Evaluation of Oxidative Stress Parameters and Antioxidant Status in Coronary Artery Disease Patients.

A surge in oxidative stress and weakened antioxidant defense contributes to the initiation and progression of Coronary Artery Diseases (CAD). The resultant burst in free radicals causes oxidation of lipoproteins mainly oxidized low-density lipoprotein (oxLDL). Further studies need to be conducted to find whether the management of CAD can be evaluated within the context of oxidant/antioxidant balance with the contribution of newer markers. This study was performed to evaluate, compare, and correlate oxidative stress parameters and antioxidant status in CAD patients with controls and evaluate and compare pro-oxidant, a pro-inflammatory enzyme, myeloperoxidase (MPO) and anti-oxidant, anti-inflammatory enzyme, and paraoxonase (PON) between CAD patients and controls. OxLDL, an oxidation product of low-density lipoprotein, malondialdehyde (MDA), an oxidative marker, and reduced glutathione (GSH), an anti-oxidant marker, and lipid profile were assessed and compared in CAD patients and controls. The activity of MPO was correlated with that of PON, and MDA level was correlated with GSH level. A total of 100 clinically proven CAD patients, in the age range of 35-70 years, were selected from the Out Patient Department (OPD) of our Institute. A total of 60 controls in the same age range and without CAD were selected after undergoing health checkups in the hospital. Based on the obtained results, oxLDL, MDA, and MPO were significantly increased in patients than in controls (P<0.05), and PON and GSH were significantly lowered in patients than in controls (P<0.05). Total cholesterol, triglyceride, and LDL were significantly high in CAD patients. A significant negative correlation was observed between MPO and PON levels and between MDA and GSH levels. Increased oxidative stress and decreased antioxidant status were observed in patients with CAD. Formation of oxLDL increased MPO and decreased PON are all additional risk factors for the development of CAD and can be targeted for future therapeutic purposes. Lifestyle modifications and treatment methods can reduce CAD risk through the reduction of oxidative stress and improvement of antioxidant status.

Towards optimal toe-clearance in synthesizing polycentric prosthetic knee mechanism.

Stability at the stance phase and near normal able-bodied swing phase kinematics are essential in designing the prosthetic knee mechanism for transfemoral amputees. Primarily, insufficient mid swing toe clearance results in asymmetrical gait patterns, leading to muscular-skeletal pain and joint degeneration. The present work is focused on synthesizing a polycentric knee mechanism to enhance the toe-clearance at mid-swing for safe level ground walking of amputees in developing countries. Both fixed and moving centrodes of the four-bar knee mechanism are considered in optimal synthesis of the mechanism for achieving able-bodied gait patterns using evolutionary algorithms in mechanism design software tools. The knee stability at heel contact, stabilizing moment at push-off, stable knee flexion range, maximum knee flexion and maximum toe-clearance at mid-swing are the parameters used for comparing the knee design with the existing commercially available designs. The optimized results are then verified experimentally by building a functional prototype using a 3 D printing technique. The designed mechanism executes nominal performance in four parameters and offers enhanced toe-clearance during mid-swing. This is a significant improvement over the existing designs for amputees to navigate comfortably on irregular terrain in developing countries.

Isoprenoid phosphonophosphates as glycosyltransferase acceptor substrates.

Glycosyltransferases that act on polyprenol pyrophosphate substrates are challenging to study because their lipid-linked substrates are difficult to isolate from natural sources and arduous to synthesize. To facilitate access to glycosyl acceptors, we assembled phosphonophosphate analogues and showed these are effective substrate surrogates for GlfT1, the essential product of mycobacterial gene Rv3782. Under chemically defined conditions, the galactofuranosyltransferase GlfT1 catalyzes the formation of a tetrasaccharide sequence en route to assembly of the mycobacterial galactan.

High prevalence of tobacco use, alcohol use and overweight in a rural population in Tamil Nadu, India.

BACKGROUND: Cardiovascular diseases are one of the leading causes of death in India. There is high prevalence of cardiovascular risk factors in urban Tamil Nadu. There are limited data on the prevalence of behavioral risk factors and overweight in rural Tamil Nadu. AIM: We estimated prevalence of behavioral risk factors, overweight and central obesity in a rural population in Tamil Nadu, India. SETTING AND DESIGN: We conducted a cross-sectional survey in 11 villages in Kancheepuram/Thiruvallur districts, Tamil Nadu. MATERIALS AND METHODS: Study population included 10,500 subjects aged 25-64 years. We collected data on behavioral risk factors and anthropometric measurements. Body mass index (BMI) was categorized using the classification recommended for Asians. Central obesity was defined as waist circumference ≥90 cm for men and ≥80 cm for women. We computed proportions for all risk factors and used trend chi-square to examine trend. RESULTS: Among the 10,500 subjects, 4927 (47%) were males. Among males, 1852 (37.6%) were current smokers and 3073 (62.4%) were current alcohol users. Among females, 840 (15.1%) were smokeless tobacco users. BMI was ≥23.0 kg/m 2 for 1618 (32.8%) males and 2126 (38.2%) females. 867 (17.6%) males and 1323 (23.7%) females were centrally obese. Most commonly used edible oil was palm oil followed by sunflower oil and groundnut oil. CONCLUSION: We observed high prevalence of tobacco use, alcohol use and central obesity in the rural population in Tamil Nadu. There is need for health promotion programs to encourage adoption of healthy lifestyle and policy interventions to create enabling environment.

IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL.

Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis and relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell. In contrast, deletions and nonsense mutations in IKZF1 (IKAROS) were highly enriched and consistently preserved at the time of relapse. A targeted copy number screen in an unselected cohort of 131 precursor B-ALL cases, enrolled in the dexamethasone-based Dutch Childhood Oncology Group treatment protocol ALL9, revealed that IKZF1 deletions are significantly associated with poor relapse-free and overall survival rates. Separate analysis of ALL9-treatment subgroups revealed that non-high-risk (NHR) patients with IKZF1 deletions exhibited a approximately 12-fold higher relative relapse rate than those without IKZF1 deletions. Consequently, IKZF1 deletion status allowed the prospective identification of 53% of the relapse-prone NHR-classified patients within this subgroup and, therefore, serves as one of the strongest predictors of relapse at the time of diagnosis with high potential for future risk stratification.

Design of a bisamidinium claisen rearrangement catalyst for monodentate substrates.

A bisamidinium catalyst has been designed for the Claisen rearrangement. The primary design feature is a dual hydrogen bonding array that can coordinate a singular oxygen atom of the substrate. The ability to function as a dual hydrogen donor is key as the bisamidinium accelerates the Claisen rearrangement to a greater extent than Brønsted acids with lower pK(a) values.

Predisposition to colorectal cancer: exploiting copy number variation to identify novel predisposing genes and mechanisms.

Although cancer is mostly regarded as an acquired disease, familial predisposition plays a significant role in many cancer types. Thus far, several high penetrant cancer predisposing genes have been identified. As yet, however, these genes explain only a fraction of the familial and/or hereditary cases of cancer. This has led to the exploration of the human genome for novel cancer predisposing genes. The identification of such genes will not only increase our understanding of cancer predisposition and development, but will also have direct implications for genetic counseling and personalized management of the patients and their family members. Here we provide an inventory of currently known molecular mechanisms related to familial colorectal cancer development and an outline of copy number analysis-based strategies to identify new predisposing genes. Finally, we discuss a novel copy number-associated epigenetic mechanism underlying the predisposition to colorectal cancer.