In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

Introducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy (ART) on neurodevelopment. Methods We systematically searched OVID Medline, PsycINFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full-text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV-exposed uninfected children compared to HIV-unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV-exposed uninfected and HIV-unexposed uninfected children and using exposures consistent with current clinical care

Genomic and gene regulatory signatures of cryptozoic adaptation: Loss of blue sensitive photoreceptors through expansion of long wavelength-opsin expression in the red flour beetle Tribolium castaneum

Abstract Background Recent genome sequence analysis in the red flour beetle Tribolium castaneum indicated that this highly crepuscular animal encodes only two single opsin paralogs: a UV-opsin and a long wavelength (LW)-opsin; however, these animals do not encode a blue (B)-opsin as most other insects. Here, we studied the spatial regulation of the Tribolium single LW- and UV-opsin gene paralogs in comparison to that of the five opsin paralogs in the retina of Drosophila melanogaster. Results In situ hybridization analysis reveals that the Tribolium retina, in contrast with other insect retinas, constitutes a homogenous field of ommatidia that have seven LW-opsin expressing photoreceptors and one UV-/LW-opsin co-expressing photoreceptor per eye unit. This pattern is consistent with the loss of photoreceptors sensitive to blue wavelengths. It also identifies Tribolium as the first example of a species in insects that co-expresses two different opsins across the entire retina in violation of the widely observed one receptor rule of sensory cells. Conclusion Broader studies of opsin evolution in darkling beetles and other coleopteran groups have the potential to pinpoint the permissive and adaptive forces that played a role in the evolution of vision in Tribolium castaneum

Diets of European polecat Mustela putorius in Great Britain during fifty years of population recovery

Following nineteenth-century declines, polecats Mustela putorius are recolonising Great Britain. Polecat diet relates to two potential risks to recovery. First, rabbits Oryctolagus cuniculus, which are important prey for polecats, have experienced extreme population fluctuations, with near extirpation due to myxomatosis in the 1950s, recovery in 1960s–1990s and declines in 1990s–2010s. Second, polecats are secondarily exposed to anticoagulant rodenticides by eating contaminated rodents, and the frequency of polecat exposure to rodenticides is increasing. We analysed stomach contents from 99 polecats collected in 2012–2016 and compared results with earlier studies. Lagomorphs were the most abundant prey (66% frequency of occurrence, 95% confidence interval 53–74%), followed by other mammals (12%, 4–18%), amphibians (10%, 3–16%) and birds (7%, 1–13%). Diet varied seasonally; lagomorph occurrence was highest in spring and summer and lowest in autumn. Dietary niche breadth was greater in the 1960s, when rabbits were scarce, than in other decades, but did not differ between the 1990s and 2010s, indicating that diets have not diversified with recent rabbit declines. This may be because rabbit abundance is not yet low enough to cause dietary diversification or because polecats were collected in areas where rabbits were still abundant. Rodents did not increase in diet between the 1990s and 2010s and still occur with < 10% frequency, indicating that rodents need not contribute much to diet to expose polecats to rodenticides. This potentially limits the effectiveness of management actions designed to minimise polecat exposure to contaminated rodent prey

Drugs-related death soon after hospital discharge among drug treatment clients in Scotland:record linkage, validation and investigation of risk factors.

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting

Testing the Cosmic Coincidence Problem and the Nature of Dark Energy

Dark energy models which alter the relative scaling behavior of dark energy and matter could provide a natural solution to the cosmic coincidence problem - why the densities of dark energy and dark matter are comparable today. A generalized class of dark energy models is introduced which allows non-canonical scaling of the ratio of dark matter and dark energy with the Robertson-Walker scale factor a(t). Upcoming observations, such as a high redshift supernova survey, application of the Alcock-Paczynski test to quasar pairs, and cluster evolution, will strongly constrain the relative scaling of dark matter and dark energy as well as the equation of state of the dark energy. Thus, whether there actually is a coincidence problem, and the extent of cosmic coincidence in the universe's recent past can be answered observationally in the near future. Determining whether today is a special time in the history of the universe will be a SNAP.Comment: 5 pages, 3 figures, revtex4, submitted to PR

Universal ideals in local realities: online viewing in South Korea, Brazil and India

The potential of the internet to act as a global distribution outlet for screen content has long come into conflict with the nationally-focused strategies of producers, broadcasters, governments and internet service providers. Online viewing therefore acts as a useful case study for interrogating how tensions between ‘global’ and ‘local’ manifest within an increasingly digitized media landscape. This article examines the online viewing markets in three countries at different stages of digital maturity (South Korea, Brazil, India) to consider how online viewing has evolved in each. It then examines audience questionnaire and interview data generated in each country to explore how viewers are making sense of and valuing online viewing services. By interrogating all three samples before focusing specifically on India in more detail, it examines two tensions within the global expansion of online film and television distribution: between global trends and local infrastructures, and between the ideals of online viewing services and the grounded realities of their daily use

Normalizing glycosphingolipids restores function in CD4+ T cells from lupus patients

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE) have multiple defects in lymphocyte signaling and function that contribute to disease pathogenesis. Such defects could be attributed to alterations in metabolic processes, including abnormal control of lipid biosynthesis pathways. Here, we reveal that CD4+ T cells from SLE patients displayed an altered profile of lipid raft–associated glycosphingolipids (GSLs) compared with that of healthy controls. In particular, lactosylceramide, globotriaosylceramide (Gb3), and monosialotetrahexosylganglioside (GM1) levels were markedly increased. Elevated GSLs in SLE patients were associated with increased expression of liver X receptor β (LXRβ), a nuclear receptor that controls cellular lipid metabolism and trafficking and influences acquired immune responses. Stimulation of CD4+ T cells isolated from healthy donors with synthetic and endogenous LXR agonists promoted GSL expression, which was blocked by an LXR antagonist. Increased GSL expression in CD4+ T cells was associated with intracellular accumulation and accelerated trafficking of GSL, reminiscent of cells from patients with glycolipid storage diseases. Inhibition of GSL biosynthesis in vitro with a clinically approved inhibitor (N-butyldeoxynojirimycin) normalized GSL metabolism, corrected CD4+ T cell signaling and functional defects, and decreased anti-dsDNA antibody production by autologous B cells in SLE patients. Our data demonstrate that lipid metabolism defects contribute to SLE pathogenesis and suggest that targeting GSL biosynthesis restores T cell function in SLE

Dissemination and Effectiveness of the Peer Marketing and Messaging of a Web-Assisted Tobacco Intervention: Protocol for a Hybrid Effectiveness Trial

BACKGROUND: Smoking continues to be the leading preventable cause of death. Digital Interventions for Smoking Cessation (DISCs) are health communication programs accessible via the internet and smartphones and allow for greater reach and effectiveness of tobacco cessation programs. DISCs have led to increased 6-month cessation rates while also reaching vulnerable populations. Despite this, the impact of DISCs has been limited and new ways to increase access and effectiveness are needed. OBJECTIVE: We are conducting a hybrid effectiveness-dissemination study. We aim to evaluate the effectiveness of a machine learning-based approach (recommender system) for computer-tailored health communication (CTHC) over a standard CTHC system based on quit rates and risk reduction. In addition, this study will assess the dissemination of providing access to a peer recruitment toolset on recruitment rate and variability of the sample. METHODS: The Smoker-to-Smoker (S2S) study is a 6-month hybrid effectiveness dissemination trial conducted nationally among English-speaking, current smokers aged \u3e /=18 years. All eligible participants will register for the DISC (Decide2quit) and be randomized to the recommender system CTHC or the standard CTHC, followed by allocation to a peer recruitment toolset group or control group. Primary outcomes will be 7-day point prevalence and risk reduction at the 6-month follow-up. Secondary outcomes include recruitment rate, website engagement, and patient-reported outcomes collected via the 6-month follow-up questionnaire. All primary analyses will be conducted on an intent-to-treat basis. RESULTS: The project is funded from 2017 to 2020 by the Patient Centered Outcomes Research Institute. Enrollment was completed in early 2019, and 6-month follow-ups will be completed by late 2019. Preliminary data analysis is currently underway. CONCLUSIONS: Conducting a hybrid study with both effectiveness and dissemination hypotheses raises some unique challenges in the study design and analysis. Our study addresses these challenges to test new innovations and increase the effectiveness and reach of DISCs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14814

Human Neurobrucellosis with Intracerebral Granuloma Caused by a Marine Mammal Brucella spp.

We present the first report of community-acquired human infections with marine mammal–associated Brucella spp. and describe the identification of these strains in two patients with neurobrucellosis and intracerebral granulomas. The identification of these isolates as marine mammal strains was based on omp2a sequence and amplification of the region flanking bp26

Infectious complications after deployment trauma: Following wounded US military personnel into Veterans Affairs care

BACKGROUND: Infectious complications related to deployment trauma significantly contribute to the morbidity and mortality of wounded service members. The Trauma Infectious Disease Outcomes Study (TIDOS) collects data on US military personnel injured in Iraq and Afghanistan in an observational cohort study of infectious complications. Patients enrolled in TIDOS may also consent to follow-up through the Department of Veterans Affairs (VA). We present data from the first 337 TIDOS enrollees to receive VA healthcare. METHODS: Data were collected from the Department of Defense (DoD) Trauma Registry, TIDOS infectious disease module, DoD and VA electronic medical records, and telephone interview. Cox proportional hazard analysis was performed to identify predictors of post-discharge infections related to deployment trauma. RESULTS: Among the first 337 TIDOS enrollees who entered VA healthcare, 111 (33%) had 244 trauma-related infections during their initial trauma hospitalization (2.1 infections per 100 person-days). Following initial discharge, 127 (38%) enrollees had 239 trauma-related infections (170 during DoD follow-up and 69 during VA time). Skin and soft-tissue infections and osteomyelitis were predominant during and after the initial trauma hospitalization. In a multivariate model, a shorter time to development of a new infection following discharge was independently associated with injury severity score ≥10 and occurrence of ≥1 inpatient infection during initial trauma hospitalization. CONCLUSIONS: Incident infections related to deployment trauma continue well after initial hospital discharge and into VA healthcare. Overall, 38% of enrolled patients developed a new trauma-related infection after their initial hospital discharge, with 29% occurring after the patient left military service