Proton/solute cotransport in rat kidney brush-border membrane vesicles: relative importance to both d-glucose and peptide transport

AbstractWe have determined the relative importance of the transmembrane proton electrochemical gradient to the transport of d-[ 14C]glucose and [ 14C]glycylsarcosine (gly-sar) in rat kidney brush-border membrane vesicles (BBMV) from superficial renal cortex. Electrogenic [14C]gly-sar transport was first optimised by imposing a pH gradient (pHo = 5.7, pHi = 8.4) and an interior negative p.d. (using outwardly directed K+ gradient plus valinomycin). Under identical conditions (pHo = 5.7, pHi = 8.4), an acceleration f of initial d-[14C]glucose (at 100 μM) transport by 2.0 ± 0.7-fold was observed compared to no proton gradient (pHo = 8.4, pHi = 8.4). This increase was due primarily to an effect of external protons, since acidic conditions (pHo = pHi = 5.7) also resulted in ann acceleration of d-glucose influx (2-fold). The increase ind-glucose transport in the presence of external acidity was reduced by the uncoupler FCCP, even in the absence of a proton gradient. Furthermore, the increased d-glucose transport with external acidity in the presence of a proton gradient was insensitive to a K+ gradient-driven diffusion potential in the presence of valinomycin. In no instance was an overshoot accumulation ofd-[14C]glucose observed in H+ gradient conditions. H+-stimulatedd-[14C]glucose transport showed a linear dependence on d-glucose concentration up to 20 mMd-glucose, unlike electrogenic Na+-dependentd-glucose transport, whose Km was 1.77 ± 0.35 mM. In contrast, the initial rate of [14C]gly-sar (100 μM) transport by the renal H+/di-tripeptide transporter was accelerated 15.7 ± 3.3-fold and stimulated a marked overshoot of 5.1 ± 0.4-fold over equilibrium values. Conversely, the electrogenic, Na+/glucose transporter could be readily demonstrated, whilst [14C]gly-sar transport could not be energised by an inward Na+ gradient. The absence of electrogenicd-glucose transport in H+ gradient conditions is clear evidence against H+/glucose cotransport in Na+-free conditions mediated by SGLT2 (sodium-glucose transporter, renal cortex). Furthermore, since a proton gradient does not increase brush-border membraned-glucose uptake in Na+-rich media, it is unlikely that in vivo renald-glucose transport mediated via SGLT2 may be energised by the transmembrane proton gradient

Farmers are not seeking help: what does service provision have to do with it?

Aim The rate of suicide in farmers is twice that of the general population. Help-seeking from health professionals, if this occurs in a timely manner, can significantly minimise the negative consequences of mental ill-health. However, it has now been demonstrated that farmers as a group are reluctant to seek help for mental ill-health, which likely contributes to this problem. Previous research has demonstrated that General Practitioners are the most commonly visited health professional in rural farming areas, however, they are under-utilised as a means of seeking help. This research aimed to examine the potential barriers and facilitators of mental health help-seeking in farmers, that relate to the provision of service from the perspective of farmers. Methods The present research draws on findings from semi‐structured interviews with 10 farmers residing in Queensland. The techniques of Braun and Clarke (2006) were used to guide the thematic analysis. Results Several key factors relating to services were identified as having the potential to directly or indirectly influence mental health help-seeking. These include: how services are marketed/packaged and delivered, availability and accessibility, continuity of care, having ‘knowledgeable bush practitioners’ as well as perception of good outcomes. Conclusion It is expected that this research will create a better understanding of the farmers’ perspective relating to service provision for the purpose of seeking help for mental health. The outcomes have implications for developing and providing interventions for farmers to promote services for the purpose of mental health help-seeking as well as create awareness in service provider and other stakeholders of issues that prevent timely help-seeking

Chronic Pulmonary Aspergillosis: A Brief Review.

Chronic Pulmonary Aspergillosis (CPA) is a destructive pulmonary disease caused by a fungal infection, affecting mainly individuals with prior or concurrent pulmonary conditions. It has a global prevalence of 42 per 100,000 population, but in the US and Europe, prevalence is less than 1 per 100,000. The clinical definition of CPA is based on various factors accounting for comorbidities, clinical presentation, and duration. It may be categorized into five subtypes that the disease may evolve between over time. Based on global consensus covering the spectrum of low-resource to high-resource settings, diagnosis is a multi-factorial process that involves a combination of clinical presentation persisting over 3 months, radiological findings, positive culture growth, and serological tests. CPA remains underdiagnosed due to a lack of awareness and is often misdiagnosed due to the comorbidities present. Treatment options are limited due to a lack of research. Furthermore, associated comorbidities and drug interactions further complicate treatment plans. Follow-up throughout treatment should be based on understanding the predictors of mortality. Identification of potential relapse or resistance to antifungal therapy is crucial to limit the low long-term survival rate. Awareness surrounding this devastating disease needs to be raised further to enable earlier identification, improve understanding of patient factors associated with prognosis, and the future potential for targeted therapies. This review aims to raise awareness of this rare condition among practitioners, by providing an overview of common risk factors influencing the prevalence and incidence of the disease. We further discuss current approaches and recent advancements in CPA diagnosis and treatment

Stories from Queensland farmers: 'why we don't seek help for mental health'

Farming as an occupation and lifestyle has many inherent stressors and farmers demonstrate suicide rates twice that of the general population (Arnautovska, McPhedran, & De Leo, 2014). There are also reports that indicate farmers may show fewer help-seeking behaviours, although research to date has failed to uncover clear reasons for this. Mental health help-seeking includes behaviours directed towards seeking help from health professionals for issues relating to mental health or distress (Rickwood & Thomas, 2012); if this occurs in a timely manner then negative consequences may be minimised. There is an urgent need to identify factors specific to farmers that make mental health help seeking difficult. The research presented here is part of a program of research aiming to understand the barriers and facilitators of mental health help-seeking in farmers from regional communities. The present research draws on findings from semi‐structured interviews with 10 farmers residing in Queensland. The interviews were analysed drawing on the techniques of Braun and Clarke (2006). Several key factors were identified as having the potential to directly or indirectly influence mental health help-seeking including, the weather (with a strong focus on drought), finances, support, health services, mental health literacy and stigma. This paper discusses these factors from the farmer perspective. The findings from this study advance knowledge in understanding what factors may influence mental health help-seeking in Queensland farmers. The outcomes have implications for developing and providing intervention to reduce barriers, and reinforce or strengthen facilitators of mental health help-seeking in farmers

The barriers and facilitators of farmer mental health help-seeking: a mixed methods approach

Farming as an occupation has many inherent stressors, and farmers demonstrate suicide rates twice that of the general population (Arnautovska, McPhedran, & De Leo, 2014). There are also reports that indicate farmers may show fewer help-seeking behaviours, although research to date has failed to uncover clear reasons for this (Brew, Inder, Allen, Thomas, & Kelly, 2016). If mental health help-seeking behaviours, such as seeking mental health support from health professionals, occurs promptly, then negative consequences may be minimised. There is an urgent need to identify factors specific to farmers that prevent and promote mental health help-seeking. To address this problem a two-phase program of research using mixed methods was conducted. The first phase was qualitative, using semi-structured interviews and thematic analysis as per Braun and Clarke’s (2006) recommendations to explore farmer mental health help-seeking with three samples: farmers, farmers’ partners, and General Practitioners (GPs). From the analysis, three superordinate themes were reported as part of Phase 1: ‘Farming life’, ‘Services’, and ‘Personal factors’. Farming life encompassed ‘Lifestyle and culture’, ‘Farming priorities’, and ‘The challenges of farming life’ themes. The services superordinate theme was comprised of three themes: ‘How the service is delivered’, ‘Services are provided within a complex system’, and ‘Emerging technologies: The users, practitioners, and systems’. Lastly, personal factors included the themes of ‘Mental health literacy’, ‘Stigma of mental illness and help-seeking’, ‘Support, the partners’ role in help-seeking’ and ‘The intersectionality between being a farmer, age, and gender’. The Phase 1 findings provided the basis for Phase 2 hypotheses generation. In Phase 2, correlational analyses and logistic regression demonstrated which of the factors identified in Phase 1 had bivariate and predictive relationships with intentions to seek mental health help. Further, the farmers’ intentions for seeking mental health help from a GP and a mental health professional were considered separately. With respect to intentions to seek mental health help from a GP, many factors demonstrated a bivariate relationship, and together these factors accounted for a large amount of the variance. One factor, comfort with mental health services, was a key predictor. There was a different pattern of relationships for intentions to seek help from a mental health professional, but many factors also demonstrated a bivariate relationship. Together, the factors accounted for a large amount of the variance in intentions to seek help from a mental health professional, and two factors were key predictors: comfort with mental health services and psychological openness. The findings from this research advance knowledge in a number of ways. Firstly, this research provides an understanding of the barriers and facilitators farmers experience with respect to mental health help-seeking. Additionally, Phase 2 provides information regarding the strength of these factors’ influence on farmer help-seeking intentions, and the importance of considering each health profession separately, because intentions to seek help from each were related to, and predicted by, different groups of factors. While further research is still needed, given the emerging state of the literature, this research has utility and highlights the complexity of preventive and promotive factors impacting on farmer mental health help-seeking

Farmers tell us how to help improve their mental health help-seeking

Farmers’ mental health help-seeking is reported to be poor. Mental health help-seeking is seeking help from professionals such as GPs and psychologists for issues relating to distress or mental health (Rickwood & Thomas, 2012). Timely mental health help-seeking behaviour is important because it may minimise any negative outcomes. At present, there is no research that has identified how to target farmers to improve their mental health help-seeking. It is known that tailored approaches to intervention are superior and this is likely to be so for intervening with farmers whom have a strong culture and a vastly different situation than metropolitan populations. This study is part of a body of work exploring the factors that influence mental health help-seeking in farmers. Semi-structured interviews were conducted with 10 farmers (farming as their occupation) as well as 10 farmers’ partners (for their additional insight), all of whom resided/worked in Queensland. Braun and Clarke’s (2006) technique of thematic analysis was used to analyse the data. Based on the data three themes were developed regarding intervention: education (what needs to be taught and how to teach it), the medium (which mediums preferred and engagement with them) and multi-faceted programs (Many aspects important such as community input and role of GPs, family, and friends). This research improves the knowledge on how to target interventions, including the medium, specifically to farmers for mental health help-seeking. The findings could be utilised in the design process to create interventions that are more likely to have an impact, specific for farmers to improve their mental health help-seeking behaviour

Farmers aren't seeking help for mental health: their partners tell us why

There are many stressors that impact on farmers and recent research has found that Queensland farmers’ rate of suicide is twice that of the general population (Arnautovska et al.,2014). It is reported that mental health help-seeking behaviour is lacking in farmers. Seeking help for mental health is seeking services from a health professional for distress or mental health issues (Rickwood & Thomas, 2012). Farmers’ partners reportedly have a role in the help-seeking of farmers, such as facilitation and support, and may also be able to offer insight into their mental health help-seeking behaviour (Doherty & Kartalova-O’Doherty, 2010; Kolves et al., 2012). There is an urgent need to identify factors specific to farmers that make mental health help seeking difficult, including those outside their awareness. The research presented is part of a program of research exploring the barriers and facilitators of mental health help-seeking in farmers from regional Queensland. The present research draws on semi-structured interviews with 10 partners of farmers, where the farmer resides in Queensland with farming as their occupation. The interviews were analysed drawing on the techniques of Braun and Clarke (2006). Several key factors were identified as having the potential to directly or indirectly influence mental health help-seeking, including the weather, mental health literacy, stigma, health services, farming lifestyle and ‘culture’, finances and coping mechanisms. Further, the key role partners play in the farmers’ help-seeking processes was also identified. This paper discusses these factors from the farmer’s partners’ perspective. The findings from this research advance the understanding of the factors that influence the mental health help-seeking of farmers, by including additional insight from a source close to the farmers. The implications of this research include that interventions could be developed and provided to reduce the barriers and reinforce or strengthen the facilitators of mental health help seeking in farmers, including factors that farmers themselves may not be aware of

Colleague appraisal of Australian general practitioners in training: an analysis of multisource feedback data

Background: Multisource feedback is an evidence-based and validated tool used to provide clinicians, including those in training, feedback on their professional and interpersonal skills. Multisource feedback is mandatory for participants in the Royal Australian College of General Practitioners Practice Experience Program and for some Australian General Practice Training Registrars. Given the recency of the Practice Experience Program, there are currently no benchmarks available for comparison within the program and to other comparable cohorts including doctors in the Australian General Practice Training program. The aim of this study is to evaluate and compare colleague feedback within and across General Practice trainee cohorts. Methods: Colleague feedback, from multisource feedback of Practice Experience Program participants and Australian General Practice Training Registrars, collected between January 2018 and April 2020, was compared to identify similarities and differences. Analyses entailed descriptive statistics, between and within groups rater consistency and agreement measures, principal component analysis, t-tests, analysis of variance, and psychometric network analysis. Results: Colleague ratings of Practice Experience Program participants (overall average 88.58%) were lower than for Registrars (89.08%), although this difference was not significant. ‘Communication with patients’ was rated significantly lower for Practice Experience Program participants (2.13%) while this group was rated significantly better for their ‘Ability to say no’ (1.78%). Psychometric network analyses showed stronger linkages between items making up the behavioural component (compared to the items of the performance and self-management components, as found by principal component analysis) for Practice Experience Program participants as compared to Registrars. Practice Experience Program participants were stronger in clinical knowledge and skills as well as confidentiality, while Registrars were stronger in communicating with patients, managing their own stress, and in their management and leadership skills. Conclusions: The multisource feedback scores of doctors undertaking the Practice Experience Program suggests that, while all mean values are ‘very good’ to ‘excellent’, there are areas for improvement. The linkages between skills suggests that Practice Experience Program doctors’ skills are somewhat isolated and have yet to fully synthesise. We now have a better understanding of how different groups of General Practitioners in training compare with respect to professional and interpersonal skills. Based on the demonstrated differences, the Practice Experience Program might benefit from the addition of educational activities to target the less developed skills

A comparison of patient appraisal of professional skills for GPs in training participating in differing education programs

Background: Medical boards and healthcare providers internationally are coming under increasing pressure to attract international medical graduates (IMGs) and overseas trained doctors (OTDs) to cope with predicted general practice (GP) doctor shortages. Various pathways to registration are made available for this purpose. There is very little understanding of the effects of different training pathways to licensing and registration on the ability of IMGs and OTDs, as well as locally trained doctors, to acquire the desirable professional skills deemed necessary for working effectively in the primary care sector. Methods: Feedback from patients was collected at the end of their scheduled consultation with their doctor using a questionnaire consisting of 13 Likert scale items that asked them to rate their experience of the consultation. Feedback was obtained for doctors going through the Royal Australian College of General Practice (RACGP) Practice Experience Program (PEP) and the Australian General Practice Training Program (AGPT), with the former intended primarily for IMGs and OTDs, and the latter for local medical graduates including from New Zealand. Patient feedback was also obtained for patients visiting already Fellowed and experienced GPs for comparative purposes, resulting in data for three groups of doctors (two trainee, one already Fellowed). Rater consistency and agreement measures, analysis of variance, principal component analysis, t-tests and psychometric network analysis were undertaken between and within groups to identify similarities and differences in patient experience and professionalism of doctors. Results: There was a small but significant difference in average patient raw scores given to PEP and AGPT doctors (90.25, 90.97%), with the highest scores for ‘Respect shown’ (92.24, 93.15%) and the lowest for ‘Reassurance’ 89.38, 89.84%). Male patients gave lower scores (89.56%) than female patients (91.23%) for both groups of doctors. In comparison, patients gave experienced GPs an average 91.38% score, with male patients giving a lower average score than female patients (90.62, 91.93%). Two components were found in the patient data (interpersonal communication, caring/empathy) that account for over 80% of the variance. When patient scores were aggregated by doctor, the average PEP and AGPT doctor scores received were 90.27 and 90.99%, in comparison to the average experienced GP score of 91.43%. Network analysis revealed differences in the connectedness of items between these two groups as well as in comparison with experienced GPs, suggesting that PEP doctors’ skills are less cohesively developed in the areas of listening ability, explaining and providing reassurance. Conclusions: The small but statistically significant differences between doctor groups reported in this preliminary study are supplemented by percentile analysis, network analysis and principal component analysis to identify areas for further exploration and study. There is scope for improving the integration of interpersonal communication skills of GPs in Training with their caring and empathy skills, when compared with experienced GPs as a benchmark. Suggestions are made for enhancing professional skills from a patients’ perspective in future training programs

Kinetic Measurements of Di- and Tripeptide and Peptidomimetic Drug Transport in Different Kidney Regions Using the Fluorescent Membrane Potential-Sensitive Dye, DiS-C3-(3).

Tri- and dipeptides are transported in the kidney by PEPT1 and PEPT2 isoforms. The aim of this study was to investigate differences in transport kinetics between renal brush border (BBMV) and outer medulla (OMMV) membrane vesicles (where PEPT1 and PEPT2 are sequentially available) for a range of di- and tripeptides and peptidomimetic drugs. This was accomplished through the use of the potential-sensitive fluorescent dye 3,3'-dipropylthiacarbocyanine iodide [DiS-C3-(3)]. BBMV and OMMV were prepared from the rat kidney using standard techniques. The presence of PEPT1 in BBMV and PEPT2 in OMMV was confirmed using Western blotting. Fluorescence changes were measured when extravesicular medium at pH 6.6 containing 0-1 mM substrates was added to a cuvette containing vesicles pre-equilibrated at pH 7.4 and 2.71 μM DiS-C3-(3). An increase in fluorescence intensity occurred upon substrate addition reflecting the expected positive change in membrane potential difference. Of the range of substrates studied, OMMV manifested the highest affinity to cefadroxil and valacyclovir (K m 4.3 ± 1.2 and 11.7 ± 3.2 µM, respectively) compared to other substrates, whilst the BBMV showed a higher affinity to Gly-His (K m 15.4 ± 3.1 µM) compared to other substrates. In addition, OMMV showed higher affinity and capacity to Gly-Gln (K m 47.1 ± 9.8 µM, 55.5 ± 2.8 ΔF/s/mg protein) than BBMV (K m 78.1 ± 13.3 µM and 35.5 ± 1.7 ΔF/s/mg protein, respectively). In conclusion, this study successfully separated the expression of PEPT1 and PEPT2 into different vesicle preparations inferring their activity in different regions of the renal proximal tubule