Sree Chitra Thirunal Institute for Medical Sciences and Technology

Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour.

Current wound dressings have disadvantages such as less flexibility, poor mechanical strength, lack of porosity, and a tendency for dressings to adhere onto the wound surface; in addition, a majority of the dressings did not possess antibacterial activity. Hydrogel-based wound dressings would be helpful to provide a cooling sensation and a moisture environment, as well as act as a barrier to microbes. To overcome these hassles, we have developed flexible and microporous chitosan hydrogel/nano zinc oxide composite bandages (CZBs) via the incorporation of zinc oxide nanoparticles (nZnO) into chitosan hydrogel. The prepared nanocomposite bandages were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). In addition, swelling, degradation, blood clotting, antibacterial, cytocompatibility, cell attachment on the material, and cell infiltration into the composite bandages were evaluated. The nanocomposite bandage showed enhanced swelling, blood clotting, and antibacterial activity. Cytocompatibility of the composite bandage has been analyzed in normal human dermal fibroblast cells. Cell attachment and infiltration studies showed that the cells were found attached to the nanocomposite bandages and penetrated into the interior. Furthermore, the in vivo evaluations in Sprague-Dawley rats revealed that these nanocomposite bandages enhanced the wound healing and helped for faster re-epithelialization and collagen deposition. The obtained data strongly encourage the use of these composite bandages for burn wounds, chronic wounds, and diabetic foot ulcers.

Chitosan, a mucopolysaccharide of marine origin, was studied for its safety and hemostatic potential. Its surface was treated with glutaraldehyde, carbodiimide, and plasma glow discharge to elicit effects of enzyme degradation. Of the seven enzymes used, leucine amino peptidase caused maximum degradation. Autoclaving appeared to be an ideal sterilizing method as it caused least decrease in tensile strength and effected a negligible rate of hemolysis. Sterilizing with glutaraldehyde with a physiologic pH retained the maximum tensile strength of chitosan. In vivo toxicity tests indicated that it is nontoxic, and the sterilized films were free of pyrogen. Coagulation and hemagglutination tests showed that the hemostatic mechanism of chitosan seems to be independent of the classical coagulation cascade and appears to be an interaction between the cell membrane of erythrocytes and chitosan.

The inquisitiveness about what happens in the brain has been there since the beginning of humankind. Functional magnetic resonance imaging is a prominent tool which helps in the non-invasive examination, localisation as well as lateralisation of brain functions such as language, memory, etc. In recent years, there is an apparent shift in the focus of neuroscience research to studies dealing with a brain at 'resting state'. Here the spotlight is on the intrinsic activity within the brain, in the absence of any sensory or cognitive stimulus. The analyses of functional brain connectivity in the state of rest have revealed different resting state networks, which depict specific functions and varied spatial topology. However, different statistical methods have been introduced to study resting state functional magnetic resonance imaging connectivity, yet producing consistent results. In this article, we introduce the concept of resting state functional magnetic resonance imaging in detail, then discuss three most widely used methods for analysis, describe a few of the resting state networks featuring the brain regions, associated cognitive functions and clinical applications of resting state functional magnetic resonance imaging. This review aims to highlight the utility and importance of studying resting state functional magnetic resonance imaging connectivity, underlining its complementary nature to the task-based functional magnetic resonance imaging.

BACKGROUND: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. METHODS: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. RESULTS: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622-5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5-9.8) per 100 000 which equated to 695 771 (644 927-741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897-17 636 830) YLLs, 19 252 699 (13 725 429-26 140 433) YLDs and 35 940 787 (30 185 695-42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age. CONCLUSIONS: This study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.

In contrast to newborns, who spend 16-20 h in sleep each day, adults need only about sleep daily. However, many elderly may struggle to obtain those 8 h in one block. In addition to changes in sleep duration, sleep patterns change as age progresses. Like the physical changes that occur during old age, an alteration in sleep pattern is also a part of the normal ageing process. As people age, they tend to have a harder time falling asleep and more trouble staying asleep. Older people spend more time in the lighter stages of sleep than in deep sleep. As the circadian mechanism in older people becomes less efficient, their sleep schedule is shifted forward. Even when they manage to obtain 7 or 8 h sleep, they wake up early, as they have gone to sleep quite early. The prevalence of sleep disorders is higher among older adults. Loud snoring, which is more common in the elderly, can be a symptom of obstructive sleep apnoea, which puts a person at risk for cardiovascular diseases, headaches, memory loss, and depression. Restless legs syndrome and periodic limb movement disorder that disrupt sleep are more prevalent in older persons. Other common medical problems of old age such as hypertension diabetes mellitus, renal failure, respiratory diseases such as asthma, immune disorders, gastroesophageal reflux disease, physical disability, dementia, pain, depression, and anxiety are all associated with sleep disturbances.

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias.

The natural history of aortoarteritis was studied in 88 patients (54 women and 34 men). The average age was 24.0 +/- 8.8 years at onset of symptoms and 28.3 +/- 9.9 years at diagnosis. The follow-up period was 83.6 +/- 74.4 months from onset and 33.2 +/- 37.0 months from diagnosis. Ten patients (11.4%) died during follow-up (0.016 deaths/patient year), and 22 patients (25%) suffered major nonfatal events (0.042 events/patient year). The cumulative survival at 5 and 10 years after the onset was 91.0 +/- 3.3% and 84.0 +/- 5.6% (mean +/- SEM), respectively. The event-free survival rates at the same intervals after onset were 74.9 +/- 5.0% and 64.0 +/- 7.4%, respectively. The overall survival and event-free survival at 10 years after diagnosis was 80.3 +/- 6.5% and 61.6 +/- 7.5%, respectively. Patients with no complications or a mild single complication at diagnosis had a higher event-free survival rate than those with severe single complication or multiple complications at 5 years--97.0 +/- 2.9% and 59.7 +/- 7.3%, respectively (p less than 0.001). Severe hypertension (p less than 0.01), severe functional disability (p less than 0.01), and evidence of cardiac involvement (p less than 0.05) were good predictors of either death or major event on follow-up. These data are useful in making an objective assessment of the prognosis and in planning elective interventions.

Among biomaterials used as implants in human body, sutures constitute the largest groups of materials having a huge market exceeding $1.3 billion annually. Sutures are the most widely used materials in wound closure and have been in use for many centuries. With the development of the synthetic absorbable polymer, poly(glycolic acid) (PGA) in the early 1970s, a new chapter has opened on absorbable polymeric sutures that got unprecedented commercial successes. Although several comparative evaluations of suture materials have been published, there were no serious attempts of late on a comprehensive review of production, properties, biodegradability, and performance of suture materials. This review proposes to bring to focus scattered data on chemistry, properties, biodegradability, and performance of absorbable polymeric sutures.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Chitosan microspheres having good spherical geometry and a smooth surface were prepared by the glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in paraffin oil using dioctyl sulphosuccinate as the stabilizing agent. Microspheres having different degrees of swelling were made by varying the cross-linking density. Microspheres were prepared by incorporating theophylline, aspirin or griseofulvin. Drug incorporation efficiencies exceeding 80% could be achieved for these drugs. In-vitro release studies of these drugs were carried out in simulated gastric and intestinal fluids at 37 degrees C. It was observed that the drug release rates were influenced by the cross-linking density, particle size and initial drug loading in the microspheres.

AIMS: There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. We aimed to develop a prospective registry to address treatment and health systems gaps in the management of ACSs in Kerala, India. METHODS AND RESULTS: We prospectively collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125 hospitals in Kerala. We evaluated data on presentation, management, and in-hospital mortality and major adverse cardiovascular events (MACE). We created random-effects multivariate regression models to evaluate predictors of outcomes while accounting for confounders. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types [ST-segment myocardial infarction (STEMI) = 37%; non-STEMI = 31%; unstable angina = 32%]. In-hospital anti-platelet use was high (>90%). Thrombolytics were used in 41% of STEMI, 19% of non-STEMI, and 11% of unstable angina admissions. Percutaneous coronary intervention rates were marginally higher in STEMI admissions. Discharge medication rates were variable and generally suboptimal (<80%). In-hospital mortality and MACE rates were highest for STEMI (8.2 and 10.3%, respectively). After adjustment, STEMI diagnosis (vs. unstable angina) [odds ratio (OR) (95% confidence interval = 4.06 (2.36, 7.00)], symptom-to-door time >6 h [OR = 2.29 (1.73, 3.02)], and inappropriate use of thrombolysis [OR = 1.33 (0.92, 1.91)] were associated with higher risk of in-hospital mortality and door-to-needle time <30 min [OR = 0.44 (0.27, 0.72)] was associated with lower mortality. Similar trends were seen for risk of MACE. CONCLUSION: These data represent the largest ACS registry in India and demonstrate opportunities for improving ACS care.

Anthraquinones represent a large family of compounds having diverse biological properties. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a naturally occurring anthraquinone present in the roots and barks of numerous plants, molds, and lichens, and an active ingredient of various Chinese herbs. Earlier studies have documented mutagenic/genotoxic effects of emodin, mainly in bacterial system. Emodin, first assigned to be a specific inhibitor of the protein tyrosine kinase p65lck, has now a number of cellular targets interacting with it. Its inhibitory effect on mammalian cell cycle modulation in specific oncogene overexpressed cells formed the basis of using this compound as an anticancer agent. Identification of apoptosis as a mechanism of elimination of cells treated with cytotoxic agents initiated new studies deciphering the mechanism of apoptosis induced by emodin. At present, its role in combination chemotherapy with standard drugs to reduce toxicity and to enhance efficacy is pursued vigorously. Its additional inhibitory effects on angiogenic and metastasis regulatory processes make emodin a sensible candidate as a specific blocker of tumor-associated events. Additionally, because of its quinone structure, emodin may interfere with electron transport process and in altering cellular redox status, which may account for its cytotoxic properties in different systems. However, there is no documentation available which reviews the biological activities of emodin, in particular, its growth inhibitory effects. This review is an attempt to analyze the biological properties of emodin, a molecule offering a broad therapeutic window, which in future may become a member of anticancer armamentarium.

BACKGROUND & OBJECTIVES: Kerala State is a harbinger of what will happen in future to the rest of India in chronic non-communicable diseases (NCD). We assessed: (i) the burden of NCD risk factors; (ii) estimated the relations of behavioural risk factors to socio-demographic correlates, anthropometric risk factors with behavioural risk factors; (iii) evaluated if socio-demographic, behavioural and anthropometric risk factors predicted biochemical risk factors; and (iv) estimated awareness, treatment and adequacy of control of hypertension and diabetes, in Kerala state. METHODS: A total of 7449 individuals (51% women) stratified by age group, sex and place of residence were selected and information on behavioural risk factors; tobacco use, diet, physical activity, alcohol use, measured anthropometry, blood pressure was collected. Fasting blood samples were analysed for blood glucose, total cholesterol, high density lipoprotein cholesterol and triglycerides in a sample subset.Using multiple logistic regression models the associations between socio-demographic and anthropometric variables with biochemical risk factors were estimated. RESULTS: The burden of NCD risk factors was high in our sample. Prevalence of behavioural and each of the biochemical risk factors increased with age, adjusting for other factors including sex and the place of residence. The odds ratios relating anthropometric variables to biochemical variables were modest, suggesting that anthropometric variables may not be useful surrogates for biochemical risk factors for population screening purposes. INTERPRETATION & CONCLUSIONS: In this large study of community-based sample in Kerala, high burden of NCD risk factors was observed, comparable to that in the United States. These data may serve to propel multisectoral efforts to lower the community burden of NCD risk factors in India in general, and in Kerala, in particular.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

Current classifications of pulmonary hypertension have contributed a great deal to our understanding of pulmonary vascular disease, facilitated drug trials, and improved our understanding of congenital heart disease in adult survivors. However, these classifications are not applicable readily to pediatric disease. The classification system that we propose is based firmly in clinical practice. The specific aims of this new system are to improve diagnostic strategies, to promote appropriate clinical investigation, to improve our understanding of disease pathogenesis, physiology and epidemiology, and to guide the development of human disease models in laboratory and animal studies. It should be also an educational resource. We emphasize the concepts of perinatal maladaptation, maldevelopment and pulmonary hypoplasia as causative factors in pediatric pulmonary hypertension. We highlight the importance of genetic, chromosomal and multiple congenital malformation syndromes in the presentation of pediatric pulmonary hypertension. We divide pediatric pulmonary hypertensive vascular disease into 10 broad categories.

This paper reports the use of fluorescent gold nanoclusters synthesized using bovine serum albumin (Au-BSA) for the sensing of copper ions in live cells. The fluorescence of the clusters was found to be quenched by Cu(2+) enabling its detection in cells. The selectivity of the nanosensor was demonstrated in the presence of several cations excluding Hg(2+). We did not study the effect of Hg(2+) since it was reported earlier. The present study suggests that Cu(2+) induced fluorescence quenching is due to its binding to BSA rather than the fluorescence quenching by metal-metal interaction as in the case of Hg(2+). The Au-BSA showed excellent selectivity to Cu(2+) at various pH conditions. The 'turn off' of fluorescence can be retrieved by a Cu(2+) chelator glycine. Our results showed that gold clusters can be used as a 'turn off' sensor for copper and a 'turn on' sensor for glycine. Under the experimental conditions, the probe showed a response for Cu(2+) over a range of 100 μM to 5 mM with a detection limit of 50 μM. The role of Cu(2+) in the misfolding and disassembly of Prion Protein (PrP) leading to various maladies is well ascertained. The methodology we reported here seems to be useful in supplementing other techniques in predicting disease conditions involving Cu(2+).

PURPOSE: To ascertain the prevalence and pattern of epilepsy and to characterize and quantify knowledge, attitude, and practice (KAP) toward epilepsy among the people of the state of Kerala, which is distinguished from the rest of India by a high level of literacy and health awareness of its population. METHODS: We conducted a door-to-door survey covering the entire population of 238,102 people residing in 43,681 households in a semiurban area of central Kerala. The screening questionnaire administered by medical social workers had a sensitivity of 100% for identifying persons with epilepsy. Neurologists examined all the individuals suspected of having epilepsy. We evaluated KAP toward epilepsy among 1,118 subjects (439 males and 679 females; mean age, 33.3 years; age range, 15-85 years) from households without epilepsy in the study area. RESULTS: Through a three-phased survey, we ascertained 1,175 cases (616 males and 559 females) with active epilepsy, providing a crude point prevalence ratio of 4.9 cases per 1,000 people and an age-adjusted prevalence ratio of 4.7 cases per 1,000 population. The highest age-specific prevalence rate of 6.5 per 1,000 occurred in the 10- to 19-year-old age group. Sex-specific prevalence rates did not significantly differ. The proportion of generalized and localization-related epilepsies was 58.8% and 30.6%, respectively. Ninety-nine percent of the KAP respondents had read or heard about epilepsy. Thirty-one percent and 27% thought epilepsy was a hereditary disorder and a form of insanity, respectively. About 40% of the respondents felt that individuals with epilepsy could not be properly educated or employed. Eleven percent would object to their children having contact with epileptic children. CONCLUSIONS: The prevalence and pattern of epilepsy in central Kerala, South India, do not differ from that of developed countries. Although the awareness of epilepsy among the people of Kerala was comparable to that of developed countries, the attitudes were much more negative. The need for educating the people of Kerala on epilepsy and for incorporating an adequate knowledge of epilepsy in the school curricula cannot be overemphasized.