Structural basis of the mycobacterial stress-response RNA polymerase auto-inhibition via oligomerization

Biological processes can be regulated via oligomerization of macromolecules into high-order symmetric structures. Here, authors reported high-order structure of RNA polymerase and its role in regulation of gene expression in pathogenic bacterium

Evaluation of short-term outcomes of impaired creatinine clearance in patients with acute coronary syndromes: A prospective cohort study at tertiary care center

Background: Chronic kidney disease is commonly seen in patients presenting with acute coronary syndrome (ACS), and it has been shown to have poor outcomes. We evaluated the prevalence of impaired creatinine clearance and its impact on short-term clinical outcomes in patients admitted with ACS without prior documented chronic renal disease. Materials and Methods: The present study was an observational, prospective cohort study conducted at a tertiary care center in North India. In patients admitted with a diagnosis of ACS, glomerular filtration rate was estimated (eGFR) by the Modification of Diet in Renal Disease Study Equation. Patients with eGFR 90 mL/min comprised control group. The study group was further categorized into three subgroups on the basis of eGFR (<30 mL/min; 30–59 mL/min; 60–89 ml/min). The primary outcomes compared between study and control group were major adverse cardiac event (MACE) (composite of death, reinfarction, congestive heart failure, cardiogenic shock, and arrhythmia). The secondary outcome measures were individual components of primary outcome. Results: Among the 200 enrolled patients with ACS, the prevalence of impaired creatinine clearance was 29.5%. The study cohort had higher rates of MACE (28.8 vs. 9.2%, P ≤≤ 0.0001), in-hospital mortality (13.6 vs. 3.5%, P = 0.009), and overall mortality (15.3 vs. 5.1%, P = 0.014) as compared to control group. However, the 30-day mortality was not significantly different. The MACE in the study subgroups was higher in eGFR 30–60 mL/min (odds ratio [OR] 3.97) subgroup followed by eGFR 1.5 mg/dl) enhances the ability to predict death by 33% and MACE events by 143%. The OR for predicting death with various cutoff of eGFR was as follows: eGFR <30 ml/min – 3.61, eGFR: 30–60 ml/min – 4.2 and eGFR: 60–90 ml/min – 0.5. Conclusion: Almost one-third of the patients presenting with ACS have impaired creatinine clearance. Patients with impaired creatinine clearance have worse outcome in hospital vis-a-vis their contemporary groups with normal eGFR. eGFR is a better risk assessment parameter than SCr for predicting MACE and overall mortality in ACS patients

Lipid Profile and Small Dense Low-Density Lipoprotein in Acute Coronary Syndrome Patients: Relationships to Demographic, Clinical, Angiographic, and Therapeutic Variables

Background: Several lines of evidence have supported small dense low-density lipoproteins (sd-LDL) as a marker of cardiovascular disease. The present study assessed the relationship between lipid profile and sd-LDL levels with demographic, clinical, angiographic, and therapeutic variables in acute coronary syndrome (ACS) patients. Methods: This was a single-centre, prospective, cross-sectional study conducted from September 2014 to September 2015. Patients with a diagnosis of ACS were included in this study. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined by direct homogenous assay and sd-LDL levels were calculated using an earlier described equation by Srisawadi et al. Results: A total of 200 patients with a diagnosis of ACS were studied. Males constituted 78% of the population cohort and almost 45% of participants were aged &lt;45 years. Patients aged &le;45 years displayed higher mean sd-LDL levels of 30.40 &plusmn; 14.18 mg/dL versus patients aged &gt;45 years with mean sd-LDL levels of 28.01 &plusmn; 11.58 mg/dL, but the difference was not statistically significant (p = 0.19). Females also displayed higher mean sd-LDL levels, but the difference also failed to achieve statistical significance (30.95 &plusmn; 13.44 mg/dL and 28.54 &plusmn; 12.64, respectively; p = 0.185). Diabetics had higher mean sd-LDL levels (33.64 &plusmn; 13.01 mg/dL and 28.07 &plusmn; 12.60 mg/dL; p = 0.273) whilst smokers had lower mean levels (27.21 &plusmn; 12.12 mg/dL and 30.51 &plusmn; 13.21 mg/dL, respectively; p = 0.071). However, the ratio of sd-LDL/lb-LDL (large buoyant LDL) was significantly higher in diabetics (0.48 vs. 0.39; p = 0.023). In the angiography cohort (n = 88), single-vessel disease was the most predominant overall while among patients aged &gt;45 years, triple-vessel disease was significantly higher (p = 0.005). Similarly, the sd-LDL levels were 33.12 &plusmn; 11.13 mg/dL, 27.68 &plusmn; 9.80 mg/dL, and 31.65 &plusmn; 15.26 mg/dL among patients with single, double, and triple-vessel disease and did not differ significantly (p = 0.262). Prior statin users had significantly lower mean sd-LDL levels of 24.79 &plusmn; 12.23 mg/dL compared to statin-na&iuml;ve patients with a mean sd-LDL of 30.01 &plusmn; 12.79 mg/dL (p = 0.027). Non-HDL levels were also significantly lower in prior statin users (112.83 mg/dL vs. 128.9 mg/dL; p = 0.017). Conclusion: In this cohort of ACS patients, age, sex, diabetes, smoking, and the angiographic severity of coronary artery disease had no significant impact on sd-LDL levels, while prior statin usage led to significantly lower sd-LDL levels. Diabetic patients, however, did have significantly higher sd-LDL/lb-LDL ratios

Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme

Introduction Around 9% of India’s children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants &lt;5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures.Methods This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants’ GMs twice, that is, within 2 months after birth and at 3–5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12–24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12–24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA.Ethics and dissemination G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings