Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

Background & objectives: Hepatitis E is the main cause of enterically transmitted non-A, non-B hepatitis in developing countries. In the developed countries such as the USA, Japan and Taiwan, the viruses infecting humans and swine share the same genotype with a high sequence similarity. Genotype 1 circulates in humans whereas genotype 4 in pigs in India. The present study was designed to investigate the presence of anti-HEV antibodies and HEV-RNA in swine population from north India, to investigate the genotype prevalent in it, and to compare it with other swine and human HEV strains from India. Methods: A total of 67 serum samples were collected from pigs of age period (1-6 months) from Indian Veterinary Research Institute (IVRI), Izatnagar, Bareily and subjected to anti-HEV IgG and HEV RNA detection. A phylogenetic tree was constructed using the neighbor-joining method and evaluated using the interior branch test method with MEGA 4 software. Results: Anti-HEV IgG and HEV RNA was found in 38.8 and 4.5 per cent of swine samples studied respectively. The above samples were observed to be of genotype 4e. The three new sequences had nucleotide similarity with other swine sequences in genotype 4 ranging from 80-98 per cent. Interpretation & conclusions: The three sequences observed in the present study showed nucleotide similarity with other swine sequences from southern and western India. The present study suggests that genotype 4 'e' is prevalent in the north India.

Background & objectives: Resistance to nevirapine (NVP) has been described with single dose preventive regimens in other populations. Our aim was to study the pattern and prevalence of HIV drug resistance (DR) at baseline (during pregnancy) and after delivery among antenatal women exposed to single dose NVP for prevention of parent to child transmission (PPTCT). Methods: HIV-infected, ART-naive primigravidae between 18-25 years of age, attending government antenatal clinics in Chennai, Vellore or Madurai were recruited. Drug resistance testing was carried out during pregnancy and after Sd-NVP treatment (one month after delivery) by Viroseq sequencing. HIV-1 testing by DNA PCR was done in newborns at 30 days. Results: Thirty one women were enrolled but only twenty six plasma specimens were analyzable (24 paired and two postnatal only). No major mutations were observed in any drug class at baseline though many polymorphisms were observed in both the reverse transcriptase and protease genes. Mutations to non-nucleoside reverse transcriptase inhibitors (NNRTI) were observed post-delivery in 33 per cent of women who were treated with Sd-NVP. None of the infants were HIV-positive. Interpretation & conclusions: Among pregnant ART-naοve women, baseline HIV drug resistance was not observed. A high rate of development of NNRTI class resistance among women treated with single-dose NVP was observed. Our results emphasize the need to implement more effective PPTCT regimens, minimizing emergence of drug resistance and thereby preserving long-term treatment options for HIV-infected women in India.

Background & objectives: The usefulness of cation exchange high performance liquid chromatography (CE-HPLC) as a tool for detection of thalassaemia/haemoglobin variants was evaluated in a prospective study in a tertiary care centre in north India. We also tried to evaluate the effect of concurrent nutritional deficiency on the HPLC pattern in the local ethnic population. Methods: A total of 800 blood samples were analyzed on the Bio-Rad Variant HPLC system by β-thal short program. The retention times, proportion of the haemoglobin (%), and the peak characteristics for all haemoglobin fractions were recorded. Alkaline and acid haemoglobin electrophoresis was performed to document the identities of the haemoglobin variants, wherever necessary. Many cases were subjected to family studies for a definitive diagnosis. Results: Among 800 samples tested, 553 (69.1%) were found to have normal HPLC pattern. Apart from β- thalassaemia, nine additional variants were encountered; HbS (2.8%), HbE (2.5%) and HbD (1.1%) being the most common variants present. Other variants included Hb Q-India, Hb-Lepore, δβ-thalassemia/ HPFH, HbD-Iran, HbJ-Meerut and HbH disease. There was a significant decrease in the level of HbA₂ associated with iron deficiency anaemia (IDA) (P=0.004) and increase in megaloblastic anaemia (P<0.001) among subjects with normal HPLC pattern. Interpretation & conclusions: HPLC was found to be a simple, rapid and reliable method for the detection of hemoglobin variants. An accurate diagnosis can be provided in majority of cases by use of retention time, proportion of total haemoglobin, and peak characteristics of HPLC. Haemoglobin electrophoresis and family studies play a valuable role in difficult cases. Concurrent nutritional deficiency also has an effect on HbA ₂ levels.

High blood pressure (BP) is a major public health problem in India and its prevalence is rapidly increasing among urban and rural populations. Reducing systolic and diastolic BP can decrease cardiovascular risk and this can be achieved by non-pharmacological (lifestyle measures) as well as pharmacological means. Lifestyle changes should be the initial approach to hypertension management and include dietary interventions (reducing salt, increasing potassium, alcohol avoidance, and multifactorial diet control), weight reduction, tobacco cessation, physical exercise, and stress management. A number of pharmaceutical agents, well evidenced by large randomized clinical trials, are available for initial treatment of high BP. These include older molecules such as thiazide diuretics and beta-blocking agents and newer molecules, dihydropyridine calcium channel blockers (CCB), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARB). In view of the recent clinical trials data, some international guidelines suggest that CCB, ACE inhibitors or ARB and not beta-blockers or diuretics should be the initial therapy in hypertension management. Comprehensive hypertension management focuses on reducing overall cardiovascular risk by lifestyle measures, BP lowering and lipid management and should be the preferred initial treatment approach.

Cardiovascular disease has become the leading cause of morbidity and mortality in India during the last 3 decades. The genetic predisposition and acquisition of traditional risk factors at a rapid rate as a result of urbanization seems to be the major cause. While efforts are being made to contain this epidemic by educating public and applying preventive measures, the ever increasing burden of patients with symptomatic and life threatening manifestations of the disease is posing a major challenge. This requires a concerted effort to develop modern facilities to treat these patients. The healthcare facilities to manage these high risk patients by contemporary methods like percutaneous coronary revascularization and surgical methods have shown a very promising trend during the last decade. The facilities of modern diagnostic methods and new proven techniques to offer symptomatic relief and improve their prognosis are available in most parts of the country. The lack of social security and health insurance for the large majority of the population, however, is a serious limitation. Unregulated availability of some of the newer devices for these techniques had become a very concerning issue. However, in the last few years serious efforts have been made to streamline these procedures. Indigenous research and scientific data acquisition in relation to the modern technology for achieving coronary revascularization has also started on a promising note.

Heart failure is a common cardiovascular disease with high morbidity and mortality. Unlike western countries where heart failure is predominantly a disease of the elderly, in India it affects younger age group. Important risk factors include coronary artery disease, hypertension, diabetes mellitus, valvular heart disease and cardiomyopathies. Plasma brain natriuretic peptide levels are helpful in the diagnosis of heart failure. Echocardiography is the primary imaging modality of choice, through recently cardiac magnetic resonance imaging (MRI) has been found to play an increasing role. Aim of management is to improve symptoms & enhance survival. Diuretics are important in relieving symptoms. Beta-blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers and adosterone antagonists improve survival in patients with impaired systolic function. Device therapy including cardiac resynchronization therapy and implantable cardiac defibrillators, though expensive are useful in selected patients. Unlike in patients with systolic heart failure where several therapies have been shown to improve survival, clinical trial results in diastolic heart failure have been disappointing and therapy in these patients is restricted to symptom improvement and risk factor control. Therapies like stem cell therapy are being evaluated in clinical trials and appear promising. Early diagnosis and appropriate therapy helps in reversing the process of remodelling and clinical improvement in most of the patients.

Coronary heart diseases (CHD) have reached epidemic proportions among Indians. The recently concluded INTERHEART study emphasizes the role of behavioural and conventional risk factors in the prediction of CHD risk among Indians. These findings have implication for the health care providers and policy makers in the country due to the fact that all these conventional risk factors are potentially modifiable and are good starting points for prevention. The policy measures by means of legislation and regulatory approaches on agriculture and food industry or tobacco or physical activity will have large impact on CHD risk factor reduction in the population. In addition, the health system needs to focus on: (i) providing information for increasing awareness and an enabling environment for adoption of healthy living habits by the community; (ii) early detection of persons with risk factors and cost-effective interventions for reducing risk; and (iii) early detection of persons with clinical disease and cost-effective secondary prevention measures to prevent complications. The evidence from INTERHEART provides rationale for developing treatment algorithms and treatment guidelines for CHD at various levels of health care. In addition, INTERHEART provides answer for the quest for a single reliable biomarker, Apo B/ApoA 1 ratio that can predict the future CHD risk among individuals. Further to this, the INTERHEART study also opens up several unanswered questions on the pathobiology of the premature onset of myocardial infarction among Indians and calls for the need to developing capacity in clinical research in CHD in India.

Coronary artery disease (CAD) is a leading cause of death and disability worldwide. In addition to lifestyle and environmental factors which are major aetiologic determinants, there is considerable familial clustering of the disease indicating a genetic component in its causation. Although the total genetic contribution to CAD risk can be quantified, the determination of the size and number of contributing effects is impossible without identifying all CAD susceptibility genes. However, despite extensive studies, strong evidence of a molecular genetic association with coronary artery disease or myocardial infarction remains elusive. Genome wide association studies have been successful in identifying robust associations of single nucleotide polymorphisms (SNP) with CAD. Identifying the causal variant and dissecting pathways linking these variants to disease process is a major challenge. Technologies from whole genome sequencing, proteomics, transcriptomics and metabolomics are now available to extend analysis to a more complete range of potential susceptibility variants, and to support more explicit modelling of the joint effects of genes and environment. The availability of these high throughput technologies does not diminish the importance of rigorous phenotyping and appropriate study designs in all the endeavours to understand the aetiopathogenesis of CAD. Combining classical epidemiology with modern genomics will require collaborative efforts within the cardiovascular disease community at both bench and bedside and this will have the potential to expand our understanding of CAD and translate discoveries into clinically useful applications that will have a major impact on public health.

Recent advances in molecular biology have advanced our understanding of the genetic substrate predisposing to sudden death, especially in monogenic disorders. Numerous ion channels along with membrane structural proteins have been extensively investigated for their role in the genesis of serious ventricular tachyarrhythmias. The complex interplay of various biological pathways culminating in the more prevalent form of sudden death due to coronary artery disease however still remains to be unraveled. The concept of multi-factorial causation of arrhythmias where a second clinical or environmental factor is necessary for expression of an underlying genetic susceptibility to ventricular arrhythmias is a serious possibility. This article briefly outlines the current understanding about the role of genetics in sudden cardiac death.

Coronary heart disease (CHD) is currently the leading cause of death worldwide and together with diabetes, poses a serious health threat, particularly in the Indian Asian population. Risk factor management has evolved considerably with the continued emergence of new and thought-provoking evidence. The stream of laboratory- and population-based research findings as well as unresolved controversies may pose dilemmas and conflicting impulses in most clinicians, and even in our more well-informed patients. As results of the most recent clinical trials on glycaemic control for macrovascular risk reduction are woven into concrete clinical practice guidelines, this paper seeks to sort through unwieldy evidence, keeping these findings in perspective, to deliver a clearer message for the context of South Asia and cardio-metabolic risk management.

Worldwide, obesity trends are causing serious public health concern and in many countries threatening the viability of basic health care delivery. It is an independent risk factor for cardiovascular diseases and significantly increases the risk of morbidity and mortality. The last two decades have witnessed an increase in health care costs due to obesity and related issues among children and adolescents. Childhood obesity is a global phenomenon affecting all socio-economic groups, irrespective of age, sex or ethnicity. Aetiopathogenesis of childhood obesity is multi-factorial and includes genetic, neuroendocrine, metabolic, psychological, environmental and socio-cultural factors. Many co-morbid conditions like metabolic, cardiovascular, psychological, orthopaedic, neurological, hepatic, pulmonary and renal disorders are seen in association with childhood obesity. The treatment of overweight and obesity in children and adolescents requires a multidisciplinary, multi-phase approach, which includes dietary management, physical activity enhancement, restriction of sedentary behaviour, pharmacotherapy and bariatric surgery. A holistic approach to tackle the childhood obesity epidemic needs a collection of activities including influencing policy makers and legislation, mobilizing communities, restructuring organizational practices, establishing coalitions and networks, empowering providers, imparting community education as well as enriching and reinforcing individual awareness and skills. The implications of this global phenomenon on future generations will be serious unless appropriate action is taken.

Globalization has made calorie rich, cheap, convenient marketed foods the main menu for the common man. Indians are particularly susceptible to the adverse outcomes of this dietary change because of ethnic, epigenetic reasons and sarcopenic adiposity (less muscle more fat for the same body weight). Children have smaller body frame making them more susceptible to adverse effects of hyperglycaemia leading to stress on beta cells and their damage. This has resulted in escalation of lifestyle diseases by three-fold, that too at our younger age group at lower body mass indices. Preventive measures are necessary in early life to protect the beta cells, to achieve a metabolically healthy society. This will help in sustaining optimal beta cell function throughout a person's life. Modification in dietary habits by educating the society, proper food labelling and legal regulation, restricting calorie, sugar, saturated fat, trans-fat and salt intake has proved its benefits in the developed world. Changes in the quality of food is as important as restricting calorie intake. This includes facilitation of increased consumption of dietary fiber, complex carbohydrates, nuts, fruits and vegetables. Restrictions are needed to reduce trans-fats, saturated fats and cooking habits such as deep frying which oxidizes cholesterol and lipids. Foods with long shelf-life shorten the life line because of their salt, sugar or trans-fat content. Individual meals need to be targeted in the general dietary guidelines, to minimize the post-prandial metabolic insult. In general, we need healthy start to early life particularly the first twenty years of life so that the habits cultured during childhood are sustained for the rest of productive years.

Cardiovascular diseases (CVD) are the leading cause of death and disability in both developed and developing countries. In developed countries socio-economic mortality differentials have been studied extensively showing that the low socio-economic group suffers the highest mortality. As the epidemiological transition is taking place against a background of economic globalization, CVD risk factors among the urban poor and middle class are rapidly increasing in India. Recent evidences from India also suggest reversal of social gradient with excess burden of CVD morbidity in the low socio-economic group. Understanding the social determinants of environmental and behavioural exposures, in determining the risk factors for cardiovascular disease is an important challenge for public health professionals as well as communities. Socio-economic disadvantage is not simply a proxy for poor cardiovascular risk factor status, but also an indication of the likely trajectory that an individual or a community may follow in the course of their life. The paucity of intervention research seeking to address the role of social determinants in shaping lifestyle practices among individuals in culturally and socially diverse population groups within India is definitely a measure of inadequacy in public health research. This review article provides an overview of the role of social determinants of CVD and its possible conceptual pathways with special focus on acute coronary syndrome (ACS) outcomes among Indians.

There is a popular perception that clinical judgement and evidence-based medicine are at loggerheads with each other. We examine the concepts of evidence and judgment as applied to clinical practice, and attempt to understand the reasons behind this imaginary divide.

Diagnosis of acute coronary syndrome (ACS) encompasses a wide spectrum of myocardial ischaemia varying from assuredly benign to potentially fatal. Cardiac biomarkers have had a major impact on the management of this disease and are now the cornerstone in its diagnosis and prognosis. In this review we discuss both the established and the newer emerging biomarkers in ACS and their role in highlighting not only myocardial necrosis but also different facets of the pathophysiology of ACS. The future of cardiac biomarker testing may be in multimarker testing to better characterize each patient of ACS and thus tailor both short-term and long-term therapy accordingly. This novel concept, however, needs to be tested in clinical trials for its incremental value and cost-effectiveness.

There is a rise of non-communicable diseases (NCDs) burden, which is causing increasing morbidity and premature mortality in developing countries. In 1990, cardiovascular diseases (CVD) accounted for 63 per cent of all deaths and India contributed to 17 per cent to the worldwide mortality. Several surveys conducted across the country over the past two decades have shown a rising prevalence of major risk factors for CVD in urban and rural populations. These surveys are limited by their generalisability to other parts of the country, and more was required to roll out of an action plan. There was lack of an organized national system for monitoring these risk factors over time so as to inform policy and programme for appropriate interventions. The Indian Council of Medical Research (ICMR) leveraged its research on NCD risk factor surveillance to the development of the national plan under the Integrated Disease Surveillance Project (IDSP) which will obtain State-based prevalence of selected risk factors. This review provides the scenario of CVD in India and the need for a surveillance system. By examining similar experiences globally, it outlines the scope of CVD surveillance in India.

Despite significant progress in medical research, cardiovascular diseases (CVDs) continue to be the largest contributors of morbidity and mortality both in developed and developing countries. The status of public health interventions related to CVDs prevention was reviewed to identify actions that are required to bridge the existing gap between the evidence and the policy. We used a framework comprising two steps - "bench to bedside" and from "bedside to community" to evaluate translational research. Available literature was reviewed to document the current status of CVD prevention and control at national level in India. Case studies of risk factor surveillance, tobacco control and blood pressure measurement were used to understand different aspects of translational research. National level initiatives in non-communicable diseases surveillance, prevention and control are a recent phenomena in India. The delay in translation of research to policy has occurred primarily at the second level, i.e., from 'bedside to community'. The possible reasons for this were: inappropriate perception of the problem by policy makers and programme managers, lack of global public health guidelines and tools, and inadequate nationally relevant research related to operationalization and cost of public health interventions. Public health fraternity, both nationally and internationally, needs to establish institutional mechanisms to strengthen human resource capacity to initiate and monitor the process of translational research in India. Larger public interest demands that focus should shift to overcoming the barriers at community level translation. Only this will ensure that the extraordinary scientific advances of this century are rapidly translated for the benefit of more than one billion Indians.