Vitamin D status of pregnant women and their infants in South India: VIPIS study

Background: Aim was to estimate the prevalence of vitamin D deficiency in pregnant women and their infants and to analyse the effect of maternal vitamin D deficiency on the infant.Methods: A prospective study was done in the Department of Obstetrics and Neonatology in a tertiary centre in South India with 150 women seen in the antenatal clinic after 36 weeks of pregnancy were recruited. Serum vitamin D levels were obtained. Babies were followed up and sampled once between 10 and 20 weeks of age for vitamin D, calcium, phosphate and alkaline phosphatase. Vitamin D levels less than 20 ng/ml was considered as deficiency. Analysis of the data was done using SPSS 16.0 version.Results: Vitamin D deficiency was seen in 64.8% of the pregnant women. Follow up of 76 babies showed vitamin D deficiency in 72.6% infants. Significantly high levels of alkaline phosphatase were noted in infants who were born to mothers with vitamin D deficiency, which indicates risk of developing bone disease.Conclusions: This study highlights the high prevalence of Vitamin D deficiency in pregnant women and their infants in South India in a region with abundant sunshine. This study also emphasises treating vitamin D deficiency in pregnancy to reduce the risk of developing rickets in infancy

CRISPR/Cas9 and next generation sequencing in the personalized treatment of Cancer

Background: Cancer is caused by a combination of genetic and epigenetic abnormalities. Current cancer therapies are limited due to the complexity of their mechanism, underlining the need for alternative therapeutic approaches. Interestingly, combining the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system with next-generation sequencing (NGS) has the potential to speed up the identification, validation, and targeting of high-value targets. Main text: Personalized or precision medicine combines genetic information with phenotypic and environmental characteristics to produce healthcare tailored to the individual and eliminates the constraints of “one-size-fits-all” therapy. Precision medicine is now possible thanks to cancer genome sequencing. Having advantages over limited sample requirements and the recent development of biomarkers have made the use of NGS a major leap in personalized medicine. Tumor and cell-free DNA profiling using NGS, proteome and RNA analyses, and a better understanding of immunological systems, are all helping to improve cancer treatment choices. Finally, direct targeting of tumor genes in cancer cells with CRISPR/Cas9 may be achievable, allowing for eliminating genetic changes that lead to tumor growth and metastatic capability. Conclusion: With NGS and CRISPR/Cas9, the goal is no longer to match the treatment for the diagnosed tumor but rather to build a treatment method that fits the tumor exactly. Hence, in this review, we have discussed the potential role of CRISPR/Cas9 and NGS in advancing personalized medicine

Half-sandwich Ru(η6-C6H6) complexes with chiral aroylthioureas for enhanced asymmetric transfer hydrogenation of ketones – experimental and theoretical studies

The reactions of [RuCl2(η6-C6H6)]2 with chiral aroylthiourea ligands yielded pseudo-octahedral half-sandwich “piano-stool” complexes. All the Ru(II) complexes were characterized by analytical and spectral (UV-visible, FT-IR, 1H NMR and 13C NMR) studies. The molecular structures of the ligands (L2 and L4) and the complexes (2, 4 and 5) were confirmed by single crystal XRD. All the complexes were successfully screened as catalysts for the asymmetric transfer hydrogenation (ATH) of ketones using 2-propanol as the hydrogen source in the presence of KOH. The ATH reactions proceeded with excellent yields (up to 99%) and very good enantioselectivity (up to 99% ee). The scope of the present catalytic system was extended to substituted aromatic ketones and few hetero-aromatic ketones. Density functional theory (DFT) calculations predicted non-classical, concerted transition states for the ATH reactions. The catalytic activity of Ru–benzene complexes toward asymmetric reduction of ketones was significantly higher compared to that of p-cymene complex analogues. Such enhanced efficiency and product selectivity of Ru–benzene complexes compared to those of Ru–p-cymene complexes were rationalized by the computational study

Association of Initial and Serial C-Reactive Protein Levels with Adverse Cardiovascular Events and Death after Acute Coronary Syndrome: A Secondary Analysis of the VISTA-16 Trial

Importance: Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized. Objective: To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death. Design, Setting, and Participants: Secondary analysis of the double-blind, multicenter, randomized clinical Vascular Inflammation Suppression to Treat Acute Coronary Syndromes for 16 Weeks (VISTA-16) trial conducted between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012), which included 5145 patients from 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America assigned to receive varespladib or placebo on a background of atorvastatin treatment beginning within 96 hours of presentation with an ACS. The present study evaluated data from patients with available baseline and longitudinal hsCRP levels measured at weeks 1, 2, 4, 8, and 16 after randomization to treatment or placebo. Statistical analysis was performed from June 15, 2018, through September 15, 2018. Main Outcomes and Measures: Outcomes were MACE (composite of cardiovascular death, myocardial infarction, nonfatal stroke, or unstable angina with documented ischemia requiring hospitalization), cardiovascular death, and all-cause death after adjustment for baseline clinical, treatment, and laboratory characteristics, including baseline hsCRP levels. Results: Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P =.001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P <.001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41], P =.02; longitudinal: HR, 1.26 per SD [95% CI, 1.19-1.34], P <.001) and between baseline and longitudinal hsCRP levels and all-cause death (baseline: HR, 1.58 per SD [95% CI, 1.07-2.35], P =.02; longitudinal: HR, 1.25 per SD [95% CI, 1.18-1.32], P <.001). Conclusions and Relevance: Initial and subsequent increases in hsCRP levels during 16 weeks after ACS were associated with a greater risk of the combined MACE end point, cardiovascular death, and all-cause death despite established background therapies. Serial measurements of hsCRP during clinical follow-up after ACS may help to identify patients at higher risk for mortality and morbidity.

LDL-C Targets in Secondary Prevention: How Low Should We Go?

The benefits of lowering low-density lipoprotein cholesterol (LDL-C), mainly using high-intensity statin therapy, and its impact on decreasing the recurrence of atherosclerotic cardiovascular disease (ASCVD) in secondary prevention has been well established. With the advent of non-statin medications, particularly PCSK-9 inhibitors, which can lower LDL-C to very low levels not seen before, it is important to answer some important questions regarding LDL-C lowering and the uses of these medications in clinical practice: how low should we go with LDL-C reduction? Is there a threshold beyond which lower LDL-C is not associated with any benefit and possibly harm? Does the benefit derived from more aggressive LDL-C lowering justify the cost of additional therapies? Our review has found overwhelming evidence to support the conclusion that lower achieved LDL-C levels correlate with a decreased burden of atherosclerosis and better clinical outcomes in secondary prevention. The concern for adverse effects with very low LDL-C levels is not backed by the literature, and side effects appear to be medication-specific. There still remains a question of the cost-effectiveness of some non-statin therapies particularly PCSK9 inhibitors, in spite of recent price decreases, and whether the benefit is worth the cost. It is prudent to always pursue an individualized patient-level approach to LDL-C lowering that considers the patient’s global cardiovascular risk, their side effect profile, and the cost-effectiveness of therapies in order to derive maximal benefit from aggressive lipid lowering.Other Information Published in: Current Cardiovascular Risk Reports License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s12170-019-0619-8</p