In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational ...age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011–2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: − 27.1, − 14.1;
p
< 0.001) and 15 days (95%CI: − 22.1, − 8.2;
p
< 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7,
p
< .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5,
p
= 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the current global pandemic that has caused a death toll of >1.12 million worldwide and number continues to climb ...in several countries. Currently, there are neither specific antiviral drugs nor vaccines for the treatment and prevention of COVID-19. We screened in silico, a group of natural spice and herbal secondary metabolites (SMs) for their inhibition efficacy against multiple target proteins of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 protein. Docking and simulation results indicated that epicatechin, embelin, hesperidin, cafestol, murrayanine and murrayaquinone-A have higher inhibition efficacy over at least one of the known antiviral drugs such as Hydroxychloroquine, Remdesivir and Ribavirin. Combination of these potentially effective SMs from their respective plant sources was analysed, and its absorption and acute oral toxicity were examined in Wistar rats and classified as category 5 as per the Globally Harmonized System. The identified SMs may be useful in the development of preventive nutraceuticals, food supplements and antiviral drugs.
Communicated by Ramaswamy H. Sarma
Summary Background The combination of three blood-pressure-lowering drugs at low doses, with a statin, aspirin, and folic acid (the polypill), could reduce cardiovascular events by more than 80% in ...healthy individuals. We examined the effect of the Polycap on blood pressure, lipids, heart rate, and urinary thromboxane B2, and assessed its tolerability. Methods In a double-blind trial in 50 centres in India, 2053 individuals without cardiovascular disease, aged 45–80 years, and with one risk factor were randomly assigned, by a central secure website, to the Polycap (n=412) consisting of low doses of thiazide (12·5 mg), atenolol (50 mg), ramipril (5 mg), simvastatin (20 mg), and aspirin (100 mg) per day, or to eight other groups, each with about 200 individuals, of aspirin alone, simvastatin alone, hydrochlorthiazide alone, three combinations of the two blood-pressure-lowering drugs, three blood-pressure-lowering drugs alone, or three blood-pressure-lowering drugs plus aspirin. The primary outcomes were LDL for the effect of lipids, blood pressure for antihypertensive drugs, heart rate for the effects of atenolol, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, and rates of discontinuation of drugs for safety. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00443794. Findings Compared with groups not receiving blood-pressure-lowering drugs, the Polycap reduced systolic blood pressure by 7·4 mm Hg (95% CI 6·1–8·1) and diastolic blood pressure by 5·6 mm Hg (4·7–6·4), which was similar when three blood-pressure-lowering drugs were used, with or without aspirin. Reductions in blood pressure increased with the number of drugs used (2·2/1·3 mm Hg with one drug, 4·7/3·6 mm Hg with two drugs, and 6·3/4·5 mm Hg with three drugs). Polycap reduced LDL cholesterol by 0·70 mmol/L (95% CI 0·62–0·78), which was less than that with simvastatin alone (0·83 mmol/L, 0·72–0·93; p=0·04); both reductions were greater than for groups without simvastatin (p<0·0001). The reductions in heart rate with Polycap and other groups using atenolol were similar (7·0 beats per min), and both were significantly greater than that in groups without atenolol (p<0·0001). The reductions in 11-dehydrothromboxane B2 were similar with the Polycap (283·1 ng/mmol creatinine, 95% CI 229·1–337·0) compared with the three blood-pressure-lowering drugs plus aspirin (350·0 ng/mmol creatinine, 294·6–404·0), and aspirin alone (348·8 ng/mmol creatinine, 277·6–419·9) compared with groups without aspirin. Tolerability of the Polycap was similar to that of other treatments, with no evidence of increasing intolerability with increasing number of active components in one pill. Interpretation This Polycap formulation could be conveniently used to reduce multiple risk factors and cardiovascular risk. Funding Cadila Pharmaceuticals, Ahmedabad, India.
OBJECTIVES
Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart defect that has been associated with myocardial ischaemia and sudden death. There is an ongoing controversy ...over the indications for surgical intervention and the efficacy of that treatment compared with the natural history. The purpose of this study was to evaluate the medium-term results of surgical repair of AAOCA.
METHODS
Seventy-six patients underwent surgical repair of AAOCA at our institution from 1999 to 2013. There were 55 males and 21 females, and the median age at surgery was 15 years. Forty-seven (62%) of the 76 patients had an anomalous right coronary artery, 27 had an anomalous left coronary and 2 had an eccentric single coronary ostia. Forty-one patients had preoperative symptoms of myocardial ischaemia.
RESULTS
Surgical repair was accomplished by unroofing of an intramural coronary in 55, reimplantation in 7 and pulmonary artery translocation in 14. There has been no early or late mortality, with a median duration of follow-up of 6 years. One patient presented with severe myocardial ischaemia and subsequently underwent heart transplantation a year following AAOCA surgery. The remaining patients have all remained free of cardiac symptoms.
CONCLUSIONS
The results of this study demonstrate two major principles. First, surgical repair of AAOCA is quite safe in centres that take care of a significant number of patients with this entity. Secondly, the surgery is highly effective in eliminating symptoms of myocardial ischaemia. The growing amount of data on postoperative patients suggests that surgical repair can prevent the adverse events seen in the untreated ‘natural’ history. Based on these observations, it is our current recommendation that all teenagers identified with AAOCA should undergo surgical repair.
Abstract Background Moderate alcohol consumption is known to be protective against coronary heart disease (CHD). However, the INTERHEART study, a case–control study of acute myocardial infarction ...(MI) patients, revealed that alcohol consumption in South Asians was not protective against CHD. We therefore planned to study cardiovascular risk factor and CHD prevalence among male alcohol users as compared to age matched lifetime abstainers. Methods The subjects for this study were recruited from a cross-sectional survey carried out among employees and their family members aged 20–69 years in 10 medium-to-large industries from diverse sites in India, using a stratified random sampling technique. Information on education, behavioral, clinical and biochemical risk factors of CHD and alcohol use was obtained through standardized instruments. CHD diagnosis was based on Rose Questionnaire or a prior physician diagnosed CHD. Results A total of 4465 subjects were present or past alcohol users. The mean age of alcohol users and lifetime abstainers was 42.8 ± 11.0 years and 42.8 ± 11.1 years, respectively ( p = 0.90). Systolic blood pressure and diastolic blood pressure were significantly higher in alcohol users (128.7 ± 17.6 mmHg/80.1 ± 11.3 mmHg) as compared to lifetime abstainers (126.9 ± 15.9 mmHg/79.5 ± 10.3 mmHg, p < 0.01). Fasting blood sugar in alcohol users (98.7 ± 30.5 mg%) was also significantly higher than lifetime abstainers (96.6 ± 26.0 mg%, p < 0.01). Total cholesterol was lower in alcohol users (179.1 ± 41.1 mg%) as compared to lifetime abstainers (182.7 ± 38.2 mg%, p < 0.01). HDL cholesterol was higher in alcohol users (42.9 ± 10.8 mg%) as compared to lifetime abstainers (41.3 ± 10.0 mg%, p < 0.01). Body mass index (BMI) was lower in alcohol users as compared to lifetime abstainers (22.7 ± 4.1 kg/m2 vs. 24.0 ± 3.3 kg/m2 , p < 0.001). Tobacco use was significantly higher in alcohol users (63.1% vs. 20.7%). The odds ratio (OR) of having CHD after adjusting for tobacco use, BMI and education was 1.4 (95%CI 1.0–1.9) in alcohol users as compared to controls. The OR was 1.2 (95%CI 0.8–1.6) in occasional alcohol users, 1.6 (95%CI 1.0–2.2) in regular alcohol users and 2.1 (95% CI 1.1–3.0) in past alcohol users as compared to controls. Conclusion We did not observe an inverse (protective) association between alcohol intake and the prevalence of CHD. In contrast, our study indicated an association in the reverse direction, suggesting possible harm of alcohol for coronary risk in Indian men. This relationship needs to be further examined in large, prospective study.
In the present scenario of a looming food crisis, improving per hectare rice productivity at a greater pace is among the topmost priorities of scientists and breeders. In the past decades, ...conventional, mutational, and marker-assisted breeding techniques have played a significant role in developing multiple desired rice varieties. However, due to certain limitations, these techniques cannot furnish the projected food security of the 2050 population’s aching stomachs. One of the possible options would be precise crop genome editing using various tools, viz., TALENs and CRISPR/Cas9 to resolve this multifaceted crisis. Initially, the potentiality of these technologies was tested only in the rice protoplasts. Later, the techniques were employed to edit calli with help of modified vectors, CRISPR variants, cassette cloning systems, and delivery methods. With the continuous technological advancements such as base editing, multiplexing, etc., the precision, rapidness, efficiency, reliability, potency, and range of applications of these platforms have increased and even been used for gene function studies. This leads to a revolution in the field of the rice improvement program, especially the stress tolerance against various pests and pathogens in which the susceptibility factors located within the rice genome are targeted through genome editing tools. Therefore, in this current article, we have summarized the advancements in the rice genome editing tools during the last decade concerning enhanced biotic stress tolerance. Additionally, we have focused on the regulatory aspects of genome editing with associated risks and limitations, and the prospects to reshape the rice genome for durable resistance to complex biotic stress.
Prerenal acute kidney injury (prerenal AKI), hepatorenal syndrome (HRS–AKI), and acute tubular necrosis (ATN–AKI) are the various phenotypes of acute kidney injury, which are described in ...decompensated cirrhosis. It has therapeutic and prognostic implications. We aimed to evaluate the diagnostic utility of fractional excretion of sodium and urea (FENa and FEUrea) for differentiating AKI phenotypes.
A prospective analysis was performed in 200 patients with decompensated cirrhosis with AKI to derive receiver operating curve, optimal cut-off, sensitivity, and specificity. These findings were validated in an independent cohort (n = 50) to differentiate ATN–AKI, HRS–AKI, and prerenal AKI.
The incidence of prerenal AKI, HRS–AKI, and ATN–AKI were 37.5%, 34%, and 28.5% in the derivation cohort and 28%, 38%, and 34% in the validation cohort respectively. The median FENa was significantly different in various phenotypes of AKI in the derivation and validation cohort (P 0.001); FEUrea was significantly different in the derivation cohort (P 0.0001), not in the validation cohort (P 0.106). The AUC for FENa (cut-off, sensitivity/specificity) was 86.6% (0.567, 89/71) and for FEUrea was 60.3% (34.73, 70/58) for ATN–AKI vs. non-ATN–AKI. The area under the curve for FENa to differentiate between HRS–AKI vs. non-HRS–AKI was 74.5%. FEUrea could not differentiate HRS-AKI vs. non-HRS–AKI (AUC 60.4%) satisfactorily. FENa and FEUrea were unable to differentiate between prerenal AKI and HRS-AKI (AUC <70%).
Among cirrhotics FENa at admission is a simple, commonly available clinical tool that can be used to differentiate structural AKI from prerenal AKI and HRS–AKI. The newly derived lowered cut-off value of FENa makes the diagnosis of ATN-AKI easier, faster and thus obviates the need for extensive workup in a significant proportion of patients. FENa appears better than FEUrea in decompensated cirrhosis with AKI.
There are conflicting reports regarding the importance of mitral stenosis and aortic atresia as a risk factor for Norwood mortality. This study reviews outcomes of this anatomic subgroup at our ...institution and examines the utility of preoperative cardiac catheterization and its correlation with clinical outcomes and pathology findings.
This is a single-center, retrospective review of hypoplastic left heart syndrome patients who underwent modified Norwood operation between October 2005 and May 2013.
Fourteen of 74 hypoplastic left heart syndrome patients (19%) had mitral stenosis and aortic atresia. Operative mortality for MS/AA was 29% versus 7% for all other hypoplastic left heart syndrome anatomic subgroups (p = 0.04). Although only 19% of the entire cohort, the mitral stenosis and aortic atresia subgroup constituted 50% of the total operative mortality and the only interstage deaths. Autopsies support myocardial ischemia as the mechanism of death. Although preoperative angiography defined the presence of ventriculo-coronary connections, it did not clearly risk stratify patients in regard to operative mortality.
Mitral stenosis and aortic atresia is a risk factor for perioperative myocardial ischemia and mortality. Further exploration of myocardial reserve is warranted.
Key message
The topoisomerase II expression varies as a function of cell proliferation. Maximal topoisomerase II expression was tightly coupled to S phase and G2/M phase via both transcriptional and ...post-transcriptional regulation. Investigation in meiosis using pollen mother cells also revealed that it is not the major component of meiotic chromosomes, it seems to diffuse out once meiotic chromosomal condensation is completed.
Synchronized tobacco BY-2 cell cultures were used to study the role of topoisomerase II in various stages of the cell cycle. Topoisomerase II transcript accumulation was observed during the S- and G2/M- phase of cell cycle. This biphasic expression pattern indicates the active requirement of topoisomerase II during these stages of the cell cycle. Through immuno-localization of topoisomerase II was observed diffusely throughout the nucleoplasm in interphase nuclei, whereas, the nucleolus region exhibited a more prominent immuno-positive staining that correlated with rRNA transcription, as shown by propidium iodide staining and BrUTP incorporation. The immuno-staining analysis also showed that topoisomerase II is the major component of mitotic chromosomes and remain attached to the chromosomes during cell division. The inhibition of topoisomerase II activity using specific inhibitors revealed quite dramatic effect on condensation of chromatin and chromosome individualization from prophase to metaphase transition. Partially condensed chromosomes were not arranged on metaphase plate and chromosomal perturbations were observed when advance to anaphase, suggesting the importance of topoisomerase II activity for proper chromosome condensation and segregation during mitosis. Contrary, topoisomerase II is not the major component of meiotic chromosomes, even though mitosis and meiosis share many processes, including the DNA replication, chromosome condensation and precisely regulated partitioning of chromosomes into daughter cells. Even if topoisomerase II is required for individualization and condensation of meiotic chromosomes, it seems to diffuse out once meiotic chromosomal condensation is completed.
Fertilizers and herbicides are two major components in the agriculture system for achieving crop productivity. Massive use of orthophosphate fertilizers and herbicides poses threats to phosphate ...reserves and aids the evolution of herbicide tolerant weed biotypes. Phosphite (Phi), a phosphate analog, has been proposed as more beneficial than traditionally used phosphate fertilizers and herbicides in the agriculture. We developed
overexpressing transgenic rice that minimizes the phosphate loss and contributes to weed management in the agriculture. The
rice lines showed improved root, shoot length and total biomass production under phosphite conditions. Additionally, the complete phenotype and productivity of
lines under the phosphite treatment attained was similar to that of plants under phosphate sufficient condition. The Phi metabolizing properties of the
overexpressed lines improved under the Phi application and phi treatment enabled controlling of weeds without compromising the yield of transgenic rice plants. Our results indicated that
alone or in combination with other Phi metabolizing gene(s) can possibly be used as an effective ameliorating system for improving crop plants for phi-based fertilization and weed management strategy in the agriculture.
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