Facilitators and Barriers to Prescribing PreExposure Prophylaxis (PrEP) for the Prevention of HIV

Background: What is PrEP and who gets it? PrEP is the use of medication by individuals to prevent HIV contraction, approved in 2012 after demonstrating safety and efficacy in the iPrEx study and Partners PrEP2 trials. HIV infection risk is 92% lower in patients using PrEP. Truvada®, a combination of tenofovir and emtricitabine taken orally daily, is the only approved PrEP regimen and is intended to compliment other prevention strategies such as condoms. HIV negative-individuals at risk for exposure to HIV have been identified as men who have sex with men (MSM), IV drug users, heterosexuals who have unprotected sex with partners of unknown HIV status, and those in serodiscordant relationships. Barriers to PrEP Implementation PrEP is effective when patients adhere; however, both the medical community and some high-risk populations have been slow to adopt it as an HIV prevention strategy. Surveys have shown clinicians perceived barriers to PrEP such as adverse side effects, viral drug resistance, increased high-risk behavior, cost, and training. HIV in Vermont New diagnoses of HIV among Vermont residents has remained relatively stable over the last twenty years. Vermont CARES, a non-profit, offers free and anonymous HIV tests and in-person risk-reduction counseling. Clients are increasingly asking about PrEP as a prevention strategy, but the response from the medical community is difficult to ascertain.https://scholarworks.uvm.edu/comphp_gallery/1235/thumbnail.jp

Short-Eared Owl Land-Use Associations During the Breeding Season in the Western United States

The Short-eared Owl (Asio flammeus) is a species of conservation concern in the western USA, with evidence for declining population sizes. Monitoring of Short-eared Owls is complicated because of their low site fidelity and nomadic movements. We recruited community-science participants to implement a multi-year survey of Short-eared Owls across eight states in the western USA, resulting in a program of sufficient temporal and spatial dimensions to overcome many of the challenges in monitoring this species. We implemented both multi-scale occupancy and colonization/extinction modeling to provide insights into land-cover use, and to identify which cover types supported higher occurrence. Short-eared Owls were associated with native and anthropogenic land-cover types, but site occupancy varied among these categories and at different scales. Native grasslands, marsh/riparian, hay/fallow agriculture, and cultivated croplands were occupied most consistently across years. Occupancy rates differed at different scales (e.g., marsh/ riparian was the only land-cover type positively associated with occupancy at both transect and point scales). Contrary to expectations, native shrubland was negatively associated with occupancy at the point scale, and exhibited low colonization and high extinction rates. Our results suggest that conserving native landscapes in general, and grasslands, marsh, and riparian areas specifically, would benefit Short-eared Owls. Furthermore, Short-eared Owl occupancy was positively associated with hay/fallow land-cover types, suggesting that some nonnative land-cover types can function as Short-eared Owl habitat. Lastly, our results highlight how developing a broad-scale community science survey can inform conservation for a species not well monitored by existing survey programs

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor

Background: Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. Methods: We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Results: Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. Discussion: The data from this study indicate that medication cessation is common following unilateral DBS for ET

Identification of enhanced IFN-γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry

Polyarticular juvenile idiopathic arthritis (JIA) is among the most challenging of the JIA subtypes to treat. Even with current biologic therapies, the disease remains difficult to control in a substantial subset of patients, highlighting the need for new therapies. The aim of this study was to use the high dimensionality afforded by mass cytometry with phospho-specific antibodies to delineate signaling abnormalities in immune cells from treatment-naive polyarticular JIA patients. Peripheral blood mononuclear cells were isolated from 17 treatment-naive polyarticular JIA patients, 10 of the patients after achieving clinical remission, and 19 healthy controls. Samples were stimulated for 15 minutes with IL-6 or IFN-γ and analyzed by mass cytometry. Following IFN-γ stimulation, increased STAT1 and/or STAT3 phosphorylation was observed in subsets of CD4 T cells and classical monocytes from treatment-naive patients. The enhanced IFN-γ signaling was associated with increased expression of JAK1 and SOCS1 in CD4 T cells. Furthermore, substantial heterogeneity in surface marker expression was observed among the subsets of CD4 T cells and classical monocytes with increased IFN-γ responsiveness. The identification of enhanced IFN-γ signaling in CD4 T cells and classical monocytes from treatment-naive polyarticular JIA patients provides mechanistic support for investigations into therapies that attenuate IFN-γ signaling in this disease

Breast cancer family history and allele-specific DNA methylation in the Legacy Girls Study

Family history, a well-established risk factor for breast cancer, can have both genetic and environmental contributions. Shared environment in families as well as epigenetic changes that also may be influenced by shared genetics and environment may also explain familial clustering of cancers. Epigenetic regulation, such as DNA methylation, can change the activity of a DNA segment without a change in the sequence; environmental exposures experienced across the life course can induce such changes. However, genetic-epigenetic interactions, detected as methylation quantitative trait loci (mQTLs; a.k.a. meQTLs) and haplotype-dependent allele-specific methylation (hap-ASM), can also contribute to inter-individual differences in DNA methylation patterns. To identify differentially methylated regions (DMRs) associated with breast cancer susceptibility, we examined differences in white blood cell DNA methylation in 29 candidate genes in 426 girls (ages 6-13 years) from the LEGACY Girls Study, 239 with and 187 without a breast cancer family history (BCFH). We measured methylation by targeted massively parallel bisulfite sequencing (bis-seq) and observed BCFH DMRs in two genes: ESR1 (Δ4.9%, P = 0.003) and SEC16B (Δ3.6%, P = 0.026), each of which has been previously implicated in breast cancer susceptibility and pubertal development. These DMRs showed high inter-individual variability in methylation, suggesting the presence of mQTLs/hap-ASM. Using single nucleotide polymorphisms data in the bis-seq amplicon, we found strong hap-ASM in SEC16B (with allele specific-differences ranging from 42% to 74%). These findings suggest that differential methylation in genes relevant to breast cancer susceptibility may be present early in life, and that inherited genetic factors underlie some of these epigenetic differences

Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells

Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency. In this study, we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population. Lineage tracing distinguished macrophages from classical DCs, neutrophils, and B cells in all organs examined. At steady state, Langerhans cells (LCs) were lineage traced but also expressed Zbtb46-GFP, a phenotype not observed in any other population. After exposure to house dust mite antigen, Zbtb46-negative CD64(+) inflammatory cells infiltrating the lung were substantially lineage traced, but Zbtb46-positive CD64(−) cells were not. These results provide new evidence for the unique identity of LCs and challenge the notion that some inflammatory cells are a population of monocyte-derived DCs

Opening a new window to other worlds with spectropolarimetry

A high level of diversity has already been observed among the planets of our own Solar System. As such, one expects extrasolar planets to present a wide range of distinctive features, therefore the characterisation of Earth- and super Earth-like planets is becoming of key importance in scientific research. The SEARCH (Spectropolarimetric Exoplanet AtmospheRe CHaracerisation) mission proposal of this paper represents one possible approach to realising these objectives. The mission goals of SEARCH include the detailed characterisation of a wide variety of exoplanets, ranging from terrestrial planets to gas giants. More specifically, SEARCH will determine atmospheric properties such as cloud coverage, surface pressure and atmospheric composition, and may also be capable of identifying basic surface features. To resolve a planet with a semi major axis of down to 1.4AU and 30pc distant SEARCH will have a mirror system consisting of two segments, with elliptical rim, cut out of a parabolic mirror. This will yield an effective diameter of 9 meters along one axis. A phase mask coronagraph along with an integral spectrograph will be used to overcome the contrast ratio of star to planet light. Such a mission would provide invaluable data on the diversity present in extrasolar planetary systems and much more could be learned from the similarities and differences compared to our own Solar System. This would allow our theories of planetary formation, atmospheric accretion and evolution to be tested, and our understanding of regions such as the outer limit of the Habitable Zone to be further improved.Comment: 23 pages, accepted for publication in Experimental Astronom

Association of candy consumption with body weight measures, other health risk factors for cardiovascular disease, and diet quality in US children and adolescents: NHANES 1999–2004

Objective : The purpose of this study was to determine the effects of total, chocolate, or sugar candy consumption on intakes of total energy, fat, and added sugars; diet quality; weight/adiposity parameters; and risk factors for cardiovascular disease in children 2–13 years of age (n=7,049) and adolescents 14–18 years (n=4,132) participating in the 1999–2004 National Health and Nutrition Examination Survey. Methods : Twenty-four hour dietary recalls were used to determine intake. Diet quality was determined using the Healthy Eating Index-2005 (HEI-2005). Covariate-adjusted means, standard errors, and prevalence rates were determined for each candy consumption group. Odds ratios were used to determine the likelihood of associations with weight status and diet quality. Results : In younger children, total, chocolate, and sugar candy consumption was 11.4 g±1.61, 4.8 g±0.35, and 6.6 g±0.46, respectively. In adolescents, total, chocolate, and sugar candy consumption was 13.0 g±0.87, 7.0 g±0.56, and 5.9 g±0.56, respectively. Total candy consumers had higher intakes of total energy (2248.9 kcals±26.8 vs 1993.1 kcals±15.1, p<0.0001) and added sugars (27.7 g±0.44 vs 23.4 g±0.38, p<0.0001) than non-consumers. Mean HEI-2005 score was not different in total candy and sugar candy consumers as compared to non-consumers, but was significantly lower in chocolate candy consumers (46.7±0.8 vs 48.3±0.4, p = 0.0337). Weight, body mass index (BMI), waist circumference, percentiles/z-score for weight-for-age and BMI-for-age were lower for candy consumers as compared to non-consumers. Candy consumers were 22 and 26%, respectively, less likely to be overweight and obese than non-candy consumers. Blood pressure, blood lipid levels, and cardiovascular risk factors were not different between total, chocolate, and sugar candy consumers and non-consumers (except that sugar candy consumers had lower C-reactive protein levels than non-consumers). Conclusion : This study suggests that candy consumption did not adversely affect health risk markers in children and adolescents

T-lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls

T lymphocytes infiltrating hepatic tissues were typed and enumerated in liver biopsies of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls using monoclonal antibodies and the avidin-biotin-immunoperoxidase technique. The peripheral blood mononuclear cells were studied also by flow cytometry. In PBC, T lymphocytes were decreased (P<0.001) in the blood [absolute number was 426±200 (SE) vs 1351±416 in 15 controls], as was the helper/suppressor (T4/T8) ratio (1.0±0.1 vs normal 2.3±0.3). T lymphocytes were the most numerous mononuclear cells infiltrating portal areas of PBC livers: 749±93/5 high-power fields (HPF) in PBC vs 98±15/5 HPF (P<0.01) in controls. The T4/T8 ratios varied from 0.9 to 2.3 (mean, 1.8±0.1) in the portal triads (normal mean, 1.6±0.1), with the T4+ cells accounting for more than 75% of infiltrating T cells. In contrast, the mean T4/T8 ratio in portal triads of PSC was reduced (1.0±0.3) due to a significant increase (P<0.001) in the number of T8+ cells. The T cells around and in the walls of bile ducts in PBC were mostly T8+, and the T4/T8 ratio was 0.8±0.2. No T8+ cells were seen in this location in PSC and normal livers. Few mononuclear cells were present in hepatic lobules. Subtyping of T lymphocytes in liver tissues of patients with PBC and PSC may be helpful in the differential pathologic diagnosis. In patients with advanced PBC, a decrease in T4+ cells in the blood appeared to be accompanied by their accumulation in the portal triads. In contrast, T8+ cells accumulated preferentially around bile ducts. © 1984 Plenum Publishing Corporation