Role of Gut Microbe Composition in Psychosocial Symptom Response to Exercise Training in Breast Cancer Survivors (ROME) study: protocol for a randomised controlled trial.

INTRODUCTION: Breast cancer survivors have an increased risk for chronic fatigue and altered gut microbiota composition, both with negative health and quality of life affects. Exercise modestly improves fatigue and is linked to gut microbial diversity and production of beneficial metabolites. Studies suggest that gut microbiota composition is a potential mechanism underlying fatigue response to exercise. Randomised controlled trials testing the effects of exercise on the gut microbiome are limited and there is a scarcity of findings specific to breast cancer survivors. The objective of this study is to determine if fitness-related modifications to gut microbiota occur and, if so, mediate the effects of aerobic exercise on fatigue response. METHODS AND ANALYSIS: The research is a randomised controlled trial among breast cancer survivors aged 18-74 with fatigue. The primary aim is to determine the effects of aerobic exercise training compared with an attention control on gut microbiota composition. The secondary study aims are to test if exercise training (1) affects the gut microbiota composition directly and/or indirectly through inflammation (serum cytokines), autonomic nervous system (heart rate variability) or hypothalamic-pituitary-adrenal axis mediators (hair cortisol assays), and (2) effects on fatigue are direct and/or indirect through changes in the gut microbiota composition. All participants receive a standardised controlled diet. Assessments occur at baseline, 5 weeks, 10 weeks and 15 weeks (5 weeks post intervention completion). Faecal samples collect the gut microbiome and 16S gene sequencing will identify the microbiome. Fatigue is measured by a 13-item multidimensional fatigue scale. ETHICS AND DISSEMINATION: The University of Alabama at Birmingham Institutional Review Board (IRB) approved this study on 15 May 2019, UAB IRB#30000320. A Data and Safety Monitoring Board convenes annually or more often if indicated. Findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04088708.

Osteoporosis screening in Australian community pharmacies: A mixed methods study.

ISSUES ADDRESSED: Osteoporosis and poor bone health impact a large proportion of the Australian population, but is drastically underdiagnosed and undertreated. Community pharmacies are a strategic location for osteoporosis screening services due to their accessibility and the demographic profile of customers. The aim of this study was to develop, implement and evaluate a community pharmacy health promotion service centred on encouraging consumers to complete an anonymous osteoporosis screening survey called Know Your Bones. METHODS: The implementation process was documented using the REAIM (reach, effectiveness, adoption, implementation, maintenance) framework. Uptake of the Know Your Bones screening tool was monitored anonymously with website traffic. Surveys and interviews were designed to capture consumer outcomes after screening. Semi-structured interviews were conducted with Australian community pharmacy stakeholders during design and implementation phases to explore their perspectives of the barriers and facilitators. RESULTS: The service was implemented in 27 community pharmacies. There were 448 visits to the screening website. Interviews were conducted with 41 stakeholders. There were a range of factors that appeared to influence implementation of the service. Perceived acceptability was critical, which depended on staff training, pharmacists' altruism, and remuneration. Staff relied heavily on their existing close relationships with consumers. No consumers completed non-anonymous surveys or agreed to participate in interviews post-screening. CONCLUSION: Using an implementation science approach, a community pharmacy osteoporosis screening service for the Australian context was designed and found to be acceptable to pharmacy staff and effective in reaching the target population. SO WHAT?: This low-cost and non-invasive health promotion has potential to sustainably increase national screening rates for osteoporosis.

Socioeconomic impact and sufficiency of government financial support during COVID-19 pandemic: A retrospective study.

This study examines the socioeconomic impact of the COVID-19 pandemic and the sufficiency of government support. Based on an online survey with 920 respondents, the cross-tabulation and binary logistic regression results show: firstly, in terms of loss of income, male respondents are more likely to have a loss of income as compared to female counterparts, and secondly, among different categories of employment status, the self-employed respondents are the most vulnerable group, given that more than 20 percent of them experienced loss of income due to the COVID-19 pandemic. Moreover, respondents working in small-and-medium enterprises (SMEs) and the informal sector are more likely to face loss of income as compared to respondents working in other sectors of employment. Likewise, respondents without tertiary education level are more likely to have a loss of income as compared to respondents with university certification. The baseline results highlight the insufficiency of government financial support programs based on the perspective of Malaysians from different demographic backgrounds. As a policy implication, the findings could guide the State in formulating the right policies for target groups who need more assistance than others in the community.

Understanding Patient Perspectives on the Use of Gamification and Incentives in mHealth Apps to Improve Medication Adherence: Qualitative Study.

BACKGROUND: Medication nonadherence remains a significant health and economic burden in many high-income countries. Emerging smartphone interventions have started to use features such as gamification and financial incentives with varying degrees of effectiveness on medication adherence and health outcomes. A more consistent approach to applying these features, informed by patient perspectives, may result in more predictable and beneficial results from this type of intervention. OBJECTIVE: This qualitative study aims to identify patient perspectives on the use of gamification and financial incentives in mobile health (mHealth) apps for medication adherence in Australian patients taking medication for chronic conditions. METHODS: A total of 19 participants were included in iterative semistructured web-based focus groups conducted between May and December 2022. The facilitator used exploratory prompts relating to mHealth apps, gamification, and financial incentives, along with concepts raised from previous focus groups. Transcriptions were independently coded to develop a set of themes. RESULTS: Three themes were identified: purpose-driven design, trust-based standards, and personal choice. All participants acknowledged gamification and financial incentives as potentially effective features in mHealth apps for medication adherence. However, they also indicated that the effectiveness heavily depended on implementation and execution. Major concerns relating to gamification and financial incentives were perceived trivialization and potential for medication abuse, respectively. CONCLUSIONS: The study's findings provide a foundation for developers seeking to apply these novel features in an app intervention for a general cohort of patients. However, the study highlights the need for standards for mHealth apps for medication adherence, with particular attention to the use of gamification and financial incentives. Future research with patients and stakeholders across the mHealth app ecosystem should be explored to formalize and validate a set of standards or framework.

Engagement to collaboration ensures success.

Disruption to our daily business and functional lives is becoming more frequent, complex and costly. As leaders, what do we do with what we know, the support and tools we have, and our knowledge regarding the resources we need to acquire to navigate this disrupted world? One thing is clear: no one can do it alone. This is not a new concept - the ancient Greeks understood the power of the group. This paper argues that collaboration is the key to amplified knowledge, ability, energy, foresight and innovation, as there is obvious synergy when individuals, groups or organisations join together in a shared vision and with a dedicated purpose. This paper describes a process model developed by the Mid-Atlantic Center for Emergency Management & Public Safety to transform operational functions and spark quality engagement, the synergy of ideas and outcomes, and enhanced sustainability of purpose. This model uses a blend of new knowledge and experiences to build on collaboration models of the past, and has proven to be a success.

Walking net V ˙ O2 rises with advancing age in older women: where to go from here?

PURPOSE: Walking net V ˙ O2 tends to increase with advancing age; however, factors contributing to this relationship have not been widely described. The implications of such findings could inform targeted strategies to promote independent mobility in older adults. Herein, we evaluated the relationship between net V ˙ O2 and age at two submaximal workloads while exploring potential moderators of this relationship. METHODS: Secondary analyses were performed on 35 older (65 ± 3 years) women who completed a battery of physical assessments including fixed-speed, non-graded and graded (+ 2.5%) treadmill walking with indirect calorimetry to determine net V ˙ O2. Maximal oxygen uptake ( V ˙ O2max), knee extensor maximal isometric voluntary contraction (MVC), peak rate of torque development (RTD), and plantar flexor range-of-motion (PFROM) were also measured. RESULTS: Bivariate correlations showed non-graded (r = 0.403, p = 0.017) and graded (r = 0.413, p = 0.014) net V ˙ O2 were positively related to age. Notably, these relationships strengthened after adjusting for V ˙ O2max. Regression modeling showed age, RTD:MVC ratio (composite of muscle performance), and PFROM together explained 49% and 34% of the variance in non-graded and graded net V ˙ O2, respectively. Further analyses suggested knee extensor MVC moderates the relationship between non-graded net V ˙ O2 and age, accounting for 9% of the variance [ΔR2 = 0.090, F (1,31) = 4.13, p = 0.05]. CONCLUSION: These data support the premise that, in older women, walking net V ˙ O2 rises with advancing age, and additionally, the RTD:MVC ratio and PFROM are independent correlates of non-graded net V ˙ O2. Exercise interventions with a high degree of training specificity including explosive, velocity-based elements may promote independent mobility in older women.

Stakeholders' perspectives and experiences of the pharmacist's role in deprescribing in ambulatory care: A qualitative meta-synthesis.

BACKGROUND: Deprescribing is an effective strategy to manage polypharmacy and improve patient outcomes. The notion of a potential role for pharmacists in a multidisciplinary team approach to deprescribing has been identified in quantitative and qualitative literature. However, stakeholders' perceptions of this role, and factors that may impede or facilitate the pharmacist's involvement have not been elucidated. The application in ambulatory care also requires clarification. Understanding stakeholders' views is essential to optimise involvement of the pharmacist in deprescribing and improve practice. OBJECTIVES: First, to synthesize the perspectives and experiences of stakeholders (primary care providers, pharmacists, patients, and carers) regarding the role and involvement of the pharmacist in deprescribing in ambulatory care settings. Second, to identify barriers and strategies to enhancing pharmacist involvement in deprescribing. METHODS: A systematic search was conducted across CINAHL, Embase, Medline, and Scopus from database inception to April 2023 for qualitative studies in English exploring the pharmacist's role in deprescribing. Data were extracted for iterative and inductive development of themes. A meta-synthesis facilitated the identification of overarching themes. Qualitative secondary analysis enabled identification of barriers and facilitators to the pharmacist's involvement in deprescribing. RESULTS: From 285 articles identified, 9 studies were included which explored the views of general practitioners, specialist physicians, pharmacists, nurse practitioners, patients, carers, and general practice and clinic staff as stakeholders in deprescribing in ambulatory care. The meta-synthesis identified 4 over-arching themes: (1) therapeutic impetus and the status quo mentality, (2) role and responsibility, (3) multidisciplinary care, and (4) conflicting interests in pharmacy practice. Strategies to enhance pharmacists' involvement in deprescribing emerged from the data, and the pharmacist's role was strongly encouraged by stakeholders despite logistical and perceptual barriers identified. CONCLUSIONS: Incorporation of the strategies to enhance the pharmacist's involvement in deprescribing identified in this review is encouraged to optimise patient-centred care and improve practice.

Healthcare professionals' perspectives and experiences of osteoporosis medication treatment: a qualitative systematic review.

This systematic review aimed to explore healthcare professionals' (HCPs) experiences and perspectives of osteoporosis medication treatment through thematic synthesis of qualitative studies. We found themes about how osteoporosis is perceived as a disease, treatment decision-making and what empowers HCPs to provide the best possible care. PURPOSE: The systematic review aimed to describe the perspectives and experiences of HCPs regarding osteoporosis medication treatment. METHODS: We performed searches in four electronic databases (Medline, Embase, PsycINFO and CINAHL) from database inception until May 2023 in any language. Data was analysed through inductive thematic synthesis. RESULTS: We included 27 primary studies that incorporated the views of 495 different HCPs. The following themes were identified: low-priority disease, challenges in treatment decision-making, minimising drug burden, conscious of communication barriers, fragmented care and advice, confidence through experience and collaboration. CONCLUSIONS: HCPs were enthusiastic about optimising osteoporosis care through interprofessional collaboration and expertise, as well as educating and monitoring patients on treatment. They advocated for safety, comfort and reducing overall drug burden, especially in older patients with comorbidities. However, they had differences in opinions regarding who has responsibility for diagnosing and treating osteoporosis and struggled to provide the best possible care due to competing priorities, limited time and lack of adequate knowledge or evidence. The findings highlight the important and complementary role of different HCPs in osteoporosis treatment through a multidisciplinary model of care.

Grass-Fed and Non-Grass-Fed Whey Protein Consumption Do Not Attenuate Exercise-Induced Muscle Damage and Soreness in Resistance-Trained Individuals: A Randomized, Placebo-Controlled Trial.

Eccentric muscle contractions can cause structural damage to muscle cells resulting in temporarily decreased muscle force production and soreness. Prior work indicates pasture-raised dairy products from grass-fed cows have greater anti-inflammatory and antioxidant properties compared to grain-fed counterparts. However, limited research has evaluated the utility of whey protein from pasture-raised, grass-fed cows to enhance recovery compared to whey protein from non-grass-fed cows. Therefore, using a randomized, placebo-controlled design, we compared the effect of whey protein from pasture-raised, grass-fed cows (PRWP) to conventional whey protein (CWP) supplementation on indirect markers of muscle damage in response to eccentric exercise-induced muscle damage (EIMD) in resistance-trained individuals. Thirty-nine subjects (PRWP, n = 14; CWP, n = 12) completed an eccentric squat protocol to induce EIMD with measurements performed at 24, 48, and 72 h of recovery. Dependent variables included: delayed onset muscle soreness (DOMS), urinary titin, maximal isometric voluntary contraction (MIVC), potentiated quadriceps twitch force, countermovement jump (CMJ), and barbell back squat velocity (BBSV). Between-condition comparisons did not reveal any significant differences (p ≤ 0.05) in markers of EIMD via DOMS, urinary titin, MIVC, potentiated quadriceps twitch force, CMJ, or BBSV. In conclusion, neither PRWP nor CWP attenuate indirect markers of muscle damage and soreness following eccentric exercise in resistance-trained individuals.

Computational fluid dynamics of upper airway aerodynamics for exercise-induced laryngeal obstruction: A feasibility study.

Objective: Use of computational fluid dynamic (CFD) simulations to measure the changes in upper airway geometry and aerodynamics during (a) an episode of Exercise-Induced Laryngeal Obstruction (EILO) and (b) speech therapy exercises commonly employed for patients with EILO. Methods: Magnetic resonance imaging stills of the upper airway including the nasal and oral cavities from an adult female were used to re-construct three-dimensional geometries of the upper airway. The CFD simulations were used to compute the maximum volume flow rate (l/s), pressure (Pa), airflow velocity (m/s) and area of cross-section opening in eight planes along the vocal tract, separately for inhalation and exhalation. Results: Numerical predictions from three-dimensional geometrical modeling of the upper airway suggest that the technique of nose breathing for inhalation and pursed lip breathing for exhalation show most promising pressure conditions and cross-sectional diameters for rescue breathing exercises. Also, if EILO is due to the constriction at the vocal fold level, then a quick sniff may also be a proper rescue inhalation exercise. EILO affects both the inspiratory and the expiratory phases of breathing. Conclusions: A prior knowledge of the supraglottal aerodynamics and the corresponding upper airway geometry from CFD analysis has the potential to assist the clinician in choosing the most effective rescue breathing technique for optimal functional outcome of speech therapy intervention in patients with EILO and in understanding the pathophysiology of EILO on a case-by-case basis with future studies. Level of Evidence: 4.

Perinatal depression screening in community pharmacy: Exploring pharmacists' roles, training and resource needs using content analysis.

BACKGROUND: Perinatal depression (PND) screening is often recommended in primary care settings, which includes the community pharmacy setting. However, there is limited research exploring pharmacists' perspectives on their roles in screening for perinatal mental illness. AIM: This study aimed to explore pharmacists' views of pharmacists' roles in PND screening, as well as training and resource needs for PND screening in community pharmacy settings. METHOD: A questionnaire including three open-ended questions focusing on pharmacists' perspectives of their role in PND screening, their training, and resource needs in this area, was disseminated to pharmacists across Australia via professional organisations and social media. Each open-ended question was separately analysed by inductive content analysis. Subcategories were deductively mapped to the Theoretical Framework of Acceptability. RESULTS: Responses (N = 149) from the first open-ended question about pharmacists' roles in PND screening resulted in three categories (PND screening in primary care settings will support the community, community pharmacy environment, and system and policy changes) and ten subcategories. Responses to question two on training needs (n = 148) were categorised as: training content, training length, and training delivery while responses about resource needs (n = 147) fell into three categories: adapting community pharmacy operating structures, pharmacist-specific resources, and consumer-specific resources. CONCLUSION: While some pharmacists were accepting of a role in PND screening due to pharmacists' accessibility and positive relationships with consumers, others had concerns regarding whether PND screening was within pharmacists' scope of practice. Further training and resources are needed to facilitate pharmacists' roles in PND screening, referral and care.

Ecological Momentary Assessment of Midlife Adults' Daily Stress: Protocol for the Stress Reports in Variable Environments (STRIVE) App Study.

BACKGROUND: Daily stressors are associated with cognitive decline and increased risk of heart disease, depression, and other debilitating chronic illnesses in midlife adults. Daily stressors tend to occur at home or at work and are more frequent in urban versus rural settings. Conversely, spending time in natural environments such as parks or forests, or even viewing nature-themed images in a lab setting, is associated with lower levels of perceived stress and is hypothesized to be a strong stress "buffer," reducing perceived stress even after leaving the natural setting. However, many studies of daily stress have not captured environmental contexts and relied on end-of-day recall instead of in-the-moment data capture. With new technology, these limitations can be addressed to enhance knowledge of the daily stress experience. OBJECTIVE: We propose to use our novel custom-built Stress Reports in Variable Environments (STRIVE) ecological momentary assessment mobile phone app to measure the experience of daily stress of midlife adults in free-living conditions. Using our app to capture data in real time will allow us to determine (1) where and when daily stress occurs for midlife adults, (2) whether midlife adults' daily stressors are linked to certain elements of the built and natural environment, and (3) how ecological momentary assessment measurement of daily stress is similar to and different from a modified version of the popular Daily Inventory of Stressful Events measurement tool that captures end-of-day stress reports (used in the Midlife in the United States [MIDUS] survey). METHODS: We will enroll a total of 150 midlife adults living in greater Indianapolis, Indiana, in this study on a rolling basis for 3-week periods. As those in underrepresented minority groups and low-income areas have previously been found to experience greater levels of stress, we will use stratified sampling to ensure that half of our study sample is composed of underrepresented minorities (eg, Black, American Indian, Hispanic, or Native Pacific Islanders) and approximately one-third of our sample falls within low-, middle-, and high-income brackets. RESULTS: This project is funded by the National Institute on Aging from December 2022 to November 2024. Participant enrollment began in August 2023 and is expected to finish in July 2024. Data will be spatiotemporally analyzed to determine where and when stress occurs for midlife adults. Pictures of stressful environments will be qualitatively analyzed to determine the common elements of stressful environments. Data collected by the STRIVE app will be compared with retrospective Daily Inventory of Stressful Events data. CONCLUSIONS: Completing this study will expand our understanding of midlife adults' experience of stress in free-living conditions and pave the way for data-driven individual and community-based intervention designs to promote health and well-being in midlife adults. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51845.

Amenorrhea and oligomenorrhea risk related to exercise training volume and intensity: Findings from 3705 participants recruited via the STRAVA™ exercise application.

OBJECTIVES: To investigate associations between self-reported exercise training habits and amenorrhea/oligomenorrhea among physically active women. DESIGN: A cross-sectional survey was completed by 3705 women (median age = 40 years [quartile 1, quartile 3: 30, 45], body mass index = 22.1 kg/m2 [20.5, 24.2]) representing multiple nationalities and sports via the STRAVA™ exercise application. Respondents selected the amount of time they participated in low intensity, moderate intensity, and high intensity exercise training per week. Amenorrhea/oligomenorrhea was defined as self-reporting ≤10 menses in the last year. METHODS: Associations between weekly exercise volume for low intensity training, moderate intensity training, and high intensity training and amenorrhea/oligomenorrhea were modeled with univariate logistic regression models, followed by adjustment for age and body mass index. RESULTS: Amenorrhea/oligomenorrhea prevalence was 16 % (n = 576/3705), with no difference by country of origin or most sport modes. In adjusted models, participating in low intensity training ≥7 h/week or moderate intensity training ≥6 h/week was associated with 1.43 (95 % confidence interval: 1.04-1.96) and 1.46 (1.10-1.95) greater odds of amenorrhea/oligomenorrhea compared to 2 to 3 h/week, respectively. Similarly, high intensity training ≥5 h/week was associated with 1.41 (1.03-1.92) greater odds of amenorrhea/oligomenorrhea compared to 1 to 2 h/week. Participating in low intensity training for ≤30 min/week compared to 2 to 3 h/week was associated with reduced amenorrhea/oligomenorrhea odds (0.65 [0.44-0.94]). CONCLUSIONS: Taken together, these associations suggest greater weekly exercise volume, irrespective of intensity, may increase amenorrhea/oligomenorrhea risk among physically active women.

Optimal objective measurement of physical function and its predictive capacity for mortality among community-dwelling older women.

AIM: Objective measurements of physcial function, including gait speed, handgrip strength, and the chair stand test, have been shown to have predictive capacity for negative health-related outcomes. The aim of this study was to examine campariatively which of these common assessments may be optimal in terms of their predictive capacity for mortality. METHODS: A total of 9834 community-dwelling older women aged 65-89 years from the Study of Osteoporotic Fractures (SOF) were followed for 20 years. Gait speed, handgrip strength, and the chair stand test were measured every 2-4 years on up to 9 visits. All deaths were adjudicated. RESULTS: All three measurements of physical function were significantly associated with overall, cardiovascular disease and other mortality. Gait speed had the greatest magnitude of hazard ratios (HRs) for all outcomes of interest. A one-unit standard deviation increase in gait speed was associated with a 33% (HR = 0.67, 95% confidence interval [95% CI]: 0.64-0.70) lower risk for overall mortality, a 31% (HR = 0.69, 95% CI: 0.64-0.73) lower risk for cardiovascular disease mortality, a 15% (HR = 0.85, 95% CI: 0.78-0.92) lower risk for cancer mortality and a 42% (HR = 0.58, 95% CI: 0.55-0.62) lower risk for other mortality. Further examination of gait speed identified two cut-points (0.9 and 0.7 m/s) that were strongly indicative of increased mortality risk. CONCLUSION: Our large prospective study indicates that gait speed possesses a better prediction of mortality among older women compared with handgrip strength or the chair stand test. Using cut-points of 0.9 and 0.7 m/s can help identify older women at higher mortality risk, who may benefit from physical function improvement interventions. Geriatr Gerontol Int 2023; 23: 715-721.

Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management reviews in primary care.

INTRODUCTION: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia's Home Medicine Review (HMR) can reduce patients' intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF. METHOD AND ANALYSIS: Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants' cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care. ETHICS AND DISSEMINATION: Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up. TRIAL REGISTRATION NUMBER: ACTRN12622000261718.

Fluid balance during physical work in the heat is not modified by the menstrual cycle when fluids are freely available.

We tested the hypothesis that women may be more at risk of becoming dehydrated during physical work in the heat in the early follicular phase (EF), compared with the late follicular (LF) and mid-luteal (ML) phases of the menstrual cycle when allowed free access to drink. Twelve healthy, eumenorrheic, unacclimated women (26 ± 5 yr) completed three trials (EF, LF, and ML phases) involving 4 h of exposure to 33.8 ± 0.8 °C, 54 ± 1% relative humidity. Each hour, participants walked on a treadmill for 30 min at a rate of metabolic heat production of 338 ± 9 W. Participants drank a cool, flavor-preferred non-caloric sport drink ad libitum. Nude body weight was measured pre- and post-exposure, and percent changes in body weight loss were interpreted as an index of changes in total body water. Total fluid intake and urine output were measured and sweat rate was estimated from changes in body mass corrected for fluid intake and urine output. Fluid intake was not different between phases (EF: 1,609 ± 919 mL; LF: 1,902 ± 799 mL; ML: 1,913 ± 671; P = 0.202). Total urine output (P = 0.543) nor sweat rate (P = 0.907) differed between phases. Percent changes in body mass were not different between phases (EF: -0.5 ± 0.9%; LF: -0.3 ± 0.9%; ML: -0.3 ± 0.7%; P = 0.417). This study demonstrates that the normal hormonal fluctuations that occur throughout the menstrual cycle do not alter fluid balance during physical work in the heat.NEW & NOTEWORTHY The effect of the menstrual cycle on fluid balance during physical work in the heat when fluids are freely available is unknown. This study demonstrates that fluid balance is not modified in women across three distinct phases of the menstrual cycle during physical work in the heat These results indicate that when women have free access to cool fluid during physical work in the heat, they respond similarly across all three phases to maintain fluid homeostasis across the menstrual cycle.

Structure and Function of the Dot/Icm T4SS.

The Legionella pneumophila Dot/Icm type IV secretion system (T4SS) delivers effector proteins into host cells during infection. Despite its significance as a potential drug target, our current understanding of its atomic structure is limited to isolated subcomplexes. In this study, we used subtomogram averaging and integrative modeling to construct a nearly-complete model of the Dot/Icm T4SS accounting for seventeen protein components. We locate and provide insights into the structure and function of six new components including DotI, DotJ, DotU, IcmF, IcmT, and IcmX. We find that the cytosolic N-terminal domain of IcmF, a key protein forming a central hollow cylinder, interacts with DotU, providing insight into previously uncharacterized density. Furthermore, our model, in combination with analyses of compositional heterogeneity, explains how the cytoplasmic ATPase DotO is connected to the periplasmic complex via interactions with membrane-bound DotI/DotJ proteins. Coupled with in situ infection data, our model offers new insights into the T4SS-mediated secretion mechanism.

The role of perceived service quality and price competitiveness on consumer patronage of and intentions towards community pharmacies.

BACKGROUND: When consumers choose a service provider, they trade-off their perceptions of service quality with their perceptions of the cost of engaging with the service provider. For community pharmacy owners and managers, it is important to understand the relative impact on loyalty of providing the extra resources to improve service quality versus forsaking gross profit by discounting prices. The aim of this study was to explore the relative effects of consumers' perceptions of service quality (pSQ) and price competitiveness (pPC) on patronage loyalty (patronage history of the rated pharmacy), patronage disloyalty (patronage history at other pharmacies) and loyalty intentions. METHODS: This was a cross-sectional study conducted within Australia using an online survey administered to members of a consumer marketing panel. Eligible participants were adults taking 2 or more prescription medicines and had attended a community pharmacy within the past 4 weeks. Participants were asked to rate the pharmacy they had last visited, self-report patronage history of that and other pharmacies and report the brand of pharmacy visited. Previously validated scales were used for consumers' perceptions of service quality (pSQ) and loyalty intentions. New scales were developed for pPC and self-reported patronage loyalty and disloyalty. Confirmatory Factor Analysis (CFA) was used to validate the measurement model. Structural Equation Modelling (SEM) with robust estimator (EQS) was used to test the relationships between the variables. Sensitivity analysis, in the presence of covariates were performed with multivariate regression analysis with bootstrapping. RESULTS: Surveys were completed by 303 participants. Most consumers had visited the rated pharmacy more often than once monthly and most had visited only 1 or 2 pharmacies in the past 12 months for prescription medicines. Overall, participants rated pSQ, pPC highly and expressed high loyalty intentions. The SEM was a good fit for the data. The model predicted 12%, 15% and 69% of the variation in patronage loyalty and patronage disloyalty and loyalty intentions, respectively. The effect of pSQ on patronage was 0.38 (p < 0.05) for loyalty and -0.38 (p < 0.05) on disloyalty whereas the effect of pPC was marginal. The total effect of pSQ and pPC on loyalty intentions was 0.64 (<0.05) and 0.20 (p < 0.05) and in sensitivity analyses, no other covariate, including pharmacy brand was significant. CONCLUSION: In order to drive loyalty behavior and generate loyalty intentions, providing a high-quality service appears to be far more effective than creating perceptions that the pharmacy has competitive prices. This finding affords a motivation for both discount AND non-discount brand pharmacies to undertake the steps needed to improve service quality.

Proteinase 3 promotes formation of multinucleated giant cells and granuloma-like structures in patients with granulomatosis with polyangiitis.

OBJECTIVES: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are autoimmune vasculitides associated with antineutrophil cytoplasm antibodies that target proteinase 3 (PR3) or myeloperoxidase (MPO) found within neutrophils and monocytes. Granulomas are exclusively found in GPA and form around multinucleated giant cells (MGCs), at sites of microabscesses, containing apoptotic and necrotic neutrophils. Since patients with GPA have augmented neutrophil PR3 expression, and PR3-expressing apoptotic cells frustrate macrophage phagocytosis and cellular clearance, we investigated the role of PR3 in stimulating giant cell and granuloma formation. METHODS: We stimulated purified monocytes and whole peripheral blood mononuclear cells (PBMCs) from patients with GPA, patients with MPA or healthy controls with PR3 or MPO and visualised MGC and granuloma-like structure formation using light, confocal and electron microscopy, as well as measuring the cell cytokine production. We investigated the expression of PR3 binding partners on monocytes and tested the impact of their inhibition. Finally, we injected zebrafish with PR3 and characterised granuloma formation in a novel animal model. RESULTS: In vitro, PR3 promoted monocyte-derived MGC formation using cells from patients with GPA but not from patients with MPA, and this was dependent on soluble interleukin 6 (IL-6), as well as monocyte MAC-1 and protease-activated receptor-2, found to be overexpressed in the cells of patients with GPA. PBMCs stimulated by PR3 formed granuloma-like structures with central MGC surrounded by T cells. This effect of PR3 was confirmed in vivo using zebrafish and was inhibited by niclosamide, a IL-6-STAT3 pathway inhibitor. CONCLUSIONS: These data provide a mechanistic basis for granuloma formation in GPA and a rationale for novel therapeutic approaches.

Structural and metabolic correlates of neuropsychological profiles in multiple system atrophy and Parkinson's disease.

BACKGROUND: Despite increased recognition of cognitive impairment in Multiple System Atrophy (MSA), its neuroanatomical correlates are not well defined. We aimed to explore cognitive profiles in MSA with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) and their relationship to frontostriatal structural and metabolic changes. METHODS: Detailed clinical and neuropsychological evaluation was performed together with diffusion tensor imaging (DTI) and [18F]-fluoro-deoxyglucose positron emission tomography ([18F]-FDG-PET) in patients with MSA-P (n = 11) and PD (n = 11). We compared clinical and neuropsychological data to healthy controls (n = 9) and correlated neuropsychological data with imaging findings in MSA-P and PD. RESULTS: Patients with MSA-P showed deficits in executive function (Trail Making Test B-A) and scored higher in measures of depression and anxiety compared to those with PD and healthy controls. Widespread frontostriatal white matter tract reduction in fractional anisotropy was seen in MSA-P and PD compared to an imaging control group. Stroop Test interference performance correlated with [18F]-FDG uptake in the bilateral dorsolateral prefrontal cortex (DLPFC) and with white matter integrity between the striatum and left inferior frontal gyrus (IFG) in PD. Trail Making Test performance correlated with corticostriatal white matter integrity along tracts from the bilateral IFG in MSA-P and from the right DLPFC in both groups. CONCLUSION: Executive dysfunction was more prominent in patients with MSA-P compared to PD. DLPFC metabolism and frontostriatal white matter integrity seem to be a driver of executive function in PD, whereas alterations in corticostriatal white matter integrity may contribute more to executive dysfunction in MSA-P.