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Purpose: The Dobbs v Jackson Women's Health Organization (Dobbs) Supreme Court decision revoked the constitutional right to abortion. Now, restrictive state abortion laws may contribute to the shortage and strain already felt in primary care practice, especially related to the provision of reproductive health care. The purpose of this study is to evaluate perceived impacts of state abortion legislation on family medicine clinicians' practice and medical education regarding reproductive health care., Methods: Ten questions were added to the 2022 Council of Academic Family Medicine Educational Research Alliance general membership survey to evaluate impact on relevant themes in reproductive health care and training after the Dobbs decision. Responses were categorized by severity of restriction of state abortion policies., Results: Of 1,196 respondents, 49.7% reported employment in states with very restrictive or restrictive abortion policies. The 991 respondents with clinical responsibilities reported significant ( P <.05) changes in their counseling practices, clinical decision making, worry of legal risks, and trust in patients' self-reported reproductive medical history, compared with peers in protective states. Perceived patient trust toward clinicians remained unchanged. Almost one-half of clinical respondents reported an absence of reproductive health care guidance or recommendations. Restrictive abortion policies significantly ( P <.05) reduced the desirability and confidence in resident training programs., Conclusions: Reported changes to clinical activities and training, coming early after the Dobbs decision, affect our current and future workforce and therefore, our patients. Future studies are needed to document continued impact of state restrictions and inform policy to support family medicine clinicians in reproductive health practice and education., (© 2024 Annals of Family Medicine, Inc.)

Objective: This paper explores the complexities that impact access to mental health services in rural New Zealand. Historical, cultural, social and political factors will be examined against the philosophical positioning of Foucault and Fairclough., Study Design: This research is a single-embedded case study design exploring participants' discourses in the context of a rural, bounded geographical area of New Zealand., Results: The results show that mental health support that addresses people's actual needs rather than the needs that governments map against ever-changing policy is required and that an awareness of context within case study research is important., Discussion: The process of case study design is described, including building upon a rationale for selecting the case, collecting data and conducting case analysis and interpretation. This study examines factors influencing the real-life rural context of accessing mental health support. This article demonstrates that case-study research can be valuable for navigating context complexity and developing nuanced understandings of complex phenomena., Conclusion: The paper highlights how the multifaceted case study context is more than mapping discourses against a rural backdrop. It is necessary to consider the power dynamics that shape experiences and their impact on service creation and its consequent delivery., Implications for Research Policy and Practice: Rather than services being created that are complex and not meeting people's needs, there is a need to listen to the people who have experienced mental health distress and provide services and support in locations other than clinical settings., (© 2024 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Malanin is a new type II ribosome-inactivating protein (RIP) purified from Malania oleifera , a rare, endangered tree is only found in the southwest of Guangxi Province and the southeast of Yunnan Province, China. The gene coding sequence of malanin was found from the cDNA library of M. oleifera seeds by employing the ten N-terminal amino acid sequences of malanin, DYPKLTFTTS for chain-A and DETXTDEEFN (X was commonly C) for chain-B. The results showed a 65% amino acid sequence homology between malanin and ricin by DNAMAN 9.0 software, the active sites of the two proteins were consistent, and the four disulfide bonds were in the same positions. The primary sequence and three-dimensional structures of malanin and ricin are likely to be very similar. Our studies suggest that the mechanism of action of malanin is expected to be analogous to ricin, indicating that it is a member of the type II ribosome-inactivating proteins. This result lays the foundation for further study of the anti-tumor activities of malanin, and for the application of malanin as a therapeutic agent against cancers., Competing Interests: The authors declare no conflicts of interest.

The assessment of medical decision-making capacity as part of the process of clinical informed consent has been considered a bioethical housekeeping matter for decades. Yet in practice, the reality bears little resemblance to what is described in the medical literature and professed in medical education. Most literature on informed consent refers to medical decision-making capacity as a precondition to the consent process. That is, a clinician must first determine if a patient has capacity, and only then may the clinician engage with the patient for the rest of informed consent. The problem with this two-step approach is that it makes no sense in actual practice. We see the assessment of medical decision-making capacity within the process of informed consent as a spiral staircase, not just two steps, requiring clinicians to keep circling up and around, making progress, until they get to where they need to be: 1. Clinicians start with a general presumption of capacity for most adults, sometimes having a provisional appraisal of capacity based on prior patient contact. 2. Then, they begin performing informed consent for the current situation and intervention options. 3. Next, they must reassess capacity during this process. 4. After that, they continue with informed consent. 5. If capacity is not yet clear, they repeat 1-4., Competing Interests: Declaration of Competing Interest On behalf of David Satin, Philip Day and myself, I wish to declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The research employs a single embodied case study design with the aim to examine the discourse of men accessing and receiving mental health support alongside those who are the providers of the support. Three groups of adults were interviewed: men who had experienced mental health problems and had attempted to access mental health support; lay people who supported them, such as partners and non-mental health professionals and professionals, such as mental health nurses, social workers, clinical psychologists and general practitioners. Critical discourse analysis (CDA) is used to identify discourses around three emergent themes: well-being, power and dominance and social capital. Participants seeking mental health support often referred to mental health services as not listening or that what was offered was not useful. A lack of belonging and community disconnectedness was apparent throughout all participant interviews. The study is reported according to the COREQ guidelines., (© 2024 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Background: An embedded single case-study design was used to explore the experiences of men in rural New Zealand accessing mental health services. It is essential for researchers to acknowledge positionality in case study research and the lead author used reflexive practice to acknowledge his values and beliefs., Aim: To explore and demonstrate the reflexive process of the lead author's position as an inside researcher., Discussion: Three groups were involved in the research: men with mental health challenges, their partners, and mental health clinicians. The article presents the initial research through memos and diarying in the context of current literature., Conclusion: Reflexivity is essential for ensuring the research process is complete and biases are identified. Positionality exists on a continuum and it is critical for researchers to be honest with themselves, the topic and the group being investigated, to show respect for the participants and the people they represent, as well as to be committed to revealing the truth., Implications for Practice: Insider research has the potential to bridge the gap between academia and practice. It facilitates the transfer of research knowledge directly to practitioners, leading to more evidence-informed decision-making and practice., Competing Interests: None declared, (© 2024 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Cyclin dependent kinase 7 (CDK7) is an important therapeutic kinase best known for its dual role in cell cycle regulation and gene transcription. Here, we describe the application of protein engineering to generate constructs leading to high resolution crystal structures of human CDK7 in both active and inactive conformations. The active state of the kinase was crystallized by incorporation of an additional surface residue mutation (W132R) onto the double phosphomimetic mutant background (S164D and T170E) that yielded the inactive kinase structure. A novel back-soaking approach was developed to determine crystal structures of several clinical and pre-clinical inhibitors of this kinase, demonstrating the potential utility of the crystal system for structure-based drug design (SBDD). The crystal structures help to rationalize the mode of inhibition and the ligand selectivity profiles versus key anti-targets. The protein engineering approach described here illustrates a generally applicable strategy for structural enablement of challenging molecular targets., Competing Interests: Declaration of interests At the time of work, M.M., P.J.D., D.L., J.A.B-C., A.J.W., C.G-J., S.H., C.E., and M.O’R. were all employees of Astex Pharmaceuticals. At the time of work, S.B. was a paid consultant for Astex Pharmaceuticals working on this project., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disease that is known to accumulate amyloid-β (Aβ) and tau protein. Clinical studies have not identified pathogenesis mechanisms or produced an effective cure for AD. The Aβ monoclonal antibody lecanemab reduces Aβ plaque formation for the treatment of AD, but more studies are required to increase the effectiveness of drugs to reduce cognitive decline. The lack of AD therapy targets and evidence of an association with an acute neuroinflammatory response caused by several bacteria and viruses in some individuals has led to the establishment of the infection hypothesis during the last 10 years. How pathogens cross the blood-brain barrier is highly topical and is seen to be pivotal in proving the hypothesis. This review summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.

The clinical management of malignant tumours is challenging, often leading to severe adverse effects and death. Drug resistance (DR) antagonises the effectiveness of treatments, and increasing drug dosage can worsen the therapeutic index (TI). Current efforts to overcome DR predominantly involve the use of drug combinations, including applying multiple anti-cancerous drugs, employing drug sensitisers, which are chemical agents that enhance pharmacokinetics (PK), including the targeting of cellular pathways and regulating pertinent membrane transporters. While combining multiple compounds may lead to drug-drug interactions (DDI) or polypharmacy effect, the use of drug sensitisers permits rapid attainment of effective treatment dosages at the disease site to prevent early DR and minimise side effects and will reduce the chance of DDI as lower drug doses are required. This review highlights the essential use of TI in evaluating drug dosage for cancer treatment and discusses the lack of a unified standard for TI within the field. Commonly used benefit-risk assessment criteria are summarised, and the critical exploration of the current use of TI in the pharmaceutical industrial sector is included. Specifically, this review leads to the discussion of drug sensitisers to facilitate improved ratios of effective dose to toxic dose directly in humans. The combination of drug and sensitiser molecules might see additional benefits to rekindle those drugs that failed late-stage clinical trials by the removal of detrimental off-target activities through the use of lower drug doses. Drug combinations and employing drug sensitisers are potential means to combat DR. The evolution of drug combinations and polypharmacy on TI are reviewed. Notably, the novel binary weapon approach is introduced as a new opportunity to improve TI. This review emphasises the urgent need for a criterion to systematically evaluate drug safety and efficiency for practical implementation in the field.

Silver has long been recognized for its potent antimicrobial properties, but achieving a slow and longer-term delivery of silver ions presents significant challenges. Previous efforts to control silver ion dosages have struggled to sustain release for extended periods in biomimetic environments, especially in the presence of complex proteins. This challenge is underscored by the absence of technology for sustaining antimicrobial activity, especially in the context of orthopedic implants where long-term efficacy, extending beyond 7 days, is essential. In this study, the tunable, slow, and longer-term release of silver ions from the two-dimensional (2D) nanocapillaries of graphene oxide (GO) laminates incorporated with silver ions (Ag-GO) for antimicrobial applications are successfully demonstrated. To closely mimic a physiologically relevant serum-based environment, a novel in vitro study model using 100% fetal bovine serum (FBS) is introduced as the test medium for microbiology, biocompatibility, and bioactivity studies. To emulate fluid circulation in a physiological environment, the in vitro studies are challenged with serum exchange protocols on different days. The findings show that the Ag-GO coating can sustainably release silver ions at a minimum dosage of 10 µg cm -2  day -1 , providing an effective and sustained antimicrobial barrier for over ten days., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2. Structure-guided optimization, including several computational methods, led to the discovery of two structurally distinct series of SHP2 inhibitors binding to the previously reported allosteric tunnel binding site (Tunnel Site). One of these series was advanced to a low-nanomolar lead that inhibited tumor growth when dosed orally to mice bearing HCC827 xenografts. Furthermore, a third series of SHP2 inhibitors was discovered binding to a previously unreported site, lying at the interface of the C-terminal SH2 and catalytic domains.

Abstract: COVID-19 has led to marked increases in healthcare worker distress. Studies of these phenomena are often limited to a particular element of distress or a specific subset of healthcare workers. We administered the Moral Injury Symptom Scale for Healthcare Professionals, Copenhagen Burnout Inventory, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 via online survey to 17,000 employees of a large academic medical center between December 2021 and February 2022. A total of 1945 participants completed the survey. Across all roles, the prevalence of moral injury, burnout, depression, and anxiety were 40.9%, 35.3%-60.6%, 25.4%, and 24.8%, respectively. Furthermore, 8.1% had been bothered by thoughts that they would be better off dead or of hurting themselves for "several days" or more frequently. Healthcare workers across all roles and practice settings are experiencing unsustainable levels of distress, with 1 in 12 regularly experiencing thoughts of self-harm., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We sought to assess self-care perception consistency between patients with type 2 diabetes mellitus and their physicians and characterize the psychosocial parameters influencing their respective perceptions., Methods: We conducted a study of 627 patients with type 2 diabetes and their physicians throughout 12 family medicine residency clinics in Texas to analyze their respective perceptions of patient self-care. We utilized linear regression testing., Results: There was a lack of consistency in self-care perception between patients and physicians 31.2% of the time. Patient self-care perception was best predicted by the patients' diabetes distress scores ( P <.001) and last HbA1c ( P <.001)., Conclusion: Measuring a patient's diabetes distress may help physicians better understand a patient's self-care perception. By understanding a patient's self-care perception, the physician may be able to explore these notions of positive or negative self-care perception and even gently correct them when necessary. This may allow physicians to better align themselves with the patient, provide behavioral health interventions, and better target and communicate effective plans., Practical Implications: We suggest periodic assessment of diabetes distress and self-care perception to inform the need for education to improve self-efficacy., (© 2023 by the Society of Teachers of Family Medicine.)

Objectives: The objective of the study was to explore antimicrobial resistance gene determinant, and phenotypic antibiotic susceptibility, data for Fusobacterium necrophorum from a collection of UK strains. Antimicrobial resistance genes detected in publicly available assembled whole genome sequences were investigated for comparison., Methods: Three hundred and eighty five F. necrophorum strains (1982-2019) were revived from cryovials (Prolab). Subsequent to sequencing (Illumina) and quality checking, 374 whole genomes were available for analysis. Genomes were interrogated, using BioNumerics (bioMérieux; v 8.1), for the presence of known antimicrobial resistance genes (ARGs). Agar dilution susceptibility results for 313 F. necrophorum isolates (2016-2021) were also examined., Results: The phenotypic data for the 313 contemporary strains demonstrated potential resistance to penicillin in three isolates, using EUCAST v 11.0 breakpoints, and 73 (23%) strains using v 13.0 analysis. All strains were susceptible to multiple agents using v 11.0 guidance other than clindamycin (n = 2). Employing v 13.0 breakpoints, metronidazole (n = 3) and meropenem (n = 13) resistance were also detected. The tet(O), tet(M), tet(40), aph(3')-III, ant(6)-la and bla OXA-85 ARGs were present in publicly available genomes. tet(M), tet(32), erm(A) and erm(B) were found within the UK strains, with correspondingly raised clindamycin and tetracycline minimum inhibitory concentrations., Conclusions: Susceptibility to antibiotics recommended for the treatment of F. necrophorum infections should not be assumed. With evidence of potential ARG transmission from oral bacteria, and the detection of a transposon-mediated beta-lactamase resistance determinant in F. necrophorum, surveillance of both phenotypic and genotypic antimicrobial susceptibility trends must continue, and increase., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Mental health needs of transgender individuals can be complex with individual, social, and medical factors impacting symptoms. This study examines predictors of mood or anxiety problems among transgender individuals seeking hormone therapy (HT)., Methods: A retrospective chart review was conducted at 2 clinics providing gender-affirming HT. Cross-sectional data from initial patient encounters (N = 311) were used in this study. Bivariate correlations and multiple logistic regression analyses were carried out., Results: Transgender women (TW) were 2.2 times more likely to have mood or anxiety problems while transgender men (TM) were 2.6 times more likely as the number of medical comorbidities increased. For both TW and TM, White race significantly increased the likelihood of mood or anxiety problems. Neither previous nor current HT were associated with mood or anxiety problems for TW and TM. However, receiving multiple gender-affirming procedures decreased the likelihood of mood or anxiety problems for TM., Conclusions: Gender-affirming care and addressing comorbidities can be important aspects of mental health needs for transgender individuals., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Perceived discrimination is a significant risk factor for worse ageing health outcomes. Yet, the specific individual and relational stress pathways linking discrimination to disease are less understood, especially in the context of cardiometabolic health. We tested family stress and psychophysiological distress (negative affect and high-risk lipid/fat metabolism) as mediators linking perceived discrimination to cardiometabolic morbidity and health appraisal over 20 years for midlife adults. Using data from participants who completed the Biomarker Project (2004-2009) of the Midlife in the U.S. project, and examining data over the study's three waves (1995-1996, 2004-2006, and 2013-2014), we used structural equation modelling to test pathways for participants who reported zero cardiometabolic conditions at baseline (n = 799). Greater Time 1 discrimination was associated with greater Time 2 family strain, which was in turn associated with worse negative affect; worse Time 2 negative affect was associated with worse Time 3 health appraisal; metabolic lipids risk did not serve as an indirect pathway to Time 3 cardiometabolic morbidity (χ 2  = 147.74, p < 0.001; RMSEA = 0.056; CFI = 0.902; SRMR = 0.047). The inclusion of family in interventions to mitigate the impact of discrimination may be indicated for promoting cardiometabolic wellness., (© 2022 John Wiley & Sons Ltd.)

Background and Objectives: Despite the significant effects of homelessness on health, medical and health professions students rarely receive formal education in caring for individuals experiencing homelessness. We describe the implementation and evaluation of a novel student-run Patient Navigator Program (PNP) and its prerequisite elective that trains students in patient navigation principles specific to homelessness in the local community., Methods: We analyzed pre- and postsurvey matched responses from students immediately before and after course completion. The survey utilizes the externally-validated instruments Health Professional Attitudes Toward the Homeless Inventory (HPATHI) and the Student-Run Free Clinic Project (SRFCP) survey. We examined differences using paired t tests and Wilcoxon signed-rank tests. Students also completed separate end-of-curriculum evaluation forms assessing satisfaction with the course., Results: After completing the elective, students (n=45) demonstrated improvement in self-assessed attitude towards individuals experiencing homelessness (P=.03), specifically an increase in reported social advocacy (P<.001); and an increase in self-perceived knowledge about (P<.001), efficacy in working with (P=.01), and skills in caring for (P<.001) underserved groups. The elective also received high student satisfaction ratings., Conclusions: Formal education in patient navigation and caring for individuals experiencing homelessness improves self-assessed preparedness of future health care providers in serving homeless and underserved populations.

Purpose: The purpose of this study is to establish the psychometric properties and diagnostic accuracy of the Teen Hurt-Insult-Threaten-Scream-Sex (TeenHITSS), a 5-item measure used to screen adolescents for family violence in clinical settings., Methods: Study participants included 251 adolescent participants (n=197 not at-risk subsample; n=56 at-risk subsample), recruited from ambulatory care clinics, a medical center at-risk referral clinic, and area shelters. Participants completed a cross-sectional survey, including the TeenHITSS and Parent-Child Conflict Tactics Scales (CTSPC) questionnaires. We calculated internal reliability, validity, and sensitivity and specificity for the full sample and both subsamples for each screening instrument., Results: Concurrent validity between the TeenHITSS and CTSPC was strong (r=.71, P&lt;.000). We determined an optimal cutpoint based on sensitivity and specificity for correctly identifying abuse victims as a score of one or greater on the TeenHITSS. The TeenHITSS also proved slightly superior to the CTSPC in differentiating between victims and nonvictims of adolescent abuse (AUC=.79 vs .73, respectively)., Conclusions: The TeenHITSS screening tool performed as well as the CTSPC in correctly classifying at-risk and not-at-risk teenagers and offers much greater utility to providers by supplying an actionable cut score. The findings of this study suggest that TeenHITSS is a valid and reliable tool to screen for physical and sexual abuse in children ages 13 years and older in clinical settings and can help health care providers detect adolescent abuse and initiate intervention and prevention of future abuse.

Background: Medicolegal dilemmas faced by Sports Medicine providers differ from those of other primary care physicians in type and frequency. Exotic, high-profile challenges are widely covered in the literature and offer guidance on how to navigate challenging situations. However, there is a gap in the literature on how to approach more mundane, but nevertheless common, medicolegal dilemmas., Purpose: The purpose of this article is to provide Sports Medicine providers simple tools for determining whether a course of action is legal or ethical and offer Sports Medicine educators a model for teaching these skills., Methods: We searched U.S. federal and state law using the LexisNexis® database for laws regulating Sports Medicine practice, and PubMed for articles related to physician approaches to Sports Medicine legal and ethical challenges. Searches started with the term sports medicine, and included winnowing terms of ethics, ethical practice, ethical guidelines, law, and legal guidelines. We used current ethical practice guidelines followed by the American Medical Association and described in detail by Beauchamp and Childress., Results: We offer a framework for how to approach legal challenges in Sports Medicine and apply it to four common scenarios that Sports Medicine physicians often face. We further suggest that the profession formally address this literature gap with a standardized curriculum in Sports Medicine law., Conclusion: A curriculum using this framework and clinical vignettes provides learners and practitioners with familiarity and confidence when legal and ethical challenges arise in Sports Medicine., Competing Interests: Conflict of interest: The authors report no conflicts., (© Copyright by the American Board of Family Medicine.)

Type 2 diabetes mellitus (diabetes) is increasing in frequency and creating a significant burden on the United States healthcare system. Adverse childhood experiences (ACE) and interpersonal violence (IV) have been shown to have detrimental effects on mental and physical health. How ACE can influence IV as an adult and how this can influence the management of diabetes is not known. The purpose of the current study is to understand the relationship between violence and social determinants of health (SDoH), and its effect on patients with type 2 diabetes mellitus. A practiced-based research network (PBRN) of family medicine residency programs was utilized to collect cross-sectional data from seven family medicine residency program primary care clinics. In total, 581 participants with type 2 diabetes were recruited. A serial/parallel mediation model were analyzed. The majority of participants (58.3%) had a Hemoglobin A1c (HbA1c) that was not controlled. ACE was associated with an increase in Hurt-Insult-Threaten-Scream (HITS) scores, which in turn was positively associated with an increase in emotional burden, and finally, emotional burden decreased the likelihood that one's HbA1c was controlled (Effect = -.054, SE = .026 CI [-.115, -.013]). This indirect pathway remained significant even after controlling for several SDoH and gender. The impact of ACE persists into adulthood by altering behaviors that make adults more prone to experiencing family/partner violence. This in turn makes one more emotionally distressed about their diabetes, which influences how people manage their chronic condition. Family physicians should consider screening for both ACE and family/partner violence in those patients with poorly controlled diabetes.

Aims: This research aimed to identify the factors that impact why men do not view nursing as a career choice., Design: Qualitative description was utilized to capture the rich narratives and insight of participants., Methods: Through convenience sampling, nine New Zealand qualified male nurses within their first three years of practice were recruited. Semi-structured interviews were conducted between November 2019 and January 2020 via zoom from sites across New Zealand. All interviews were recorded and transcribed, with the data analysed using Braun and Clarke's thematic analysis., Results: The findings reflected the experiences of the research participants as they made sense of a predominantly female-dominated work environment both during their undergraduate training and prior to recruitment. The research identified two key themes: The first found that men in nursing experienced isolation due to the societal gendering of nursing influencing the participant's knowledge and understanding of what nursing was, as a career. The second theme found that for participants, nursing was not prominent in their awareness when leaving school and making career choices., Conclusion: This research indicates that nursing as a career choice for men is still underpinned by a lack of understanding of the actual role of the nurse and what nurses do, and is more supported by a societal perception that nursing is still a feminized profession. Findings can be used to make recommendations for change in the profession to strengthen diversity in the workforce and redefine the recruitment of men into nursing., Impact: This research reviewed the career choices of men in nursing and why they chose nursing as a profession. Understanding the barriers of why men do not consider nursing as a career choice assists with finding strategies in both the clinical and academic environments that can enable greater gender diversity within the nursing profession., No Patient or Public Contribution: This applies to this research as the focus was on male registered nurses only., (© 2022 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Introduction: The needs of medically-underserved populations (MUPs) are consistently outpacing the number of physicians caring for them. Medical students' motivations toward working with MUPs consistently decline as they progress through medical school. Given the shortage of doctors caring for MUPs, the objective of our study was to further investigate factors that influence medical students' motivation to work with MUPs while they progress through their education. By identifying these elements, we hope to recommend identified factors within medical education that support the development of more physicians who care for MUPs., Methods: This cross-sectional study is an assessment of medical students at the University of Texas at Southwestern Medical School (UTSW). The study utilized the Medical Student Attitudes Toward the Underserved (MSATU), a validated survey that assesses medical student motivations toward the provision of medical care to MUPs. Surveys were administered at three time points selected to represent key transition points in medical education., Results: There was no significant difference between MSATU scores among the three time points. MSATU scores were higher among students who identified as female, had higher empathy, had higher value placed on teamwork, and had higher community-centeredness. MSATU scores were also higher among students planning to specialize in primary care compared to students planning to specialize in a non-primary care field ( P =.239)., Conclusion: This study identifies factors associated with high MSATU scores within UTSW medical education, including female identification, higher empathy score, higher emphasis on teamwork, higher community-centeredness, and plans to practice primary care. Additionally, the results support maintenance of MSATU scores across all three time points. Future research should examine individual-level data to determine whether individual students are maintaining their MSATU scores or if individual fluctuations are neutralized by group changes., (© 2022 by the Society of Teachers of Family Medicine.)

In nature, plants experience rapid changes in light intensity and quality throughout the day. To maximize growth, they have established molecular mechanisms to optimize photosynthetic output while protecting components of the light-dependent reaction and CO 2 fixation pathways. Plant phenotyping of mutant collections has become a powerful tool to unveil the genetic loci involved in environmental acclimation. Here, we describe the phenotyping of the transfer-DNA (T-DNA) insertion mutant line SALK&#95;008491, previously known as nhd1-1 . Growth in a fluctuating light regime caused a loss in growth rate accompanied by a spike in photosystem (PS) II damage and increased non-photochemical quenching (NPQ). Interestingly, an independent nhd1 null allele did not recapitulate the NPQ phenotype. Through bulk sequencing of a backcrossed segregating F 2 pool, we identified an ~14-kb large deletion on chromosome 3 (Chr3) in SALK&#95;008491 affecting five genes upstream of NHD1 . Besides NHD1 , which encodes for a putative plastid Na + /H + antiporter, the stromal NAD-dependent D-3-phosphoglycerate dehydrogenase 3 ( PGDH3 ) locus was eradicated. Although some changes in the SALK&#95;008491 mutant's photosynthesis can be assigned to the loss of PGDH3, our follow-up studies employing respective single mutants and complementation with overlapping transformation-competent artificial chromosome (TAC) vectors reveal that the exacerbated fluctuating light sensitivity in SALK&#95;008491 mutants result from the simultaneous loss of PGDH3 and NHD1. Altogether, the data obtained from this large deletion-carrying mutant provide new and unintuitive insights into the molecular mechanisms that function to protect the photosynthetic machinery. Moreover, our study renews calls for caution when setting up reverse genetic studies using T-DNA lines. Although second-site insertions, indels, and SNPs have been reported before, large deletion surrounding the insertion site causes yet another problem. Nevertheless, as shown through this research, such unpredictable genetic events following T-DNA mutagenesis can provide unintuitive insights that allow for understanding complex phenomena such as the plant acclimation to dynamic high light stress., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Despite the numerous scientific and technological advances made within the last decade the attrition rates for new drug discovery remain as high as 95% for anticancer drugs. Recent drug development has been in part guided by Lipinski's Rule of 5 (Ro5) even though many approved drugs do not comply to these rules. With Covid-19 vaccine development strategy dramatically accelerating drug development perhaps it is timely to question the generic drug development process itself to find a more efficient, cost effective, and successful approach. It is widely believed that drugs permeate cells via two methods: phospholipid bilayer diffusion and carrier mediated transporters. However, emerging evidence suggests that carrier mediated transport may be the primary mechanism of drug uptake and not diffusion as long believed. Computational biology increasingly assists drug design to achieve desirable absorption, distribution, metabolism, elimination and toxicity (ADMET) properties. Perfecting drug entry into target cells as a prerequisite to intracellular drug action is a logical and compelling route and is expected to reduce drug attrition rates, particularly gaining favour amongst chronic lifelong therapeutics. Novel drug development is rapidly expanding from the utilisation of beyond the rule of five (bRo5) to pulsatile drug delivery systems and fragment based drug design. Utilising transporters as drug targets and advocating bRo5 molecules may be the solution to increasing drug specificity, reducing dosage and toxicity and thus revolutionising drug development. This review explores the development of cell surface transporter exploitation in drug development and the relationship with improved therapeutic index., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carmichael and Day.)

Purpose: The UMass Chan Medical School/New England AIDS Education and Training Center Community-Based HIV and Viral Hepatitis Fellowship was launched in 2014 to train physicians and nurse practitioners to become experts in outpatient management of HIV, hepatitis B and C, and latent tuberculosis. The purpose of this study was to identify areas of strength and improvement and understand fellows' perceptions of the program and its impact on their current positions and career trajectories., Methods: Qualitative study utilizing a semi-structured interview guide with (11) fellowship graduates (8 MDs; 3 NPs). 45 to 60 min interviews were conducted in April and May 2021, recorded and transcribed. Transcripts were analyzed for representative themes and general patterns in the data., Results: Results indicate high satisfaction with the fellowship, which left a positive and indelible impact on their careers and patient care. Fellows highlighted the program's commitment to health equity, its role in transforming them into leaders and advocates for HIV in primary care, and their ability to balance their work and training demands with their personal lives and needs. The fellowship motivated them to become more involved in public health initiatives, serve marginalized communities and reduce their health disparities. They expressed confidence in their ability to independently manage outpatient HIV, viral hepatitis B and C, and latent tuberculosis, and found areas of overlap with their work in primary care., Conclusion: As the care of people with HIV becomes more commonplace in primary care clinics, it is imperative that primary care providers receive the necessary training and education to meet this need. Our study of 11 former fellows shows that the Community-Based HIV and Viral Hepatitis Fellowship offers such training, spreads it to other institutions, and can be a model for other programs nationwide.

Background: Few studies have discussed school-based health programs in Montessori education. Lumin has a network of Montessori elementary schools serving mainly lower income families in Dallas, Texas. Since 2015, our medical school has partnered with Lumin to design and implement fitness and nutrition curricula adherent to Montessori principles., Objectives: To describe a novel Montessori school-based health program and determine avenues for improvement based on lessons learned., Methods: Led by medical students with guidance from faculty mentors, the program was developed collaboratively with Lumin leaders based on a critical need in their community and shaped with results from a cross-sectional health needs assessment among Lumin families. Data were collected to measure the impact of the program and a program evaluation was conducted after 5 years of operation to explore curriculum refinement.Results and Lessons Learned: The greatest challenges were recruitment of student volunteers, scheduling and coordination, and garnering community interest for secondary activities (e.g., health fairs)., Conclusions: Despite challenges, this partnership has resulted in a successful program that relies on faculty and student volunteers, incorporates community-based participatory research and service learning concepts, and follows Montessori principles.

Two decades ago, large cation currents were discovered in the envelope membranes of Pisum sativum L. (pea) chloroplasts. The deduced K+-permeable channel was coined fast-activating chloroplast cation channel but its molecular identity remained elusive. To reveal candidates, we mined proteomic datasets of isolated pea envelopes. Our search uncovered distant members of the nuclear POLLUX ion channel family. Since pea is not amenable to molecular genetics, we used Arabidopsis thaliana to characterize the two gene homologs. Using several independent approaches, we show that both candidates localize to the chloroplast envelope membrane. The proteins, designated PLASTID ENVELOPE ION CHANNELS (PEC1/2), form oligomers with regulator of K+ conductance domains protruding into the intermembrane space. Heterologous expression of PEC1/2 rescues yeast mutants deficient in K+ uptake. Nuclear POLLUX ion channels cofunction with Ca2+ channels to generate Ca2+ signals, critical for establishing mycorrhizal symbiosis and root development. Chloroplasts also exhibit Ca2+ transients in the stroma, probably to relay abiotic and biotic cues between plastids and the nucleus via the cytosol. Our results show that pec1pec2 loss-of-function double mutants fail to trigger the characteristic stromal Ca2+ release observed in wild-type plants exposed to external stress stimuli. Besides this molecular abnormality, pec1pec2 double mutants do not show obvious phenotypes. Future studies of PEC proteins will help to decipher the plant's stress-related Ca2+ signaling network and the role of plastids. More importantly, the discovery of PECs in the envelope membrane is another critical step towards completing the chloroplast ion transport protein inventory., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

The review investigated the barriers and facilitators associated with assessing and engaging with mental health in a rural setting. The aim is to describe and synthesize the literature that examines the experiences of adults who access or attempt to access mental health services in rural settings. A systematic search from 2010 to 2020 was conducted using CINAHL, PsycINFO, Web of Science Core Collection, PubMed, Psychology and Behavioural Sciences Collection, Google Scholar, and Scopus. PRISMA protocols located 32 relevant papers from the overall 573 first selected. Braun and Clarke (Qualitative Research in Psychology, 3:77-101, 2006) thematic analysis methodology was applied to the data resulting in two themes: first theme identified help-seeking with subthemes of stigma and locality of health services. The second theme was connectedness, inclusive of subthemes of support systems and personal identity. The review identified gender-related perspectives concerning accessing mental health support, exposing the need for more research to examine the diverse social connections and support networks in rural communities. The findings suggest the need to further explore the impediments that reduce the likelihood of accessing mental health services in rural communities., (© 2021 John Wiley & Sons Australia, Ltd.)

Objectives: The purpose of this study was to examine the perspectives of primary care physicians in Texas around vaccine acceptance and potential patient barriers to vaccination. National surveys have shown fluctuating levels of acceptance for COVID-19 vaccination, and primary care physicians could play a crucial role in increasing vaccine uptake., Design: This study employed a cross-sectional anonymous survey design to collect data using an online questionnaire. Participants were asked about vaccination practices and policies at their practice site, perceptions of patient and community acceptance and confidence in responding to patient vaccine concerns., Setting: From November 2020 to January 2021, family medicine physicians and paediatricians completed an online questionnaire on COVID-19 vaccination that was distributed by professional associations., Participants: The survey was completed by 573 practising physicians, the majority of whom identified as family medicine physicians (71.0%) or paediatricians (25.7%), who are currently active in professional associations in Texas., Results: About three-fourths (74.0%) of participants reported that they would get the vaccine as soon as it became available. They estimated that slightly more than half (59.2%) of their patients would accept the vaccine, and 67.0% expected that the COVID-19 vaccine would be accepted in their local community. The majority of participants (87.8%) reported always, almost always or usually endorsing vaccines, including high levels of intention to recommend COVID-19 vaccination (81.5%). Participants felt most confident responding to patient concerns related to education about vaccine types, safety and necessity and reported least confidence in responding to personal or religious objections to COVID-19 vaccination., Conclusions: The majority of the physicians surveyed stated that they would receive the COVID-19 vaccination when it was available to them and were confident in their ability to respond to patient concerns. With additional education, support and shifting COVID-19 vaccinations into primary care settings, primary care physicians can use the trust they have built with their patients to address vaccine hesitancy and potentially increase acceptance and uptake., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Parental vaccine hesitancy is a growing concern. Less is known about provider or practice characteristics that encounter HPV-specific vaccine-hesitant parents, the providers' confidence in responding to HPV vaccine concerns, and the attitudes and use of vaccine dismissal policies (i.e., removing patients from the practice). North Texas providers completed an online survey. Dependent variables assessed: (1) percentage of HPV vaccine-hesitant parents encountered in practice defined as substantive, or high (≥11%, or among more than one out of ten adolescent patient encounters) versus low (≤10%) levels; (2) confidence in responding to 11 HPV vaccine concerns; (3) attitudes and use of vaccine dismissal policies. Chi-square and Fisher's exact tests were conducted. Among 156 providers, 29% reported high HPV vaccine hesitancy (≥11% of patient population). Overall, providers reported being "very confident" in addressing vaccine concerns (mean: 3.37 out of 4, SD: 0.57). Mean confidence scores were significantly higher for white (vs. non-white) providers and for pediatricians (vs. family practitioners). Providers were least confident in responding to parents' religious/personal beliefs (69%). Some providers (25%) agreed with policies that dismissed vaccine-hesitant parents after repeated counseling attempts. More providers used dismissal policies for childhood (19%) than adolescent (10%) immunizations. Provider communication training should include parental religious/personal beliefs to effectively address HPV vaccine hesitancy. Other regions should examine their HPV-specific vaccine hesitancy levels to understand how the use of dismissal policies might vary between adolescent and childhood immunizations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erika Thompson is a consultant for Merck Pharmaceuticals related to HPV vaccination. She became a consultant after the paper was originally submitted for publication., (© 2021 The Author(s).)

Mixing alcohol and opioid prescription medications can have serious health consequences. This study examines demographic and geographic differences in opioid use disorders (OUD) and alcohol use disorders (AUD) in emergency department (ED) presentations in the state of Texas. Using all diagnosis codes, the study examined discharge records for ED visits related to AUD and OUD in Texas for 2017. The study classified visits into three mutually exclusive groups (AUD-only, OUD-only, and AUD/OUD) and reported the number of visits, fatalities, total charges, proportions, and rates per 100,000 population by patient demographic characteristics. Chi square statistics assessed the association between patient characteristics and ED visit type, and the study used analysis of variance to compare ED visit rates by patient demographics. The study also fitted a multinomial logistic regression w to predict ED visit type by patient demographic and geographic characteristics. There were 221,363 OUD and AUD ED visits from Texans in 2017. Among them, 3863 had both AUD and OUD. There were 2443 fatalities related to AUD-only ED visits, whereas this rate was 292 for OUD-only ED visits. The majority of these patients had Medicare and Medicaid. AUD-only ED visits were more prevalent (680.7 vs 112.5 per 100,000 population) and resulted in higher overall charges than OUD-only ED visits ($6.1 billion vs $1 billion in total charges). However, AUD/OUD ED visits resulted in higher total charges on average than either OUD-only or AUD-only ED visits. Compared to patients with outpatient discharge, patients with inpatient admissions were more likely to belong to the OUD-only visit group (OR = 1.20, 95% CI: 1.17-1.23) or the AUD/OUD visit group (OR = 2.44, 95% CI: 2.28-2.61) than to the AUD-only visit group. Compared to urban patients, rural patients were less likely to belong to OUD-related visit groups than the AUD-only visit group. In conclusions, AUD was more prevalent than OUD among ED visits and resulted in a higher number of fatalities and higher medical charges. Current health policy regarding substance use that is heavily tilted toward curbing the opioid crisis remains woefully tolerant to AUDs. While efforts to curb opioid misuse should continue, future efforts should raise awareness among ED providers of the disease burden of and social harms caused by alcoholism and alcohol addiction., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The Accreditation Council for Graduate Medical Education (ACGME) requires family medicine residents to complete a quality improvement (QI) project. There is a need for more QI training activities to be shared to meet this requirement. Our objective was to describe an activity for residents to improve women's preventive health services in an underserved clinic. Specific aims were to determine: (1) how women's receipt of preventive services compared to benchmarks, (2) physician and staff knowledge of the process and barriers to receiving services, and (3) whether an intervention to increase awareness among physicians and staff improved preventive services., Methods: Residents (N=30) evaluated charts (N=505) to determine receipt of mammograms, pap tests, colon cancer screenings, and pneumonia vaccines. We compared estimates to existing clinic benchmarks. We presented initial (preintervention) results to physicians and staff at clinic team meetings. We collected perceptions of processes and barriers to preventive services. Preintervention methods were replicated (N=100) and results were compared (postintervention)., Results: Preintervention, mammograms (72%) and Pap tests (65%) were lower than clinic benchmarks. Most (81%) women ages 65 and older received a pneumonia vaccine; however, this was lower than the national Healthy People 2020 goal. Fear, knowledge, and scheduling were identified as top barriers. Post-intervention, there was a statistically significant increase in Pap tests ( P =.0013)., Conclusion: This activity trained residents how to impact their practice through QI methods and can be used in other programs as a foundation for developing basic QI initiatives. Future efforts should focus on evaluating barriers to preventive services from the patient perspective., (© 2021 by the Society of Teachers of Family Medicine.)

After 40 years of attributing high rates of physician career dissatisfaction, attrition, alcoholism, divorce and suicide to 'burnout', there is growing recognition that these outcomes may instead be caused by moral injury. This has led to a debate about the relative diagnostic merits of these two terms, a recognition that interventions designed to treat burnout may be ineffective, and much perplexity about how-if at all-this changes anything.The current research seeks to develop the construct of moral injury outside military contexts, generate more robust validity tests and more fully describe and measure the experiences of persons exposed to moral harms. Absent from the literature is a mechanism through which to move from the collective moral injury experience of physicians to a systematic change in the structure of medical practice. To address this, after providing a brief history, definitions and contrasts between burnout, moral distress and moral injury, we review the interplay of moral and ethical codes in the context of moral injury. We conclude by suggesting that professional associations can potentially prevent moral injury by providing protections for physicians within their codes of ethics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Transgender adults have difficulty accessing health care due to multiple barriers. This study examined the health care-related needs of transgender patients in Dallas, Texas. Methods: This study examined cross-sectional data from a survey completed by 62 patients who identified as transgender. Results: Many participants reported depression (50%) and anxiety (51%). Over half did not receive preventive screenings (60%) or health care (61%) elsewhere. One-third of patients felt their primary care physician outside the clinic was not transgender-friendly. Conclusion: These findings provide evidence that transgender patients demonstrate increased reported mental health disorders and decreased access to medical care., Competing Interests: No competing financial interests exist., (Copyright 2021, Mary Ann Liebert, Inc., publishers.)

During photosynthesis, electrons travel from light-excited chlorophyll molecules along the electron transport chain to the final electron acceptor nicotinamide adenine dinucleotide phosphate (NADP) to form NADPH, which fuels the Calvin-Benson-Bassham cycle (CBBC). To allow photosynthetic reactions to occur flawlessly, a constant resupply of the acceptor NADP is mandatory. Several known stromal mechanisms aid in balancing the redox poise, but none of them utilizes the structurally highly similar coenzyme NAD(H). Using Arabidopsis (Arabidopsis thaliana) as a C3-model, we describe a pathway that employs the stromal enzyme PHOSPHOGLYCERATE DEHYDROGENASE 3 (PGDH3). We showed that PGDH3 exerts high NAD(H)-specificity and is active in photosynthesizing chloroplasts. PGDH3 withdrew its substrate 3-PGA directly from the CBBC. As a result, electrons become diverted from NADPH via the CBBC into the separate NADH redox pool. pgdh3 loss-of-function mutants revealed an overreduced NADP(H) redox pool but a more oxidized plastid NAD(H) pool compared to wild-type plants. As a result, photosystem I acceptor side limitation increased in pgdh3. Furthermore, pgdh3 plants displayed delayed CBBC activation, changes in nonphotochemical quenching, and altered proton motive force partitioning. Our fluctuating light-stress phenotyping data showed progressing photosystem II damage in pgdh3 mutants, emphasizing the significance of PGDH3 for plant performance under natural light environments. In summary, this study reveals an NAD(H)-specific mechanism in the stroma that aids in balancing the chloroplast redox poise. Consequently, the stromal NAD(H) pool may provide a promising target to manipulate plant photosynthesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

In-flight emergencies (IFE) reportedly occur globally in about 1 in 604 flights 1 . During training, family medicine (FM) residents acquire the skills necessary to counsel patients who are at risk, provide comprehensive management, and respond in emergent situations. The purpose of this study was to assess FM resident's knowledge about IFE, counseling, and attitudes towards responding to IFEs. A 15-question survey was sent to FM residents in the Dallas-Fort Worth area. IFE training options were also reviewed. Survey results revealed gaps in knowledge, yet a willingness to assist if necessary. A didactic IFE training format was found to be more achievable., (© International Association of Medical Science Educators 2021.)

Up until recently, it was believed that pharmaceutical drugs and their metabolites enter into the cell to gain access to their targets via simple diffusion across the hydrophobic lipid cellular membrane, at a rate which is based on their lipophilicity. An increasing amount of evidence indicates that the phospholipid bilayer-mediated drug diffusion is in fact negligible, and that drugs pass through cell membranes via proteinaceous membrane transporters or carriers which are normally used for the transportation of nutrients and intermediate metabolites. Drugs can be targeted to specific cells and tissues which express the relevant transporters, leading to the design of safe and efficacious treatments. Furthermore, transporter expression levels can be manipulated, systematically and in a high-throughput manner, allowing for considerable progress in determining which transporters are used by specific drugs. The ever-expanding field of miRNA therapeutics is not without its challenges, with the most notable one being the safe and effective delivery of the miRNA mimic/antagonist safely to the target cell cytoplasm for attaining the desired clinical outcome, particularly in miRNA-based cancer therapeutics, due to the poor efficiency of neo-vascular systems revolting around the tumour site, brought about by tumour-induced angiogenesis. This acquisition of resistance to several types of anticancer drugs can be as a result of an upregulation of efflux transporters expression, which eject drugs from cells, hence lowering drug efficacy, resulting in multidrug resistance. In this article, the latest available data on human microRNAs has been reviewed, together with the most recently described mechanisms for miRNA uptake in cells, for future therapeutic enhancements against cancer chemoresistance.

Alzheimer's disease (AD) is characterized by the presence of β-amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in the brain. The prevalence of the disease is increasing and is expected to reach 141 million cases by 2050. Despite the risk factors associated with the disease, there is no known causative agent for AD. Clinical trials with many drugs have failed over the years, and no therapeutic has been approved for AD. There is increasing evidence that pathogens are found in the brains of AD patients and controls, such as human herpes simplex virus-1 (HSV-1). Given the lack of a human model, the route for pathogen entry into the brain remains open for scrutiny and may include entry via a disturbed blood-brain barrier or the olfactory nasal route. Many factors can contribute to the pathogenicity of HSV-1, such as the ability of HSV-1 to remain latent, tau protein phosphorylation, increased accumulation of Aβ in vivo and in vitro , and repeated cycle of reactivation if immunocompromised. Intriguingly, valacyclovir, a widely used drug for the treatment of HSV-1 and HSV-2 infection, has shown patient improvement in cognition compared to controls in AD clinical studies. We discuss the potential role of HSV-1 in AD pathogenesis and argue for further studies to investigate this relationship.

The practice around informed consent in clinical medicine is both inconsistent and inadequate. Indeed, in busy, contemporary health care settings, getting informed consent looks little like the formal process developed over the past sixty years and presented in medical textbooks, journal articles, and academic lectures. In this article, members of the Society of Teachers of Family Medicine (STFM) Collaborative on Ethics and Humanities review the conventional process of informed consent and its limitations, explore complementary and alternative approaches to doctor-patient interactions, and propose a new model of consent that integrates these approaches with each other and with clinical practice. The model assigns medical interventions to a consent continuum defined by the discrete categories of traditional informed consent, assent, and nondissent. Narrative descriptions and clinical exemplars are offered for each category. The authors invite colleagues from other disciplines and from the academic ethics community to provide feedback and commentary., (© 2021 The Hastings Center.)

Background: Known physiological changes occur while transgender patients are taking hormone therapy (HT). However, knowledge is limited about when laboratory values stabilize and if there are any long-term impacts, making it challenging for physicians to provide adequate gender-affirming care. We aim to analyze laboratory values with HT use over 5 years and after discontinuation of HT to define when values achieve stability., Methods: We performed a multicenter retrospective analysis of 126 transgender women (TW) and 91 transgender men (TM) at consecutive clinic visits. Labs included complete metabolic panel, complete blood count, lipids, and hormone levels and were monitored for 5 years. Absolute measurement and percentage change from baseline were calculated for each analyte value. We collected the laboratory studies described from patients off HT and the duration of discontinuation to determine the time to return to baseline levels., Results: During HT, red blood cell (RBC; erythrocyte) indexes reach stable levels within 6 months (P < 0.001) and are unchanged long term. Some analytes such as HDL and platelets showed increases beyond the first year of HT in TW (P = 0.001 and P < 0.001, respectively). LDL and alanine aminotransferase increased beyond 1 year in TM (P < 0.005 and P < 0.001, respectively), whereas HDL decreased beyond 1 year (P < 0.001). Time for laboratory values to return to baseline occurred around 10 weeks., Conclusions: Most analytes reach stable levels within 6 months (RBC and creatinine), whereas others change in the long term (LDL, HDL, platelets). This information can be used to guide physicians as they monitor their transgender patients in all stages of their progress through HT., (© American Association for Clinical Chemistry 2020.)

Introduction: Home visits can improve quality of care and health outcomes and provide a unique opportunity to learn more about patients' social context and assess patients' various social determinants of health (SDH). The objectives of this study were to assess patient self-reported SDH, resident reflections on patient social status, the utility of a SDH survey during home visits, and resident comfort levels addressing patient SDH., Methods: This was a mixed-methods pilot study utilizing patient self-reported data and open-ended reflection questions. Participants included adult patients aged more than 18 years from an urban safety-net clinic and family medicine residents who provide their care., Results: We received forty-two surveys from 42 home visits. Most patients were female (61.9%) and African-American (45.2%), aged from 25 to 88 years (mean=60.24). Top patient-reported SDH include transportation, paying bills, and food insecurity. Common themes of resident responses included positive utility of the survey for assessing patient SDH; variation in comfort level when inquiring about patient SDH with positive influence from prior experience, assistance from colleagues, or prior good relations with patients; and expressed intention to include SDH assessment in future practice., Conclusions: Residents recognized the value of assessing SDH during home visits and expressed intent to include it in future practice. Thorough assessment of patient SDH may help to craft a more robust and standardized system to prioritize patients who would most benefit from receiving home visits., (© 2021 by the Society of Teachers of Family Medicine.)

Background: Patient beliefs about pain and opioids have been reported from qualitative data. To overcome limitations of unstructured assessments and small sample sizes, we determined if pain and pain medication beliefs varied by chronic pain status and opioid analgesic use (OAU) duration in primary care patients., Methods: Cross-sectional survey data obtained in 2017 and 2018 from 735 patients ≥ 18 years of age. The eight-item Barriers Questionnaire (BQ) measured beliefs about pain and pain medication. Patients reported OAU and use of other pain treatments. Multiple linear regression models estimated the association between never OAU, 1-90 day OAU and >90 day OAU and each BQ item., Results: Overall, respondents were 49.1 (±15.4) years old, 38.7 percent white, 28.4 percent African-American, 23.5 percent Hispanic, and 68.6 percent female. About one-third never used opioids, 41.8 percent had 1-90 day OAU, and 21.6 percent had > 90 day OAU. Multiple linear regression analyses showed that compared to never OAU, > 90 day OAU had lower average agreement that analgesics are addictive (β = -0.50; 95 percent CI: -0.96, -0.03), and 1-90 day OAU (β = -0.53; 95 percent CI: -0.96, -0.10) and > 90 OAU (β = -0.55; 95 percent CI: -1.04, -0.06) had lower average agreement that analgesics make people do or say embarrassing things., Conclusions: Patients with chronic OAU reported less concern about addiction and opioid-related behavior change. Never users were most likely to agree that opioids are addictive. There continues to be a need to educate patients about opioid risks. Assessing patients' beliefs may identify patients at risk for chronic OAU.

Introduction: It is widely but erroneously believed that drugs get into cells by passing through the phospholipid bilayer portion of the plasma and other membranes. Much evidence shows, however, that this is not the case, and that drugs cross biomembranes by hitchhiking on transporters for other natural molecules to which these drugs are structurally similar. Untargeted metabolomics can provide a method for determining the differential uptake of such metabolites., Objectives: Blood serum contains many thousands of molecules and provides a convenient source of biologically relevant metabolites. Our objective was to detect and identify metabolites present in serum, but to also establish a method capable of measure their uptake and secretion by different cell lines., Methods: We develop an untargeted LC-MS/MS method to detect a broad range of compounds present in human serum. We apply this to the analysis of the time course of the uptake and secretion of metabolites in serum by several human cell lines, by analysing changes in the serum that represents the extracellular phase (the 'exometabolome' or metabolic footprint)., Results: Our method measures some 4000-5000 metabolic features in both positive and negative electrospray ionisation modes. We show that the metabolic footprints of different cell lines differ greatly from each other., Conclusion: Our new, 15-min untargeted metabolome method allows for the robust and convenient measurement of differences in the uptake of serum compounds by cell lines following incubation in serum. This will enable future research to study these differences in multiple cell lines that will relate this to transporter expression, thereby advancing our knowledge of transporter substrates, both natural and xenobiotic compounds.

Background: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease., Methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic., Results: Analysis of differentially expressed genes showed that interferon signalling, and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM ( n  = 5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1 positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target ( ADK, CD28 and SLC4A10 ) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK ., Conclusion: MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

We recently introduced the Gini coefficient (GC) for assessing the expression variation of a particular gene in a dataset, as a means of selecting improved reference genes over the cohort ('housekeeping genes') typically used for normalisation in expression profiling studies. Those genes (transcripts) that we determined to be useable as reference genes differed greatly from previous suggestions based on hypothesis-driven approaches. A limitation of this initial study is that a single (albeit large) dataset was employed for both tissues and cell lines. We here extend this analysis to encompass seven other large datasets. Although their absolute values differ a little, the Gini values and median expression levels of the various genes are well correlated with each other between the various cell line datasets, implying that our original choice of the more ubiquitously expressed low-Gini-coefficient genes was indeed sound. In tissues, the Gini values and median expression levels of genes showed a greater variation, with the GC of genes changing with the number and types of tissues in the data sets. In all data sets, regardless of whether this was derived from tissues or cell lines, we also show that the GC is a robust measure of gene expression stability. Using the GC as a measure of expression stability we illustrate its utility to find tissue- and cell line-optimised housekeeping genes without any prior bias, that again include only a small number of previously reported housekeeping genes. We also independently confirmed this experimentally using RT-qPCR with 40 candidate GC genes in a panel of 10 cell lines. These were termed the Gini Genes. In many cases, the variation in the expression levels of classical reference genes is really quite huge (e.g. 44 fold for GAPDH in one data set), suggesting that the cure (of using them as normalising genes) may in some cases be worse than the disease (of not doing so). We recommend the present data-driven approach for the selection of reference genes by using the easy-to-calculate and robust GC.