Analyzing indications for caesarean delivery in a tertiary care facility in India by Robsons Ten Group Classification System: journey to reduce maternal mortality-audit caesarean rates: a prospective observational design

Background: Rising caesarean rates pose a challenge to obstetricians, the healthcare system, and the national economy. High rate of caesarean without clear evidence of a decrease in maternal and neonatal morbidity is matter of concern. The era of impatient obstetricians, and caesareans on demand are major contributing factors. The purpose of this study is to validateTGCS classification for indications of caesarean. This would help to audit and streamline the indications of caesarean. Standardization of indications is the need of the hour. Learning from what has happened in background of local situations is the main aim of this work. Methods: In a prospective observational design, 1140 women who underwent caesarean for varied indications in C R Gardi Hospital Ujjain were recruited. Patients were classified according to Robson’s Ten Group Classification System. Every woman was observed for post-cesarean morbidities like wound dehiscence, anemia, postpartum hemorrhage, and puerperal sepsis. Neonates were observed for NICU admission, low birth weight, prematurity, respiratory distress syndrome, meconium aspiration syndrome, and death. Chi- Square and student t test were used for analysis. Results: 45.8% of women were of group 5. Modifiable indications were 60.2% in the primary caesarean of group 5. PPH, puerperal sepsis, PNC anemia, wound dehiscence, DVT, rupture uterus and NICU admission, respiratory distress syndrome of neonates were significantly high in group 5 ( p= less than 0.05). Conclusions: Out of all caesarean 45.8% are second caesarean for previous one caesarean. PPH, puerperal sepsis, wound dehiscence and PNC anemia are significantly high in group 5

Impaired recognition and regulation of disgust is associated with distinct but partially overlapping patterns of decreased gray matter volume in the ventroanterior insula

Background The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. Methods We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased gray matter volume at a significance level p <=.05 corrected for family-wise error across the whole brain and within the insula. Results Patients with behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less gray matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased gray matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased gray matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. Conclusions These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes

NGC 5846-UDG1: A Galaxy Formed Mostly by Star Formation in Massive, Extremely Dense Clumps of Gas

It has been shown that ultra-diffuse galaxies (UDGs) have higher specific frequencies of globular clusters, on average, than other dwarf galaxies with similar luminosities. The UDG NGC 5846-UDG1 is among the most extreme examples of globular cluster-rich galaxies found so far. Here we present new Hubble Space Telescope observations and analysis of this galaxy and its globular cluster system. We find that NGC 5846-UDG1 hosts 54 ± 9 globular clusters, three to four times more than any previously known galaxy with a similar luminosity and higher than reported in previous studies. With a galaxy luminosity of L V,gal ≈ 6 × 107 L ⊙ (M ⋆ ≈ 1.2 × 108 M ⊙) and a total globular cluster luminosity of L V,GCs ≈ 7.6 × 106 L ⊙, we find that the clusters currently comprise ∼13% of the total light. Taking into account the effects of mass loss from clusters during their formation and throughout their lifetime, we infer that most of the stars in the galaxy likely formed in globular clusters, and very little to no normal low-density star formation occurred. This result implies that the most extreme conditions during early galaxy formation promoted star formation in massive and dense clumps, in contrast to the dispersed star formation observed in galaxies today

A novel rapamycin analog is highly selective for mTORC1 in vivo.

Rapamycin, an inhibitor of mechanistic Target Of Rapamycin Complex 1 (mTORC1), extends lifespan and shows strong potential for the treatment of age-related diseases. However, rapamycin exerts metabolic and immunological side effects mediated by off-target inhibition of a second mTOR-containing complex, mTOR complex 2. Here, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for mTORC1 than rapamycin. DL001 inhibits mTORC1 in cell culture lines and in vivo in C57BL/6J mice, in which DL001 inhibits mTORC1 signaling without impairing glucose homeostasis and with substantially reduced or no side effects on lipid metabolism and the immune system. In cells, DL001 efficiently represses elevated mTORC1 activity and restores normal gene expression to cells lacking a functional tuberous sclerosis complex. Our results demonstrate that highly selective pharmacological inhibition of mTORC1 can be achieved in vivo, and that selective inhibition of mTORC1 significantly reduces the side effects associated with conventional rapalogs

Galaxies lacking dark matter produced by close encounters in a cosmological simulation

The standard cold dark matter plus cosmological constant model predicts that galaxies form within dark-matter haloes, and that low-mass galaxies are more dark-matter dominated than massive ones. The unexpected discovery of two low-mass galaxies lacking dark matter immediately provoked concerns about the standard cosmology and ignited explorations of alternatives, including self-interacting dark matter and modified gravity. Apprehension grew after several cosmological simulations using the conventional model failed to form adequate numerical analogues with comparable internal characteristics (stellar masses, sizes, velocity dispersions and morphologies). Here we show that the standard paradigm naturally produces galaxies lacking dark matter with internal characteristics in agreement with observations. Using a state-of-the-art cosmological simulation and a meticulous galaxy-identification technique, we find that extreme close encounters with massive neighbours can be responsible for this. We predict that ~30% of massive central galaxies (with at least 1011 solar masses in stars) harbour at least one dark-matter-deficient satellite (with 108–109 solar masses in stars). This distinctive class of galaxies provides an additional layer in our understanding of the role of interactions in shaping galactic properties. Future observations surveying galaxies in the aforementioned regime will provide a crucial test of this scenario

Development and Validation of a Prediction Model for Perinatal Arterial Ischemic Stroke in Term Neonates

Importance: Perinatal arterial ischemic stroke (PAIS) is a focal brain injury in term neonates that is identified postnatally but is presumed to occur near the time of birth. Many pregnancy, delivery, and fetal factors have been associated with PAIS, but early risk detection is lacking; thus, targeted treatment and prevention efforts are currently limited. Objective: To develop and validate a diagnostic risk prediction model that uses common clinical factors to predict the probability of PAIS in a term neonate. Design, Setting, and Participants: In this diagnostic study, a prediction model was developed using multivariable logistic regression with registry-based case data collected between January 2003, and March 2020, from the Alberta Perinatal Stroke Project, Canadian Cerebral Palsy Registry, International Pediatric Stroke Study, and Alberta Pregnancy Outcomes and Nutrition study. Criteria for inclusion were term birth and no underlying medical conditions associated with stroke diagnosis. Records with more than 20% missing data were excluded. Variable selection was based on peer-reviewed literature. Data were analyzed in September 2021. Exposures: Clinical pregnancy, delivery, and neonatal factors associated with PAIS as common data elements across the 4 registries. Main Outcomes and Measures: The primary outcome was the discriminative accuracy of the model predicting PAIS, measured by the concordance statistic (C statistic). Results: Of 2571 term neonates in the initial analysis (527 [20%] case and 2044 [80%] control individuals; gestational age range, 37-42 weeks), 1389 (54%) were male, with a greater proportion of males among cases compared with controls (318 [60%] vs 1071 [52%]). The final model was developed using 1924 neonates, including 321 cases (17%) and 1603 controls (83%), and 9 clinical factors associated with risk of PAIS in term neonates: maternal age, tobacco exposure, recreational drug exposure, preeclampsia, chorioamnionitis, intrapartum maternal fever, emergency cesarean delivery, low 5-minute Apgar score, and male sex. The model demonstrated good discrimination between cases and controls (C statistic, 0.73; 95% CI, 0.69-0.76) and good model fit (Hosmer-Lemeshow P = .20). Internal validation techniques yielded similar C statistics (0.73 [95% CI, 0.69-0.77] with bootstrap resampling, 10-fold cross-validated area under the curve, 0.72 [bootstrap bias-corrected 95% CI, 0.69-0.76]), as did a sensitivity analysis using cases and controls from Alberta, Canada, only (C statistic, 0.71; 95% CI, 0.65-0.77). Conclusions and Relevance: The findings suggest that clinical variables can be used to develop and internally validate a model to predict the risk of PAIS in term neonates, with good predictive performance and strong internal validity. Identifying neonates with a high probability of PAIS who could then be screened for early diagnosis and treatment may be associated with reductions in lifelong morbidity for affected individuals and their families

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations—Special report from the ILAE Task Force on Neonatal Seizures

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic–ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor

Predicting Friendship Quality in Autism Spectrum Disorders and Typical Development

The role played by social relationship variables (attachment security; mother–child relationship qualities) and social-cognitive capacities (theory of mind) was examined in both observed friendship behaviors and in children’s descriptions of friendships (age 8–12) with high functioning children with autism spectrum disorders (HFASD) (n = 44) and with typical development (TYP) (n = 38). Overall, half of the HFASD sample (54.45%) reported maternal attachment security, corroborating data from younger children with ASD. The hypothesized predictors and their interrelations had both direct and indirect effects on friendship for both groups of children, highlighting the importance of these factors in children’s friendship development and suggesting both compensatory and amplification mechanisms for friendship qualities. Practical and clinical implications are discussed for friendship support in both ASD and TYP

25-hydroxyvitamin D concentration is inversely associated with serum MMP-9 in a cross-sectional study of African American ESRD patients

BACKGROUND: Circulating 25-hydroxyvitamin D [25(OH)D] concentration is inversely associated with peripheral arterial disease and hypertension. Vascular remodeling may play a role in this association, however, data relating vitamin D level to specific remodeling biomarkers among ESRD patients is sparse. We tested whether 25(OH)D concentration is associated with markers of vascular remodeling and inflammation in African American ESRD patients.METHODS: We conducted a cross-sectional study among ESRD patients receiving maintenance hemodialysis within Emory University-affiliated outpatient hemodialysis units. Demographic, clinical and dialysis treatment data were collected via direct patient interview and review of patients records at the time of enrollment, and each patient gave blood samples. Associations between 25(OH)D and biomarker concentrations were estimated in univariate analyses using Pearson's correlation coefficients and in multivariate analyses using linear regression models. 25(OH) D concentration was entered in multivariate linear regression models as a continuous variable and binary variable (<15 ng/ml and =15 ng/ml). Adjusted estimate concentrations of biomarkers were compared between 25(OH) D groups using analysis of variance (ANOVA). Finally, results were stratified by vascular access type.RESULTS: Among 91 patients, mean (standard deviation) 25(OH)D concentration was 18.8 (9.6) ng/ml, and was low (<15 ng/ml) in 43% of patients. In univariate analyses, low 25(OH) D was associated with lower serum calcium, higher serum phosphorus, and higher LDL concentrations. 25(OH) D concentration was inversely correlated with MMP-9 concentration (r = -0.29, p = 0.004). In multivariate analyses, MMP-9 concentration remained negatively associated with 25(OH) D concentration (P = 0.03) and anti-inflammatory IL-10 concentration positively correlated with 25(OH) D concentration (P = 0.04).CONCLUSIONS: Plasma MMP-9 and circulating 25(OH) D concentrations are significantly and inversely associated among ESRD patients. This finding may suggest a potential mechanism by which low circulating 25(OH) D functions as a cardiovascular risk factor