted from inception through January 2015 for all English-language articles using the term palliative care, supportive care, end-of-life care, withdrawal of life-sustaining therapy, limitation of life support, prognosis, or goals of care together with neurocritical care, neurointensive care, neurological, stroke, subarachnoid hemorrhage, intracerebral hemorrhage, or brain injury. DATA EXTRACTION AND SYNTHESIS: We reviewed the existing literature on delivery of palliative care in the neurointensive care unit setting, focusing on challenges and strategies for establishing realistic and appropriate goals of care, symptom management, organ donation, and other considerations related to use and limitation of life-sustaining therapies for neurocritically ill patients. Based on review of these articles and the experiences of our interdisciplinary/interprofessional expert advisory board, this report was prepared to guide critical care staff, palliative care specialists, and others who practice in this setting. CONCLUSIONS: Most neurocritically ill patients and their families face the sudden onset of devastating cognitive and functional changes that challenge clinicians to provide patient-centered palliative care within a complex and often uncertain prognostic environment. Application of palliative care principles concerning symptom relief, goal setting, and family emotional support will provide clinicians a framework to address decision making at a time of crisis that enhances patient/family autonomy and clinician professionalism

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians, and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus (mQTL), expression quantitative trait locus (eQTL), and expression quantitative trait methylation (eQTM) analyses to assess whether the top SNP in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents. In the meta-analysis of GWAS, a SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbations (95% confidence interval=1.34 to 1.79, p=6.3×10-9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10-7). Thus, SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1)