GBA deficit helps bring about SNCA/α-synuclein piling up by way of autophagic inhibition by simply inactivated PPP2A.
Consanguineous marriage (CM) has been linked to spontaneous abortion (SAB), although studies have largely been cross-sectional and likely underestimated early loss. We aimed to determine the relationships between CM and SAB in a prospective pregnancy cohort study in Telangana State, India. Data from 661 participants aged 15-35years in the Longitudinal Indian Family hEalth (LIFE) study actively followed for pregnancy and pregnancy loss were analyzed. SAB was classified as early (< 8) or late (8-22) weeks gestation. We used logistic regression to model the relationships between CM, defined by first-cousin marriage, and SAB, adjusted for maternal age. Women in CM were at a modestly increased risk of any (OR 1.15, 95% CI 0.69, 1.91) and early (OR 2.03, 95% CI 0.85, 4.83) SAB compared to women in non-CM, although results were not statistically significant. There was no relationship between CM and late SAB. Among couples in southern India, there was a modest increase in early but not late SAB among CMs which may be explained by the expected influence of chromosomal abnormalities and lethal homozygous recessive disease on early loss. Pre- and Peri-marital Health Counseling that addresses this risk may be warranted. The online version contains supplementary material available at 10.1007/s13224-021-01498-7. The online version contains supplementary material available at 10.1007/s13224-021-01498-7.It is common in obstetric practice to encounter couples who seek prenatal genetic counseling and testing in view of history of known or suspected genetic disorders in the previous offspring or in other family members. Recent advances in genetic testing techniques, especially the availability of the next-generation sequencing (NGS) technology, have greatly facilitated genetic evaluation of the proband and/or the consultand couple and enabled provision of accurate genetic counseling and prenatal genetic testing in such clinical scenarios. However, even in this era of NGS, comprehensive clinical history taking and detailed phenotype characterization through clinical examination and thorough perusal of available medical records, are very important and essential for accurate diagnosis, as reiterated by this report of a 30-year-old third gravida, who was referred for prenatal genetic counseling and testing, in view of history of death of the first offspring due to a suspected neurogenetic disorder. Retrospective clinical diagnosis for the deceased index child with the help of available medical records and reports, followed by relevant NGS-based clinical exome sequencing of the couple, helped to arrive at a definitive diagnosis of fucosidosis, based on which accurate prenatal genetic testing could be done. Preeclampsia (PE) affects 5-7% of the pregnancies worldwide, and is one of the most dreaded disorders of pregnancy contributing to maternal and neonatal mortality. PE is mostly presented in the third trimester of pregnancy. Here, we used serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to develop a model for predicting PE in Indian women in early second trimester. In this case-control study, a total 1452 healthy pregnant women were recruited. Blood samples were collected at the following gestational weeks (GWs), 12-20 (GW1), 21-28 (GW2) and 29-term (GW3), and post-delivery. Body mass index (BMI) was calculated by anthropometric measurements. Serum sFlt-1, PIGF and VEGF were analyzed by ELISA. A predictive model for PE was developed using multivariable logistic regression analysis. In PE cases, serum PlGF and VEGF levels were significantly lower at each GW, while serum sFlt-1 was lower only at GW1, relative to age-matched controls, ( = 132/group). Age-matched comparison between PE cases and controls indicated that sFlt-1 was associated with decreased PE outcome (Odds ratio. OR = 0.988, CI = 0.982-0.993), whereas sFlt-1/PlGF ratio (OR = 1.577, CI = 1.344-1.920) and BMI (OR = 1.334, CI = 1.187-1.520) were associated with increased PE outcome. buy Idasanutlin Logistic regression was used to develop a predictive model for PE at GW1. Using testing dataset, model was externally validated which resulted in 88% accuracy in predicting PE cases at 0.5 probability cutoff. Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20weeks in women with optimal sensitivity and specificity. Prediction model using sFlt-1, sFlt-1/PlGF ratio and BMI may be useful to predict PE as early as 12-20 weeks in women with optimal sensitivity and specificity. Otocephaly is a rare malformation characterized by agnathia (absence of the mandible), melotia (medially displaced ear pinna), aglossia (absence of the tongue) and microstomia (small oral aperture). This results due to failure of migration of the neural crest cells and is a defect of the first branchial arch. It is incompatible with life and early prenatal diagnosis is useful. Our patient a primigravida with 19 weeks 6 days gestationwas referred for micrognathia and polyhydramnios. On ultrasound examination, she had unilateral mild ventriculomegaly and posterior fossa cystin the fetal brain. The fetus had agnathia and anophthalmia. There was an echogenic intracardiac focus and echogenic bowel. The stomach was not seen clearly. This could be due to agnathia and microstomia leading to swallowing difficulties. The patient was explained about the guarded prognosis. The pregnancy was terminated. A diagnosis of otocephaly was made. Otocephaly is a rare disorder of development of the first branchial arch. The osis is important. A detailed face evaluation in the first trimester can help detect this defect as early as 11-14 weeks. Early diagnosis of lethal anomalies helps in completing the fetal work up and offering a safer termination. Correct diagnosis and work up of fetal anomalies allows for documentation and awareness of the presence of these conditions in our population. Menopause is a hypoestrogenic state. Menopausal symptoms like hot flushes, depression, joint pains and urinary symptoms all correlate with falling estrogen levels. Four hundred postmenopausal women who underwent natural menopause were included in the study conducted from Nov 2018 to March 2020. Surgical menopause, premature menopause and those on hormone replacement were excluded. Serum estradiol was measured and assessment of severity of menopausal symptoms was done using MRS questionnaire. MRS score of 0-4, 5-8, 9-15 and more than 16 were taken as none/minimal, mild, moderate and severe postmenopausal symptoms, respectively. Correlation between serum estradiol and symptoms was analyzed statistically. Mean age of menopause in our study population was found to be 47.2 ± 3.96years. Somatic symptoms were found maximum out of all 3 subscales in study population. Psychological subscale which included depression and mood changes was found to have the strongest correlation with serum estradiol level compared to other two subscales (somatic and genito-urinary). Psychological symptoms, somatic symptoms and genitor urinary symptoms at menopause show correlation with falling estrogen levels. We found maximum correlation of psychological symptoms with low serum estradiol level. There is an inverse correlation of serum estradiol value with menopausal symptoms, with psychological symptoms (depression, anxiety, mood changes) showing highest correlation with low estrogen levels. There is an inverse correlation of serum estradiol value with menopausal symptoms, with psychological symptoms (depression, anxiety, mood changes) showing highest correlation with low estrogen levels. Being born with low birthweight is a major determinant of perinatal, neonatal, and infant survival. Even though low birthweight-related neonatal mortality is high, there is an information gap regarding the survival status of low birthweight neonates and their predictors of mortality in Ethiopia. This study was conducted to assess the survival status and predictors of mortality among low birthweight neonates admitted to Amhara region referral hospitals in Ethiopia. A retrospective follow-up study was conducted on randomly selected low birthweight neonates admitted to the Amhara region referral hospital between January 01-2017 and December 30-2018. Data were entered into Epi-data 4.4.2.1 and exported to Stata 14 for cleaning and analysis. A cox regression model was used to analyze the data. Tables, charts, and text were used to report the results. This study revealed that 35.2% of participants died with incidence rates of 37.86 per 1000 person-day observations (95%CI 31.79-45.10). Sepsis (AHR1.72(95% CI 1.05-2.81), respiratory distress (AHR 2.03 (95% CI1.36-3.03), necrotizing enterocolitis (AHR 2.47 (95% CI 1.17-5.20), congenital anomalies (AHR2.37 (95% CI 1.36-4.13), extreme low birth weight (AHR2.62 (95% CI1.54-4.44) and prematurity (AHR 2.55 (95% CI1.10-5.92) were independent predictors of mortality. Sepsis, respiratory distress, necrotizing enterocolitis, congenital anomalies, extremely low birth weight, and premature birth were the independent predictors of mortality. Therefore, it is better for all stakeholders to focus more on the early diagnosis and management of low birth weight neonates with the factors associated with mortality. Sepsis, respiratory distress, necrotizing enterocolitis, congenital anomalies, extremely low birth weight, and premature birth were the independent predictors of mortality. Therefore, it is better for all stakeholders to focus more on the early diagnosis and management of low birth weight neonates with the factors associated with mortality.Neutrophilic dermatosis (ND) is a category of diseases characterized by trauma-induced, autoinflammatory cutaneous eruption. Comorbid systemic disease is common with a predilection for malignancy, inflammatory bowel disease, and rheumatologic disease. Rarely, it can manifest with aseptic shock, an entity referred to as necrotizing neutrophilic dermatosis (NND). NND may occur in the postoperative setting and is often misdiagnosed as a necrotizing soft tissue infection. Unfortunately, the treatment for a necrotizing soft tissue infection, namely, wide debridement, is often detrimental in the setting of NND. We present the case of a woman with underlying myelodysplastic syndrome who developed episodic postoperative hemodynamic collapse followed by delayed necrotic peristomal ulceration following colonic diversion for complicated diverticulitis. Infectious workup and operative re-exploration were unrevealing. Pathologic assessment of affected skin tissue showed changes consistent with ND, ultimately leading to the diagnosis of NND. Her clinical course dramatically improved with the initiation of immunosuppressive therapy. The mimicry of NND to a potentially lethal necrotizing soft-tissue infection creates a grave diagnostic dilemma in the postoperative period. A general lack of knowledge of NND among non-dermatologic specialists produces an opportunity for misdiagnosis and inappropriate surgical interventions, namely, serial debridement. Several clinical cues may aid in the earlier recognition of NND. The cornerstone of treatment involves systemic corticosteroid therapy with adjunctive therapy for refractory cases. NND must be considered in the differential diagnosis of necrotizing soft tissue infection as early recognition may result in the avoidance of deleterious surgical interventions.