Brief screening for co-occurring disorders among women entering substance abuse treatment

BACKGROUND: Despite the importance of identifying co-occurring psychiatric disorders in substance abuse treatment programs, there are few appropriate and validated instruments available to substance abuse treatment staff to conduct brief screen for these conditions. This paper describes the development, implementation and validation of a brief screening instrument for mental health diagnoses and trauma among a diverse sample of Black, Hispanic and White women in substance abuse treatment. With input from clinicians and consumers, we adapted longer existing validated instruments into a 14 question screen covering demographics, mental health symptoms and physical and sexual violence exposure. All women entering treatment (methadone, residential and out-patient) at five treatment sites were screened at intake (N = 374). RESULTS: Eighty nine percent reported a history of interpersonal violence, and 70% reported a history of sexual assault. Eighty-eight percent reported mental health symptoms in the last 30 days. The screening questions administered to 88 female clients were validated against in-depth psychiatric diagnostic assessments by trained mental health clinicians. We estimated measures of predictive validity, including sensitivity, specificity and predictive values positive and negative. Screening items were examined multiple ways to assess utility. The screen is a useful and valid proxy for PTSD but not for other mental illness. CONCLUSION: Substance abuse treatment programs should incorporate violence exposure questions into clinical use as a matter of policy. More work is needed to develop brief screening tools measures for front-line treatment staff to accurately assess other mental health needs of women entering substance abuse treatmen

Acceptance patterns and decision-making for human papillomavirus vaccination among parents in Vietnam: an in-depth qualitative study post-vaccination

BACKGROUND: The GAVI Alliance’s decision in late 2011 to invite developing countries to apply for funding for human papillomavirus (HPV) vaccine introduction underscores the importance of understanding levels of HPV vaccine acceptance in developing country settings. In this paper, we present findings from qualitative research on parents’ rationales for vaccinating or not vaccinating their daughters (vaccine acceptance) and their decision-making process in the context of an HPV vaccination demonstration project in Vietnam (2008–2009). METHODS: We designed a descriptive qualitative study of HPV vaccine acceptability among parents of girls eligible for vaccination in four districts of two provinces in Vietnam(a). The study was implemented after each of two years of vaccinations was completed. In total, 133 parents participated in 16 focus group discussions and 27 semi-structured interviews. RESULTS: Focus group discussions and in-depth interviews with parents of girls vaccinated revealed that they were generally very supportive of immunization for disease prevention and of vaccinating girls against HPV. The involvement of the National Expanded Program of Immunization in the demonstration project lent credibility to the HPV vaccine, contributing to high levels of acceptance. For parents who declined participation, concerns about side effects, the possibility that the vaccine was experimental, and the possible impact of the vaccine on future fertility rose to the surface. In terms of the decision-making process, many parents exhibited ‘active decision-making,’ reaching out to friends, family, and opinion leaders for guidance prior to making their decision. CONCLUSION: Vietnam’s HPV vaccination experience speaks to the importance of close collaboration with the government to make the most of high levels of trust, and to reduce suspicions about new vaccines that may arise in the context of vaccine introduction in developing country settings

Regulation of valve endothelial cell vasculogenic network architectures with ROCK and Rac inhibitors

Objective: The age- and disease-dependent presence of microvessels within heart valves is an understudied characteristic of these tissues. Neovascularization involves endothelial cell (EC) migration and cytoskeletal reorientation, which are heavily regulated by the Rho family of GTPases. Given that valve ECs demonstrate unique mesenchymal transdifferentiation and cytoskeletal mechanoresponsiveness, compared to vascular ECs, this study quantified the effect of inhibiting two members of the Rho family on vasculogenic network formation by valve ECs. Approach and results: A tubule-like structure vasculogenesis assay (assessing lacunarity, junction density, and vessel density) was performed with porcine aortic valve ECs treated with small molecule inhibitors of Rho-associated serine-threonine protein kinase (ROCK), Y-27632, or the Rac1 inhibitor, NSC-23766. Actin coordination, cell number, and cell migration were assessed through immunocytochemistry, MTT assay, and scratch wound healing assay. ROCK inhibition reduced network lacunarity and interrupted proper cell–cell adhesion and actin coordination. Rac1 inhibition increased lacunarity and delayed actin-mediated network formation. ROCK inhibition alone significantly inhibited migration, whereas both ROCK and Rac1 inhibition significantly reduced cell number over time compared to controls. Compared to a vascular EC line, the valve ECs generated a network with larger total vessel length, but a less smooth appearance. Conclusions: Both ROCK and Rac1 inhibition interfered with key processes in vascular network formation by valve ECs. This is the first report of manipulation of valve EC vasculogenic organization in response to small molecule inhibitors. Further study is warranted to comprehend this facet of valvular cell biology and pathology and how it differs from vascular biology

Group-based trajectories of maternal intake of sugar-sweetened beverage and offspring oral health from a prospective birth cohort study

OBJECTIVES: To investigate the trajectory of maternal intake of sugar-sweetened beverages (SSB) during the first five years of their child's life and its effect on the child's dental caries at five years-of-age. METHODS: This is an ongoing prospective population-based birth cohort study in Adelaide, Australia. Mothers completed questionnaires on their SSB intake, socioeconomic factors and health behaviors at the birth of their child and at the ages of one, two and five years. Child dental caries measured as decayed, missing, or filled tooth surfaces was collected by oral examination. Maternal SSB intake was used to estimate the trajectory of SSB intake. The trajectories then became the main exposure of the study. Dental caries at age five years were the primary outcomes. Adjusted mean- and prevalence-ratios were estimated for dental caries, controlling for confounders. RESULTS: 879 children had dental examinations at five years-of-age. Group-based trajectory modeling identified three trajectories of maternal SSB intake: 'Stable low' (40.8%), 'Moderate but increasing' (13.6%), and 'High early' trajectory (45.6%). Multivariable regression analysis found children of mothers in the 'High early' and 'Moderate but increasing' groups to have greater experience of dental caries (MR: 1.37 (95%CI 1.01-1.67), and 1.24 (95%CI 0.96-1.60) than those in the 'Stable low' trajectory, respectively. CONCLUSION: Maternal consumption of SSB during pregnancy and in the early postnatal period influenced their offspring's oral health. It is important to create a low-sugar environment from early childhood. The results suggest that health promotion activities need to be delivered to expecting women or soon after childbirth

Monoclonal Antibodies to Distinct Regions of Human Myelin Proteolipid Protein Simultaneously Recognize Central Nervous System Myelin and Neurons of Many Vertebrate Species

Myelin proteolipid protein (PLP), the major protein of mammalian CNS myelin, is a member of the proteolipid gene family (pgf). It is an evolutionarily conserved polytopic integral membrane protein and a potential autoantigen in multiple sclerosis (MS). To analyze antibody recognition of PLP epitopes in situ, monoclonal antibodies (mAbs) specific for different regions of human PLP (50–69, 100–123, 139–151, 178–191, 200–219, 264–276) were generated and used to immunostain CNS tissues of representative vertebrates. mAbs to each region recognized whole human PLP on Western blots; the anti-100–123 mAb did not recognize DM-20, the PLP isoform that lacks residues 116–150. All of the mAbs stained fixed, permeabilized oligodendrocytes and mammalian and avian CNS tissue myelin. Most of the mAbs also stained amphibian, teleost, and elasmobranch CNS myelin despite greater diversity of their pgf myelin protein sequences. Myelin staining was observed when there was at least 40% identity of the mAb epitope and known pgf myelin proteins of the same or related species. The pgf myelin proteins of teleosts and elasmobranchs lack 116–150; the anti-100–123 mAb did not stain their myelin. In addition to myelin, the anti-178– 191 mAb stained many neurons in all species; other mAbs stained distinct neuron subpopulations in different species. Neuronal staining was observed when there was at least approximately 30% identity of the PLP mAb epitope and known pgf neuronal proteins of the same or related species. Thus, anti-human PLP epitope mAbs simultaneously recognize CNS myelin and neurons even without extensive sequence identity. Widespread anti-PLP mAb recognition of neurons suggests a novel potential pathophysiologic mechanism in MS patients, i.e., that anti-PLP antibodies associated with demyelination might simultaneously recognize pgf epitopes in neurons, thereby affecting their functions

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/

Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria.

Artemether-lumefantrine is a first-line regimen for the treatment of uncomplicated malaria during the second and third trimesters of pregnancy. Previous studies have reported changes in the pharmacokinetics and clinical outcomes following treatment with artemether-lumefantrine in pregnant women compared to nonpregnant adults; however, the results are inconclusive. We conducted a study in rural Uganda to compare the pharmacokinetics of artemether-lumefantrine and the treatment responses between 30 pregnant women and 30 nonpregnant adults with uncomplicated Plasmodium falciparum malaria. All participants were uninfected with HIV, treated with a six-dose regimen of artemether-lumefantrine, and monitored clinically for 42 days. The pharmacokinetics of artemether, its metabolite dihydroartemisinin, and lumefantrine were evaluated for 21 days following treatment. We found no significant differences in the overall pharmacokinetics of artemether, dihydroartemisinin, or lumefantrine in a direct comparison of pregnant women to nonpregnant adults, except for a statistically significant but small difference in the terminal elimination half-lives of both dihydroartemisinin and lumefantrine. There were seven PCR-confirmed reinfections (5 pregnant and 2 nonpregnant participants). The observation of a shorter terminal half-life for lumefantrine may have contributed to a higher frequency of reinfection or a shorter posttreatment prophylactic period in pregnant women than in nonpregnant adults. While the comparable overall pharmacokinetic exposure is reassuring, studies are needed to further optimize antimalarial efficacy in pregnant women, particularly in high-transmission settings and because of emerging drug resistance. (This study is registered at ClinicalTrials.gov under registration no. NCT01717885.)

Robust and prototypical immune responses towards COVID-19 BNT162b2 vaccines in Indigenous people

SARS-CoV-2 has led to >270 million infections and >5 million deaths globally. Indigenous people are disproportionately affected by infectious diseases, therefore also more susceptible to the COVID-19 pandemic. There are an estimated 476 million indigenous people globally, including an estimated 798,365 Aboriginal and Torres Strait Islander in Australia. With the high vulnerability to COVID-19, this knowledge is urgently needed to better protect indigenous populations. We evaluated a breadth of immune responses in indigenous (n=57) and non-indigenous (n=49) individuals after COVID-19 vaccination. We tested RBD antibodies, spike/RBD-probe-specific B cells, peptide stimulations with activation-induced marker (AIM) assay and intracellular cytokine staining. We found 22% and 34% seroconversion rates after 1st dose of BNT162b2 vaccine for Indigenous and non-indigenous individuals, respectively, which increased to 100% at 1-mth after 2nd dose for both groups. RBD-specific IgG levels in indigenous individuals at 1-mth after 2nd dose positively correlated with their body mass index. At 1-mth after the 2nd COVID-19 vaccination, CD4+ and CD8+ T cell responses via AIM expression and IFN-γ+TNF+ production was comparable between indigenous and non-indigenous individuals. We are also going to assess the longevity of antibodies and T cells. Therefore, COVID-19 vaccination induced similar immune responses in indigenous and non-indigenous individuals