Primary Care Provider Awareness and Attitudes Regarding Updated BRCA1/2 Screening Recommendations and Genetic Testing

Detection of BRCA1/2 gene mutations opens the door for breast cancer prevention; however, many high-risk individuals are not screened until after their first cancer diagnosis. The United States Preventive Services Task Force (USPSTF) updated its BRCA1/2 screening recommendations in 2019. This study explores provider awareness of this update and attitudes towards BRCA1/2 genetic testing. A survey was sent to Obstetrics/ Gynecology (Ob/Gyn), Internal Medicine (IM), and Family Medicine (FM) providers at Thomas Jefferson University Hospitals (TJUH). 66% of responders felt familiar with BRCA1/2 screening guidelines, and 38% were aware of the 2019 USPSTF update. Ob/Gyn providers were more familiar with BRCA1/2 screening recommendations compared to IM and FM providers (p= 0.003). PCP concerns centered around the potential for negative psychological and financial impact, unnecessary testing, and test result uncertainty. Results highlight the need to increase provider awareness of BRCA1/2 screening measures and guidelines while addressing concerns regarding the impact of genetic testing on patients

Intolerance of Uncertainty and Attitudes Towards Persons Living with Disabilities in Medical Students: Is There a Correlation?

INTRODUCTION: Patients living with a disability experience an illness trajectory that may be uncertain. While navigating clinical uncertainty has been well-researched, health professionals\u27 intolerance of uncertainty for patients living with disabilities has yet to be explored. We examined the relationship between medical students\u27 intolerance of uncertainty with their attitudes towards people living with disabilities to better inform curricular efforts. METHODS: We employed a survey-based design consisting of the Intolerance of Uncertainty Scale (IUS) and Disability Attitudes in Healthcare (DAHC) Scale to medical students upon completion of core clerkships (end of third-year of training). Data were de-identified. Mean DAHC and IUS scores were compared with published values RESULTS: Response rate was 97% (268/275 students). Mean IUS score did not differ from previously cited medical student scores, but mean DAHC score was significantly higher than previously cited scores. We observed a statistically-significant relationship between IUS and DAHC scores. Students with greater intolerance of uncertainty had lower scores for disability attitudes [ CONCLUSION: We identified a weak negative correlation between IUS and DAHC scores in medical students. Further research is needed to clarify findings and identify best practices that equip trainees with skills to care for patients with uncertain illness trajectories and patients living with disabilities

Populations of Radial Glial Cells Respond Differently to Reelin and Neuregulin1 in a Ferret Model of Cortical Dysplasia

Radial glial cells play an essential role during corticogenesis through their function as neural precursors and guides of neuronal migration. Both reelin and neuregulin1 (NRG1) maintain the radial glial scaffold; they also induce expression of Brain Lipid Binding Protein (BLBP), a well known marker of radial glia. Although radial glia in normal ferrets express both vimentin and BLBP, this coexpression diverges at P3; vimentin is expressed in the radial glial processes, while BLBP appears in cells detached from the ventricular zone. Our lab developed a model of cortical dysplasia in the ferret, resulting in impaired migration of neurons into the cortical plate and disordered radial glia. This occurs after exposure to the antimitotic methylazoxymethanol (MAM) on the 24th day of development (E24). Ferrets treated with MAM on E24 result in an overall decrease of BLBP expression; radial glia that continue to express BLBP, however, show only mild disruption compared with the strongly disrupted vimentin expressing radial glia. When E24 MAM-treated organotypic slices are exposed to reelin or NRG1, the severely disrupted vimentin+ radial glial processes are repaired but the slightly disordered BLBP+ processes are not. The realignment of vimentin+ processes was linked with an increase of their BLBP expression. BLBP expressing radial glia are distinguished by being both less affected by MAM treatment and by attempts at repair. We further investigated the effects induced by reelin and found that signaling was mediated via VLDLR/Dab1/Pi3K activation while NRG1 signaling was mediated via erbB3/erbB4/Pi3K. We then tested whether radial glial repair correlated with improved neuronal migration. Repairing the radial glial scaffold is not sufficient to restore neuronal migration; although reelin improves migration of neurons toward the cortical plate signaling through ApoER2/Dab1/PI3K activation, NRG1 does not

I Don\u27t Have a Diagnosis for You: Preparing Medical Students to Communicate Diagnostic Uncertainty in the Emergency Department

Introduction: Diagnostic uncertainty abounds in medicine, and communication of that uncertainty is critical to the delivery of high-quality patient care. While there has been training in communicating diagnostic uncertainty directed towards residents, a gap remains in preparing medical students to understand and communicate diagnostic uncertainty. We developed a session to introduce medical students to diagnostic uncertainty and to practice communicating uncertainty using a checklist during role-play patient conversations. Methods: This virtual session was conducted for third-year medical students at the conclusion of their core clerkships. It consisted of prework, didactic lecture, peer role-play, and debriefing. The prework included reflection prompts and an interactive online module. The role-play featured a patient complaining of abdominal pain being discharged from the emergency department without a confirmed diagnosis. Students participated in the role of patient, provider, or observer. Results: Data from an anonymous postsession survey (76% response rate; 202 of 265 students) indicated that most students (82%; 152 of 185) felt more comfortable communicating diagnostic uncertainty after the session. A majority (83%; 166 of 201) indicated the session was useful, and most (81%; 149 of 184) indicated it should be included in the curriculum. Discussion: This virtual session requires few facilitators; has peer role-play, eliminating the need for standardized patients; and is adaptable for in-person teaching. As its goal was to introduce an approach to communicating diagnostic uncertainty, not achieve mastery, students were not individually assessed for proficiency using the Uncertainty Communication Checklist. Students felt the session intervention was valuable

The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity

Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy

Intolerance of Uncertainty and Self-Compassion in Medical Students: Is There a Relationship and Why Should We Care?

Managing the uncertainty of clinical practice represents a significant source of stress for clinicians, including medical students transitioning into the clinical workplace. Self-compassion, a strategy to better cope with stress and burnout, may represent a skill that can be leveraged to better prepare learners for the uncertainty inherent in clinical practice. A negative correlation between intolerance of uncertainty and self-compassion has been demonstrated in undergraduate students and in the general population. An examination of this relationship in medical students may help inform future curricular development for addressing burnout in undergraduate medical education. We electronically administered the Intolerance of Uncertainty Short Scale and the Self-Compassion Short Form to 273 third-year medical students from a single institution and analyzed data via regression. A significant negative correlation was found between intolerance of uncertainty and self-compassion (p \u3c 0.0001). Students with higher levels of self-compassion showed lower levels of intolerance of uncertainty. This is consistent with findings in other populations. Our findings offer a starting point for designing training experiences that strengthen student self-compassion to enhance their ability to reconcile the uncertainty they will encounter in clinical practice