A study on intersectional discrimination in employment against disabled women in the UK

The present study examined the employment status of disabled and nondisabled men and women in the United Kingdom. Using the 2009–14 Life Opportunities Survey (N = 32,355 observations), the study empirically examined how the intersection of disability and gender affects disabled women and their employment status in the UK. Random effects multinomial and logistic regression models were used. Findings indicated that disabled women were significantly less likely to be employed and more likely to be economically inactive than disabled men, nondisabled women, and nondisabled men. They were also significantly the least likely to work full-time among the four groups. Disabled women were significantly less likely to be supervisors than disabled men and felt more limited in the type or amount of paid work they could do than nondisabled women. The present study provided empirical evidence to policymakers interested in developing policies that better address intersectional discrimination and enhance disabled women’s employment status.</p

Efficacy of exercise interventions in patients with advanced cancer: a systematic review

To critically analyse the literature surrounding the efficacy of exercise interventions in patients with advanced cancer.A literature search was undertaken of health and medical electronic databases (PubMED, Medline, CINAHL, Embase, PEDRO, Web of Science and Scopus) until 1 March 2017.Studies were included if they were published in the English language and met the following criteria: structured exercise as the primary intervention, ≥80% study participants diagnosed with advanced cancer that is unlikely to be cured; reported outcomes concerning physical function, quality of life, fatigue, body composition, psychosocial function, sleep quality pain and/or survival.Following title and abstract screening, 68 articles were eligible for full-text review, with a total of 25 studies (n=1188; 16 controlled trials, 9 non-controlled trials) included in the quantitative synthesis. Two reviewers assessed methodological quality using the Cochrane Risk of Bias Tool for controlled trials and a modified Newcastle-Ottawa Scale for non-controlled trials.Aerobic exercise was utilised in six studies, resistance training in three studies and combination training (aerobic and resistance) in 15 studies. Significant between- and within-group improvements were reported with exercise in ≥50% of studies assessing physical function (83%), quality of life (55%), fatigue (50%), body composition (56%), psychosocial function (56%), and sleep quality (100%). Improvement within or between groups in pain following exercise was only observed in two studies (25%), while survival was unaffected in any study.Most studies reported significant between- and/or within-group improvements in physical function, quality of life, fatigue, body composition, psychosocial function and sleep quality in patients with advanced cancer, although the effects on pain and survival rates are unclear. Exercise appears to be an effective adjunct therapy in the advanced cancer context, although targeted studies are required to determine the optimal exercise dose to enhance outcomes for specific cancer diagnoses

Benefits beyond cardiometabolic health: the potential of frequent high intensity ‘exercise snacks’ to improve outcomes for those living with and beyond cancer

High intensity interval training (HIIT) has been shown to consistently elicit rapid and significant adaptations in a number of physiological systems, across many different healthy and clinical populations. In addition, there is increasing interest in how some acute, yet transient responses to high intensity exercise potentially reduce the risks of particular diseases. Recent work has shown that discrete, brief bouts of high intensity exercise (termed ‘exercise snacks’) can improve glucose control and vascular health and thus counter the negative cardiometabolic consequences of prolonged, uninterrupted periods of inactivity. In this brief review, we advance the case, using evidence available from pre‐clinical studies in the exercise oncology literature, that brief, frequently completed bouts of high intensity exercise embedded within an individual's overall daily and weekly physical activity schedule, may transiently impact the tumour microenvironment and improve the health outcomes for those who have been diagnosed and treated for cancer. imag

Proteomic analysis of Plasmodium falciparum histone deacetylase 1 complex proteins

Plasmodium falciparum histone deacetylases (PfHDACs) are an important class of epigenetic regulators that alter protein lysine acetylation, contributing to regulation of gene expression and normal parasite growth and development. PfHDACs are therefore under investigation as drug targets for malaria. Despite this, our understanding of the biological roles of these enzymes is only just beginning to emerge. In higher eukaryotes, HDACs function as part of multi-protein complexes and act on both histone and non-histone substrates. Here, we present a proteomics analysis of PfHDAC1 immunoprecipitates, identifying 26 putative P. falciparum complex proteins in trophozoite-stage asexual intraerythrocytic parasites. The co-migration of two of these (P. falciparum heat shock proteins 70-1 and 90) with PfHDAC1 was validated using Blue Native PAGE combined with Western blot. These data provide a snapshot of possible PfHDAC1 interactions and a starting point for future studies focused on elucidating the broader function of PfHDACs in Plasmodium parasites

Velocity, oxygen uptake and metabolic cost of pull, kick and whole body swimming

Purpose: The contributions of the limbs to velocity and metabolic parameters in front-crawl swimming at different intensities have not been identified considering both stroke and kick rate. Consequently, velocity, oxygen uptake (VO2), and metabolic cost of swimming with the whole body (swim), the upper limbs only (pull), and lower limbs only (kick) were compared with stroke and kick rate controlled. Methods: Twenty elite swimmers completed six 200-m trials: 2 swim, 2 pull, and 2 kick. Swim trials were guided by underwater lights at paces equivalent to 65% +/- 3% and 78% +/- 3% of participants' 200-m-freestyle personal-best pace; paces were described as low and moderate, respectively. In the pull and kick trials, swimmers aimed to match the stroke and kick rates, respectively, recorded during the swim trials. (V)over dot O-2 was measured continuously, with velocity and metabolic cost calculated for each 200-m effort. Results: The velocity contribution of the upper limbs (mean +/- SD; low 63.9% +/- 6.2%, moderate 59.6% +/- 4.2%) was greater than that of the lower limbs to a large extent at both intensities (low ES = 4.40, moderate ES = 4.60). The (V) over dot O-2 used by the upper limbs differed between the intensities (low 55.5% +/- 6.9%, moderate 51.4% +/- 4.0%; ES = 0.74). The lower limbs were responsible for a greater percentage of the metabolic cost than the upper limbs at both intensities (low 56.1% +/- 9.5%, ES = 1.30; moderate 55.1% +/- 6.6%, ES = 1.55). Conclusions: Implementation of this testing protocol before and after a pull-or kick-training block will enable sport scientists to determine how the velocity contributions and/or metabolic cost of the upper-and lower-limb actions have responded to the training program

Saquinavir Inhibits the malaria parasite's chloroquine resistance transporter

The antiretroviral protease inhibitors (APIs) ritonavir, saquinavir, and lopinavir, used to treat HIV infection, inhibit the growth of Plasmodium falciparum at clinically relevant concentrations. Moreover, it has been reported that these APIs potentiate the activity of chloroquine (CQ) against this parasite in vitro. The mechanism underlying this effect is not understood, but the degree of chemosensitization varies between the different APIs and, with the exception of ritonavir, appears to be dependent on the parasite exhibiting a CQ-resistant phenotype. Here we report a study of the role of the P. falciparum chloroquine resistance transporter (PfCRT) in the interaction between CQ and APIs, using transgenic parasites expressing different PfCRT alleles and using the Xenopus laevis oocyte system for the heterologous expression of PfCRT. Our data demonstrate that saquinavir behaves as a CQ resistance reverser and that this explains, at least in part, its ability to enhance the effects of CQ in CQ-resistant P. falciparum parasites. Copyrigh

A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability

Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the Striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PJPAP). Unlike other P. falciparum aminopeptidases, PJPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PJPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PJPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies. (C) 2016 Elsevier Inc. All rights reserved

Peer support for the maintenance of physical activity and health in cancer survivors: the PEER trial - a study protocol of a randomised controlled trial

BACKGROUND: Despite an overwhelming body of evidence showing the benefits of physical activity (PA) and exercise for cancer survivors, few survivors meet the exercise oncology guidelines. Moreover, initiating, let alone maintaining exercise programs with cancer survivors continues to have limited success. The aim of this trial is to evaluate the influence of peer support on moderate-to-vigorous PA (MVPA) and various markers of health 12 months following a brief supervised exercise intervention in cancer survivors. METHODS: Men and women previously diagnosed with histologically-confirmed breast, colorectal or prostate cancer (n = 226), who are \u3e1-month post-treatment, will be invited to participate in this trial. Once enrolled, participants will complete 4 weeks (12 sessions) of supervised high intensity interval training (HIIT). On completion of the supervised phase, both groups will be provided with written recommendations and verbally encouraged to achieve three HIIT sessions per week, or equivalent exercise that meets the exercise oncology guidelines. Participants will be randomly assigned to receive 12 months of peer support, or no peer support (control). Primary and secondary outcomes will be assessed at baseline, after the 4-week supervised HIIT phase and at 3-, 6- and 12-months. Primary outcomes will include accelerometry-derived MVPA and prescribed HIIT session adherence; whilst secondary outcomes will include cardiorespiratory fitness ([Formula: see text]), body composition, quality of life and select cytokines, myokines and inflammatory markers. Random effects mixed modelling will be used to compare mean changes in outcomes between groups at each time point. A group x time interaction will be used to formally test for differences between groups (alpha =0.05); utilising intention-to-treat analyses. DISCUSSION: If successful, peer support may be proposed, adopted and implemented as a strategy to encourage cancer survivors to maintain exercise beyond the duration of a short-term, supervised intervention. A peer support-exercise model has the long-term potential to reduce comorbidities, improve physical and mental wellbeing, and significantly reduce the burden of disease in cancer survivors. ETHICS: Human Research Ethics Committee of Bellberry Ltd. (#2015-12-840). TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry 12618001855213 . Retrospectively registered 14 November 2018. Trial registration includes all components of the WHO Trial Registration Data Set, as recommended by the ICMJE

The aminopeptidase inhibitor CHR-2863 is an orally bioavailable inhibitor of murine malaria

Malaria remains a significant risk in many areas of the world, with resistance to the current antimalarial pharmacopeia an everincreasing problem. The M1 alanine aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) are believed to play a role in the terminal stages of digestion of host hemoglobin and thereby generate a pool of free amino acids that are essential for parasite growth and development. Here, we show that an orally bioavailable aminopeptidase inhibitor, CHR-2863, is efficacious against murine malaria

The relationship between physical activity, and physical performance and psycho-cognitive functioning in older adults living in residential aged care facilities

Insight into modifiable factors related to falls risk in older adults living in residential aged care facilities (RACFs) is necessary to tailor preventive strategies for this high-risk population. Associations between physical activity (PA), physical performance and psycho-cognitive functioning have been understudied in aged care residents. This study investigated associations between PA, and both physical performance and psycho-cognitive functioning in older adults living in RACFs.Cross-sectional study.Forty-four residents aged 85±8years were recruited from four RACFs located in Southeast Queensland. PA was assessed as the average time spent walking in hours/day using activPAL3™. Physical performance tests included balance, gait speed, dual-task ability, reaction time, coordination, grip strength, and leg strength and power. Psycho-cognitive questionnaires included quality of life, balance confidence, fear of falling and cognitive functioning. Associations between PA and each outcome measure were analysed using linear or ordinal regression models.The average time spent walking was 0.5±0.4h/day. Higher levels of PA were significantly associated with better balance (compared with low PA, medium: B=1.6; high: B=1.3) and dual-task ability (OR=7.9 per 0.5h/day increase). No statistically significant associations were found between PA and the other physical and psycho-cognitive measures.More physically active residents scored higher on balance and dual-task ability, which are key predictors of falls risk. This suggests that physical activity programs targeting balance and dual-task ability could help prevent falls in aged care residents