Beta-blocker therapy and severe heart failure: myth or reality?

The medical management of heart failure has undergone remarkable progress in the past 10 years. The paradigm shift is toward long-term reparative strategies that help in altering the biologic properties of the failing heart. Together with angiotensin-converting enzyme inhibitors, beta blockers have emerged as standard therapy for heart failure, especially for patients with mild to moderate heart failure. Since most of the clinical trials demonstrating the benefits of betablockers have been done in patients with mild to moderate heart failure, some controversy exists about the utility of beta-blocking agents in patients with advanced heart failure. This review will summarize the rationale and the use of beta blockers, a very challenging therapeutic strategy, in patients with severe heart failure.     

Carotid artery stenting: a therapeutic alternative in subtotal internal carotid artery occlusions

Carotid artery stenting (CAS) is emerging as a less invasive modality for treating atherosclerotic occlusive disease of the internal carotid artery (ICA). Randomized trials like the SAPPHIRE trial have demonstrated that CAS is not inferior to carotid endarterectomy (CEA) in the treatment of carotid artery stenosis, and maybe even superior in high-risk symptomatic patients. However, patients with subtotal ICA occlusions with thrombus are excluded from randomized CAS trials and CAS registries. To our knowledge, carotid angioplasty with stenting has not been attempted in these cases. We present three cases of symptomatic subtotal ICA occlusions successfully treated with CAS without any periprocedural complications. With careful patient selection and technical expertise, endovascular management could be considered as a treatment option in subtotal carotid occlusions.     

Usefulness of the combined index of systolic and diastolic myocardial performance to identify cardiac allograft rejection

Systolic and diastolic myocardial performance characteristics are altered during allograft rejection. Noninvasive diagnostic markers of allograft rejection have thus far not been found to be clinically useful and have not replaced routine endomyocardial biopsy as a method to detect rejection. We examined the clinical utility of the Index of Myocardial Performance (IMP), or the Tei index, a combined index of systolic and diastolic performance (derived as a composite ratio of isovolumetric contraction time and isovolumetric relaxation time to the ejection time), in evaluating and following cardiac allograft rejection. Twenty heart transplant recipients with moderate cellular rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 3A) underwent echocardiographic assessment to derive the IMP at baseline (rejection free), during treatment of rejection, and after recovery from rejection (group I). A parallel group of 20 nonrejecters (ISHLT grade 1A) were also similarly examined to serve as controls (group II). In group I patients, there was a mean increase of IMP by 98% (p <0.0001) during the rejection episode compared with baseline. After treatment, IMP decreased to its baseline value. In the control group there was no significant change in IMP over time. An IMP increase of >/=20% from baseline had 90% sensitivity and 90% specificity in detecting high-grade cardiac allograft rejection. The change in IMP in patients with grade 3A cellular rejection was independent of both the ejection fraction at baseline and change in ejection fraction during the rejection episode. These results indicate that changes in IMP, a sensitive marker of early diastolic and systolic performance, accurately evaluate the development of, and recovery from, cardiac allograft rejection. IMP can provide a clinically useful noninvasive indicator to assess the impact of therapy for amelioration of allograft rejection.     

Deep Learning Based Skin Lesion Segmentation and Classification of Melanoma Using Support Vector Machine (SVM)

Objective: The main objective of this study is to improve the classification performance of melanoma using deeplearning based automatic skin lesion segmentation. It can be assist medical experts on early diagnosis of melanomaon dermoscopy images. Methods: First A Convolutional Neural Network (CNN) based U-net algorithm is used forsegmentation process. Then extract color, texture and shape features from the segmented image using Local BinaryPattern ( LBP), Edge Histogram (EH), Histogram of Oriented Gradients (HOG) and Gabor method. Finally all thefeatures extracted from these methods were fed into the Support Vector Machine (SVM), Random Forest (RF), K-NearestNeighbor (KNN) and Naïve Bayes (NB) classifiers to diagnose the skin image which is either melanoma or benignlesions. Results: Experimental results show the effectiveness of the proposed method. The Dice co-efficiency valueof 77.5% is achieved for image segmentation and SVM classifier produced 85.19% of accuracy. Conclusion: In deeplearning environment, U-Net segmentation algorithm is found to be the best method for segmentation and it helps toimprove the classification performance.     

Effects of cardiac rehabilitation and exercise training on indexes of dispersion of ventricular repolarization in patients after acute myocardial infarction

We studied 50 consecutive patients with relatively preserved systolic function (ejection fraction >40%, mean 53 +/- 11%) after acute myocardial infarction, and assessed indexes of dispersion of ventricular repolarization before and after a formal, phase II cardiac rehabilitation and exercise training program. After cardiac rehabilitation, statistically significant reductions occurred in QT dispersion, JT dispersion, and in the heart rate corrected indexes. These benefits add to the proven benefits of formal cardiac rehabilitation and exercise training programs and may reduce the subsequent risks of malignant ventricular arrhythmias and sudden cardiac death.     

Waist to height ratio for recording the risks of overweight in schoolchildren in Kerala

The prevalence of overweight/obesity among 6000 children at 7–12 years was monitored using the established methodologies. Prevalence rates obtained using percentiles were proximate to that using waist-to-height ratio (WHTR) 0.50 and were on par with the reported rates. The prevalence were worked out with WHTR values from 0.45 to 0.53 and compared with percentiles. The minimum per cent deviation of 5.4 was observed at WHTR of 0.48 (against 6.4% at WHTR 0.50) and further the deviation at this point was distributed near-uniformly (2.6% above and 2.8% below the WHTR), suggesting that this is the optimum cutoff point for children in this region. ROC analysis against percentiles has given a higher sensitivity of 0.630 at WHTR 0.48 in this region and area under ROC curve was 0.827 at WHTR 0.48.     

Design and synthesis of 2-quinolones as antioxidants and antimicrobials: a rational approach

As an important class of compounds, 2-quinolones are isomeric to 4-quinolones and isosteric to coumarins. The compounds that have 2-quinolone moiety are associated with interesting biologic activities such as antibacterial, anticancer, antiviral, cardiotonic, and N-methyl-D-aspartate receptor inhibitor functions, among others. In the current study, based on the rational approach, lead molecules of the 2-quinolone skeleton were designed for binding to the bacterial DNA gyrase subunit A. Docking simulations and quantitative structure activity relationship (QSAR) analysis were performed using the Molegro Virtual Docker and Sarchitech softwares. Based on these studies, the 7-amino-4-methylquinolin-2(1H)-one parent compound and its carboxamides (JST 1–15) were synthesized using Conrad Limpach synthesis. The synthesized test compounds then were characterized by thin-layer chromatography and melting point determination, as well as by ultraviolet, infrared (IR), ¹H-NMR, and MS studies. All synthesized and purified compounds were tested for antioxidant and antibacterial activity.     

Elucidation of structure-activity relationship of 2-quinolone derivatives and exploration of their antitumor potential through Bax-induced apoptotic pathway

3-Aryl-2-quinolone derivates were extensively investigated for their inhibition of farnesyl transferase. Taking this as a cue, we studied the other possible mechanism of antitumor activity of 2-quinolone derivates. A series of new 2-quinolone derivatives have been synthesized and screened for their cytotoxicity by trypan blue assay on Ehrlich ascites carcinoma cells and MTT assay on MCF-7 cells. Compound 1a (nJST) was found to be more effective in both studies with the lowest CTC(50) value among all nine synthesized compounds. This compound was further screened on four different cell lines, viz. human breast adenocarcinoma (MCF-7, MDA-MB-231), colon cancer (HCT-15), murine melanoma (B16F10) cell lines for 24 and 48 h. The CTC(50) value of the compound was found to be <10 μm. Compound 1a induced DNA damage which was revealed by DNA fragmentation studies and further confirmed by nuclear staining. The compound also showed significant elevation in Bax and reduction Bcl-2 gene expression levels. Acute toxicity study in mice indicated that the compound is safe till 2000 mg/kg. Two different doses 50 and 100 mg/kg were selected and studied in Ehrlich ascites carcinoma model of cancer and have shown significant improvement in survival time and hematological parameters.     

Augmenting BMI and Waist-Height Ratio for Establishing More Efficient Obesity Percentiles among School-going Children

Research Questions:

1. Are all the existing methods for estimating the obesity and overweight in school going children in India equally efficient? 2. How to derive more efficient obesity percentiles to determine obesity and overweight status in school-going children aged 7-12 years old?

Objectives:

1. To investigate and analyze the prevalence rate of obesity and overweight children in India, using the established standards. 2. To compare the efficiency among the tools with the expected levels in the Indian population. 3. To establish and demonstrate the higher efficiency of the proposed percentile chart.

Study Design:

A cross-sectional study using a completely randomized design.

Settings:

Government, private-aided, unaided, and central schools in the Thrissur district of Kerala.

Participants:

A total of 1500 boys and 1500 girls aged 7-12 years old.

Results:

BMI percentiles, waist circumference percentiles, and waist to height ratio are the ruling methodologies in establishing the obese and overweight relations in school-going children. Each one suffers from the disadvantage of not considering either one or more of the obesity contributing factors in human growth dynamics, the major being waist circumference and weight. A new methodology for mitigating this defect through considering BMI and waist circumference simultaneously for establishing still efficient percentiles to arrive at obesity and overweight status is detailed here. Age-wise centiles for obesity and overweight status separately for boys and girls aged 7-12 years old were established. Comparative efficiency of this methodology over BMI had shown that this could mitigate the inability of BMI to consider waist circumference. Also, this had the advantage of considering body weight in obesity analysis, which is the major handicap in waist to height ratio. An analysis using a population of 1500 boys and 1500 girls has yielded 3.6% obese and 6.2% overweight samples, which is well within the accepted range for Indian school-going children.

Conclusion:

The percentiles for school-going children based on age and sex were derived by comparing all other accepted standards used for measurement of obesity and overweight status. Hence, augmenting BMI and waist to height ratio is considered to be the most reliable method for establishing obesity percentiles among school-going children.