Literature as Catharsis: Women\u27s Voices on Male Violence

We see specific examples of women\u27s feelings concerning our culture\u27s attitudes towards male violence in Margaret Atwood\u27s poem Half Hanged Mary and May Swenson\u27s poem Bleeding

Pharmacodynamic Assays to Facilitate Preclinical and Clinical Development of Pre-mRNA Splicing Modulatory Drug Candidates

The spliceosome has recently emerged as a new target for cancer chemotherapy and novel antitumor spliceosome targeted agents are under development. Here, we describe two types of novel pharmacodynamic assays that facilitate drug discovery and development of this intriguing class of innovative therapeutics; the first assay is useful for preclinical optimization of small-molecule agents that target the SF3B1 spliceosomal protein in animals, the second assay is an ex vivo validated, gel-based assay for the measurement of drug exposure in human leukocytes. The first assay utilizes a highly specific bioluminescent splicing reporter, based on the skipping of exons 4-11 of a Luc-MDM2 construct, which specifically yields active luciferase when treated with small-molecule spliceosome modulators. We demonstrate that this reporter can be used to monitor alternative splicing in whole cells in vitro. We describe here that cell lines carrying the reporter can be used in vivo for the efficient pharmacodynamic analysis of agents during drug optimization and development. We also demonstrate dose- and time-dependent on-target activity of sudemycin D6 (SD6), which leads to dramatic tumor regression. The second assay relies on the treatment of freshly drawn human blood with SD6 ex vivo treatment. Changes in alternative splicing are determined by RT-PCR using genes previously identified in in vitro experiments. The Luc-MDM2 alternative splicing bioluminescent reporter and the splicing changes observed in human leukocytes should allow for the more facile translation of novel splicing modulators into clinical application

Proceedings from the Ice Hockey Summit III: Action on Concussion

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey

Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles

To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT), indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER) and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER

Proceedings from the Ice Hockey Summit III: Action on Concussion

Objectives The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: (1) describe sport related concussion (SRC) epidemiology, (2) classify prevention strategies, (3) define objective, diagnostic tests, (4) identify treatment and (5) integrate science and clinical care into prioritized action plans and policy. Methods Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches and officials) voted to prioritize these action items in the final Summit session. Results (1) establish a national and international hockey data base for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care (POC); and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity and consequences of concussion in the sport of ice hockey

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Surrender to God Predicts Lower Levels of Substance Use Addiction

Religiousness has been shown to have an inverse relationship with at least some types of addiction. The present study examined whether intrinsic religiousness predicts substance addiction in a sample of participants that included mostly undergraduate students from the Appalachian region, as well as some participants surveyed with the use of social media advertisements. Intrinsic religiousness has been defined as internalizing the tenets of one’s faith. Participants self-reported their religiousness using the Religious Surrender and Attendance Scale – 3 (RSAS-3), which has been shown to measure intrinsic religiousness. Substance use was measured by the TCU Drug Screen V (TCUDS). Religiousness, as measured by the RSAS-3, predicted lower levels of substance use addiction as measured by the TCUDS both continuously and dichotomized: X2 (1, N=517) =8.296, p=.004. The odds ratio for the model was 3.724 95% CI [1.305, 10.625] meaning that the odds of being addicted to a substance was 3.724 times more likely for someone who did not meet the threshold for being high in religious commitment than for someone who did. The present study extends findings regarding religiousness and addiction but further research should be done to analyze different theological traditions and their relationship with health outcomes

Association of VH4-59 Antibody Variable Gene Usage with Recognition of an Immunodominant Epitope on the HIV-1 Gag Protein

The human antibody response against HIV-1 infection recognizes diverse antigenic subunits of the virion, and includes a high level of antibodies to the Gag protein. We report here the isolation and characterization of a subset of Gag-specific human monoclonal antibodies (mAbs) that were prevalent in the antibody repertoire of an HIV-infected individual. Several lineages of Gag-specifc mAbs were encoded by a single antibody heavy chain variable region, VH4-59, and a representative antibody from this group designated mAb 3E4 recognized a linear epitope on the globular head of the p17 subunit of Gag. We found no evidence that mAb 3E4 exhibited any function in laboratory studies aimed at elucidating the immunologic activity, including assays for neutralization, Ab-dependent cell-mediated virus inhibition, or enhanced T cell reactivity caused by Gag-3E4 complexes. The findings suggest this immunodominant epitope in Gag protein, which is associated with VH4-59 germline gene usage, may induce a high level of B cells that encode binding but non-functional antibodies that occupy significant repertoire space following HIV infection. The studies define an additional specific molecular mechanism in the immune distraction activity of the HIV virion

Learning needs and perceived barriers and facilitators to end-of-life care: a survey of front-line nurses on acute medical wards

Objectives Caring for dying hospitalised patients is a healthcare priority. Our objective was to understand the learning needs of front-line nurses on the general internal medicine (GIM) hospital wards, and perceived barriers to, and facilitators of, optimal end-of-life care.Methods We developed an 85-item survey informed by the Theoretical Domains Framework and Capability–Opportunity–Motivation–Behaviour system. We included demographics and two main domains (knowledge and practice; delivering end-of-life care) with seven subsections. Nurses from four GIM wards and the nursing resource team completed this survey. We analysed and compared results overall, by Capability, Opportunity, and Motivation, and by survey domain. We considered items with median scores <4/7 barriers. We conducted an a priori subgroup analysis based on duration of practice (≤5 and >5 years).Results Our response rate was 60.5% (144/238). 51% had been practising for >5 years; most respondents were female (93.1%). Nurses had similar scores on the knowledge (mean 76.0%; SD 11.6%) and delivering care (mean 74.5% (8.6%)) domains. Scores for items associated with Capability were higher than those associated with Opportunity (median (first, third quartiles) 78.6% (67.9%, 87.5%) vs 73.9% (66.0%, 81.8%); p=0.04). Nurses practising >5 years had significantly higher scores on all analyses. Barriers included engaging with families having strong emotional reactions, managing goals of care conflicts between patients and families, and staffing challenges on the ward. Additional requested resources included formal training, information binders and more staff. Opportunities for consideration include formalised on-the-job training, access to comprehensive information, including symptom management at the end of life, and debriefing sessions.Conclusions Front-line nurses reported an interest in learning more about end-of-life care and identified important barriers that are feasible to address. These results will inform specific knowledge translation strategies to build capacity among bedside nurses to enhance end-of-life care practices for dying patients on GIM wards