ABSTRACT
A retrospective (N = 140) and a prospective (N = 102) observational Israeli study by Bar-Sela and colleagues about cannabis potentially adversely impacting the response to immunotherapy have together been cited 202 times, including by clinical practice guidelines. There have also been concerns on PubPeer outlining irregularities and unverifiable information in their statistics and numerous errors in calculating percentages. This reanalysis attempted to verify the data analysis while including non-parametric statistics. The corrected prospective report contained 22 p-values, but only one (4.5%) could be verified despite the authors being transparent about the N and statistics employed. Cannabis users were significantly (p < 0.0025) younger than non-users, but this was not reported in the retrospective report. There were also errors in percentage calculations (e.g., 13/34 reported as 22.0% instead of 38.2%). Overall, these observational investigations, and especially the prospective, appear to contain gross inaccuracies which could impact the statistical decisions (i.e., significant findings reported as non-significant or vice-versa). Although it is mechanistically plausible that cannabis could have immunosuppressive effects which inhibit the response to immunotherapy, these two reports should be viewed cautiously. Larger prospective studies of this purported drug interaction that account for potential confounds (e.g., greater nicotine smoking among cannabis users) may be warranted.
ABSTRACT
Introduction Transgender patients face substantial systemic healthcare barriers and inadequate care from providers who often demonstrate clinical gaps in the medical needs of the transgender community. Providing interventions in which affirming transgender healthcare is explored, is crucial to delivering competent transgender-patient care and building compassionate physician-patient relationships. The Northeast Pennsylvania (NEPA) Trans Health Conference was established to address the growing need for an educational forum where transgender people could voice their narratives. In this educational intervention study, changes in the knowledge, attitudes, and beliefs about the psychosocial and medical needs of the transgender community in first-year undergraduate medical students were examined pre- and post-trans health conference attendance. Materials and methods In the late spring of both 2018 and 2019, first-year medical students attended the NEPA Trans Health Conference, hosted by the Geisinger Commonwealth School of Medicine (GCSOM). Student knowledge, attitudes, and beliefs, regarding the healthcare needs of the transgender community were evaluated prior to and directly after the conference (intervention). Though the surveys shared thematic similarities, the 2018 and 2019 surveys were different and thus were not used comparatively. Results In 2018, 35.24% of first-year medical students (37/105 participants) completed both the pre- and post-survey. Overall, 62.5% (5/8) of survey items yielded significant differences. In 2019, 25.5%, of first-year medical students (28/110 participants) completed both the pre- and post-survey and 47.6% (9/21) of survey items yielded significant results. Overall, although the majority of first-year medical students displayed positive attitudes toward trans people pre-intervention, the students also demonstrated increased knowledge, empathy, and understanding of the transgender healthcare narrative post-intervention. Conclusion Providing medical students with a humanistic intervention within the medical curriculum that is focused on the transgender person, in addition to their past and present healthcare experiences, offers a bridge between academic content and providing inclusive gender-affirming healthcare to all patients.
ABSTRACT
During myocardial ischemia, upregulation of the hedgehog (Hh) pathway promotes neovascularization and increases cardiomyocyte survival. The canonical Hh pathway activates a transcriptional program through the Gli family of transcription factors by derepression of the seven-transmembrane protein smoothened (Smo). The mechanisms linking Smo to Gli are complex and, in some cell types, involve coupling of Smo to Gi proteins. In the present study, we investigated, for the first time, the transcriptional response of cardiomyocytes to sonic hedgehog (Shh) and the role of Gi protein utilization. Our results show that Shh strongly activates Gli1 expression by quantitative PCR in a Smo-dependent manner in neonatal rat ventricular cardiomyocytes. Microarray analysis of gene expression changes elicited by Shh and sensitive to a Smo inhibitor identified a small subset of 37 cardiomyocyte-specific genes regulated by Shh, including some in the PKA and purinergic signaling pathways. In addition, neonatal rat ventricular cardiomyocytes infected with an adenovirus encoding GiCT, a peptide that impairs receptor-Gi protein coupling, showed reduced activation of Hh targets. In vitro data were confirmed in transgenic mice with cardiomyocyte-inducible GiCT expression. Transgenic GiCT mice showed specific reduction of Gli1 expression in the heart under basal conditions and failed to upregulate the Hh pathway upon ischemia and reperfusion injury, unlike their littermate controls. This study characterizes, for the first time, the transcriptional response of cardiomyocytes to Shh and establishes a critical role for Smo coupling to Gi in Hh signaling in the normal and ischemic myocardium.
