Still "Don't Ask" more than a decade later: The impact of research barriers for LGB+ military couples.

Despite the repeal of "Don't Ask, Don't Tell" (DADT) over a decade ago, military processes and policies continue to function as significant structural and institutional barriers to research aimed at optimizing resources for military couples and families with marginalized sexual identities. Such research is essential given the apparent mental health and related disparities among lesbian, gay, bisexual, and those with other marginalized sexual identities (LGB+) active-duty service members (SMs), as well as the absence of appropriately tailored resources to support these members of the military community. In this paper, we review the empirical literature on the experiences and psychological health of LGB+ military couples, revealing severe limitations in our understanding of these diverse military romantic partnerships. We illuminate process-related barriers to conducting this essential research through an illustrative case example. Our review concludes with specific recommendations for reform and advocacy distinguished by coordinated efforts inclusive of all five military branches, policymakers, military leaders, researchers, and LGB+ stakeholders.

Risk factors for posterior reversible encephalopathy syndrome in hypertensive pregnant women presenting with seizures.

Pregnant women developing generalised tonic-clonic seizures in the absence of a prior neurological disorder are often diagnosed as eclamptic. Posterior reversible encephalopathy syndrome (PRES) is a distinct neuroimaging condition associated with long-term sequelae, which may occur in pregnancy. Some reports suggested PRES to be the pathophysiological process leading to eclampsia, whereas others observed PRES and eclampsia to have varying clinical severity and risk factors. In this case-control study, risk factors associated with PRES were compared to those for eclampsia in women with hypertension presenting with seizures who had undergone neuroimaging. PRES was noted to occur in 22.5% (51/227) hypertensive pregnant women presenting with seizures that otherwise would have been classified as eclampsia. An additional 51 women with eclampsia underwent neuroimaging. Women who had PRES had higher systolic (155.3 vs 144.5, p = 0.04), diastolic (99.2 vs 93.4, p = 0.006) and mean (117.9 vs 110.4, p = 0.001) blood pressure at admission compared to those with eclampsia. Eclampsia and PRES may occur through a similar pathophysiological mechanism, resulting in the same spectrum of neurological complications of preeclampsia, with PRES being the severest form of the disease process. PRES is difficult to differentiate from eclampsia based on clinical and laboratory investigation, except for high blood pressures, without adjunctive MRI/CT neuroimaging. Future studies should assess the role of biomarkers as well as long-term neurological sequelae in pregnant women with a diagnosis of PRES.

COVID-19 Vaccine hesitancy among pregnant women: A facility-based cross-sectional study in Imphal, Manipur.

Background: Vaccine hesitancy has been recognized as a public health issue which needs to be addressed urgently. Pregnant women with COVID-19 are at increased risk of adverse pregnancy outcomes. An assessment of the determinants of vaccine hesitancy will aid in the acceleration of vaccine administration among pregnant women. Objectives: The present study aimed to determine COVID-19 vaccine hesitancy among pregnant women in Imphal, Manipur and assess associated factors. Methods: Across-sectional study was conducted among pregnant women attending Obstetrics and Gynecology Department of a Tertiary Care Institute in Imphal, Manipur during August 2021. One hundred and sixty-three pregnant women were interviewed using a structured questionnaire over phone calls. Univariate analysis was carried out using the Chi-square test and multivariable logistic regression was performed to determine the factors significantly associated with vaccine acceptance. Results: The mean age of the participants was 28.3 ± 5.5 years and majority, 102 (62.6%) were multigravida and 27 (16.6%) had comorbidities. Vaccine hesitancy was found in 127 (77.9%) participants. Logistic regression analysis indicated that awareness on COVID-19 vaccine eligibility (P = 0.002), disagreement of vaccine being unsafe during pregnancy (P = 0.005), and agreement on vaccine benefiting the baby (P = 0.003) were the significant predictors of vaccine acceptance. Conclusion: Nearly four out of every five pregnant women had COVID-19 vaccine hesitancy. Pregnant women should be informed about the benefits and encouraged to take COVID-19 vaccine.

Preparedness of healthcare facilities of manipur in the management of noncommunicable diseases: A cross-sectional study.

Background: India is experiencing a rapid health transition with a rising burden of noncommunicable diseases (NCDs), causing significant morbidity and mortality. Cost-effective interventions for comprehensive NCD management can only be designed after assessing the readiness of various health facilities. Objectives: This study aimed to assess the preparedness of healthcare facilities of Manipur in the management of NCDs and to assess the knowledge of doctors regarding NCDs. Methods: A cross-sectional study was conducted in 21 public healthcare facilities in seven districts of Manipur during October 2021. Readiness of these facilities was assessed through observation and interview of doctors and nurses using a checklist adapted from the WHO Package of Essential NCDs. Knowledge of 153 doctors was also assessed using a self-administered, structured questionnaire. Data were entered in SPSS-26 and expressed using descriptive statistics. Results: General readiness index of primary health centers (PHCs), community health centers (CHCs), district hospitals (DHs), and tertiary care centers (TCCs) was 47%, 66.3%, 73.2%, and 70%, respectively. CHCs were ready in the domains of patient care services (80%), human resources (75%), and advocacy (91.7%). DHs and TCCs were ready in terms of patient care services, human resources, record maintenance, referral system, and advocacy. PHCs were not ready in any of the nine domains. Majority of the doctors (88%) had inadequate knowledge regarding NCDs. Conclusion: PHCs and CHCs were not adequately prepared, but DHs and TCCs were ready to manage NCDs. More than four-fifth of the doctors had inadequate knowledge. Strengthening PHCs and CHCs and training of healthcare workers are needed for integrated NCD management.

Postpartum urinary retention in women undergoing instrumental delivery: A cross-sectional analytical study.

INTRODUCTION: Women undergoing instrumental delivery are known to be at higher risk of urinary retention, which can lead to long-term complications such as voiding dysfunction. Nulliparous women undergo a pronounced and sudden change in the perineum due to stretching during delivery, which may add to the perineal trauma from an episiotomy, increasing the risk of urinary retention. We aim to study the incidence and risk factors associated with postpartum urinary retention in women undergoing instrumental delivery. MATERIAL AND METHODS: Pregnant women who had an instrumental delivery after 37 weeks of gestation at JIPMER, Puducherry, India, between January 2017 and June 2017 were included in the study. Postpartum urinary retention was defined as the inability to void spontaneously or ultrasonographic documentation of post-void residual volume of >150 mL, 6 hours after delivery. Demographic factors, clinical profile and follow-up of these patients were noted. Multivariate logistic regression analysis was performed to assess the risk factors associated with urinary retention and was presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Postpartum urinary retention was noted in 124 (20.6%) women undergoing instrumental delivery. Overt and covert urinary retention occurred in 2.3% and 18.3%, respectively. After adjusting for other risk factors, nulliparity (adjusted OR = 4.05, 95% CI 2.02-8.12 compared with multiparity) and prolonged second stage (OR = 3.96, 95% CI 1.53-10.25) compared with suspected fetal compromise as an indication for instrumental delivery was associated with increased risk of postpartum urinary retention. Interaction was noted between parity and episiotomy on the occurrence of postpartum urinary retention (P = .010). Among nulliparous women, those with episiotomy (adjusted OR = 6.10, 95% CI 2.65-14.04) have higher odds of developing postpartum urinary retention compared with those without episiotomy. CONCLUSIONS: Approximately one of five (20.6%) women undergoing instrumental delivery developed postpartum urinary retention. Among women undergoing instrumental delivery, episiotomy increased the chances of developing postpartum retention in nulliparous but not multiparous women. Prolonged second stage as an indication for instrumental delivery also increased the chances of retention. Future studies are needed to define the cutoff for diagnosis and to evaluate the long-term effects of covert postpartum urinary retention, as well to study the effect of episiotomy on development of postpartum urinary retention in women undergoing instrumental delivery.

FoxO restricts growth and differentiation of cells with elevated TORC1 activity under nutrient restriction.

TORC1, a central regulator of cell survival, growth, and metabolism, is activated in a variety of cancers. Loss of the tumor suppressors PTEN and Tsc1/2 results in hyperactivation of TORC1. Tumors caused by the loss of PTEN, but not Tsc1/2, are often malignant and have been shown to be insensitive to nutrient restriction (NR). In Drosophila, loss of PTEN or Tsc1 results in hypertrophic overgrowth of epithelial tissues under normal nutritional conditions, and an enhanced TORC1-dependent hyperplastic overgrowth of PTEN mutant tissue under NR. Here we demonstrate that epithelial cells lacking Tsc1 or Tsc2 also acquire a growth advantage under NR. The overgrowth correlates with high TORC1 activity, and activating TORC1 downstream of Tsc1 by overexpression of Rheb is sufficient to enhance tissue growth. In contrast to cells lacking PTEN, Tsc1 mutant cells show decreased PKB activity, and the extent of Tsc1 mutant overgrowth is dependent on the loss of PKB-mediated inhibition of the transcription factor FoxO. Removal of FoxO function from Tsc1 mutant tissue induces massive hyperplasia, precocious differentiation, and morphological defects specifically under NR, demonstrating that FoxO activation is responsible for restricting overgrowth of Tsc1 mutant tissue. The activation status of FoxO may thus explain why tumors caused by the loss of Tsc1-in contrast to PTEN-rarely become malignant.

Conservative management of corpus luteum haemorrhage in patients on anticoagulation: a report of three cases and review of literature.

INTRODUCTION: Severe bleeding into the peritoneal cavity from a ruptured corpus luteum cyst is a rare complication in women receiving anticoagulation therapy. Surgical management has been a traditional approach in managing corpus luteum haemorrhage, however, conservative management is now dominating the trend in carefully selected patients. MATERIAL AND METHODS: We report here a series of three cases of corpus luteum haemorrhage with variable presentation. Conservative management was started in all the three patients and was successful in two cases. Finding a safe, effective, and acceptable method to inhibit ovulation in women on anticoagulation for mechanical heart valve is a challenge. All three patients were prescribed cyclical oral Desogestrel for long-term ovulation suppression. CONCLUSION: Selected patients with haemorrhage secondary to deranged coagulation can undergo conservative management in consultation with cardiologist and hematologist.

Aversion of surgical exploration in patients with complex ovarian cysts secondary to overt hypothyroidism: A series of three cases.

Long-standing, overt hypothyroidism-induced bilateral multiloculated ovarian cysts represent an infrequent occurrence. Our first case, presented with bilateral complex ovarian masses, exhibited overt hypothyroidism symptoms, including lethargy, weight gain and subfertility, prompting consideration for surgical intervention. Similarly, in the second case, a girl aged 11 years with stunting, delayed bone age and academic challenges was referred for surgical exploration due to bilateral complex ovarian masses. Both cases revealed elevated thyroid-stimulating hormone levels during preoperative workup. Commencing levothyroxine replacement therapy resulted in complete regression of ovarian cysts and substantial symptom improvement within an 8-week timeframe. The third case, a previously diagnosed patient with Hashimoto's thyroiditis, benefited from the lessons gleaned in managing the initial cases, responding well to levothyroxine therapy, thereby averting the necessity for surgery in all three instances. These cases underscore the significance of considering thyroid function in the evaluation of ovarian masses and highlight the efficacy of levothyroxine replacement therapy in resolving both hypothyroidism and associated ovarian cysts, thereby obviating the need for surgical intervention.

The Effect of the Levonorgestrel-Releasing Intrauterine System on Myometrial Blood Flow in Patients With Heavy Menstrual Bleeding.

Background Abnormal uterine bleeding constitutes a vexing issue among female patients, substantially impacting their quality of life. Surgical interventions, particularly hysterectomy, contribute to the psychological, physical, and financial burden on families and, by extension, the healthcare system. Levonorgestrel-releasing intrauterine system (LNG-IUS) represents a conservative management approach and emerges as a beneficial option for affected patients. The present study aims to elucidate color Doppler changes in the uterine artery pre- and post-LNG-IUS insertion. Objective The primary objectives encompass an investigation into the variations in Doppler indices (resistance index (RI) and pulsatility index (PI)) within the arcuate and radial branches of the uterine artery, as well as the assessment of endometrial thickness before LNG-IUD insertion, at three months, and six months post-insertion. Secondary outcomes include evaluating changes in pictorial blood assessment chart (PBAC) scores before insertion, at three months, and at six months after LNG-IUS insertion. Methods A cross-sectional study was conducted at the Department of Obstetrics and Gynecology at All India Institute Of Medical Sciences (AIIMS), Nagpur. A cohort of 25 women underwent LNG-IUS insertion. The endometrial cavity, RI, and PI of both arcuate and radial arteries were assessed before LNG-IUS insertion and at three and six months after insertion. Results The PI of the arcuate artery exhibited minimal alteration over the six-month duration, with a p-value of 0.43. Conversely, the RI demonstrated a statistically significant increase over the same period (p = 0.03). Conversely, the radial artery exhibited no statistically significant changes in either PI or RI (p = 0.39 or 0.13, respectively). Conclusion Following six months of LNG-IUS utilization, a substantial reduction in endometrial thickness and menstrual flow was observed, concomitant with an improvement in hemoglobin levels. Notably, the PI of both the arcuate and radial arteries demonstrated no significant change. Although the RI of the arcuate artery increased, its clinical relevance may be limited. Consequently, the observed reduction in menstrual bleeding cannot conclusively be ascribed to diminished blood flow in uterine arteries.

APOBEC3 mutagenesis drives therapy resistance in breast cancer.

Acquired genetic alterations commonly drive resistance to endocrine and targeted therapies in metastatic breast cancer 1-7 , however the underlying processes engendering these diverse alterations are largely uncharacterized. To identify the mutational processes operant in breast cancer and their impact on clinical outcomes, we utilized a well-annotated cohort of 3,880 patient samples with paired tumor-normal sequencing data. The mutational signatures associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) enzymes were highly prevalent and enriched in post-treatment compared to treatment-naïve hormone receptor-positive (HR+) cancers. APOBEC3 mutational signatures were independently associated with shorter progression-free survival on antiestrogen plus CDK4/6 inhibitor combination therapy in patients with HR+ metastatic breast cancer. Whole genome sequencing (WGS) of breast cancer models and selected paired primary-metastatic samples demonstrated that active APOBEC3 mutagenesis promoted resistance to both endocrine and targeted therapies through characteristic alterations such as RB1 loss-of-function mutations. Evidence of APOBEC3 activity in pre-treatment samples illustrated a pervasive role for this mutational process in breast cancer evolution. The study reveals APOBEC3 mutagenesis to be a frequent mediator of therapy resistance in breast cancer and highlights its potential as a biomarker and target for overcoming resistance.

Optimal systemic treatment and real-world clinical application of ctDNA in patients with metastatic HER2-mutant lung cancer.

INTRODUCTION: No definitive answers currently exist regarding optimal first-line therapy for HER2-mutant NSCLC. Access to rapid tissue sequencing is a major barrier to precision drug development in the first-line setting. ctDNA analysis has the potential to overcome these obstacles and guide treatment. METHODS: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing and received systemic therapy at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx LungTM assay. Primary endpoints were time to the next treatment (TTNT) and overall survival (OS). RESULTS: Sixty-three patients were included in the primary analysis. Chemoimmunotherapy (33/63, 52.4 %) was the predominant first-line treatment with a median TTNT of 5.1 months (95 %CI 4.1 - 6.1) whereas 55.0 % (22/40) of patients who received second-line T-DXd obtained a median TTNT of 9.2 m (95 % CI, 0-22.2). Plasma ctDNA was tested before first-line therapy in 40 patients with a median OS of 28.0 months (95 % CI 21-34), in whom 31 patients (78.0 %) had detectable ctDNA. HER2 mutations were detected on ctDNA with a median turnaround time of 13 days, occasionally co-occurred with EGFR and MET alterations and were tracked longitudinally correlating with treatment response. Patients with detectable baseline ctDNA had significantly shorter OS (hazard ratio (HR), 5.25; 95 % CI, 1.2-23.9; p = 0.019). CONCLUSION: Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

Ascariasis presenting as acute abdomen during pregnancy and puerperium.

Ascariasis can have various clinical presentations. We present three cases of ascariasis in pregnant or postpartum women, presenting with acute abdomen. The diagnosis of ascariasis was made clinically with the passage of ascaris worms in the vomitus or stool and was supported by ultrasonography. All three patients were treated successfully using anthelmintics. One patient underwent exploratory laparotomy.

Vaginal mesh erosion - a challenging entity.

Pelvic reconstructive surgery with mesh for pelvic organ prolapse (POP) has been reported to have a superior anatomical cure rate compared with traditional repair methods. Mesh-related adverse events are increasing worldwide. We describe a case of excision of mesh erosion following vaginal hysterectomy. A 45yr old lady presented with 3 × 2 cm infected mesh erosion on the anterior vaginal wall following a vaginal hysterectomy a year earlier in a camp setting. Cystoscopy was normal. Under anesthesia, the mesh was dissected from the vagina and excised. The vaginal edges were freshened, and approximated Postoperative period was uneventful, and she was discharged home the next day. Surgical revision is indicated for large or multiple erosions. Mesh excision can be a challenging procedure with difficulty in gaining access and increased risk of surgical bleeding. A multidisciplinary approach in conjunction with a urologist will help optimise outcomes.

Comparing the efficacy of oral labetalol with oral amlodipine in achieving blood pressure control in women with postpartum hypertension: randomized controlled trial (HIPPO study-Hypertension In Pregnancy & Postpartum Oral-antihypertensive therapy).

De novo - or as a continuum of antenatal hypertension -postpartum hypertension complicates ~2% of pregnancies. Many maternal complications, such as eclampsia and cerebrovascular accidents, occur in the postpartum period. Despite widespread use of antihypertensives during pregnancy and childbirth, there is a paucity of data on preferred medications in the postpartum period. This randomized controlled study enrolled 130 women who were started on antihypertensives. They were randomized to receive oral Labetalol(LAB, maximum 900 mg per day in three doses) or oral Amlodipine(AML, maximum 10 mg per day given in two doses). In the immediate postpartum, all women were closely monitored for neurological symptoms, blood pressure, heart rate, respiratory rate, urine output, and deep tendon reflex. The primary outcome was the time to achieve sustained blood pressure control for 12 h from the initiation of medication; secondary outcomes included side effects of both medications. Mean time to achieve sustained blood pressure control was lower in women who received AML than in those who received LAB-(mean difference 7.2 h; 38 95% CI 1.4, 12.9, p = 0.011). There were fewer severe hypertensive episodes among those with AML than in those who received LAB. However, the proportion of women who continued to require antihypertensives at discharge was higher in the AML group than in the LAB group (55.4% versus 32.3%, p = 0.008). None of the participants developed drug-related side effects. Among women with postpartum persistence or new-onset hypertension, oral AML achieved sustained blood pressure control in a shorter duration, with fewer hypertensive emergencies than oral LAB. (CTRI/2020/02/023236).Trial Registration details: The study protocol was registered with Clinical Trial Registry of India with CTRI Number CTRI/2020/02/023236 dated 11.02.2020. Protocol can be accessed at https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=40435&EncHid=&modid=&compid=%27,%2740435det%27 .

ADCs or: How I Learned to Stop Worrying and Love Chemotherapy.

Antibody-drug conjugates are transforming cancer treatment, and payload characteristics are emerging as crucial determinants of clinical activity. As exemplified by Weng and colleagues, advancements in the linker and payload chemistry may provide the next evolutionary step in enabling this class of drugs to overcome chemoresistance and deliver even more profound responses. See related article by Weng et al., p. 950 (2).

Rise of Antibody-Drug Conjugates: The Present and Future.

Antibody-drug conjugates (ADCs) embody a simple, but elegant, vision for cancer therapy-the delivery of a potent cytotoxic agent to tumor cells with minimal damage to normal cells-so-called smart chemo. Although there were significant challenges in achieving this milestone culminating in the first Food and Drug Administration approval in 2000, subsequent advancements in technology have led to rapid drug development with regulatory approvals for ADCs targeting a variety of tumor types. The most successful application for solid tumors has been in breast cancer, with ADCs becoming the standard of care across traditional human epidermal growth factor receptor 2 (HER2)+, hormone receptor+ (HR+) and triple-negative disease subtypes. Moreover, the improved features and gains in potency with the development of ADCs have expanded the treatment-eligible population to those with low/heterogeneous expression of the target antigen on the tumor with trastuzumab deruxtecan or in the case of sacituzumab govitecan, agnostic to target expression. Despite their antibody-directed homing, these novel agents come with their share of toxicities obligating appropriate patient selection and vigilant monitoring while on treatment. As more ADCs are included in the treatment armamentarium, mechanisms of resistance need to be studied and understood for optimal sequencing. Modifying the payload to use immune-stimulating agents or combination therapies with immunotherapy and other effective targeted therapies may further extend the utility of these agents in the treatment of solid tumors.

Maternal and perinatal outcome in pregnancies complicated with portal hypertension: a systematic review and meta-analysis.

BACKGROUND: Portal hypertension is secondary to either cirrhotic or non-cirrhotic causes, and complicating pregnancy poses a challenge to the treating team. A systematic review was performed to determine maternal and perinatal outcomes in women with portal hypertension. Outcomes were compared among those with cirrhotic (CPH) with non-cirrhotic portal hypertension (NCPH) as well as non-cirrhotic portal fibrosis (NCPF) with extra-hepatic portal vein obstruction (EHPVO). METHODS: Medline and EMBASE databases were searched for studies reporting outcomes among pregnant women with portal hypertension. Reference lists from relevant papers and reviews were hand-searched for appropriate citations. Data were extracted to describe maternal complications, obstetric and neonatal outcomes. A random-effects model was used to derive pooled estimates of various outcomes, and final estimates were reported as percentages with a 95% confidence interval (CI). Cumulative, sequential and sensitivity analysis was studied to assess the temporal trends of outcomes over the period. RESULTS: Information on 895 pregnancies among 581 patients with portal hypertension was included from 26 studies. Portal hypertension was diagnosed during pregnancy in 10% (95% CI 4-24%). There were 22 maternal deaths (0%, 95% CI 0-1%), mostly following complications from variceal bleeding or hepatic decompensation. Variceal bleeding complicated in 14% (95% CI 9-20%), and endoscopic interventions were performed in 12% (95% CI 8-17%) during pregnancy. Decompensation of liver function occurred in 7% (95% CI 3-12%). Thrombocytopenia was the most common complication (41%, 95% CI 23-60%). Miscarriages occurred in 14% (95% CI 8-20%), preterm birth in 27% (95% CI 19-37%), and low birth weights in 22% (95% CI 15-30%). Risk of postpartum hemorrhage was higher (RR 5.09, 95% CI 1.84-14.12), and variceal bleeding was lower (RR 0.51, 95% CI 0.30-0.86) among those with CPH compared to NCPH. Risk of various outcomes was comparable between NCPF and EHPVO. CONCLUSION: One in ten pregnancies complicated with portal hypertension is diagnosed during pregnancy, and thrombocytopenia is the most common complication. Hepatic decompensation and variceal bleeding remain the most common cause of maternal deaths, with reduced rates of bleeding and its complications reported following the introduction of endoscopic procedures during pregnancy. CPH increases the risk of postpartum hemorrhage, whereas variceal bleeding is higher among NCPH.