Two C. elegans DM domain proteins, DMD-3 and MAB-3, function in late stages of male somatic gonad development.

To bring about sexual dimorphism in form, information from the sex determination pathway must trigger sex-specific modifications in developmental programs. DM-domain encoding genes have been found to be involved in sex determination in a multitude of animals, often at the level of male somatic gonad formation. Here we report our findings that the DM-domain transcription factors MAB-3 and DMD-3 function together in multiple steps during the late stages of C. elegans male somatic gonad development. Both mab-3 and dmd-3 are expressed in the linker cell and hindgut of L4 males and dmd-3 is also expressed in presumptive vas deferens cells. Furthermore, dmd-3, but not mab-3, expression in the linker cell is downstream of nhr-67, a nuclear hormone receptor that was previously shown to control late stages of linker cell migration. In mab-3; dmd-3 double mutant males, the last stage of linker cell migration is partially defective, resulting in aberrant linker cell shapes and often a failure of the linker cell to complete its migration to the hindgut. When mab-3; dmd-3 double mutant linker cells do complete their migration, they fail to be engulfed by the hindgut, indicating that dmd-3 and mab-3 activity are essential for this process. Furthermore, linker cell death and clearance are delayed in mab-3; dmd-3 double mutants, resulting in the linker cell persisting into adulthood. Finally, DMD-3 and MAB-3 function to activate expression of the bZIP transcription factor encoding gene zip-5 and downregulate the expression of the zinc metalloprotease ZMP-1 in the linker cell. Taken together, these results demonstrate a requirement for DM-domain transcription factors in controlling C. elegans male gonad formation, supporting the notion that the earliest DM-domain genes were involved in male somatic gonad development in the last common ancestor of the bilaterians.

Vaginal estrogen use for genitourinary symptoms in women with a history of uterine, cervical, or ovarian carcinoma.

OBJECTIVE: Menopausal symptoms may adversely affect quality of life and health in women diagnosed with a gynecologic malignancy. The aim of this study was to determine the incidence of adverse outcomes, including cancer recurrence, venous thromboembolism, and secondary malignancies, among patients with a history of endometrial, ovarian, or cervical cancer prescribed vaginal estrogen for genitourinary syndrome of menopause. METHODS: A retrospective cohort study was performed including women who were diagnosed with endometrial, ovarian, or cervical cancer from January 1, 1991 to December 31, 2017 and subsequently treated with vaginal estrogen for genitourinary syndrome of menopause. Patients were included if not undergoing active cancer treatment and were disease-free based on most recent cancer surveillance visit with physical exam and/or imaging. Demographics, oncologic variables, estrogen use, and adverse outcomes were recorded. Descriptive statistics and univariate analysis were performed. RESULTS: Of 244 women who received vaginal estrogen, 52% (n=127) had a history of endometrial, 25.4% (n=62) cervical, 18.9% (n=46) ovarian cancer, and 3.7% (n=9) low malignant potential tumors. The mean age and body mass index were 55.5±12.5 years and 29.2±8.6 mg/kg2, respectively. With a median follow-up of 80.2 months, the incidence of recurrence for endometrial, ovarian, and cervical cancer was 7.1% (n=9), 18.2% (n=10), and 9.7% (n=6), respectively. In patients with endometrial cancer who recurred, the incidence was 2.4% (n=3) for stage I/II and 4.7% (n=6) for stage III/IV disease. Similarly, recurrence rates for ovarian cancer were 4.3% (n=2) for stage I/II and 17.4% (n=8) for stage III/IV disease. All cervical cancer recurrences were in patients with stage I/II disease. Adverse outcomes including breast cancer (1.6%, n=4), secondary malignancy (2.5%, n=6), and venous thromboembolism (2.5%, n=6) were rare. CONCLUSION: In women with a history of endometrial, ovarian, or cervical cancer prescribed vaginal estrogen use for genitourinary syndrome of menopause, adverse outcomes, including recurrence and thromboembolic events, are infrequent. Vaginal estrogen may be considered safe in gynecologic cancer survivors.

IVIG-Associated Maternal Pancytopenia during Treatment for Neonatal Alloimmune Thrombocytopenia.

Background Treatment for neonatal alloimmune thrombocytopenia (NAIT) primarily involves maternal administration of intravenous immunoglobulin (IVIG) therapy and prednisone according to protocols based on risk stratification. While IVIG is generally well tolerated, hematologic side effects are a potential complication. Case We present the successful management of a rare complication of maternal pancytopenia following standard IVIG treatment. Diagnosis was made during routine obstetric exams. Management included reducing IVIG dosage and adding daily prednisone. Additionally, infusion Lots possibly associated with the event were identified and avoided. Interventions resulted in the resolution of pancytopenia and the birth of a healthy infant without thrombocytopenia. Conclusion Pancytopenia is a rare complication of IVIG treatment in women with pregnancies complicated by NAIT. Serial complete blood counts at the time of treatment would allow for early detection and timely management of the patient. Additionally, limiting the number of infusion Lots may decrease the chance of the described complications.

Activation of p38 and Erk Mitogen-Activated Protein Kinases Signaling in Ocular Rosacea.

Purpose: Rosacea-related cutaneous inflammation is a common cause of ocular surface disease. Currently, there are no specific pharmacologic therapies to treat ocular rosacea. Here, we aimed at determining the differences in intracellular signaling activity in eyelid skin from patients with and without ocular rosacea. Methods: This was an observational, comparative case series including 21 patients undergoing lower lid ectropion surgery at one practice during 2013 and 2014 (18 patients with rosacea, 13 control patients), and 24 paraffin-embedded archival samples from Albany Medical Center, selected randomly (12 patients with rosacea, 12 control patients). Cutaneous biopsies resulting from elective lower lid ectropion surgery were analyzed by Proteome Profiler Human Phospho-Kinase Array, Western blot, and/or immunohistochemistry. Results: Samples derived from ocular rosacea patients showed increased levels of phosphorylated (active) p38 and Erk kinases. Phosphoproteins were mainly localized to the epidermis of affected eyelids. Conclusions: This finding provides a novel potential therapeutic target for treatment of ocular rosacea and possibly other forms of rosacea. Further testing is required to determine if p38 and Erk activation have a causal role in ocular rosacea. The selective activation of keratinocytes in the affected skin suggests that topical pathway inhibition may be an effective treatment that will ultimately prevent ocular surface damage due to ocular rosacea.

Sex and gender in medical education: a national student survey.

BACKGROUND: Gender- and sex-specific medicine is defined as the practice of medicine based on the understanding that biology (dictated by sex chromosomes) and social roles (gender) are important in and have implications for prevention, screening, diagnosis, and treatment in men and women. In light of the many ways that sex and gender influence disease presentation and patient management, there have been various initiatives to improve the integration of these topics into medical education curriculum. Although certain schools may include the topics, their impact on the student body's knowledge has not been as fully studied. By studying the opinions of US allopathic and osteopathic-enrolled students on the extent to which their schools address these topics and their understanding of these topics, this study examined the role of gender specific medicine in the US medical school curriculum. METHODS: An email solicitation with link to an anonymous survey was sent to approximately 35,876 student members of five US medical student organizations. The survey instrument consisted of yes/no, multiple choice, and attitude awareness questions. Data was analyzed as a complete data set to evaluate national trends and via subset analysis using chi-square, paired t test, and one-way anova. RESULTS: A total of 1097 students responded. The majority of respondents strongly agreed that sex and gender medicine (SGBM) improves patient management (96.0 %) and should be included as a part of the medical school curriculum (94.4 %). Only 2.4 % of participants agreed that SGBM is the same as Women's Health. When asked specifically about inclusion of an identified sex and gender-based medicine curriculum at their institution, students answered not sure at 40.8, 25.1, 19.1, and 20.3 % from first year to fourth year, respectively. Males reported a higher rate of exposure to SGBM content areas (in medical history taking, domestic violence) than women. CONCLUSIONS: Medical students recognize the differentiation between SGBM principles and women's health, and understand the translational value of sex and gender-specific principles in the clinical setting. However, current curricular offerings fall short of providing students with adequate coverage of specific evidence-based health differences.