The Associations Between Gender Minority Stressors and PTSD Symptom Severity Among Trauma-Exposed Transgender and Gender Diverse Adults.

This study investigates associations between minority stressors, traumatic stressors, and post-traumatic stress disorder (PTSD) symptom severity in a sample of transgender and gender diverse (TGD) adults. We utilized surveys and clinical interview assessments to assess gender minority stress exposures and responses, and PTSD. Our sample (N = 43) includes adults who identified as a minoritized gender identity (i.e., 39.5% trans woman or woman, 25.6% trans man or man, 23.3% genderqueer or nonbinary, 11.6% other identity). All participants reported at least one traumatic event (i.e., life threat, serious injury, or sexual harm). The most common trauma events reported by the sample were sexual (39.5%) and physical violence (37.2%), with 40.9% of participants anchoring their symptoms to a discrimination-based event. PTSD symptom severity was positively correlated with both distal (r = 0.36, p = .017) and proximal minority stressors (r = 0.40, p < .01). Distal minority stress was a unique predictor of current PTSD symptom severity (b = 0.94, p = .017), however, this association was no longer significant when adjusting for proximal minority stress (b = 0.18, p = 0.046). This study suggests that minority stress, especially proximal minority stress, is associated with higher PTSD symptom severity among TGD adults.

Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. It is marked by extraordinary resistance to conventional therapies including chemotherapy and radiation, as well as to essentially all targeted therapies evaluated so far. More than 90% of PDAC cases harbor an activating KRAS mutation. As the most common KRAS variants in PDAC remain undruggable so far, it seemed promising to inhibit a downstream target in the MAPK pathway such as MEK1/2, but up to now preclinical and clinical evaluation of MEK inhibitors (MEKi) failed due to inherent and acquired resistance mechanisms. To gain insights into molecular changes during the formation of resistance to oncogenic MAPK pathway inhibition, we utilized short-term passaged primary tumor cells from ten PDACs of genetically engineered mice. We followed gain and loss of resistance upon MEKi exposure and withdrawal by longitudinal integrative analysis of whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and mass spectrometry data. RESULTS: We found that resistant cell populations under increasing MEKi treatment evolved by the expansion of a single clone but were not a direct consequence of known resistance-conferring mutations. Rather, resistant cells showed adaptive DNA hypermethylation of 209 and hypomethylation of 8 genomic sites, most of which overlap with regulatory elements known to be active in murine PDAC cells. Both DNA methylation changes and MEKi resistance were transient and reversible upon drug withdrawal. Furthermore, MEKi resistance could be reversed by DNA methyltransferase inhibition with remarkable sensitivity exclusively in the resistant cells. CONCLUSION: Overall, the concept of acquired therapy resistance as a result of the expansion of a single cell clone with epigenetic plasticity sheds light on genetic, epigenetic and phenotypic patterns during evolvement of treatment resistance in a tumor with high adaptive capabilities and provides potential for reversion through epigenetic targeting.

Supporting the implementation of written exposure therapy for posttraumatic stress disorder in an obstetrics-substance use disorder clinic in the Northeastern United States.

Pregnant people with comorbid posttraumatic stress disorder (PTSD) and substance use disorder (SUD) constitute a highly vulnerable population. PTSD and SUD confer risks to both the pregnant person and the fetus, including a host of physical and mental health consequences. When PTSD and SUD co-occur, potential negative impacts are amplified, and the symptoms of each may exacerbate and maintain the other. Pregnancy often increases engagement in the healthcare system, presenting a unique and critical opportunity to provide PTSD and SUD treatment to birthing people motivated to mitigate risks of losing custody of their children. This paper presents implementation process outcomes of Written Exposure Therapy (WET), a brief, scalable, and sustainable evidence-based PTSD treatment delivered to pregnant persons receiving care in an integrated obstetrical-addiction recovery program at Boston Medical Center. Trial participants (N = 18) were mostly White, non-Hispanic (61.1%), not currently working (77.8%), had a high school or lower level of education (55.5%), had an annual household income less than $35,000 (94.4%), and were living in a substance use residential program (55.6%). We examined intervention feasibility, acceptability, appropriateness, adoption; barriers and facilitators to implementation; and feedback on supporting uptake and sustainability of the intervention using coded qualitative sources (consultation field notes [N = 47] and semi-structured interviews [N = 5]) from providers involved in trial planning and treatment delivery. Results reflected high acceptability, appropriateness, and adoption of WET. Participants described system-, provider-, and patient-level barriers to implementation, offered suggestions to enhance uptake, but did not raise concerns about core components of the intervention. Findings suggest that WET is an appropriate and acceptable PTSD treatment for this difficult-to-reach, complex population, and has the potential to positively impact pregnant persons and their children.