Npas4 Transcription Factor Expression Is Regulated by Calcium Signaling Pathways and Prevents Tacrolimus-induced Cytotoxicity in Pancreatic Beta Cells.

Cytosolic calcium influx activates signaling pathways known to support pancreatic beta cell function and survival by modulating gene expression. Impaired calcium signaling leads to decreased beta cell mass and diabetes. To appreciate the causes of these cytotoxic perturbations, a more detailed understanding of the relevant signaling pathways and their respective gene targets is required. In this study, we examined the calcium-induced expression of the cytoprotective beta cell transcription factor Npas4. Pharmacological inhibition implicated the calcineurin, Akt/protein kinase B, and Ca(2+)/calmodulin-dependent protein kinase signaling pathways in the regulation of Npas4 transcription and translation. Both Npas4 mRNA and protein had high turnover rates, and, at the protein level, degradation was mediated via the ubiquitin-proteasome pathway. Finally, beta cell cytotoxicity of the calcineurin inhibitor and immunosuppressant tacrolimus (FK-506) was prevented by Npas4 overexpression. These results delineate the pathways regulating Npas4 expression and stability and demonstrate its importance in clinical settings such as islet transplantation.

Implementation rates of uro-oncology multidisciplinary meeting decisions.

OBJECTIVES: To assess implementation rates of the consensus plans made at the uro-oncology multidisciplinary meeting (MDM) of an Australian tertiary centre, and analyse obstacles to implementation. METHODS: A retrospective review was performed of all patients discussed at the uro-oncology MDM at our institution between 1 January and 30 June 2015. Rates of referral for MDM discussion after a new histological diagnosis of malignancy, categorised by tumour type, were assessed. Patient records were interrogated to confirm MDM plan implementation, with the outcomes examined being completion of MDM plan within 3 months and factors preventing implementation. RESULTS: During the enrolment period, from 291 uro-oncological procedures, 240 yielded malignant histology of which 160 (67%) were discussed at the MDM. Overall, 202 patients, including 32 females, were discussed at the uro-oncology MDM. MDM consensus plans were implemented in 184 (91.1%) patients. Reasons for deviation from the MDM plan included delay in care, patient deterioration or comorbidities, patient preference, consultant decision, loss to follow-up, and change in patient scenario due to additional new information. CONCLUSION: The MDM is increasingly important in the care of uro-oncology patients, with about two-thirds of new diagnoses currently captured. There appear to be few barriers to the implementation of consensus plans, with nearly all patients undergoing the recommended management.

Healthcare experiences of lesbian and bisexual women in Cape Town, South Africa.

Understanding the health needs and experiences of South African lesbian and bisexual women is imperative for implementing effective and inclusive public health strategies. Such understanding, however, is limited due to the exclusion of these women from most existing research on healthcare access in the region. This paper bridges that gap by investigating the healthcare experiences of lesbian and bisexual women in Cape Town. Data were gathered from 22 interviews with self-identified lesbian and bisexual community members and university students in the Cape Town area. Interviews explored obstacles women face in accessing affirming services, different experiences with public and private healthcare, fear of stigma/discrimination, availability of relevant sexual health information and suggestions to improve existing programmes. Findings suggest that South African lesbians and bisexual women may have a range of both positive and negative experiences in public and private health services, that they use protective strategies when 'coming out' and that they find that sexual health information pertinent to them is largely unavailable. These discussions contribute to a more inclusive understanding of the experiences of lesbian and bisexual women accessing healthcare and other services and help to inform providers, thereby enabling them to deliver more meaningful care to lesbian, gay, bisexual and transgender persons in South Africa.

Improving Family Medicine Residents' Provision of Gender-Affirming Care.

BACKGROUND AND OBJECTIVES: Family physicians are uniquely poised to provide gender-affirming care (GAC) to transgender and nonbinary patients, but current undergraduate and graduate medical education in this field is lacking. Little is known about the impact of various GAC curricula on the clinical care provided by resident physicians. We aimed to assess the efficacy of a multimodal educational framework on the quality of GAC provided by residents at a large academic family medicine program. METHODS: This pilot study used chart review to assess the impact of a multifaceted educational intervention around GAC in an academic family medicine practice. Components included faculty-specific didactics, resident feedback and didactics, standardized note templates, and compiled resources. We completed pre- and postintervention analysis of resident-led GAC encounters using a novel rubric based on standards of care and compared these results using descriptive statistics. RESULTS: Following a multimodal educational intervention, residents demonstrated improvement in multiple domains of gender-affirming care, including documenting informed consent, counseling on pregnancy and contraception, and laboratory monitoring for patients initiating gender-affirming hormone therapy. CONCLUSIONS: This widespread improvement suggested that a multimodal approach to resident and faculty education may help enhance the quality of GAC provided by family medicine residents. Chart review offers a feasible and effective method for identifying gaps in resident knowledge and documentation in GAC. Further research should specifically explore faculty development in this area and expanded patient-centered quality metrics and outcomes that encompass GAC.

Gender disparities in neuropsychological assessment research in drug abuse populations: A systematic review.

Objective: To systematically review the literature on the neurocognitive effects of drug use to determine if there are significant gender differences. Methods: In April 2023, we conducted a broad search in MEDLINE (via PubMed), PsycINFO, and Embase for original research studies that used objective neuropsychological assessment to evaluate neurocognition in persons with drug use. Data extraction was performed in a masked, duplicate fashion. Results: Our initial search returned 22,430 records, of which 273 articles were included in our analysis. We found significant underrepresentation of women as participants in the studies. Twenty-one percent of studies had exclusively male participants; when women were included, they averaged only 23% of the sample. Only 49 studies sufficiently documented an analysis of their results by gender; due to the heterogeneity in study characteristics, no conclusions about cognitive differences between women and men could be made. Conclusions: Women are significantly underrepresented in the research on cognition in drug use. Increased efforts to include more women participants and consistent analysis and reporting of data for potential gender differences will be required to close this gap in knowledge, which may lead to improved substance abuse treatment approaches for women.

Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Environmentally relevant arsenic exposure affects morphological and molecular endpoints associated with reproduction in the Western mosquitofish, Gambusia affinis.

Arsenic (As) exposure, even at low environmentally relevant levels, may cause detrimental health outcomes through developmental toxicity and by acting as an endocrine disrupting compound (EDC). Although several studies indicate that wildlife bioaccumulate As, few evaluate the health impact on fish species in their natural environment. In the U.S., As has a drinking water regulatory limit of 10 µg/L. In many parts of Arizona, surface water and groundwater have naturally elevated levels of As from geologic deposits and contamination is exacerbated by anthropogenic activity. In aquatic environments, the Western mosquitofish, Gambusia affinis, is a good bioindicator for EDC exposure because of the distinct androgen-related development of an intromittent organ, the gonapodium, in males. We evaluated morphological and reproductive outcomes in mosquitofish exposed to As. In a laboratory experiment, juvenile male mosquitofish were exposed to sodium arsenite (0 µg/L, 0.75 µg/L, 7.50 µg/L, and 75 µg/L) for 30 days, and in a field study, populations of adult male mosquitofish were collected in Arizona waterways with As levels above and below the World Health Organization's regulatory limit. In both studies, higher As exposure was significantly associated with altered hepatosomatic indices, altered fish morphology, shortened gonopodia, and lower gonopodia-somatic indices. In the field experiment, populations from surface water with higher As concentrations exhibited lower condition factors, lower gonadal-somatic indices, distinct gonopodia shapes, and altered estrogen receptor alpha and vitellogenin gene expression; androgen receptor expression was unchanged. Together, laboratory and field results suggest that As exposure at environmentally-relevant levels affects general growth and reproductive development in mosquitofish. Observed effects may further influence individual health, mobility, or reproductive function, and because G. affinis is a species known to tolerate and adapt to a wide range of environments, it serves as a local bioindicator species as well as a model organism for parallel field and laboratory studies.

Electropolymerized Molecularly Imprinted Polymer Synthesis Guided by an Integrated Data-Driven Framework for Cortisol Detection.

Molecularly imprinted polymers (MIPs), often called "synthetic antibodies", are highly attractive as artificial receptors with tailored biomolecular recognition to construct biosensors. Electropolymerization is a fast and facile method to directly synthesize MIP sensing elements in situ on the working electrode, enabling ultra-low-cost and easy-to-manufacture electrochemical biosensors. However, due to the high dimensional design space of electropolymerized MIPs (e-MIPs), the development of e-MIPs is challenging and lengthy based on trial and error without proper guidelines. Leveraging machine learning techniques in building the quantitative relationship between synthesis parameters and corresponding sensing performance, e-MIPs' development and optimization can be facilitated. We herein demonstrate a case study on the synthesis of cortisol-imprinted polypyrrole for cortisol detection, where e-MIPs are fabricated with 72 sets of synthesis parameters with replicates. Their sensing performances are measured using a 12-channel potentiostat to construct the subsequent data-driven framework. The Gaussian process (GP) is employed as the mainstay of the integrated framework, which can account for various uncertainties in the synthesis and measurements. The Sobol index-based global sensitivity is then performed upon the GP surrogate model to elucidate the impact of e-MIPs' synthesis parameters on sensing performance and interrelations among parameters. Based on the prediction of the established GP model and local sensitivity analysis, synthesis parameters are optimized and validated by experiment, which leads to remarkable sensing performance enhancement (1.5-fold increase in sensitivity). The proposed framework is novel in biosensor development, which is expandable and also generally applicable to the development of other sensing materials.

Taking Our Own Temperature: Using a Residency Climate Survey to Support Minority Voices.

BACKGROUND AND OBJECTIVES: Recruitment of underrepresented minorities (URM) in medicine has risen to the forefront as a strategy to address health inequities, but the experiences of URM residents within their own programs are poorly understood. We describe the development and implementation of a diversity, equity, and inclusion (DEI) climate survey at our residency program, the results of which have informed our DEI efforts. METHODS: A resident-faculty work group collaboratively developed an 81-item questionnaire, informed by other institutional climate surveys. We administered the survey annually from 2018 through 2021 to all residents and faculty at our large academic family medicine residency program. The anonymous survey covered six key areas: general climate, climate for specific group, personal experience with discrimination and harassment, recruitment, burnout, and curriculum. RESULTS: Average response rates were 84% and 50% for residents and faculty, respectively. Survey results show low satisfaction with resident and faculty diversity; higher rates of burnout for respondents who self-identify as URM, persons of color (POC), and/or LGBTQ; and racial and gender differences in experiences of workplace discrimination and sexual harassment. CONCLUSIONS: Instituting an annual internal climate survey at our residency has provided invaluable information regarding the perspectives and experiences of our residents and faculty that has informed our DEI initiatives. We envision that our survey will inform continual improvement and serve as a model for similar introspection leading to meaningful action at other programs.

Rehabilitation approach in oropharyngeal cancer: Case report.

INTRODUCTION: Cancer rehabilitation can be preventive, restorative, supportive, and palliative. The rehabilitation goals change as the cancer pathway alters. Following any treatment for head and neck cancer, a physiatrist plays an essential role in preventing various complications and helping patients to mitigate impairments and restore function, optimizing their quality of life. CASE DESCRIPTION: This is a case study of a 56-year-old man with squamous cell cancer of the tongue managed with glossectomy, chemotherapy, and radiotherapy. He also has a remote history of acute myeloid leukemia involving the central nervous system, presenting with seizure and infective endocarditis. He underwent a sternotomy and an aortic valve replacement. His postoperative course was complicated by sternal infection, bradycardia with agonal breathing, and a weak pulse, for which the patient underwent cardiopulmonary resuscitation and achieved return of spontaneous circulation and was intubated and managed with antibiotics. He had a tracheostomy and underwent aggressive pulmonary toileting and suctioning in acute care. As the patient stabilized, he was transferred to in-patient rehabilitation. INTERVENTIONS: While the patient was in the in-patient rehabilitation unit, cancer rehabilitation issues were addressed, including swallowing, pulmonary rehabilitation, management of upper-extremity deep venous thrombosis and infection, bowel and bladder issues, skin care, and evaluation of mental status. The patient's cancer prognosis and future were discussed in collaboration with his oncologist. He was discharged with a palliative care plan. CONCLUSION: This report illustrates the significance of physical medicine and rehabilitation in management of cancer patients, as most cancer patients experience some deconditioning that results in physical challenges. As the prognosis for most types of cancers improves, it becomes more important to ensure that all cancer patients regain maximum function in the broadest sense to maximize their independence.

Neuroimaging and Violence.

Violence is a serious public health issue across the world. This article assists clinicians in understanding the most up-to-date literature regarding structural and functional brain theories related to risk of violence. In this article, we review anatomic regions of the brain that have been implicated in violence and associated personality constructs associated with violence. We discuss different imaging techniques that have been used to uncover abnormal brain volume, associations, and functions throughout the brain in samples with violence history or risk. Finally, we discuss implications of these findings both for treatment considerations and future research directions.

Anatomical variations in the brachial plexus roots: implications for diagnosis of neurogenic thoracic outlet syndrome.

Neurogenic thoracic outlet syndrome (NTOS) is the most common type of TOS. Typically it results from impingement of the neurovasculature as it passes between the anterior and middle scalene muscles; this classic anatomical relationship being the foundation of clinical diagnosis. Positional testing relies on vascular compromise occurring when the subclavian artery is compressed in this space. This study describes several anatomical variations observed in this relationship. Sixty-five cadavers (35m/30f) were assessed to determine the frequency and extent of brachial plexus branching variants. A total of thirty-one variations from "classic" anatomy were observed (47.7%). In two specimens (3.1%), the entire superior trunk coursed completely anterior to the anterior scalene in a position of relative vulnerability. In 27 instances, a portion of or the entire superior trunk pierced the anterior scalene muscle, and in two, the middle trunk also pierced the muscle belly. Interestingly, while two bilateral branching variations were observed, the majority occurred unilaterally, and almost exclusively on the left side. There were no sex differences in frequency. The high frequency of these variations and their potential to predispose patients to neurogenic TOS suggest that current diagnostic methods may be insufficient in clinical diagnosis. Due to lack of vascular compromise, patients with the piercing variant would not display positive signs on the traditional positional tests. The use of ultrasound to determine the route of the brachial plexus could determine whether this variation is present in patients who suffer from TOS symptoms but lack a diagnosis based on traditional positional testing.