Apo-Ghrelin Receptor Forms Heteromers with DRD2 in Hypothalamic Neurons and Is Essential for Anorexigenic Effects of DRD2 Agonism

SummaryWe identified subsets of neurons in the brain that coexpress the dopamine receptor subtype-2 (DRD2) and the ghrelin receptor (GHSR1a). Combination of FRET confocal microscopy and Tr-FRET established the presence of GHSR1a:DRD2 heteromers in hypothalamic neurons. To interrogate function, mice were treated with the selective DRD2 agonist cabergoline, which produced anorexia in wild-type and ghrelin−/− mice; intriguingly, ghsr−/− mice were refractory illustrating dependence on GHSR1a, but not ghrelin. Elucidation of mechanism showed that formation of GHSR1a:DRD2 heteromers allosterically modifies canonical DRD2 dopamine signaling resulting in Gβγ subunit-dependent mobilization of [Ca2+]i independent of GHSR1a basal activity. By targeting the interaction between GHSR1a and DRD2 in wild-type mice with a highly selective GHSR1a antagonist (JMV2959) cabergoline-induced anorexia was blocked. Inhibiting dopamine signaling in subsets of neurons with a GHSR1a antagonist has profound therapeutic implications by providing enhanced selectivity because neurons expressing DRD2 alone would be unaffected

Protecting Patients from Physicians Who Inflict Harm: New Legal Resources for State Medical Boards

State medical boards (SMBs) protect the public by ensuring that physicians uphold appropriate standards of care and ethical practice. Despite this clear purpose, egregious types of wrongdoing by physicians are alarmingly frequent, harmful, and under-reported. Even when egregious wrongdoing is reported to SMBs, it is unclear why SMBs sometimes fail to promptly remove seriously offending physicians from practice. Legal and policy tools that are targeted, well-informed, and actionable are urgently needed to help SMBs more effectively protect patients from egregious wrongdoing by physicians.Past reviews of SMB performance have identified features of SMBs associated with higher rates of severe disciplinary actions against physicians, including political and professional independence and adequate funding and staffing. However, there has been little attention paid to elements of the state level legal framework that governs SMB licensing and disciplinary function, or what legal or policy tools would make SMBs more effective at protecting patients in serious cases.This Article offers solutions in the form of model language with commentary for five high-impact statutory provisions that address board composition and function, reporting to the board, and adjudication of disciplinary matters. It brings together consensus recommendations from an expert panel, the results of legal mapping of relevant state laws, and original legal and policy analysis. The model provisions and commentary are intended to serve as a new resource for SMBs, state legislatures, and other policymakers to encourage and support examination of existing medical practice acts to improve SMB function and better protect patients from harmful physicians. Note:Funding Information: The research was supported by a grant from the Greenwall Foundation..Declaration of Interests: None to declare

Pricing Policy: a Tobacco Control Guide

This tobacco control guide, co-published by CPHSS and the Public Health Law Center (formerly Tobacco Control Legal Consortium) is designed to help state and local tobacco control staff build effective and sustainable comprehensive tobacco control programs. This guide focuses on the role pricing policies can play as part of a comprehensive tobacco control program.https://openscholarship.wustl.edu/cphss/1046/thumbnail.jp

Enabling qualitative research data sharing using a natural language processing pipeline for deidentification: Moving beyond HIPAA Safe Harbor identifiers

OBJECTIVE: Sharing health research data is essential for accelerating the translation of research into actionable knowledge that can impact health care services and outcomes. Qualitative health research data are rarely shared due to the challenge of deidentifying text and the potential risks of participant reidentification. Here, we establish and evaluate a framework for deidentifying qualitative research data using automated computational techniques including removal of identifiers that are not considered HIPAA Safe Harbor (HSH) identifiers but are likely to be found in unstructured qualitative data. MATERIALS AND METHODS: We developed and validated a pipeline for deidentifying qualitative research data using automated computational techniques. An in-depth analysis and qualitative review of different types of qualitative health research data were conducted to inform and evaluate the development of a natural language processing (NLP) pipeline using named-entity recognition, pattern matching, dictionary, and regular expression methods to deidentify qualitative texts. RESULTS: We collected 2 datasets with 1.2 million words derived from over 400 qualitative research data documents. We created a gold-standard dataset with 280K words (70 files) to evaluate our deidentification pipeline. The majority of identifiers in qualitative data are non-HSH and not captured by existing systems. Our NLP deidentification pipeline had a consistent F1-score of ∼0.90 for both datasets. CONCLUSION: The results of this study demonstrate that NLP methods can be used to identify both HSH identifiers and non-HSH identifiers. Automated tools to assist researchers with the deidentification of qualitative data will be increasingly important given the new National Institutes of Health (NIH) data-sharing mandate

Barriers and facilitators to qualitative data sharing in the United States: A survey of qualitative researchers

Qualitative health data are rarely shared in the United States (U.S.). This is unfortunate because gathering qualitative data is labor and time-intensive, and data sharing enables secondary research, training, and transparency. A new U.S. federal policy mandates data sharing by 2023, and is agnostic to data type. We surveyed U.S. qualitative researchers (N = 425) on the barriers and facilitators of sharing qualitative health or sensitive research data. Most researchers (96%) have never shared qualitative data in a repository. Primary concerns were lack of participant permission to share data, data sensitivity, and breaching trust. Researcher willingness to share would increase if participants agreed and if sharing increased the societal impact of their research. Key resources to increase willingness to share were funding, guidance, and de-identification assistance. Public health and biomedical researchers were most willing to share. Qualitative researchers need to prepare for this new reality as sharing qualitative data requires unique considerations

Sexual violation of patients by physicians: A mixed-methods, exploratory analysis of 101 cases

A mixed-method, exploratory design was used to examine 101 cases of sexual violations in medicine. The study involved content analysis of cases to characterize the physicians, patient-victims, the practice setting, kinds of sexual violations, and consequences to the perpetrator. In each case, a criminal law framework was used to examine how motives, means, and opportunity combined to generate sexual misconduct. Finally, cross-case analysis was performed to identify clusters of causal factors that explain specific kinds of sexual misconduct. Most cases involved a combination of five factors: male physicians (100%), older than the age of 39 (92%), who were not board certified (70%), practicing in nonacademic settings (94%) where they always examined patients alone (85%). Only three factors (suspected antisocial personality, physician board certification, and vulnerable patients) differed significantly across the different kinds of sexual abuse: personality disorders were suspected most frequently in cases of rape, physicians were more frequently board certified in cases of consensual sex with patients, and patients were more commonly vulnerable in cases of child molestation. Drawing on study findings and past research, we offer a series of recommendations to medical schools, medical boards, chaperones, patients, and the national practitioners database

Psychological and Genetic Predictors of Pain Tolerance

Previous studies have shown associations between genetic polymorphisms and pain tolerance, but psychological evaluations are seldom measured. The objective of this study was to determine the independent effects of demographic, psychological, and genetic predictors of cold noxious pain tolerance. Healthy subjects (n = 89) completed the Pain Catastrophizing Scale (PCS) and Fear of Pain Questionnaire (FPQ-III), underwent genotyping for candidate single nucleotide polymorphisms (SNPs), and completed a cold-pressor test in a 1-2 degrees C water bath for a maximum of 3 minutes. The primary outcome measure was pain tolerance, defined as the maximum duration of time subjects left their nondominant hand in the cold-water bath. Cox proportional hazards regression indicated that female sex, Asian race, and increasing PCS and FPQ-III scores were associated with lower pain tolerance. No candidate SNP was significantly associated with pain tolerance. Future genetic studies should include demographic and psychological variables as confounders in experimental pain models.Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]