Genetic polymorphisms and organophosphate neurotoxicity amongst emerging farmers in the Western Cape

BACKGROUND: Long-term exposure to organophosphates (OPs) can cause chronic neurotoxic effects which may be modulated by genetic polymorphisms of xenobiotic metabolising enzymes (XMEs). No previous study investigated XME modulation of neurotoxicity outcomes. OBJECTIVES: To investigate whether XMEs polymorphisms modulate OP neurotoxicity among emerging farmers. METHODS: A cross-sectional study of 301 emerging farmers was conducted in the rural Western Cape of South Africa. Neurotoxicity testing included the World Health Organisation Core Test Battery (digit span forward and backward) and vibration sensitivity testing. Questionnaire items included demographic data, potential confounders and work history of pesticide exposures. Blood samples were analysed for genetic polymorphisms of the following XMEs; glutathione S-transferases (GST), N-acetyltransferases (NAT) and Paraoxonase (PON1). RESULTS: Median age was 39 (30-48) and most had 9 years of education or less (65.5%). 54% of the participants were OP pesticide applicators. There was a low prevalence of the GST null genotype (GSTT-1% and GSTM-16%) and the GA and GG genotype for NAT (10%). Modulation of OP exposure and neurotoxic outcome relationships by NAT, PON1 at position 192 and GST was indicated in multivariate analysis. The strongest evidence of modification was by NAT on the relationship between pesticide poisoning and impaired vibration sense. Poisoned individuals with the GG genotype were more likely to suffer from impaired vibration sense compared to GA and AA genotypes. CONCLUSION: Genetic polymorphisms of NAT, PON1 (at position 192) and GSTM may modify the relationship between OP exposure and neurotoxicity. Larger longitudinal studies are required to determine whether preventive strategies can be developed to improve health amongst the identified vulnerable groups

ARL Digital Scholarship Institute

This poster reflects on the Association of Research Libraries’ (ARL) upcoming inaugural week-long Digital Scholarship Institute for library professionals. Held in June 2017 at Boston College, the Institute introduced librarians and staff who are not currently involved in digital scholarship to the methodologies and considerations of such work. This multi-institutional initiative will provide an opportunity for broader transformation in the academic library ecosystem at the level necessary to create a strong community of practice around digital scholarship wor

Resurgence of HIV infection among men who have sex with men in Switzerland : mathematical modelling study

New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions

Outcomes of Antiretroviral Therapy in the Swiss HIV Cohort Study: Latent Class Analysis

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted intervention

Academically Based Community Engagement: An Idea Exchange, 2015 Report

In September 2015, faculty and staff involved in academically-based community engagement gathered to discuss ideas, resources, and barriers to the work they do. This event was organized by an ad hoc committee comprised of faculty and staff from the University of Pittsburgh including the University Honors College, PittServes, Community and Governmental Relations, and various academic departments

Rationing of nursing care and its relationship to patient outcomes: the Swiss extension of the International Hospital Outcomes Study

Objectives To explore the association between implicit rationing of nursing care and selected patient outcomes in Swiss hospitals, adjusting for major organizational variables, including the quality of the nurse practice environment and the level of nurse staffing. Rationing was measured using the newly developed Basel Extent of Rationing of Nursing Care (BERNCA) instrument. Additional data were collected using an adapted version of the International Hospital Outcomes Study questionnaire. Design Multi-hospital cross-sectional surveys of patients and nurses. Setting Eight Swiss acute care hospitals Participants Nurses (1338) and patients (779) on 118 medical, surgical and gynecological units. Main outcome measures Patient satisfaction, nurse-reported medication errors, patient falls, nosocomial infections, pressure ulcers and critical incidents involving patients over the previous year. Results Generally, nurses reported rarely having omitted any of the 20 nursing tasks listed in the BERNCA over their last 7 working days. However, despite relatively low levels, implicit rationing of nursing care was a significant predictor of all six patient outcomes studied. Although the adequacy of nursing resources was a significant predictor for most of the patient outcomes in unadjusted models, it was not an independent predictor in the adjusted models. Low nursing resource adequacy ratings were a significant predictor for five of the six patient outcomes in the unadjusted models, but not in the adjusted ones. Conclusion As a system factor in acute general hospitals, implicit rationing of nursing care is an important new predictor of patient outcomes and merits further stud

"If it is left, it becomes easy for me to get tested": use of oral self-tests and community health workers to maximize the potential of home-based HIV testing among adolescents in Lesoth

Home-based HIV testing fails to reach high coverage among adolescents and young adults (AYA), mainly because they are often absent during the day of home-based testing. ADORE (ADolescent ORal tEsting) is a mixed-method nested study among AYA in rural Lesotho, measuring the effect of home-based secondary distribution of oral HIV self-tests (HIVST) on coverage, as well as exploring how AYA perceive this HIV self-testing model.; ADORE study was nested in a cluster-randomized trial. In intervention village-clusters, oral HIVST were left for household members who were absent or declined testing during a testing campaign. One present household member was trained on HIVST use. Distributed HIVST were followed up by village health workers (VHW). In control clusters no self-tests were distributed. The quantitative outcome was testing coverage among AYA (age 12 to 24) within 120 days, defined as a confirmed HIV test result or known status, using adjusted random-effects logistic regression on the intention-to-treat population. Qualitatively, we conducted in-depth interviews among both AYA who used and did not use the distributed HIVST.; From July 2018 to December 2018, 49 and 57 villages with 1471 and 1620 consenting households and 1236 and 1445 AYA in the control and intervention arm, respectively, were enrolled. On the day of the home-visit, a testing coverage of 37% (461/1236) and 41% (596/1445) in the control and the intervention arm, respectively, were achieved. During the 120 days follow-up period, an additional 23 and 490 AYA in control and intervention clusters, respectively, knew their status. This resulted in a testing coverage of 484/1236 (39%) in the control versus 1086/1445 (75%) in the intervention arm (aOR 8.80 [95% CI 5.81 to 13.32]; p < 0.001). 21 interviews were performed. Personal assistance after the secondary distribution emerged as a key theme and VHWs were generally seen as a trusted cadre.; Secondary distribution of HIVST for AYA absent or refusing to test during home-based testing in Lesotho resulted in an absolute 36% increase in coverage. Distribution should, however, go along with clear instructions on the use of the HIVST and a possibility to easily access more personal support

Engagement in care, viral suppression, drug resistance and reasons for non-engagement after home-based same-day ART initiation in Lesotho: a two-year follow-up of the CASCADE trial

The CASCADE trial showed that compared to usual care (UC), offering same-day (SD) ART during home-based HIV testing improved engagement in care and viral suppression 12 months after diagnosis. However, open questions remain regarding long-term outcomes and the risk of propagating drug resistance.; After completion of the primary endpoint at 12 months, participants not in care in both arms were traced and encouraged to access care. At 24 months, the following outcomes were assessed in both arms: Engagement in care, viral suppression, and reasons for non-engagement. Furthermore, we explored among SD arm non-linkers the acquisition of drug resistance mutations (DRMs).; At 24 months, 64% (88/137) in the SD vs 59% (81/137) in the UC arm were in care (absolute difference 5%; 95%CI -6-16; p=0.38) and 57% (78/137) vs 54% (74/137) had documented viral suppression (3%; -9-15; p=0.28). Among 36 participants alive and not in care at 24 months with ascertained status, the majority rejected contact with the health system or were unwilling to take ART. Among eight interviewed SD arm non-linkers, six had not initiated ART upon enrolment and no acquired DRMs were detected. Two had taken the initial 30-day ART supply and acquired DRMs.; SD ART resulted in higher rates of engagement in care and viral suppression at 12 but not 24 months. Levelling off between both arms was driven by linkage beyond 12 months in the UC arm. We did not observe compensatory long-term disengagement in the SD arm. These long-term results endorse SD ART initiation policies

Neutralizing antibodies against IFN‐β in multiple sclerosis: antagonization of IFN‐β mediated suppression of MMPs

Neutralizing antibodies (NAb) against interferon‐β (IFN‐β) develop in about a third of treated multiple sclerosis patients and are believed to reduce therapeutic efficacy of IFN‐β on clinical and MRI measures. The expression of the interferon acute‐response protein, myxovirus resistance protein A (MxA) is a sensitive measure of the biological activity of therapeutically applied IFN‐β and of its reduced bioavailability due to NAb. However, MxA may not be operative in the pathogenesis of multiple sclerosis or the therapeutic effect of IFN‐β. Instead, matrix metalloproteinases (MMPs) are increased in brain tissue, CSF and blood circulation of multiple sclerosis patients and function as effector molecules in several steps of multiple sclerosis pathogenesis. One of the molecular mechanisms by which IFN‐β exerts its beneficial effect in multiple sclerosis is reduction of MMP‐9 expression and increase of its endogenous tissue inhibitor, TIMP‐1. Quantitative PCR measurements of MMP‐2 and MMP‐9, TIMP‐1 and TIMP‐2, and MxA were performed in peripheral mononuclear cells from clinically stable multiple sclerosis patients with relapsing remitting disease course after short‐term and long‐term treatment with IFN‐β. IFN‐β therapy down‐regulated the expression of MMP‐9 and abolished that of MMP‐2 in long‐term, but not short‐term treated multiple sclerosis, while levels of MxA were increased in both instances. The presence of NAb reversed these effects, i.e. led to reduced MxA and increased MMP‐2/MMP‐9 expression levels compared with NAb- patients. In contrast, expression of TIMPs in peripheral blood mononuclear cells remained unaffected by IFN‐β therapy and the presence of NAb. While MxA is able to detect the biological action and reduced bioavailability of IFN‐β on the basis of single injections, only MMP‐9 shows quantitative correlation with the NAb titre. Together with evidence that an imbalance between MMP and TIMP expression is a crucial pathogenetic feature in multiple sclerosis, these findings support the concept of a significant role of NAb in reducing the therapeutic efficacy of IFN‐