Isodicentric Y mosaicism involving a 46, XX cell line: Implications for management.

Carriers of isodicentric Y (idicY) mosaicism exhibit a wide range of clinical features, including short stature, gonadal abnormalities, and external genital anomalies. However, the phenotypic spectrum for individuals carrying an idicY and a 46, XX cell line is less clearly defined. A more complete description of the phenotype related to idicY is thus essential to guide management related to pubertal development, fertility, and gonadoblastoma risk in mosaic carriers. Findings from the evaluation of twin females with an abnormal karyotype, 48, XX, +idic(Yq) x2/47, XX, +idic(Yq)/46, XX, are presented to highlight the importance of interdisciplinary care in the management of multifaceted disorders of sex development.

Exploring co-parent experiences of sexuality in the first 3 months after birth.

INTRODUCTION: Research on postpartum sexuality has focused primarily on mothers, though new findings suggest that relational perceptions may have a strong influence over sexual desire and behavior. Little investigation exists regarding sexuality in partners of postpartum women. Additionally, recent findings point to the importance of a partner's sexuality for postpartum women's perceptions of their own sexuality in this time. AIMS: The goal of this research was to explore women's partners' sexuality in the early postpartum phase taking into account psychosocial context. METHODS: Partners (N = 114; 95 men, 18 women, 1 unspecified) of postpartum women completed a retrospective online questionnaire about their sexuality during the 3 months following their youngest child's birth. MAIN OUTCOME MEASURES: Primary measures included sexual desire (Sexual Desire Inventory), latency to sexual behavior, and enjoyment and initiation of sexual behavior. Other psychosocial variables were investigated: partners' perceptions of the birth mother's sexual desire, perceptions of the birth experience (Questionnaire Measuring Attitudes About Labor and Delivery), postpartum stress (Perceived Stress Scale), body image self-consciousness (Body Image Self-Consciousness Scale), social support (Multidimensional Scale of Perceived Social Support), fatigue, and experiences surrounding breastfeeding. RESULTS: Partners reported most frequent engagement in intercourse in the postpartum period, earliest engagement in masturbation, and highest enjoyment of receiving oral sex compared with other sexual activities. Partners' sexual desire was not correlated with the psychosocial variables measured in the study. Findings for partners' sexuality were similar by gender, except for perceptions of social support and likelihood to engage in intercourse. CONCLUSIONS: This study provided a novel perspective on the study of postpartum sexuality by investigating physical and psychosocial influences on the experiences of partners of parous women. Given parallels between sexuality reported by partners in this study and by birth mothers in past studies, this study provided evidence that sexuality in the postpartum period may be experienced similarly, highlighting the social and relational nature of the postpartum.

High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial).

BACKGROUND: Elevated hydrogen sulfide (H2S) contributes to vasodilatation and hypotension in septic shock, and traditional therapies do not target this pathophysiologic mechanism. High-dose IV hydroxocobalamin scavenges and prevents H2S formation, which may restore vascular tone and may accentuate recovery. No experimental human studies have tested high-dose IV hydroxocobalamin in adults with septic shock. RESEARCH QUESTION: In adults with septic shock, is comparing high-dose IV hydroxocobalamin with placebo feasible? STUDY DESIGN AND METHODS: We conducted a phase 2 single-center, double-blind, allocation-concealed, placebo-controlled, parallel-group pilot randomized controlled trial comparing high-dose IV hydroxocobalamin with placebo in critically ill adults with septic shock. Patients meeting Sepsis 3 criteria were randomized 1:1 to receive a single 5-g dose of high-dose IV hydroxocobalamin or equivalent volume 0.9% saline solution as placebo. The primary outcome was study feasibility (enrollment rate, clinical and laboratory compliance rate, and contamination rate). Secondary outcomes included between-group differences in plasma H2S concentrations and vasopressor dose before and after infusion. RESULTS: Twenty patients were enrolled over 19 months, establishing an enrollment rate of 1.05 patients per month. Protocol adherence rates were 100% with zero contamination. In the high-dose IV hydroxocobalamin group, compared to placebo, there was a greater reduction in vasopressor dose between randomization and postinfusion (-36% vs 4%, P < .001) and randomization and 3-h postinfusion (-28% vs 10%, P = .019). In the high-dose IV hydroxocobalamin group, the plasma H2S level was reduced over 45 mins by -0.80 ± 1.73 µM, as compared with -0.21 ± 0.64 µM in the placebo group (P = .3). INTERPRETATION: This pilot trial established favorable feasibility metrics. Consistent with the proposed mechanism of benefit, high-dose IV hydroxocobalamin compared with placebo was associated with reduced vasopressor dose and H2S levels at all time points and without serious adverse events. These data provide the first proof of concept for feasibility of delivering high-dose IV hydroxocobalamin in septic shock. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03783091; URL: www. CLINICALTRIALS: gov.

Racial, Ethnic, and Geographic Disparities in Immunization Rates Among Patients With Inflammatory Bowel Disease.

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD. Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines. Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake. Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed.

Exploring women's postpartum sexuality: social, psychological, relational, and birth-related contextual factors.

INTRODUCTION: Women's postpartum sexuality can be influenced by factors related to physical, personal, and relationship transitions after the newborn arrives. Despite this, many experiential and social factors remain unexplored. AIMS: This study aims to (i) investigate a range of variables thought to influence postpartum sexuality; (ii) expand the focus beyond latency to penis-vagina intercourse; and (iii) assess positive aspects of postpartum sexuality. METHODS: Via retrospective reporting on the first 3 months postpartum, 304 women completed an online questionnaire. MAIN OUTCOME MEASURES: The main outcome measures were retrospective reports of sexual desire (Sexual Desire Inventory), latency to resumption of sexual activity, and perceptions of partner's sexual desire. Other measures were birth experience (Questionnaire Measuring Attitudes About Labor and Delivery), breastfeeding status, perceptions of social support (Multidimensional Scale of Perceived Social Support), stress (Perceived Stress Scale), and body image (Body Image Self-Consciousness Scale). RESULTS: Significant differences in time to resumption were found. Women performed oral sex on their partners earlier than engaging in masturbation, which was followed by intercourse and then receiving oral sex. Post hoc analyses identified birth experience, social support, importance of partner's sexual fulfillment, and perception of partner's desire as contributors to this pattern. Women's postpartum sexual desire was influenced by their perceptions of their partner's postpartum sexuality and individual's level of fatigue. Results suggested that postpartum desire was not significantly influenced by breastfeeding status, vaginal issues, or psychosocial variables including stress, body image, or social support. CONCLUSION: Results suggest that women's perceptions of their partner's sexuality impact postpartum sexuality more than the physical factors most commonly studied (e.g., vaginal trauma and breastfeeding). These results portray postpartum sexuality as a multidimensional phenomenon and highlight the need for further research that addresses its social context.

Clinical tools and counseling considerations for breast cancer risk assessment and evaluation for hereditary cancer risk.

Breast cancer is a complex and heterogeneous disease. Unfortunately, it is the most common malignancy diagnosed in women in the USA, with 281,550 new cases of invasive breast cancer and 49,290 new cases of noninvasive breast cancer are diagnosed per year. In England, it is currently estimated that approximately 1 in 7 (14%) women will be diagnosed with breast cancer in their lifetime. In the UK in 2017, 54,700 women and 390 men were diagnosed with breast cancer. The risk of breast cancer is influenced by many factors, including but not limited to age, family history, reproductive history, hormonal exposure, proliferative breast lesions, physical activity, alcohol use, tobacco use, breast density, and environmental exposures. Breast cancer risk assessment is a critical part of public health. By identifying women at high risk for breast cancer, personalized recommendations can be deployed with regards to modes of screening, the age to initiate breast screening, and the frequency for completing such screens. In addition, breast cancer risk assessment can assist in determining a woman's eligibility for interventions to reduce risk, either through the use of chemoprevention medications or through surgical means with risk-reducing bilateral mastectomy. This chapter summarizes breast cancer risk assessment models and discusses interventions to reduce breast cancer risk to aid in reducing morbidity and mortality from breast cancer.

Total fertilization failure with in vitro fertilization-intracytoplasmic sperm injection related to WEE2 mutation highlights emerging importance of genetic causes of in vitro fertilization failure.

Objective: To report a unique case of total fertilization failure (TFF) after in vitro fertilization with intracytoplasmic sperm injection related to homozygous WEE2 gene mutation and summarize the current literature and management of TFF. Design: Case report. Setting: Academic fertility center. Patients: A 25-year-old woman and her 35-year-old partner with a history of near-complete fertilization failure after 2 cycles of in vitro fertilization/intracytoplasmic sperm injection. Interventions: Consultation with medical and commercial genetic testing for WEE2, PLCZ1, and TLE6. Main Outcome Measures: Oocyte fertilization. Results: The patient was homozygous for WEE2 pathogenic variant impacting oocyte activation and resulting in infertility. Conclusions: In the setting of TFF, early consideration should be given to genetic testing to assist couples in clinical decision-making and help limit the financial and emotional burden associated with unsuccessful fertility intervention.

Anti-epileptic drug topiramate upregulates TGFß1 and SOX9 expression in primary embryonic palatal mesenchyme cells: Implications for teratogenicity.

Topiramate is an anti-epileptic drug that is commonly prescribed not just to prevent seizures but also migraine headaches, with over 8 million prescriptions dispensed annually. Topiramate use during pregnancy has been linked to significantly increased risk of babies born with orofacial clefts (OFCs). However, the exact molecular mechanism of topiramate teratogenicity is unknown. In this study, we first used an unbiased antibody array analysis to test the effect of topiramate on human embryonic palatal mesenchyme (HEPM) cells. This analysis identified 40 differentially expressed proteins, showing strong connectivity to known genes associated with orofacial clefts. However, among known OFC genes, only TGFß1 was significantly upregulated in the antibody array analysis. Next, we validated that topiramate could increase expression of TGFß1 and of downstream target phospho-SMAD2 in primary mouse embryonic palatal mesenchyme (MEPM) cells. Furthermore, we showed that topiramate treatment of primary MEPM cells increased expression of SOX9. SOX9 overexpression in chondrocytes is known to cause cleft palate in mouse. We propose that topiramate mediates upregulation of TGFß1 signaling through activation of γ-aminobutyric acid (GABA) receptors in the palate. TGFß1 and SOX9 play critical roles in orofacial morphogenesis, and their abnormal overexpression provides a plausible etiologic molecular mechanism for the teratogenic effects of topiramate.

The diagnosis of inborn errors of metabolism in previously undiagnosed adults referred for medical genetics evaluation.

Traditionally thought of as a pediatric diagnostic and therapeutic dilemma, the diagnostic rate and spectrum of inborn errors of metabolism (IEM) in the adult population is largely unknown. A retrospective chart review of patients seen by the Michigan Medicine Adult Medical Genetics Clinic for clinical evaluation from 2014 to 2018 was conducted. Patients referred for a primary indication possibly consistent with an IEM were considered. Variables included age at genetic evaluation, symptom onset age, sex, clinical course, organ systems involved, developmental history, family history and prior genetic testing. Of patients evaluated during the study period, 112 were referred for an indication possibly consistent with an IEM and underwent a complete biochemical workup with an IEM diagnostic rate of 9.8% achieved. An additional 9.8% were diagnosed with a non-IEM genetic diagnosis. Management changes were implemented in all IEM diagnoses. Metabolic disorders in the adult population are under-recognized and under-diagnosed. This report demonstrates the need for clinicians to consider these diagnoses in adults and either refer to a genetics clinic or initiate a biochemical workup. As advances in diagnosis, treatment, and life expectancy of patients with IEMs increases, recognizing and diagnosing these conditions can significantly impact care.