Mechanisms of left ventricular systolic dysfunction in light chain amyloidosis: a multiparametric cardiac MRI study.

Background: Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood. Purpose: This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis. Methods: Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass. Results: Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE (r = 0.42; p < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy (n = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile (p < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; p < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; p < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden. Conclusions: In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.

Burden of Long COVID-19 in a Cohort of Recovered COVID-19 Patients in Delhi, India.

BACKGROUND: The long COVID phase is characterized by signs and symptoms persisting for at least three months after recovery from acute COVID-19 illness. There is limited data on comprehensive long-term clinical follow-up of COVID-19 patients. AIMS: This study aims to explore the burden and symptomatology of long COVID syndrome and its association with various health parameters. SETTINGS AND DESIGN: This prospective observational study was conducted in Delhi from May 2022 to March 2023. METHODS AND MATERIAL: A total of 553 adult patients who had recovered from COVID-19 were enrolled in the study. A sociodemographic and clinical profile was obtained using validated questionnaires, along with an evaluation of biochemical parameters to assess the associated factors. STATISTICAL ANALYSIS USED: Chi-square test, unpaired t-test, and bivariate regression analysis were applied using Statistical Product and Service Solutions (SPSS, version 28; IBM SPSS Statistics for Windows, Armonk, NY). A p value of <0.05 was considered significant. RESULTS: A total of 252 patients (45.6%) had long COVID syndrome, which was significantly associated with the presence of any pre-existing comorbidity (OR=1.46 (1.02-2.09); p=0.039), previous history of hypertension (OR=1.82 (1.07-3.09); p=0.027), and vaccination against COVID-19 (OR=1.392 (1.171-1.656); p=0.003). The most common symptoms reported were persistent fatigue (33.3%) and persistent dry cough (28.5%). Patients with long COVID syndrome are also reported to have poorer sleep quality. Biochemical findings showed abnormal T lymphocytes (9.3%) and raised HbA1c (11.9%). CONCLUSIONS: Multiple risk factors and symptoms associated with long COVID syndrome were identified in this study. Research efforts and knowledge regarding the pattern of illness will aid in long-term monitoring and development of interventional strategies and guidelines for the care of recovered COVID-19 patients.

Metabolic syndrome burden, determinants and treatment status in an urban slum resettlement colony in Delhi, India.

BACKGROUND: Metabolic syndrome (MetS) in low-resource settings contributes to accentuated risk of cardiovascular disease, including stroke. The study objective was to estimate the prevalence, determinants and treatment status of MetS in an urban slum resettlement population in Delhi, India. METHODS: This study was conducted from February to May 2023. Multiphase sampling was conducted with 1910 individuals screened for abdominal obesity (AO), with 996 detected as having AO, of which, 400 were selected by simple random sampling and further evaluated for triglycerides (TGs), high-density lipoprotein (HDL) and fasting glucose levels. RESULTS: Among the 400 participants detected as having AO, 211 had evidence of MetS (52.75% [95% confidence interval 47.83 to 57.62]). The most prevalent combination of MetS clustering was for all five components (AO, diabetes mellitus [DM], hypertension [HTN], low HDL and high TGs; 14.69%), followed by AO, DM and HTN (12.32%). On adjusted analysis, the odds of having MetS was found to be independently associated with increasing age (≥40 y) but not sex. CONCLUSIONS: A high burden of MetS and suboptimal treatment status is prevalent in urban slum populations. Screening of individuals with AO, especially in those >40 y of age, can be an effective programmatic strategy for early diagnosis and management of MetS and its underlying components.

Hypertension care cascade in an urban resettlement colony and slum in Delhi, India: a cross-sectional survey.

BACKGROUND: Hypertension care cascade in resource-limited settings is compromised with a majority of patients with hypertension remaining undiagnosed, untreated, non-adherent, and poorly controlled at every stage. However, there is paucity of information on care and management of hypertensive patients in community-based settings of low-income urban neighbourhoods in India. METHODS: This was a community-based cross-sectional study conducted in an urban resettlement colony and slum area in the Northeast District of Delhi. The adult population was screened for hypertension using standardized methods, and adherence to medications was assessed using the Morisky Green Levine scale. Binary logistic regression analysis was conducted to ascertain the sociodemographic predictors of the outcome (presence of hypertension, adherence to antihypertensive medication, blood pressure control). A p-value < 0.05 was considered statistically significant. RESULTS: We included 8850 adult participants including 5295 females and 3555 males in this study. Nearly 29% of the participants were hypertensive, of which 61.77% were newly diagnosed cases. Furthermore, nearly 81% of the previously diagnosed cases had been initiated on antihypertensive medication, of which 57.54% were adherent to their medications while 36.12% attained controlled blood pressure levels. The odds of having hypertension were significantly higher among males (AOR = 1.87, 95% CI: 1.63 to 2.15), age ≥ 60 years (AOR = 9.15, 95% CI: 7.82 to 10.70), high waist circumference (AOR = 2.24, 95% CI: 1.86 to 2.70) and Body Mass Index of ≥ 25.00 (AOR = 2.55, 95% CI: 2.00 to 3.26). Furthermore, on adjusted analysis, patients of hypertension having diabetes (DM) comorbidity had significantly higher odds of being adherent to anti-hypertensive medications (AOR = 1.81, 95% CI: 1.31 to 2.51) compared to those without DM comorbidity, while tobacco users had significantly lower odds of being adherent to antihypertensive medication (AOR = 0.50, 95% CI: 0.31 to 0.82). CONCLUSIONS: Hypertension care cascade in urban slum-resettlement colony setting revealed a high burden of undiagnosed hypertension, low rates of medication adherence, and poor blood pressure control. Strengthening community screening and primary care continuum of care is necessary to improve the hypertension care cascade from early diagnosis to effective management with optimal health outcomes to reduce patient complications and increase longevity.

Minimum standard assessment of informed consent for internal medicine transition to residency program: A cohort study.

Background and Aims: Interns must be proficient in obtaining informed consent (IC), which is the Association of American Medical College's 11th of 13 Entrustable Professional Activities (EPAs). Medical students have limited opportunity to practice IC during clerkships, resulting in inconsistent proficiency. We aimed to create a tool to assess whether our transition to residency (TTR) workshop enables fourth-year medical students to meet a minimum standard of obtaining IC. Methods: Sixty fourth-year medical students were enrolled in the internal medicine virtual TTR course during AY2021. The curriculum prioritizes deliberate practice activities. Pre- and postworkshop assignments involved students typing verbatim what they would say during IC encounters. We modified an IC abstraction tool created by Spatz et al. to assess a minimum standard for students' IC assignments. Our final 7-item tool consisted of the following domains: "What," "Why," "How," "Benefits," "Quantitative Risks," "Qualitative Risks," and "Alternatives," weighing 1 point each. A minimum standard was obtained with a score of 6 or more points by appropriately discussing at least one domain involving risk and all other domains. Results: Students scored highly on the prework domains pertaining to "What," "Why," and "How" of the procedure with no significant difference on postwork. Significant improvement was achieved on postwork domains covering "Benefits" (p = 0.039) and "Alternatives" (p = 0.031). For domains involving "Qualitative" and "Quantitative Risks," there were no statistically significant improvements from pre- to postwork scores. Fifteen and 22 students met the minimum standard for IC on pre- and postwork, respectively. Conclusion: Our students demonstrated a good a priori understanding of the "What," "Why," and "How" domains. After the workshop, they more reliably discussed "Benefits" and "Alternatives." Our abstraction tool helped assess the strengths and weaknesses in our students' IC skillset and helped recognize areas of our curriculum that will benefit from improvements to bring students to meet the minimum standard.

COVID-19 Booster Dose Coverage and Hesitancy among Older Adults in an Urban Slum and Resettlement Colony in Delhi, India.

BACKGROUND: The high prevalence of vaccine booster hesitancy, with the concomitant waning of humoral vaccine or hybrid immunity, and the emergence of SARS-CoV-2 variants of concern can accentuate COVID-19 morbidity and mortality. The study objective was to ascertain the COVID-19 vaccination coverage, including the administration of precaution (booster) dose vaccination, among the older population in an urban slum and resettlement colony population in Delhi, India. METHODS: We conducted a cross-sectional survey in an urban resettlement colony, slum, and village cluster in the Northeast district of Delhi among residents aged ≥50 years. RESULTS: A total of 2217 adults (58.28%) had obtained a COVID-19 booster (precaution) dose vaccine, 1404 (36.91%) had received two doses of a COVID-19 vaccine without booster dose, 121 (3.18%) were unvaccinated, while 62 (1.63%) participants received a single dose. Based on adjusted analysis, older adults (>65 years), higher education, and higher per-capita income were statistically significant predictors of booster dose vaccination. CONCLUSIONS: More than four in ten adults in an urban slum and resettlement colony in Delhi lacked COVID-19 booster dose vaccination despite high rates of double-dose vaccination (~95%). Public health programming should provide an enhanced focus on reducing complacency with renewed prioritization for improving ease of access to COVID-19 vaccination services, particularly in underserved areas.

Role of High-Sensitivity C-reactive Protein Levels in Predicting the Risk of Six-Month Event Rates in Patients With Chronic Stable Angina Undergoing Percutaneous Transluminal Coronary Angioplasty With a Drug-Eluting Stent.

Introduction This prospective observational study reports the association between baseline high-sensitivity C-reactive protein (hs-CRP) levels and adverse events at six months in patients who were diagnosed with symptomatic chronic stable angina and then underwent percutaneous transluminal coronary angioplasty (PTCA) with a drug-eluting stent (DES). Methods A total of 104 patients were examined with chronic stable angina over a period of six months. Before conducting percutaneous coronary intervention (PCI), the baseline levels of hs-CRP were measured, and based on the levels, the patients were grouped into high and low hs-CRP groups. Results The primary causes of death or the need for repeat revascularization or myocardial infarction or angina were concluded after assessing the patients for six months. A total of 104 patients were studied, among which 72 (69.23%) had low hs-CRP and 32 (30.77%) had high hs-CRP levels. The number of males in this study was 68 (65.38%) and females were 36 (34.62%). The mean age of the patients was 55.26 ± 10.31 years. There were no significant differences among the groups in terms of gender, age, comorbidities, and risk factors except for certain predisposing factors like dyslipidemia and smoking. Moreover, we did not find any significant difference among the groups in the cause of death and myocardial infarction after a follow-up of six months. However, we observed a higher need for revascularization and angina outcomes in the group with high hs-CRP compared to low hs-CRP. Conclusion It can be concluded that a higher risk of angina and repeat revascularization is related to a high baseline hs-CRP but there is no evidence whether it is somehow linked to myocardial infarction and mortality or not.

Determinants of Treatment Adherence and Health Outcomes in Patients With Type 2 Diabetes and Hypertension in a Low-Income Urban Agglomerate in Delhi, India: A Qualitative Study.

Background Diabetes and hypertension (HTN) are increasing threats to global public health. Despite evidence of effective management of diabetes and HTN by medications that help in the prevention and reducing mortality of the disease, a large proportion of people either remain undiagnosed or untreated, especially in low-resource countries. This study was conducted to explore the patient treatment pathway and their health-seeking behavior in a low-income urban area. Methodology We conducted 45 in-depth interviews of adult patients affected by type 2 diabetes mellitus (DM) and/or HTN on treatment for at least two years and attended the weekly clinic catering to an urban resettlement colony in the Northeast district of Delhi. Interviews were conducted and transcribed into Hindi and translated into English. Data analysis was done using Microsoft Excel. The patient treatment pathways were mapped, and their health-seeking behavior, treatment adherence, and experiences were described. Results Most patients reported taking treatment from the government primary health facilities due to optimal healthcare accessibility as the prescribed drugs for DM/HTN control were available free of cost at these healthcare facilities. Those who visited private facilities thought of shorter waiting times and the quality of drugs. Patients also had little knowledge of complications of diabetes and hypertensive disorders. Nearly 25% of patients had poor adherence to the medications, and lifestyle modification was rarely practiced by patients although they were aware of the same. Conclusions Expanding the role of community health workers or volunteers in providing information on noncommunicable diseases might help improve patient treatment pathways to care.

No reflow phenomenon in CAD patients after percutaneous coronary intervention: A prospective hospital based observational study.

The present study assessed incidence, risk factors, in-hospital and short-term outcomes associated with no-reflow in patients undergoing percutaneous coronary intervention (PCI) in STEMI, NSTEMI, unstable angina and stable angina. Out of 449 patients, 42 (9.3%) developed no-reflow. Hypertension, dyslipidemia, obesity and smoking were significant risk factors. There was significant association of no-reflow with left main disease, multiple stents, target lesion length≥ 20 mm and higher thrombus grade. Interestingly, 93 patients (23.4%) of normal flow had myocardial perfusion grade (MPG) of 0/1 with mortality in 9 (10%) patients. No-reflow is associated with poor in-hospital and short-term outcomes with higher incidence of death, cardiogenic shock, heart failure and MACE. Knowledge of risk factors of no-reflow portends a more meticulous approach to improve final outcomes. MPG could be better predictor of outcomes in these patients.

Health-Seeking Behaviour for Childhood Ailments in Caregivers of Under-Five Children in an Urban Resettlement Colony in Delhi, India.

This explorative qualitative study assesses the health-seeking behaviour for childhood ailments in caregivers of under-five children in a low-income neighbourhood in Delhi, India during July-September 2021. A total of 17 caregivers (mothers) of eight male and nine female under-five children were enrolled, with the mother being the caregiver in most (94%) cases. Caregivers consulted on common childhood ailments from multiple sources, including family, neighbours, healthcare providers (both licensed and unlicensed), frontline workers, and local pharmacists. The internet was often used as a source of child health information due to its ease of access but often "confused" caregivers due to the presence of too much information. Health-seeking behaviour of caregivers for childhood ailments could range from self-medication, local pharmacist dispensing, and private and public healthcare providers. Factors that influenced preference for the healthcare facility or provider were accessibility issues (waiting time, queuing), perceived physician competence, and associated out-of-pocket expenses. Caregivers reported dissatisfaction with government health facilities because of shorter operational hours, overcrowding, suboptimal sanitation, queuing with limited seating arrangements, and occasionally discourteous health staff. Self-medication and over-the-counter use of antibiotics was high due to a lack of awareness of the challenges of antibiotic resistance or any perceived side effects. Preference for unlicensed practitioners for medical treatment was low and based on long-term familial beliefs and acceptance. However, traditional practitioners enjoyed a high level of trust in the community from shared cultural values, enjoining attenuation of the perceived non-biological agents of childhood illnesses through non-medical supernatural interventions.

Perceptions of Good Health and Impact of COVID-19 Among Adolescents in a Low-Income Urban Agglomerate in Delhi, India: A Qualitative Study.

Adolescents constitute 16% of the global population and are susceptible to adverse health and illness from substance abuse, unhealthy diet, physical inactivity, and high-risk sexual behaviors. We conducted this study to assess the perceptions of good health, health-seeking behavior, and health service utilization among adolescents living in a low-income urban neighborhood after the second wave of the COVID-19 pandemic. A total of 23 adolescents, including 12 males and 11 females, were interviewed. Adolescents' perceived body image and size considerations apart from functioning at an optimum physical capacity as the principal attributes of good health, which was possible through the intake of a healthy diet and exercise. Adolescents were likely to be aware of the addiction potential and risk of cancer from using tobacco and alcohol, but attitudes towards eschewing their use were ambivalent. Adolescents perceived themselves as lacking access to reliable, adequate, and validated sources of sexual and reproductive health information. Knowledge and utilization of adolescent health services in this area were negligible, suggestive of the need to strengthen these services and improve the program outreach.

Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disease, has become a silent worldwide pandemic. The incidence of NAFLD correlates with the rise in obesity, type 2 diabetes, and metabolic syndrome. A hallmark featureof NAFLD is excessive hepatic fat accumulation or steatosis, due to dysregulated hepatic fat metabolism, which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Currently, there are no approved pharmacotherapies to treat this disease. Here, we have found that activation of the kisspeptin 1 receptor (KISS1R) signaling pathway has therapeutic effects in NAFLD. Using high-fat diet-fed mice, we demonstrated that a deletion of hepatic Kiss1r exacerbated hepatic steatosis. In contrast, enhanced stimulation of KISS1R protected against steatosis in wild-type C57BL/6J mice and decreased fibrosis using a diet-induced mouse model of NASH. Mechanistically, we found that hepatic KISS1R signaling activates the master energy regulator, AMPK, to thereby decrease lipogenesis and progression to NASH. In patients with NAFLD and in high-fat diet-fed mice, hepatic KISS1/KISS1R expression and plasma kisspeptin levels were elevated, suggesting a compensatory mechanism to reduce triglyceride synthesis. These findings establish KISS1R as a therapeutic target to treat NASH.

Isolated pulmonary valve endocarditis with pulmonary annular abscess in a patient of Noonan syndrome.

Right-sided endocarditis is a rare entity, with various series reporting an incidence of 5%-10%. Pulmonary valve (PV) is not only the least commonly involved valve in infective endocarditis (IE), with an incidence of 1.5%-2%, but 'isolated' pulmonic valve endocarditis (PVE) without tricuspid valve involvement is even rarer with limited published data. We report a middle-aged man with Noonan syndrome and a dysplastic PV with severe pulmonary stenosis. He presented with a large isolated mobile PV vegetation with moderate pulmonary regurgitation (PR). Initially, he was managed conservatively, but due to persistent fever, pulmonary regurgitation and evidence of pulmonary annular abscess extending into the right ventricular outflow tract, he required surgical intervention. Considering the low incidence of isolated PVE, it poses a challenge for physicians in prompt diagnosis and timely management of the infection.

Bacterial Cellulose Cultivations Containing Gelatin Form Tunable, Highly Ordered, Laminae Structures with Fourfold Enhanced Productivity.

Manipulation of bacterial cellulose (BC) morphology is important to tune BC properties to meet specific application requirements. In this study, gelatin was added to cultivation media at 0.1-7.5 wt %. After cultivations, gelatin was removed from the BC matrix, and its effects on BC matrix characteristics and fermentation production efficiency were determined. Higher contents of gelatin in cultivation media (up to 5%) resulted in BC that, from scanning electron microscopy observations, had larger pore sizes and formation of a lamina morphology that was highly unidirectional. Crystallinity remained unchanged between 0.1 and 5 wt % gelatin concentrations (92-95%); however, it decreased to 86% at a gelatin concentration of 7.5 wt %. Mechanical properties showed a positive trend as both the specific modulus and specific strength values increased as the gelatin concentration increased to 5 wt %. A breakdown in the ordered structure of the BC matrix occurs at 7.5 wt % gelatin, with corresponding decreases in the specific modulus and specific strength of the BC. The productivity increased by almost 4-fold relative to the control, reaching 1.64 g·L-1h-1 at the 2.5 wt % gelatin content. Also, the water holding capacity increased by 3-fold relative to the control, reaching 306.6 g of water per g BC at the 5.0 wt % gelatin content. The changes observed in these BC metrics can be explained based on literature findings associated with the formation of gelatin aggregates in the cultivation media and an increase in gel stiffness seen at higher media gelatin concentrations. Overall, this work provides a roadmap for manipulating BC properties while creating highly organized lamina morphologies.

Long term outcomes in patients with RF/RHD: Eight-year follow-up of HP-RF/RHD (Himachal Pradesh Rheumatic Fever/Rheumatic Heart Disease) registry in a Northern Indian state.

BACKGROUND: The long-term outcome data in patients with rheumatic fever/rheumatic heart disease (RF/RHD) is limited. We report the cumulative incidence of adverse outcomes in a cohort of RHD patients from a northern state of India at a median follow-up of 5.4 years. METHODS: 1714 patients with RF/RHD diagnosed using clinical and echocardiographic criteria were registered from 2011 to 2018, and their baseline clinical characteristics and treatment practices were recorded. Patients were followed up annually for a median of 5.4 years (range 1-8 years) for incident adverse outcomes. The cumulative incidence of adverse composite outcomes, all-cause mortality, hospitalization for heart failure, stroke, and/or peripheral embolism was estimated. The baseline clinical characteristics were explored to identify the potential risk predictors using a multivariate cox proportional hazard model. RESULTS: The cumulative incidence of adverse composite outcomes was 17.1% (15.3%-19.0%) at a median follow-up of 5.4 years. The predictors for the adverse composite outcomes (hazard ratio, 95% confidence interval) were age (1.03, 1.02-1.04), education status below primary level (1.60, 1.23-2.05), severe valvular heart disease (1.74, 1.36-2.23), NYHA class III/IV at enrollment (1.56, 1.18-2.07), right heart failure (4.48, 2.85-6.95), history of stroke and/or peripheral embolism (3.7, 1.5-9.2) and mitral balloon valvuloplasty (0.62, 0.40-0.96). CONCLUSIONS: The incidence of adverse outcomes is substantial in patients with RF/RHD. Thus, early detection of high-risk patients and their risk management is needed to improve outcomes.

Seroprevalence of SARS-CoV-2 and Risk Assessment Among Healthcare Workers at a Dedicated Tertiary Care COVID-19 Hospital in Delhi, India: A Cohort Study.

Background Healthcare workers (HCWs) have a substantially higher risk of Covid-19 infection but there is a paucity of information on the risk factors of disease transmission in high-burden real-world settings. The study objective was to determine the seroprevalence of SARS-CoV-2 among healthcare workers in a high-burden Covid-19 setting and to estimate the incidence and identify the risk factors of infection. Methods This was a prospective observational cohort study amongst doctors and nurses working at a dedicated Covid-19 tertiary care government hospital in Delhi, India. A baseline blood sample (2-3ml) was collected from all the participants to test for the presence of total SARS-CoV-2 antibodies. The HCWs that were seronegative (non-reactive) at baseline were followed-up for ≥21≤28 days with the collection of a second blood sample to assess for the incidence of SARS-CoV-2 infection. Results A total of 321 (51.3%, 95% C.I 47.4, 55.3) HCWs were detected with SARS-CoV-2 antibodies on baseline examination. The seroprevalence, when adjusted for assay characteristics, was 54.5% (95% C.I 50.3, 58.6). On bivariate analysis, SARS-CoV-2 antibody positivity lacked statistically significant association with either age, sex, occupation, cumulative duty duration, and smoking status. The incidence of seroconversion in the baseline seronegative cohort on follow-up after 21-28 days was observed in 35 (14.9%) HCWs (n=245). Furthermore, the self-reported adherence to infection prevention and control measures did not show a statistically significant association with antibody positivity in the HCWs, neither at baseline nor on follow-up. Conclusions  The high risk of SARS-CoV-2 transmission in HCWs may be substantially reduced by adherence to Infection Prevention Control (IPC) and protective measures.

Gender differences in the epidemiology of Rheumatic Fever/Rheumatic heart disease (RF/RHD) patient population of hill state of northern India; 9 years prospective hospital based, HP-RHD registry.

OBJECTIVES: We report the gender-based differences in the prevalence, severity, pattern of valvular involvement, and complications in patients with Rheumatic Fever/Rheumatic heart disease (RF/RHD). METHODS: The 2475 consecutive patients with RF/RHD diagnosed using clinical and echocardiographic criteria were registered prospectively from January 2011 till December 2019. The association of gender with the pattern of valvular involvement, nature, and severity of valvular dysfunction and cardiovascular complications was analyzed using a logistic regression model, and odds ratios with 95% CI were estimated. RESULTS: The mitral and tricuspid valve involvement was significantly lower in the male gender, odds ratio with 95% CI of 0.55 (0.44-0.61), and 0.69 (0.58-0.83) respectively, while the aortic valve was affected more frequently than females, odds ratio 1.36 (1.14-1.62). The severity of valvular disease had no significant association with gender, 0.99 (0.82-1.20). The association between gender and cardiovascular complications, heart failure, stroke, and atrial fibrillations were not statistically significant. The prevalence of RF/RHD was more than two-fold higher in female gender than male (71.4% vs. 29.6%, p < 0.0001). CONCLUSIONS: RF/RHD is more prevalent in females. Gender has a significant association with the pattern of valvular involvement. The severity of valvular dysfunction and cardiovascular complications had no significant association with gender.

Uterine Gpr83 mRNA is highly expressed during early pregnancy and GPR83 mediates the actions of PEN in endometrial and non-endometrial cells.

OBJECTIVE: To characterize the expression and signaling of uterine GPR83 in vivo in the nonpregnant and pregnant mouse and in vitro in human endometrial and nonendometrial cells. DESIGN: Controlled laboratory study. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Expression of uterine Gpr83 was determined by quantitative polymerase chain reaction throughout the estrous cycle and during early pregnancy in ovarian-stimulated and non-ovarian-stimulated mice and pregnant and pseudopregnant mice. Expression was also determined in ovariectomized mice after the administration of oil, E2, P4, or E2 + P4 and in stromal cells following 6 days of in vitro decidualization. GPR83 signaling was studied in human endometrial and embryonic kidney cell lines. Cells were treated by PEN, a GPR83 ligand, and PEN-induced extracellular signal-regulated kinase (ERK) phosphorylation was assayed under conditions that blocked Gαq/11 and/or ß-arrestin signaling. RESULTS: Uterine Gpr83 is expressed throughout the estrous cycle and during early pregnancy; expression increases dramatically at the time of uterine receptivity, embryo implantation, and stromal cell decidualization. In the ovariectomized mouse, hormone add-back reveals that Gpr83 expression is highly responsive to the combined treatment of E2 and P4, and studies in the ovarian-stimulated mouse show that expression is also very sensitive to changes in E2 and P4 and is therefore tightly regulated by E2 and P4. At the implantation site, expression is elevated up to D6 of pregnancy and then declines rapidly on D7 and D8, suggesting that if there is any involvement in decidualization, it is likely associated with primary but not secondary stromal cell decidualization. This premise was supported by the observation that stromal cell decidualization in vitro progresses with a decline in Gpr83 expression. In ERα/PR-expressing endometrial Ishikawa cells, GPR83 mediates PEN signals in a Gαq/11-dependent manner, and studies conducted in HEK 293 cells lacking ß-arrestin revealed that GPR83 also signals via a ß-arrestin-dependent manner. When signaling by either one or both pathways is downregulated, cells exhibit a major reduction in responsiveness to PEN treatment, demonstrating that signaling by both pathways is significant. CONCLUSION: We hypothesize that PEN/GPR83 signaling regulates uterine receptivity, embryo implantation, and primary stromal cell decidualization by coupling to Gαq/11- and ß-arrestin-dependent pathways.