A prospective study of the impact of COVID-19-related restrictions on activities and mobility upon physical activity, travel behaviour and attitudes.

Background and aims: Public health measures adopted to contain the spread of COVID-19 included restrictions on activities and mobility as people were asked to stay at home and schools moved to online learning. This may have increased risk of non-communicable disease by limiting recreational and transport-related physical activity. Building on an existing study, we assessed changes in self-reported and device-measured physical activity and travel behaviour before, during and after the peak of local COVID-19 outbreak and restrictions (March-July 2020). We examined beliefs in effectiveness of strategies to increase active and public transport after restrictions were reduced. Methods: A longitudinal study of adult infrequent bus users (average ≤ 2 trips per week; n = 70; 67% women) in Hobart, Australia. One-week assessment periods at four separate timepoints (before, during, 0-3 months after, and 3-6 months after the peak restrictions period) involved wearing an accelerometer, daily transport diaries, online surveys and tracking bus smartcard boardings. Results: Physical activity (especially among older participants), bus use and private motor vehicle use declined significantly during or 0-3 months after the peak restrictions period and returned to pre-restrictions levels by 3-6 months after the peak restrictions period, except bus use which remained significantly lower. Retrospective surveys overstated declines in bus use and active transport and self-reports understated declines in physical activity. Social distancing and improving service efficiency and frequency were seen as effective strategies for increasing bus use after restrictions but belief in effectiveness of distancing decreased over time. Conclusions: When restrictions on mobility are increased, supportive health promotion measures are needed to prevent declines in physical activity, particularly for older adults. Public transport systems need capacity to implement temporary distancing measures to prevent communicable disease transmission. Providing convenient, flexible, and efficient options for public transport may help to replenish public transport use after restrictions are reduced.

Review: exploring the role of mental health nurse-practitioner in the treatment of early psychosis.

AIMS AND OBJECTIVES: The aim of this paper is to examine high-level evidence in early intervention in psychosis and scope the potential role of the mental health nurse-practitioner in the treatment of management of early psychosis. BACKGROUND: Psychosis imposes complex symptoms that impact on the individual and their social network, often resulting in long-term disability. As specialised early intervention in psychosis is emerging, the nurse-practitioner role in mental health is also gaining momentum. The background literature highlights several critical synergies between nurse-practitioners' scope of practice and needs of patients with early psychosis. DESIGN: Literature review. METHOD: Electronic databases including Cochrane Library, CINAHL, Medline, TRIP and EMBASE. Searching was limited to articles published between 1988-2009. Eligible studies were limited to systematic reviews and randomised controlled trials. RESULTS: Two systematic reviews and five randomised controlled trials met the inclusion criteria. No studies were located which specifically addressed the nurse-practitioner role in early psychosis. CONCLUSIONS: Specific interventions require further research but there is emerging evidence that specialised intervention for people in the early phase of psychotic illness is achievable and possibly essential. It is within the scope of practice of mental health nurse-practitioners to ensure patient and carer education and support, adherence to medication and other treatments, promotion of social inclusion and social connectedness. RELEVANCE TO CLINICAL PRACTICE: Mental health nurse-practitioners have the potential to provide specialist support to meet the needs of this complex group. Central to this is an ability to build an evidence-base around the treatment and management of people with early psychosis and deliver effective education and leadership across clinical, inter-professional and organisational domains. The paper concludes by positing a set of recommendations for nurse-practitioners in the field of early psychosis in the Australian mental health setting.

Expression of GPR177 (Wntless/Evi/Sprinter), a highly conserved Wnt-transport protein, in rat tissues, zebrafish embryos, and cultured human cells.

GPR177 is an evolutionarily conserved transmembrane protein necessary for Wnt protein secretion. Little is currently known, however, regarding expression of GPR177, especially in vertebrate species. We have developed an antiserum against GPR177, and used it to examine expression of GPR177 in human tissue culture cells, adult mouse, and rat tissues, as well as developing zebrafish embryos. In rodents, GPR177 is expressed in virtually all tissue types and brain regions examined. In zebrafish, GPR177 polypeptides are expressed throughout embryogenesis, and are detectable as early as 1 hr post-fertilization. In situ hybridization analysis reveals that gpr177 mRNA expression is prominent in embryonic zebrafish brain and ear. Structural studies suggest that GPR177 is modified by N-linked sugars, and that the protein contains an even number of transmembrane segments. The relatively ubiquitous expression of GPR177 suggests that this protein may serve to regulate Wnt secretion in a variety of embryonic and adult tissue types.

Is greater public transport use associated with higher levels of physical activity in a regional setting? Findings from a pilot study.

BACKGROUND: Public transport users often accumulate more physical activity than motor vehicle users, but most studies have been conducted in large metropolitan areas with multiple public transport options with limited knowledge of the relationship in regional and rural areas. In a regional city, this pilot study aimed to (1) test the feasibility of preliminary hypotheses to inform future research, (2) test the utility of survey items, and (3) establish stakeholder engagement. METHODS: Data were collected via a cross-sectional online survey of 743 Tasmanian adults. Physical activity outcomes were walking (min/week), total moderate- to vigorous-intensity physical activity (min/week) and attainment of physical activity guidelines (yes/no). Transport variables were frequency of public and private transport use per week. Truncated and log binomial regression examined associations between public/private transport use and physical activity. RESULTS: Neither frequency of public nor private transport use was associated with minutes of walking (public transport: B - 24.4, 95% CI: - 110.7, 61.9; private transport: B - 1.1, 95% CI: - 72.4, 70.1), minutes of total physical activity (public transport: B - 90.8, 95% CI: - 310.0, 128.5; private transport: B 0.4, 95% CI: - 134.0, 134.9) or not meeting physical activity guidelines (public transport: RR 1.02, 95%CI: 0.95, 1.09; private transport: RR 1.02, 95%CI: 0.96, 1.08). CONCLUSIONS: The hypothesis that public transport users would be more physically active than private transport users was not supported in this pilot study. Stakeholders were engaged and involved in various phases of the research including development of research questions, participant recruitment, and interpretation of findings. Further studies using representative samples and refined measures are warranted to confirm or refute findings.

Low expression of D2R and Wntless correlates with high motivation for heroin.

Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.

Effect of simvastatin on bone markers in osteopenic women: a placebo-controlled, dose-ranging trial [ISRCTN85429598].

BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors increase new bone formation in vitro and in rodents. Results of epidemiologic analyses evaluating the association between use of these cholesterol-lowering drugs, bone mineral density and fracture have been mixed. METHODS: Women (n = 24) with osteopenia, assessed by broad band ultrasound attenuation, were randomized to simvastatin 20 mg, 40 mg or identical-appearing placebo for 12 weeks. Fasting lipid profiles and biochemical markers of bone formation (bone-specific alkaline phosphatase) and resorption (N-telopeptides and C-terminal propeptide of type 1 collagen) were measured at baseline, 6 and 12 weeks. RESULTS: Plasma low density lipoprotein-cholesterol concentration fell 7%, 39% (p < 0.01 vs baseline) and 47% (p < 0.01 vs baseline) after 12 weeks of treatment with placebo, simvastatin 20 mg and 40 mg, respectively. At baseline, bone marker concentrations were similar in the three treatment groups. At 6 and 12 weeks, bone marker concentrations were not different from baseline, and no significant differences in bone marker concentrations were observed between treatment groups at either 6 or 12 weeks. CONCLUSION: Among osteopenic women, treatment with simvastatin for 12 weeks did not affect markers of bone formation or resorption.

Label-free integrative pharmacology on-target of opioid ligands at the opioid receptor family.

BACKGROUND: In vitro pharmacology of ligands is typically assessed using a variety of molecular assays based on predetermined molecular events in living cells. Many ligands including opioid ligands pose the ability to bind more than one receptor, and can also provide distinct operational bias to activate a specific receptor. Generating an integrative overview of the binding and functional selectivity of ligands for a receptor family is a critical but difficult step in drug discovery and development. Here we applied a newly developed label-free integrative pharmacology on-target (iPOT) approach to systematically survey the selectivity of a library of fifty-five opioid ligands against the opioid receptor family. All ligands were interrogated using dynamic mass redistribution (DMR) assays in both recombinant and native cell lines that express specific opioid receptor(s). The cells were modified with a set of probe molecules to manifest the binding and functional selectivity of ligands. DMR profiles were collected and translated to numerical coordinates that was subject to similarity analysis. A specific set of opioid ligands were then selected for quantitative pharmacology determination. RESULTS: Results showed that among fifty-five opioid ligands examined most ligands displayed agonist activity in at least one opioid receptor expressing cell line under different conditions. Further, many ligands exhibited pathway biased agonism. CONCLUSION: We demonstrate that the iPOT effectively sorts the ligands into distinct clusters based on their binding and functional selectivity at the opioid receptor family.

Ligand-directed functional selectivity at the mu opioid receptor revealed by label-free integrative pharmacology on-target.

Development of new opioid drugs that provide analgesia without producing dependence is important for pain treatment. Opioid agonist drugs exert their analgesia effects primarily by acting at the mu opioid receptor (MOR) sites. High-resolution differentiation of opioid ligands is crucial for the development of new lead drug candidates with better tolerance profiles. Here, we use a label-free integrative pharmacology on-target (iPOT) approach to characterize the functional selectivity of a library of known opioid ligands for the MOR. This approach is based on the ability to detect dynamic mass redistribution (DMR) arising from the activation of the MOR in living cells. DMR assays were performed in HEK-MOR cells with and without preconditioning with probe molecules using label-free resonant waveguide grating biosensors, wherein the probe molecules were used to modify the activity of specific signaling proteins downstream the MOR. DMR signals obtained were then translated into high resolution heat maps using similarity analysis based on a numerical matrix of DMR parameters. Our data indicate that the iPOT approach clearly differentiates functional selectivity for distinct MOR signaling pathways among different opioid ligands, thus opening new avenues to discover and quantify the functional selectivity of currently used and novel opioid receptor drugs.