Impact of FLAMM scoring on cesarean section rate in previous one lower segment cesarean section patient

Background: The aim of this study was to evaluate the impact of Flamm scoring for Successful VBAC (vaginal birth after cesarean) and Failed TOLAC (Emergency cesarean section) in case of previous one lower segment cesarean delivery.Methods: This is prospective observation study. Out of 150, 111 patients gave consent for TOLAC. 111 patients with previous one caesarean section with gestational weeks between 37 to 40 weeks with spontaneous onset of labour admitted in labour room of Obstetrics and Gynecology Department in Sola Civil Hospital over a period of 1 year from April 2014 to April 2015.Results: In the present study, 111 (74%) patients had undergone TOLAC trial. Out of 111, 77(69.36%) patients had successful VBAC whereas 34 (30.63%) had emergency cesarean. Among the successful VBAC, 7 patients had assisted vaginal delivery to cut short the second stage in prolonged labour. 26% patients refused to give consent for TOLAC from total number of patients in this study. Mean FLAMM score for Successful VBAC was 5.35 (95% CI, 3.9 to 6.7) compared to Failed TOLAC (EME CS) was 3.62 (95% CI, 3.27 to 4.57) Chances of success of TOLAC was increased with increasing FLAMM score according to this study.Conclusions: Application of FLAMM scoring gives fare judgment of successful vaginal birth in TOLAC. So FLAMM scoring can be applied in each previous one lower segment cesarean section patient undergoing TOLAC without increasing morbidity. Practice of protocol of applying FLAMM score and monitoring by partogram will reduce the rate of cesarean section in previous one lower segment cesarean section patient

Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance

Estrogen receptors (ERs) mediate most of the biological effects of estrogen in mammary and uterine epithelial cells by binding to estrogen response elements in the promoter region of target genes or through protein-protein interactions. Anti-estrogens such as tamoxifen inhibit the growth of ER-positive breast cancers by reducing the expression of estrogen-regulated genes. However, anti-estrogen-resistant growth of ER-positive tumors remains a significant clinical problem. Here we show that phosphatidylinositol (PI) 3-kinase and AKT activate ERα in the absence of estrogen. Although PI 3-kinase increased the activity of both estrogen-independent activation function 1 (AF-1) and estrogen-dependent activation function 2 (AF-2) of ERα, AKT increased the activity of only AF-1. PTEN and a catalytically inactive AKT decreased PI 3-kinase-induced AF-1 activity, suggesting that PI 3-kinase utilizes AKT-dependent and AKT-independent pathways in activating ERα. The consensus AKT phosphorylation site Ser-167 of ERα is required for phosphorylation and activation by AKT. In addition, LY294002, a specific inhibitor of the PI 3-kinase/AKT pathway, reduced phosphorylation of ERα in vivo. Moreover, AKT overexpression led to up-regulation of estrogen-regulated pS2 gene, Bcl-2, and macrophage inhibitory cytokine 1. We demonstrate that AKT protects breast cancer cells from tamoxifen-induced apoptosis. Taken together, these results define a molecular link between activation of the PI 3-kinase/AKT survival pathways, hormone-independent activation of ERα, and inhibition of tamoxifen-induced apoptotic regression

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics

Negative Regulation of Transactivation Function but Not DNA Binding of NF-κB and AP-1 by IκBβ1 in Breast Cancer Cells

The transcription factor NF-κB regulates the expression of genes involved in cancer cell invasion, metastasis, angiogenesis, and resistance to chemotherapy. In normal cells NF-κB is maintained in the cytoplasm by protein-protein interaction with inhibitor IκBs. In contrast, in cancer cells a substantial amount of NF-κB is in the nucleus and constitutively activates target genes. To understand the mechanisms of constitutive NF-κB activation, we have analyzed the function of IκBα and IκBβ in breast cancer cells. In most cases, constitutive NF-κB DNA binding correlated with reduced levels of either IκBα or IκBβ isoforms. Overexpression of IκBα but not IκBβ1 resulted in reduced constitutive DNA binding of NF-κB in MDA-MB-231 cells. Unexpectedly, IκBβ1 overexpression moderately increased 12-O-tetradecanoylphorbol-13-acetate- and interleukin-1-inducible NF-κB DNA binding. 12-O-Tetradecanoylphorbol-13-acetate- and interleukin-1-induced transactivation by NF-κB, however, was lower in IκBβ1-overexpressing cells. Mutants of IκBβ1 lacking the C-terminal casein kinase II phosphorylation sites, which form a stable complex with DNA bound NF-κB without inhibiting its transactivation in other cell types, repressed the transactivation by NF-κB in MDA-MB-231 cells. Consistent with the results of transient transfections, the expression of urokinase plasminogen activator, an NF-κB target gene, was reduced in IκBβ1-overexpressing cells. These results suggest that depending on the cell type, IκBβ1 represses the expression of NF-κB-regulated genes by inhibiting either DNA binding or transactivation function of NF-κB

Poder, política y privilegio: la salud pública en la frontera de Tailandia y Birmania

Los participantes de un curso de métodos de investigación de campo sobre la salud de los refugiados en la frontera de Tailandia y Birmania aprendieron que más allá de los vectores biológicos y de los procesos de las enfermedades que contribuyen al sufrimiento humano, el poder, la política y el privilegio juegan papeles centrales que afectan de forma negativa a la salud de los refugiados

Potentially Heterogeneous Cross-Sectional Associations of Seafood Consumption with Diabetes and Glycemia in Urban South Asia.

Aims: In this study, we aimed to estimate cross-sectional associations of fish or shellfish consumption with diabetes and glycemia in three South Asian mega-cities. Methods: We analyzed baseline data from 2010-2011 of a cohort (n = 16,287) representing the population ≥20 years old that was neither pregnant nor on bedrest from Karachi (unweighted n = 4017), Delhi (unweighted n = 5364), and Chennai (unweighted n = 6906). Diabetes was defined as self-reported physician-diagnosed diabetes, fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), or glycated hemoglobin A1c (HbA1c) ≥6.5% (48 mmol/mol). We estimated adjusted and unadjusted odds ratios for diabetes using survey estimation logistic regression for each city, and differences in glucose and HbA1c using survey estimation linear regression for each city. Adjusted models controlled for age, gender, body mass index, waist-height ratio, sedentary lifestyle, educational attainment, tobacco use, an unhealthy diet index score, income, self-reported physician diagnosis of high blood pressure, and self-reported physician diagnosis of high cholesterol. Results: The prevalence of diabetes was 26.7% (95% confidence interval: 24.8, 28.6) in Chennai, 36.7% (32.9, 40.5) in Delhi, and 24.3% (22.0, 26.6) in Karachi. Fish and shellfish were consumed more frequently in Chennai than in the other two cities. In Chennai, the adjusted odds ratio for diabetes, comparing more than weekly vs. less than weekly fish consumption, was 0.81 (0.61, 1.08); in Delhi, it was 1.18 (0.87, 1.58), and, in Karachi, it was 1.30 (0.94, 1.80). In Chennai, the adjusted odds ratio of prevalent diabetes among persons consuming shellfish more than weekly versus less than weekly was 1.08 (95% CI: 0.90, 1.30); in Delhi, it was 1.35 (0.90, 2.01), and, in Karachi, it was 1.68 (0.98, 2.86). Conclusions: Both the direction and the magnitude of association between seafood consumption and glycemia may vary by city. Further investigation into specific locally consumed seafoods and their prospective associations with incident diabetes and related pathophysiology are warranted

Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study

BACKGROUND: Due to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE). METHODS AND RESULTS: The Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. CONCLUSIONS: Regardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future

Lifetime risk of diabetes in metropolitan cities in India.

AIMS/HYPOTHESIS: We aimed to estimate the lifetime risk of diabetes and diabetes-free life expectancy in metropolitan cities in India among the population aged 20 years or more, and their variation by sex, age and BMI. METHODS: A Markov simulation model was adopted to estimate age-, sex- and BMI-specific lifetime risk of developing diabetes and diabetes-free life expectancy. The main data inputs used were as follows: age-, sex- and BMI-specific incidence rates of diabetes in urban India taken from the Centre for Cardiometabolic Risk Reduction in South Asia (2010-2018); age-, sex- and urban-specific rates of mortality from period lifetables reported by the Government of India (2014); and prevalence of diabetes from the Indian Council for Medical Research INdia DIABetes study (2008-2015). RESULTS: Lifetime risk (95% CI) of diabetes in 20-year-old men and women was 55.5 (51.6, 59.7)% and 64.6 (60.0, 69.5)%, respectively. Women generally had a higher lifetime risk across the lifespan. Remaining lifetime risk (95% CI) declined with age to 37.7 (30.1, 46.7)% at age 60 years among women and 27.5 (23.1, 32.4)% in men. Lifetime risk (95% CI) was highest among obese Indians: 86.0 (76.6, 91.5)% among 20-year-old women and 86.9 (75.4, 93.8)% among men. We identified considerably higher diabetes-free life expectancy at lower levels of BMI. CONCLUSIONS/INTERPRETATION: Lifetime risk of diabetes in metropolitan cities in India is alarming across the spectrum of weight and rises dramatically with higher BMI. Prevention of diabetes among metropolitan Indians of all ages is an urgent national priority, particularly given the rapid increase in urban obesogenic environments across the country. Graphical abstract

Epidemiological pattern of COVID-19 and its association with periodontal health in an urban Indian cohort

BackgroundStudies have highlighted a possible influence of gingival and periodontal disease (PD) on COVID-19 risk and severity. However, the evidence is based on hospital-based studies and community-level data are sparse.ObjectivesWe described the epidemiological pattern of SARS-CoV-2 infection in Delhi and evaluated the associations of gingival and PD with incident COVID-19 disease in a regionally representative urban Indian population.MethodsIn a prospective study nested within the Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) study, participants with clinical gingival and periodontal status available at baseline (2014–16) (n = 1,727) were approached between October 2021 to March 2022. Information on COVID-19 incidence, testing, management, severity was collected as per the WHO case criteria along with COVID-19 vaccination status. Absolute incidence of COVID-19 disease was computed by age, sex, and oral health. Differences in rates were tested using log-rank test. Poisson regression models were used to evaluate independent associations between gingival and PD and incidence of COVID-19, adjusted for socio-demographic and behavioral factors, presence of comorbidity, and medication use.ResultsAmong 1,727 participants, the mean age was 44.0 years, 45.7% were men, 84.5% participants had baseline gingival or PD and 89.4% participants had received at least one dose of COVID-19 vaccine. Overall, 35% (n = 606) participants were tested for COVID-19 and 24% (n = 146/606) tested positive. As per the WHO criteria total number of cases was 210, constituting 12% of the total population. The age and sex-specific rates of COVID-19 were higher among men and older participants, but women aged >60 years had higher rates than men of same age. The incidence rate did not differ significantly between those having gingival or PD and healthy periodontium (19.1 vs. 16.5/1,000 person-years) and there was no difference in risk of COVID-19 by baseline oral disease status.ConclusionGingival and PD were not associated with increased risk of COVID-19