Tuberous sclerosis complex (TSC) is a tumor-suppressor syndrome affecting multiple organs, including the brain, skin, kidneys, heart, and lungs. TSC is associated with mutations in or resulting in hyperactivation of mTOR complex 1 (mTORC1). Clinical trials demonstrate that mTORC1 inhibitors decrease tumor volume and stabilize lung function in TSC patients; however, mTOR inhibitors are cytostatic not cytocidal, and long-term benefits and toxicities are uncertain. Previously, we identified rapamycin-insensitive upregulation of cyclooxygenase 2 (PTGS2/COX2) and prostaglandin E2 (PGE2) production in TSC2-deficient cells and postulated that the action of excess PGE2 and its cognate receptors (EP) contributes to cell survival. In this study, we identify upregulation of EP3 (PTGER3) expression in TSC2-deficient cells, TSC renal angiomyolipomas, lymphangioleiomyomatosis lung nodules, and epileptic brain tubers. TSC2 negatively regulated EP3 expression via Rheb in a rapamycin-insensitive manner. The EP3 antagonist, L-798106, selectively suppressed the viability of TSC2-deficient cells and decreased the lung colonization of TSC2-deficient cells. Collectively, these data reveal a novel function of TSC2 and Rheb in the regulation of EP3 expression and cell viability. Therapeutic targeting of an aberrant PGE2-EP3 signaling axis may have therapeutic benefit for TSC patients and for other mTOR-hyperactive neoplasms. .

Objective:Anti–N-methyl-d-aspartate receptor encephalitis is a rare but emerging cause of autoimmune encephalitis. Our objective is to present a case of this rare disease while highlighting the importance of an aggressive search for underlying malignancy as well as the common mischaracterization of primary psychiatric illness that occurs in these patients.Methods:A young Caucasian female with no known psychiatric history presented with acute onset of seizures and psychosis.Results:Magnetic resonance imaging abdomen and pelvis showed a 6-mm ovarian teratoma which was not visualized on initial computed tomographic scans. Pathology was consistent with a mature teratoma. Both serum and cerebrospinal fluid N-methyl-d-aspartate receptor antibodies were positive.Conclusion:An exhaustive search for underlying malignancy and specifically ovarian teratoma in young women should be completed in these patients. Diagnosis often is delayed given the prominent psychiatric manifestations and providers should be aware and strongly consider this in younger women with acute onset of neuropsychiatric symptoms.

Background Women are underrepresented within internal medicine (IM). Whether women leaders attract women trainees is not well explored. Objective To characterize leader and trainee gender across US academic IM and to investigate the association of leader gender with trainee gender. Design Cross-sectional study. Participants Leaders (chairs, chiefs, program directors (PDs)) in 2018 and trainees (residents, fellows) in 2012–2016 at medical school-affiliated IM and seven IM fellowship programs. Exposure Leadership (chair/chief and program director; and, for resident analyses, fellow) gender. Main Measures Our primary outcome was percent women trainees (IM residents and, separately, subspecialty fellows). We used standard statistics to describe leadership and trainee gender. We created separate multivariable linear regressions to evaluate associations of leader gender and percent women fellows with percent women IM residents. We then created separate multivariable multilevel models (site as a random effect) to evaluate associations of leader gender with percent women subspecialty fellows. Key Results Our cohort consisted of 940 programs. Women were 13.4% of IM chairs and <25% of chiefs in each fellowship subspecialty (cardiology: 2.6%; gastroenterology: 6.6%; pulmonary and critical care: 10.7%; nephrology: 14.4%; endocrinology: 20.6%; hematology-oncology: 23.2%; infectious diseases: 24.3%). IM PDs were 39.7% women; fellowship PDs ranged from nearly 25% (cardiology and gastroenterology) to nearly 50% (endocrinology and infectious disease) women. Having more women fellows (but not chairs or PDs) was associated with having more women residents (0.3% (95% CI: 0.2–0.5%) increase per 1% fellow increase, p <0.001); this association remained after adjustment (0.3% (0.1%, 0.4%), p =0.001). In unadjusted analyses, having a woman PD (increase of 7.7% (4.7%, 10.6%), p <0.001) or chief (increase of 8.9% (4.6%, 13.1%), p <0.001) was associated with an increase in women fellows; after adjustment, these associations were lost. Conclusions Women held a minority of leadership positions in academic IM. Having women leaders was not independently associated with having more women trainees. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-022-07635-w.