A microplate assay for <Emphasis Type="Italic">Leishmania amazonensis</Emphasis> promastigotes expressing multimeric green fluorescent protein

Convenient and economical assays capable of screening many compounds are vital to advance the development of drug therapy. This is particularly important for many of the infections that occur mainly in the Third World. The development of such a spectrofluorometric assay for the protozoan parasite Leishmania is presented here. Using multimeric (four monomers) green fluorescent protein (GFP), Leishmania amazonensis promastigotes were generated with brightness measurable in 96-well microtiter plates. The promastigotes maintained the parental characteristics, were infective to murine macrophages and to mice, and the level of GFP fluorescence corresponded to the number of inoculated cells. The feasibility of using this assay for testing drugs kinetically and in a concentration-dependent manner, under microplate culture condition, was demonstrated with amphotericin B and the herbicide oryzalin, respectively. This assay is the first to allow a real-time analysis of antileishmanial agents with live promastigotes. The method of expressing multimeric GFP for in vitro drug screening is likely to be extendable to many species of parasitic protozoa.     

Mechanisms of trafficking in axons and dendrites: implications for development and neurodegeneration

In the area of routing and sorting of dendritic traffic, the current phenomenological data beg questions about the cellular mechanisms utilized not only to transport material but also to modulate activity in a process, even apoptosis. To aid in formulating testable hypotheses, many plausible models are developed here and linked with some of the preliminary data that supports them. We first assume that in long dendrites the sorting of membranous proteins into transport vesicles also involves the linkage of motor proteins to the vesicles. Second, we assume that the cytoskeleton in dendrites is altered from the cytoskeleton in axons and the cell body. Viral glycoproteins, MAP2 and specific mRNA sorting into dendrites provide the simplest models for analyzing vesicular, cytoskeletal and RNA sorting. In the case of viral glycoproteins, initial sorting appears to occur at the Golgi but additional routing steps involve further complexities that could best be served by an additional sorting step at the junction of the cell body and the process. Transport of the specialized cytoskeletal proteins and specific mRNAs as well as vesicular material could be controlled by a similar gatekeeper at the mouth of a process. Studies of the microtubule-organelle motor complex, regulation of microtubule-based motility by microtubule-associated proteins, and slow axonal transport all provide insights into important aspects of the routing and sorting. These processes are in turn controlled by extracellular signals such as those generated by matrix molecules or their hydrolysis products in the case of amyloid precursor protein (APP). Routing and sorting mechanisms may be central to the development of Alzheimer's disease in view of evidence that APP processing is affected, transport is disturbed, and intracellular vesicles (early endosomes) hypertrophied. Further it is possible that routing mechanisms play a role in cell–cell interactions as, for example, the possibility that pathogenic/cellular stress signals may be passed along circuits transsynaptically.     

Estimating the impact of changes in weight and BMI on EQ-5D-3L: a longitudinal analysis of a behavioural group-based weight loss intervention

Quality of Life Research - To estimate the association between changes in BMI and changes in Health-Related Quality of Life (EQ-5D-3L). The WRAP trial was a multicentre, randomised controlled trial...     

Sex in the Era of COVID-19 in a U.S. National Cohort of Cisgender Men,Transgender Women,and Transgender Men Who Have Sex with Men: April–May 2020

Since the emergence of the COVID-19 pandemic, there has been an increasing body of research focused on the effects that measures like stay-at-home orders and social distancing are having on other aspects of health, including mental health and sexual health. Currently, there are limited extant data on the effects of the pandemic on sexual and gender minorities. Between April 15, 2020, and May 15, 2020, we invited participants in an ongoing U.S. national cohort study (Together 5000) to complete a cross-sectional online survey about the pandemic, and its effects on mental and sexual health and well-being (n?=?3991). Nearly all (97.7%) were living in an area where they were told they should only leave their homes for essentials. Most (70.1%) reported reducing their number of sex partners as a result of the pandemic. Among the 789 participants prescribed HIV pre-exposure prophylaxis (PrEP), 29.9% said they stopped taking their PrEP entirely, and 14.2% started selectively skipping doses. For those who had been taking PrEP, discontinuing PrEP was associated with having no new sex partners (β?=?0.90, 95% CI 0.40–1.40). Among the 152 HIV-positive participants, 30.9% said they were unable to maintain an HIV-related medical appointment because of the pandemic and 13.8% said they had been unable to retrieve HIV medications. Additionally, 35.3% of participants were experiencing moderate to severe anxiety because of the pandemic and 36.7% reported symptoms of depression. In a multivariable logistic regression, reporting a new sex partner in the prior 30 days was significantly associated with being aged 30 or older (vs. not, AOR?=?1.21), being Black (AOR?=?1.79) or Latinx (AOR?=?1.40, vs. white), and being unsure if they had been in close contact with someone diagnosed with COVID-19 (AOR?=?1.32, vs. no contact). It was unassociated with COVID-19-induced anxiety, depression, or knowing someone hospitalized with COVID-19. The pandemic has caused disruptions in sexual behavior (partner reduction) as well as difficulties navigating PrEP and HIV care continua. Findings will guide more comprehensive public health responses to optimize HIV prevention and treatment in the era of COVID-19.

     

2020 developments in the provision of early medical abortion by telemedicine in the UK

The COVID-19 pandemic has necessitated the rapid implementation of telemedical health services. In the United Kingdom, one service that has benefitted from this response is the provision of early medical abortion. England, Wales, and Scotland have all issued approval orders to this effect. These orders allow women to terminate pregnancies up to certain gestational limits, removing the need for them to contravene social distancing measures to access care. However, they are intended only as temporary measures for the duration of the pandemic response. In this paper, we chart these developments and further demonstrate the already acknowledged politicisation of abortion care. We focus on two key elements of the orders: (1) the addition of updated clinical guidance in the Scottish order that suggests an extended gestational limit, and (2) sunset clauses in the English and Welsh orders, as well as an indication of similar intentions in Scotland. In discussing these two issues, we suggest that the refusal of UK governments to introduce telemedical provision of early medical abortion previously has not been based on health concerns. Further, we question whether it would be appropriate for the approval orders to be lifted following the pandemic, suggesting that to do so would represent regressive and harmful policy.     

Exploring views about mindfulness groups for voice-hearing from the perspective of service users and staff: A Q-methodology study

Objectives: Despite prevailing beliefs about the potential benefits and harmfulness of mindfulness for people who hear voices, there is a paucity of research into staff and service user views. Q-methodology was used to explore views about mindfulness groups for voice-hearers. Method: Opportunistic sampling of mental healthcare staff (N?=?14) and service users with psychosis (N?=?17). Both samples were analysed using principle components factor analysis to identify the range of attitudes held by staff and service users. Results: Staff participants were particularly knowledgeable and interested in mindfulness. A single staff consensus factor was found suggesting mindfulness is helpful, and not harmful for mental health, but uncertainty surrounded its usefulness for voice-hearers. Service users held four distinct attitudes: (i) mindfulness helps to calm a racing mind; (ii) mindfulness helps to manage stress; (iii) mindfulness improves well-being, and does not alter the brain, reality beliefs, or cause madness; and (iv) mindfulness helps with managing thoughts, fostering acceptance, and is acceptable when delivered in a group format. Conclusions: Staff viewed mindfulness groups for psychosis as helpful, not harmful, but were uncertain about their utility. Consistent with previous research, service users viewed mindfulness groups as useful to promote well-being and reduce distress for individuals experiencing psychosis.