BACKGROUND
Development of treatments for obsessive-compulsive disorder (OCD) is hampered by a lack of mechanistic understanding about this prevalent neuropsychiatric condition. Although circuit changes such as elevated frontostriatal activity are linked to OCD, the underlying molecular signaling that drives OCD-related behaviors remains largely unknown. Here, we examine the significance of type 5 metabotropic glutamate receptors (mGluR5s) for behavioral and circuit abnormalities relevant to OCD.
METHODS
Sapap3 knockout (KO) mice treated acutely with an mGluR5 antagonist were evaluated for OCD-relevant phenotypes of self-grooming, anxiety-like behaviors, and increased striatal activity. The role of mGluR5 in the striatal circuit abnormalities of Sapap3 KO mice was further explored using two-photon calcium imaging to monitor striatal output from the direct and indirect pathways. A contribution of constitutive signaling to increased striatal mGluR5 activity in Sapap3 KO mice was investigated using pharmacologic and biochemical approaches. Finally, sufficiency of mGluR5 to drive OCD-like behavior in wild-type mice was tested by potentiating mGluR5 with a positive allosteric modulator.
RESULTS
Excessive mGluR5 signaling underlies OCD-like behaviors and striatal circuit abnormalities in Sapap3 KO mice. Accordingly, enhancing mGluR5 activity acutely recapitulates these behavioral phenotypes in wild-type mice. In Sapap3 KO mice, elevated mGluR5 signaling is associated with constitutively active receptors and increased and imbalanced striatal output that is acutely corrected by antagonizing striatal mGluR5.
CONCLUSIONS
These findings demonstrate a causal role for increased mGluR5 signaling in driving striatal output abnormalities and behaviors with relevance to OCD and show the tractability of acute mGluR5 inhibition to remedy circuit and behavioral abnormalities.
OBJECTIVETo define the current proportion of underrepresented minority (URM) academic urologists in leadership positions.
METHODSA cross-sectional observational study of leadership positions in active United States Urology Residency Programs in 2020 was conducted. Academic urologists in leadership positions were electronically mailed a survey asking about personal and professional demographics. Self-reported variables including administrative position, race, and ethnicity were collected and analyzed.
RESULTSOver the study period, 133 urologists completed the survey out of a possible 320 academic urologists for a response rate of 41.6%. Overall, African-Americans represented 9.0%, Hispanics represented 3.8%, and American Indians/Alaska Natives made up 0.8% of leadership roles in the study sample. African-Americans comprised 8.5% (4 of 47) and Hispanics comprised 2.1% (1 of 47) of department chairs. African-Americans made up 7.4% (4 of 54) and Hispanics made up 1.9% (1 of 54) of program directors. The highest proportion of African-Americans in leadership positions was seen in oncology (18.2%), minimally invasive surgery (18.2%), and general urology (10%).The only subspecialties with Hispanics in leadership positions were in andrology/sexual medicine (16.7%) and female urology (15.4%). There were no reported URMs in leadership positions in endourology, neurourology, pediatrics, and reconstructive urology.
CONCLUSIONSTo our knowledge, this study is the first to quantify the representation of URM urologists in academic leadership. There are multiple subspecialties without URMs in leadership positions. This information is vital to understanding the presence and lack of racial representation of the leadership of our field. UROLOGY 00: 1−7, 2021.
Brief Abstract
Scrotal lymphangioma circumscriptum (LC) is an uncommon, benign skin disorder with multiple treatment modalities. We present staged treatment of extensive LC of the scrotum using staged carbon dioxide (CO2) laser ablation. We achieved near complete resolution of lesions with excellent cosmesis in the span of four months, from presentation to treatment. Therefore, the use of staged CO2 laser ablation should be strongly considered when LC presents in the genitourinary (GU) system, as it can lead to good cosmetic outcomes and prompt symptomatic relief in a short period of time.
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