Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype

Abstract The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands

Potential influence of selection criteria on the demographic composition of students in an Australian medical school

<p>Abstract</p> <p>Background</p> <p>Prior to 1999 students entering our MBBS course were selected on academic performance alone. We have now evaluated the impact on the demographics of subsequent cohorts of our standard entry students (those entering directly from high school) of the addition to the selection process of an aptitude test (UMAT), a highly structured interview and a rural incentive program.</p> <p>Methods</p> <p>Students entering from 1985 to 1998, selected on academic performance alone (N = 1402), were compared to those from 1999 to 2011, selected on the basis of a combination of academic performance, interview score, and UMAT score together with the progressive introduction of a rural special entry pathway (N = 1437).</p> <p>Results</p> <p>Males decreased from 57% to 45% of the cohort, students of NE or SE Asian origin decreased from 30% to 13%, students born in Oceania increased from 52% to 69%, students of rural origin from 5% to 21% and those from independent high schools from 56% to 66%. The proportion of students from high schools with relative socio-educational disadvantage remained unchanged at approximately 10%. The changes reflect in part increasing numbers of female and independent high school applicants and the increasing rural quota. However, they were also associated with higher interview scores in females vs males and lower interview scores in those of NE and SE Asian origin compared to those born in Oceania or the UK. Total UMAT scores were unrelated to gender or region of origin.</p> <p>Conclusions</p> <p>The revised selection processes had no impact on student representation from schools with relative socio-educational disadvantage. However, the introduction of special entry quotas for students of rural origin and a structured interview, but not an aptitude test, were associated with a change in gender balance and ethnicity of students in an Australian undergraduate MBBS course.</p

Medical student selection criteria as predictors of intended rural practice following graduation

BACKGROUND: Recruiting medical students from a rural background, together with offering them opportunities for prolonged immersion in rural clinical training environments, both lead to increased participation in the rural workforce after graduation. We have now assessed the extent to which medical students’ intentions to practice rurally may also be predicted by either medical school selection criteria and/or student socio-demographic profiles. METHODS: The study cohort included 538 secondary school-leaver entrants to The University of Western Australia Medical School from 2006 to 2011. On entry they completed a questionnaire indicating intention for either urban or rural practice following graduation. Selection factors (standardised interview score, percentile score from the Undergraduate Medicine and Health Sciences Admission Test (UMAT) and prior academic performance (Australian Tertiary Admissions Rank), together with socio-demographic factors (age, gender, decile for the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) and an index of rurality) were examined in relation to intended rural or urban destination of practice. RESULTS: In multivariate logistic regression, students from a rural background had a nearly 8-fold increase in the odds of intention to practice rurally after graduation compared to those from urban backgrounds (OR 7.84, 95% CI 4.10, 14.99, P < 0.001). Those intending to be generalists rather than specialists had a more than 4-fold increase in the odds of intention to practice rurally (OR 4.36, 95% CI 1.69, 11.22, P < 0.001). After controlling for these 2 factors, those with rural intent had significantly lower academic entry scores (P = 0.002) and marginally lower interview scores (P = 0.045). UMAT percentile scores were no different. Those intending to work in a rural location were also more likely to be female (OR 1.93, 95% CI 1.08, 3.48, P = 0.027), to come from the lower eight IRSAD deciles (OR 2.52, 95% CI 1.47, 4.32, P = 0.001) and to come from Government vs independent schools (OR 2.02, 95% CI 1.15, 3.55, P = 0.015). CONCLUSIONS: Very high academic scores generally required for medical school entry may have the unintended consequence of selecting fewer graduates interested in a rural practice destination. Increased efforts to recruit students from lower socioeconomic backgrounds may be beneficial in terms of an ultimate intended rural practice destination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1472-6920-14-218) contains supplementary material, which is available to authorized users

GAMSAT: a 10-year retrospective overview, with detailed analysis of candidates\u27 performance in 2014

BACKGROUND: The Graduate Australian Medical Schools Admission Test (GAMSAT) is undertaken annually in centres around Australia and a small number of overseas locations. Most Australian graduate entry medical schools also use Grade Point Average and interview score for selection. The aim of this study was to review the performance of the GAMSAT over the last 10 years; the study provides an analysis of the impact of candidates’ gender, age, language background, level of academic qualification and background discipline on performance; and details on the performance of higher-scoring candidates. These analyses were undertaken on the 2014 data; and trends in the data over the 10-year period are noted. METHODS: In reviewing performance, the main variables considered were: – Overall GAMSAT score and scores for Section 1, Reasoning in Humanities and Social Sciences, Section 2, Written Communication, and Section 3, Reasoning in Biological and Physical Sciences. – Proportions of candidates achieving a Typical Entry Score. – Impact of gender, age, language background, level of academic qualification and undergraduate course (i.e. subject discipline) on test scores. Descriptive statistics and tests of significance were applied to determine the impact of demographic variables on performance. RESULTS: The number of candidates is increasing. Test reliability is consistently high. Higher scores overall are more likely for candidates who are male; are less than 24 years old; have an English-speaking background; have an Honours degree or a doctorate; and have completed a degree which is not health-related. CONCLUSIONS: Performance of the GAMSAT exam over the last 10 years has been stable with high reliability. There are significant variations in candidate performance related to age, gender, level and discipline of previous academic study and language background. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12909-015-0316-3) contains supplementary material, which is available to authorized users

Parent Attitudes Towards Predictive Testing for Autism in the First Year of Life

Abstract Background Emerging biomarker technologies (e.g., MRI, EEG, digital phenotyping, eye-tracking) have potential to move the identification of autism into the first year of life. We investigated the perspectives of parents about the anticipated utility and impact of predicting later autism diagnosis from a biomarker-based test in infancy. Methods Parents of infants were interviewed to ascertain receptiveness and perspectives on early (6-12 months) prediction of autism using emerging biomarker technologies. One group had experience parenting an older autistic child (n=30), and the other had no prior autism parenting experience (n=25). Parent responses were analyzed using inductive qualitative coding methods. Results Almost all parents in both groups were interested in predictive testing for autism, with some stating they would seek testing only if concerned about their infant’s development. The primary anticipated advantage of testing was to enable access to earlier intervention. Parents also described the anticipated emotions they would feel in response to test results, actions they might take upon learning their infant was likely to develop autism, attitudes towards predicting a child’s future support needs, and the potential impacts of inaccurate prediction. Conclusion In qualitative interviews, parents of infants with and without prior autism experience shared their anticipated motivations and concerns about predictive testing for autism in the first year of life. The primary reported motivators for testing—to have more time to prepare and intervene early—could be constrained by familial resources and service availability. Implications for ethical communication of results, equitable early intervention, and future research are discussed

The SOFIA pilot study:assessing feasibility and fidelity of coordinated care to reduce excess mortality and increase quality of life in patients with severe mental illness in a general practice setting; a cluster-randomised pilot trial

Abstract Objective To evaluate the feasibility and fidelity of implementing and assessing the SOFIA coordinated care program aimed at lowering mortality and increasing quality of life in patients with severe mental illness by improving somatic health care in general practice. Design A cluster-randomised, non-blinded controlled pilot trial. Setting General Practice in Denmark. Intervention The SOFIA coordinated care program comprised extended structured consultations carried out by the GP, group-based training of GPs and staff, and a handbook with information on signposting patients to relevant municipal, health, and social initiatives. Patients Persons aged 18 years or older with a diagnosis of psychotic, bipolar, or severe depressive disorder. Main outcome measures We collected quantitative data on the delivery, recruitment and retention rates of practices and patients, and response rates of questionnaires MMQ and EQ-5D-5 L. Results From November 2020 to March 2021, nine practices were enrolled and assigned in a 2:1 ratio to the intervention group (n = 6) or control group (n = 3). Intervention group practices included 64 patients and Control practices included 23. The extended consultations were delivered with a high level of fidelity in the general practices; however, thresholds for collecting outcome measures, and recruitment of practices and patients were not reached. Conclusion Our findings suggest that delivering the coordinated care program in a fully powered trial in primary care is likely feasible. However, the recruitment methodology requires improvement to ensure sufficient recruitment and minimize selective inclusion. Trial registration The date of pilot trial protocol registration was 05/11/2020, and the registration number is NCT04618250

A single lysine in the N-terminal region of store-operated channels is critical for STIM1-mediated gating

Store-operated Ca2+ entry is controlled by the interaction of stromal interaction molecules (STIMs) acting as endoplasmic reticulum ER Ca2+ sensors with calcium release–activated calcium (CRAC) channels (CRACM1/2/3 or Orai1/2/3) in the plasma membrane. Here, we report structural requirements of STIM1-mediated activation of CRACM1 and CRACM3 using truncations, point mutations, and CRACM1/CRACM3 chimeras. In accordance with previous studies, truncating the N-terminal region of CRACM1 or CRACM3 revealed a 20–amino acid stretch close to the plasma membrane important for channel gating. Exchanging the N-terminal region of CRACM3 with that of CRACM1 (CRACM3-N(M1)) results in accelerated kinetics and enhanced current amplitudes. Conversely, transplanting the N-terminal region of CRACM3 into CRACM1 (CRACM1-N(M3)) leads to severely reduced store-operated currents. Highly conserved amino acids (K85 in CRACM1 and K60 in CRACM3) in the N-terminal region close to the first transmembrane domain are crucial for STIM1-dependent gating of CRAC channels. Single-point mutations of this residue (K85E and K60E) eliminate store-operated currents induced by inositol 1,4,5-trisphosphate and reduce store-independent gating by 2-aminoethoxydiphenyl borate. However, short fragments of these mutant channels are still able to communicate with the CRAC-activating domain of STIM1. Collectively, these findings identify a single amino acid in the N terminus of CRAC channels as a critical element for store-operated gating of CRAC channels

Exploring the role of teams and technology in patients' medication decision making

The final publication is available at Elsevier via https://doi.org/10.1016/j.japh.2018.12.010. © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/We know little about how electronic health records (EHRs) should be designed to help patients, pharmacists, and physicians participate in interprofessional shared decision making. We used a qualitative approach to understand better how patients make decisions with their health care team, how this information influences decision making about their medications, and finally, how this process can be improved through the use of EHRs.Canadian Institutes of Health Researc

Physician and Pharmacist Medication Decision-Making in the Time of Electronic Health Records: Mixed-Methods Study

©Kathryn Mercer, Catherine Burns, Lisa Guirguis, Jessie Chin, Maman Joyce Dogba, Lisa Dolovich, Line Guénette, Laurie Jenkins, France Légaré, Annette McKinnon, Josephine McMurray, Khrystine Waked, Kelly A Grindrod. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 25.09.2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Human Factors, is properly cited. The complete bibliographic information, a link to the original publication on http://humanfactors.jmir.org, as well as this copyright and license information must be included.Background: Primary care needs to be patient-centered, integrated, and interprofessional to help patients with complex needs manage the burden of medication-related problems. Considering the growing problem of polypharmacy, increasing attention has been paid to how and when medication-related decisions should be coordinated across multidisciplinary care teams. Improved knowledge on how integrated electronic health records (EHRs) can support interprofessional shared decision-making for medication therapy management is necessary to continue improving patient care. Objective: The objective of our study was to examine how physicians and pharmacists understand and communicate patient-focused medication information with each other and how this knowledge can influence the design of EHRs. Methods: This study is part of a broader cross-Canada study between patients and health care providers around how medication-related decisions are made and communicated. We visited community pharmacies, team-based primary care clinics, and independent-practice family physician clinics throughout Ontario, Nova Scotia, Alberta, and Quebec. Research assistants conducted semistructured interviews with physicians and pharmacists. A modified version of the Multidisciplinary Framework Method was used to analyze the data. Results: We collected data from 19 pharmacies and 9 medical clinics and identified 6 main themes from 34 health care professionals. First, Interprofessional Shared Decision-Making was not occurring and clinicians made decisions based on their understanding of the patient. Physicians and pharmacists reported indirect Communication, incomplete Information specifically missing insight into indication and adherence, and misaligned Processes of Care that were further compounded by EHRs that are not designed to facilitate collaboration. Scope of Practice examined professional and workplace boundaries for pharmacists and physicians that were internally and externally imposed. Physicians decided on the degree of the Physician-Pharmacist Relationship, often predicated by colocation. Conclusions: We observed limited communication and collaboration between primary care providers and pharmacists when managing medications. Pharmacists were missing key information around reason for use, and physicians required accurate information around adherence. EHRs are a potential tool to help clinicians communicate information to resolve this issue. EHRs need to be designed to facilitate interprofessional medication management so that pharmacists and physicians can move beyond task-based work toward a collaborative approach