The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses

The equine herpesvirus type 1 (EHV-1) ORF1 and ORF71 genes have immune modulatory effects in vitro. Experimental infection of horses using virus mutants with multiple deletions including ORF1 and ORF71 showed promise as vaccine candidates against EHV-1. Here, the combined effects of ORF1 and ORF71 deletions from the neuropathogenic EHV-1 strain Ab4 on clinical disease and host immune response were further explored. Three groups of EHV-1 naïve horses were experimentally infected with the ORF1/71 gene deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or remained uninfected. In comparison to Ab4, horses infected with Ab4ΔORF1/71 did not show the initial high fever peak characteristic of EHV-1 infection. Ab4ΔORF1/71 infection had reduced nasal shedding (1/5 vs. 5/5) and, simultaneously, decreased intranasal interferon (IFN)-α, interleukin (IL)-10 and soluble CD14 secretion. However, Ab4 and Ab4ΔORF1/71 infection resulted in comparable viremia, suggesting these genes do not regulate the infection of the mononuclear cells and subsequent viremia. Intranasal and serum anti-EHV-1 antibodies to Ab4ΔORF1/71 developed slightly slower than those to Ab4. However, beyond day 12 post infection (d12pi) serum antibodies in both virus-infected groups were similar and remained increased until the end of the study (d114pi). EHV-1 immunoglobulin (Ig) G isotype responses were dominated by short-lasting IgG1 and long-lasting IgG4/7 antibodies. The IgG4/7 response closely resembled the total EHV-1 specific antibody response. Ex vivo re-stimulation of PBMC with Ab4 resulted in IFN-γ and IL-10 secretion by cells from both infected groups within two weeks pi. Flow cytometric analysis showed that IFN-γ producing EHV-1-specific T-cells were mainly CD8+/IFN-γ+ and detectable from d32pi on. Peripheral blood IFN-γ+ T-cell percentages were similar in both infected groups, albeit at low frequency (~0.1%). In summary, the Ab4ΔORF1/71 gene deletion mutant is less virulent but induced antibody responses and cellular immunity similar to the parent Ab4 strain

Pneumovirus in Dogs with Acute Respiratory Disease

To determine which respiratory viruses circulate among confined dogs, we analyzed nasal and pharyngeal swab specimens from shelter dogs with acute respiratory disease. An unknown virus was isolated. Monoclonal antibody testing indicated that it was probably a pneumovirus. PCR and sequence analysis indicated that it was closely related to murine pneumovirus

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Explaining the de-prioritization of primary prevention: Physicians' perceptions of their role in the delivery of primary care

BACKGROUND: While physicians are key to primary preventive care, their delivery rate is sub-optimal. Assessment of physician beliefs is integral to understanding current behavior and the conceptualization of strategies to increase delivery. METHODS: A focus group with regional primary care physician (PCP) Opinion Leaders was conducted as a formative step towards regional assessment of attitudes and barriers regarding preventive care delivery in primary care. Following the PRECEDE-PROCEED model, the focus group aim was to identify conceptual themes that characterize PCP beliefs and practices regarding preventive care. Seven male and five female PCPs (family medicine, internal medicine) participated in the audiotaped discussion of their perceptions and behaviors in delivery of primary preventive care. The transcribed audiotape was qualitatively analyzed using grounded theory methodology. RESULTS: The PCPs' own perceived role in daily practice was a significant barrier to primary preventive care. The prevailing PCP model was the "one-stop-shop" physician who could provide anything from primary to tertiary care, but whose provision was dominated by the delivery of immediate diagnoses and treatments, namely secondary care. CONCLUSIONS: The secondary-tertiary prevention PCP model sustained the expectation of immediacy of corrective action, cure, and satisfaction sought by patients and physicians alike, and, thereby, de-prioritized primary prevention in practice. Multiple barriers beyond the immediate control of PCP must be surmounted for the full integration of primary prevention in primary care practice. However, independent of other barriers, physician cognitive value of primary prevention in practice, a base mediator of physician behavior, will need to be increased to frame the likelihood of such integration

A case for taking the dual role of counsellor-researcher in qualitative research

This is an Accepted Manuscript of an article published by Taylor & Francis in Qualitative Research in Psychology on 3rd August 2016, available online: https://doi.org/10.1080/14780887.2016.1205694There is ongoing debate about whether the challenges of practice-based research in counselling, with clients’ discourses providing the raw data, can be overcome. This article begins by considering the argument of whether taking a dual role of counsellor-researcher within case study research is a legitimate qualitative approach. A case example using sand-tray in short-term therapy with adults from a pluralistic perspective is provided to demonstrate how the challenges of the dual role can be managed to produce effective research findings. It is suggested that this approach closes the gap between research and practice to produce findings that are highly relevant to the counselling context. The ethical considerations of taking a dual role of counsellor-researcher are considered, and opportunities and challenges when adopting this approach are identified

Is race medically relevant? A qualitative study of physicians' attitudes about the role of race in treatment decision-making

<p>Abstract</p> <p>Background</p> <p>The role of patient race in medical decision-making is heavily debated. While some evidence suggests that patient race can be used by physicians to predict disease risk and determine drug therapy, other studies document bias and stereotyping by physicians based on patient race. It is critical, then, to explore physicians' attitudes regarding the medical relevance of patient race.</p> <p>Methods</p> <p>We conducted a qualitative study in the United States using ten focus groups of physicians stratified by self-identified race (black or white) and led by race-concordant moderators. Physicians were presented with a medical vignette about a patient (whose race was unknown) with Type 2 diabetes and untreated hypertension, who was also a current smoker. Participants were first asked to discuss what medical information they would need to treat the patient. Then physicians were asked to explicitly discuss the importance of race to the hypothetical patient's treatment. To identify common themes, codes, key words and physician demographics were compiled into a comprehensive table that allowed for examination of similarities and differences by physician race. Common themes were identified using the software package NVivo (QSR International, v7).</p> <p>Results</p> <p>Forty self-identified black and 50 self-identified white physicians participated in the study. All physicians - regardless of their own race - believed that medical history, family history, and weight were important for making treatment decisions for the patient. However, black and white physicians reported differences in their views about the relevance of race. Several black physicians indicated that patient race is a central factor for choosing treatment options such as aggressive therapies, patient medication and understanding disease risk. Moreover, many black physicians considered patient race important to understand the patient's views, such as alternative medicine preferences and cultural beliefs about illness. However, few white physicians explicitly indicated that the patient's race was important over-and-above medical history. Instead, white physicians reported that the patient should be treated aggressively regardless of race.</p> <p>Conclusions</p> <p>This investigation adds to our understanding about how physicians in the United States consider race when treating patients, and sheds light on issues physicians face when deciding the importance of race in medical decision-making.</p

Attitudes towards community gambling venues and support for regulatory reform: An online panel study of residents in New South Wales, Australia

Background: Harmful gambling has been identified as an important public health issue that affects individuals, families and the broader community. One gambling product, electronic gambling machines (EGMs), has been associated with significant gambling harm in Australia. There has been limited research that has explored community perceptions of EGMs and attitudes towards reform. This study, conducted in NSW, Australia, aimed to explore community use of EGM venues (clubs and hotels containing EGMs), attitudes towards EGMs and whether the use of these venues influenced attitudes towards EGM reform. Methods: An online survey was conducted with 500 adults aged 16 years and over, representative of the population for age and gender. Discrete choice and open-ended questions were used to gather data on gambling behaviours, use of and attitudes towards EGMs and EGM venues and support for gambling harm reduction measures. Results: Three quarters of participants had visited an EGM venue in the previous year. Participants who had attended such venues were significantly more likely to use EGMs at least once per month. Participants attended EGM venues for a range of reasons including use of non-gambling facilities such as restaurants, the social aspects of the venue and ease of access to the venue. Some participants also attended EGM venues specifically for the gambling facilities. Most participants identified some negative impacts of EGMs for local communities and were supportive of measures to reduce the number of EGMs and prevent children's exposure to EGMs in such venues. Conclusions: This study shows a high level of support for EGM reform amongst both individuals who attend EGM venues and also those who do not. There is potential for government to further regulate EGMs and the environments where they are located

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes

Physician perceptions of primary prevention: qualitative base for the conceptual shaping of a practice intervention tool

BACKGROUND: A practice intervention must have its basis in an understanding of the physician and practice to secure its benefit and relevancy. We used a formative process to characterize primary care physician attitudes, needs, and practice obstacles regarding primary prevention. The characterization will provide the conceptual framework for the development of a practice tool to facilitate routine delivery of primary preventive care. METHODS: A focus group of primary care physician Opinion Leaders was audio-taped, transcribed, and qualitatively analyzed to identify emergent themes that described physicians' perceptions of prevention in daily practice. RESULTS: The conceptual worth of primary prevention, including behavioral counseling, was high, but its practice was significantly countered by the predominant clinical emphasis on and rewards for secondary care. In addition, lack of health behavior training, perceived low self-efficacy, and patient resistance to change were key deterrents to primary prevention delivery. Also, the preventive focus in primary care is not on cancer, but on predominant chronic nonmalignant conditions. CONCLUSIONS: The success of the future practice tool will be largely dependent on its ability to "fit" primary prevention into the clinical culture of diagnoses and treatment sustained by physicians, patients, and payers. The tool's message output must be formatted to facilitate physician delivery of patient-tailored behavioral counseling in an accurate, confident, and efficacious manner. Also, the tool's health behavior messages should be behavior-specific, not disease-specific, to draw on shared risk behaviors of numerous diseases and increase the likelihood of perceived salience and utility of the tool in primary care

Student Attitudes Contribute to the Effectiveness of a Genomics CURE

The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student\u27s epistemic beliefs to achieving positive learning outcomes