Brain and other nervous system disorders across the lifespan - global challenges and opportunities.

This is an exciting time for scientific discovery that aims to reduce the frequency and impact of neurological, mental health and substance-use disorders. As it became increasingly clear that low- and middle-income countries have a disproportionate share of these disorders, and that many of the problems are best addressed by indigenous researchers who can seek context-sensitive solutions, the US National Institutes of Health and other research funders began to invest more in low- and middle-income country-focused research and research capacity-building to confront this significant public health challenge. In an effort to identify existing information, knowledge gaps, and emerging research and research capacity-building opportunities that are particularly relevant to low- and middle-income countries, in February 2014 the Center for Global Health Studies at the National Institutes of Health Fogarty International Center held a workshop to explore these issues with scientific experts from low- and middle-income countries and the United States. This evolved into the preparation of the Reviews in this supplement, which is designed to highlight opportunities and challenges associated with topical areas in brain-disorders research over the coming decade. This Introduction highlights some of the over-arching and intersecting priorities for addressing causes, prevention, treatment and rehabilitation as well as best practices to promote overall nervous system health. We review some brain disorders in low- and middle-income countries, while the Reviews describe relevant issues and the epidemiology of particular conditions in greater depth.

Evaluation of Bone Mineral Density in Children With Hemophilia: An Observational Case-Control Study.

OBJECTIVES: The objectives of this study were to study bone mineral content (BMC), bone mineral density (BMD), vitamin D level, and bone turnover markers in children with hemophilia and compare it with their normal counterparts. DESIGN: This was an observational case-control study. SETTING: This study was conducted in our tertiary care institute during the period spanning from September 2016 to June 2018. MATERIALS AND METHODS: A total of 38 children with hemophilia 2 to 18 years of age and 38 age-matched and sex-matched healthy controls were included. Children with symptomatic hypocalcemia and those receiving drugs affecting BMC and BMD were excluded. Dual-energy x-ray absorptiometry was performed to estimate BMC and BMD. 25-Hydroxyvitamin D [25(OH)D], intact parathormone, osteocalcin, calcium, phosphate and alkaline phosphatase, and spot urine pyrilinks-D/creatinine ratio were estimated in them. RESULTS: BMC and BMD in cases was lower than that in controls (P<0.05). Prevalence of low BMC was seen in 22 (58%) and low BMD in 8 (21%) of cases. All controls had normal BMC and BMD for age. The prevalence of low vitamin D level (<20 ng/mL) was seen in 36 (95%) among cases and in 25 (65%) among controls (P<0.001). Serum phosphorus was lower, and serum alkaline phosphatase was higher in cases than in controls (P<0.05). CONCLUSION: BMC, BMD, and vitamin D in hemophiliacs were lower than in the general population.

A randomized study of very low-dose factor VIII prophylaxis in severe haemophilia - A success story from a resource limited country.

INTRODUCTION: Current factor prophylaxis strategy practised in developed countries is not feasible in resource constraint developing countries like India. AIM: The aim of this study was to investigate the efficacy and safety of very low-dose factor prophylaxis in India. METHODS: Children of 1-10 years of age with severe haemophilia were randomized to Prophylaxis group and Episodic (On demand) group. Children in prophylaxis group received very low-dose factor VIII (FVIII) concentrate, i.e. 10 units kg(-1) body weights on 2 days a week. Episodic group received factor concentrate in standard recommended doses. The study period was 11.5 months. RESULTS: In total 21 children were enrolled in this study, 11 assigned to prophylaxis and 10 to episodic group. Children on prophylaxis had 11 joint bleeds in comparison to 57 joint bleeds in episodic group. Mean number of haemarthrosis per patient per month were 0.08 (0.08 ± 0.13) in prophylaxis group compared to 0.48 (0.48 ± 0.34) in episodic group (P < 0.05). Total FVIII consumption was 87.51 and 56.32 units kg(-1) month(-1) in prophylaxis and episodic group respectively (P = ns). Overall median hospital emergency visits were 1 day in prophylaxis group and 9 days in episodic group (P ≤ 0.05). Median days of absenteeism from school were 25 days in episodic group and 3 days in prophylaxis group (P < 0.05). No significant complications were noted in prophylaxis group and compliance was 98%. CONCLUSION: To conclude, low-dose FVIII prophylaxis is cost effective, efficacious and a safe method of preventing joint bleeds and consequent joint damages.

Atomic-resolution spectroscopic imaging of ensembles of nanocatalyst particles across the life of a fuel cell.

The thousand-fold increase in data-collection speed enabled by aberration-corrected optics allows us to overcome an electron microscopy paradox: how to obtain atomic-resolution chemical structure in individual nanoparticles yet record a statistically significant sample from an inhomogeneous population. This allowed us to map hundreds of Pt-Co nanoparticles to show atomic-scale elemental distributions across different stages of the catalyst aging in a proton-exchange-membrane fuel cell, and relate Pt-shell thickness to treatment, particle size, surface orientation, and ordering.

O2 reduction on graphite and nitrogen-doped graphite: experiment and theory.

An experimental and theoretical study of electroreduction of oxygen to hydrogen peroxide is presented. The experimental measurements of nitrided Ketjenblack indicated an onset potential for reduction of approximately 0.5 V (SHE) compared to the onset potential of 0.2 V observed for untreated carbon. Quantum calculations on cluster models of nitrided and un-nitrided graphite sheets show that carbon radical sites formed adjacent to substitutional N in graphite are active for O2 electroreduction to H2O2 via and adsorbed OOH intermediate. The weak catalytic effect of untreated carbon is attributed to weaker bonding of OOH to the H atom-terminated graphite edges. Substitutional N atoms that are far from graphite sheet edges will be active, and those that are close to the edges will be less active. Interference from electrochemical reduction of H atoms on the reactive sites is considered, and it is shown that in the potential range of H2O2 formation the reactive sites are not blocked by adsorbed H atoms.

Breast filariasis diagnosed by fine needle aspiration cytology--a case report.

We report a case of female who presented with a lump in the right breast. Fine needle aspiration cytology of lump revealed numerous adult filarial worms. Common habitat of the adult filarial worms is the lymphatic vessels and lymph nodes of limbs and their occurrence in breast is uncommon.

Qualitative tuberculin response in the diagnosis of tuberculosis in apparently healthy schoolchildren.

SETTING: School-based cross-sectional study. OBJECTIVE: To assess the value of qualitative tuberculin responses (turgid and non-turgid type) in diagnosis of tuberculosis disease in apparently healthy schoolchildren. DESIGN: Qualitative tuberculin responses were assessed in 548 apparently healthy schoolchildren. Tuberculin-positive (> or = 10 mm) children were investigated for evidence of tuberculosis. The relationship between the types of qualitative tuberculin response and occurrence of tuberculosis was studied. RESULTS: Eighty-eight (16.1%) children were found to be tuberculin-positive. Of these, 68 had non-turgid reaction whereas 20 had turgid reaction. Most of the children with a reaction of 5-9 mm had a non-turgid type of tuberculin reaction. Only four children with non-turgid reaction had tuberculosis, while 18 children with turgid reaction had tuberculosis disease (P < 0.0001). A larger tuberculin reaction was found to be associated with a higher occurrence of tuberculosis (P = 0.016 by linear regression method). CONCLUSION: The observations indicate a possible relation between turgid reaction and tuberculosis disease.

Poliomyelitis trends in Pondicherry, south India, 1989-91.

STUDY OBJECTIVES: To assess the poliomyelitis trend, including study of the epidemiological features, and to correlate this with the immunisation coverage of infants. DESIGN: Three annual lameness surveys in children aged 0-60 months employing cluster sampling methods and a series of five cross sectional surveys of immunisation coverage in children aged 12-23 months of age were undertaken. SETTING: Pondicherry, India, 1988-92. SUBJECTS: More than 10,000 children in the age group of 0-60 months took part in the three annual lameness surveys and samples of 210 children aged 12-23 months were covered each year in immunisation coverage surveys. MEASUREMENTS AND MAIN RESULTS: Altogether 50 of 11,461, 24 of 10,093, and 17 of 11,218 children surveyed during 1989, 1990, and 1991 respectively had become lame as a result of poliomyelitis, giving prevalences of 4.4, 2.4, and 1.5 per 1000 children for the three surveys. The corrected prevalences of poliomyelitis were 5.9, 3.2, and 2.0 per 1000 children during 1989, 1990, and 1991 respectively. The proportion of cases aged up to 36 months fell from 48% in 1989 to 12.5% in 1990 and 6% in 1991. The age at onset was less than 1 year in most. The median age at onset was 10.7 months. About 54% of the affected children had received three doses of oral poliomyelitis vaccine (OPV) before the onset of paralysis. In 1988 immunisation coverage for the third dose of OPV was 91% and in 1992 it was 97.6%. The drop out rate for the first versus the third dose of OPV fell from 6.3 in 1988 to 1.9% in 1992. CONCLUSION: Three successive annual lameness surveys showed that poliomyelitis was declining between 1989 and 1991. Five immunisation coverage surveys conducted from 1988 to 1992 showed high initial coverage followed by an improvement in the form of almost universal coverage for OPV.

Increased protein glycation in non-diabetic pediatric nephrotic syndrome: possible role of lipid peroxidation.

BACKGROUND: Malondialdehyde (MDA), ascorbic acid and reduced glutathione (GSH) have been reported to play a possible role in glycation of proteins. This study was performed to evaluate this correlation in nephrotic syndrome patients by comparing the levels of fructosamine with MDA, ascorbic acid and GSH. METHODS: Fifteen children with nephrotic syndrome during relapse and 10 age- and sex-matched healthy controls were enrolled for this study. Whole blood GSH, plasma MDA, total ascorbic acid and fasting glucose were analyzed in both the groups. Partial correlation analysis was performed to predict the independent association of MDA, ascorbic acid and GSH on fructosamine. RESULTS: Plasma MDA and fructosamine levels were found to be increased in nephrotic syndrome patients when compared with controls. Plasma ascorbic acid and whole blood GSH were decreased in nephrotic group vs. healthy controls. Partial correlation analysis showed a significant positive correlation between fructosamine and MDA. CONCLUSIONS: Present data point to a possible involvement of MDA in the glycation of protein in non-diabetic nephrotic syndrome patients, and provide support for the potential use of an antioxidant therapy in these patients.

Intestinal geohelminthiasis in the developing world.

Intestinal parasitic helminths such as roundworms (Ascaris lumbricoides), hookworms (Ancylostoma doudenale and Necator americanus) and whipworm (Trichuris trichiura) are common in the developing world. Strongyloides stercoralis, though not so common, also contributes to health problems. The prevalence of intestinal worm infestation in India varies from 5% to 76%, which is similar to that in other developing countries. These parasitic infestations are acquired by ingestion, inhalation or penetration of the skin by the infective forms. Ascaris causes many intestinal and respiratory symptoms and plays an important role in precipitating protein-energy malnutrition in undernourished children. Hookworms cause anaemia and hypoproteinaemia. In areas where hookworm infestation is endemic, 90% of pregnant mothers are anaemic. Trichuriasis as a causative agent of human disease has only recently gained attention. Heavy infestation with T. trichiura can result in severe colitis and significant blood loss. This in turn can lead to impaired cognitive functions which are reversible on treatment. Though not as widely prevalent as the other geohelminths in India, Strongyloides stercoralis infestation can be fatal in debilitated and immunosuppressed children. So far, the impact of these parasites on the health of children has been underestimated and concentrated efforts to minimize the worm load and its consequences have not been given due importance in our health policies. This article reviews the pathophysiology, clinical impact and control options of the most commonly prevalent geohelminths in the developing world.

Use of serum bactericidal activity in assessing previous antibiotic therapy in acute lower respiratory tract infection in children.

Bactericidal activity in sera of children with acute lower respiratory tract infection was assayed to determine its effect on the outcome of blood culture. Parental reporting of prior antibiotic therapy was also determined. 14.4% of samples without serum bactericidal activity yielded pathogens from blood culture, whereas only 2.4% of samples with serum bactericidal activity yielded pathogens. A statistically significant correlation was found between isolation of pathogens by blood culture and serum bactericidal activity. Parental reporting could not be relied upon as there was no positive correlation.

Social status of the rural girl child in Tamil Nadu.

OBJECTIVE: The social status of the girl child in school age was assessed in a village in Tamil Nadu applying both qualitative and quantitative methods. METHODS: The home milieu was taken as the social context for the study purpose since home is the first societal unit a child comes into contact with. The various issues considered to study the social status were (1) Gender preference in having children (2) Nutrition and health care given to them (3) Importance given to their education (4) Activity pattern in daily life (5) Attitude of the community towards (a) girl child after menarche and (b) marriage. RESULT: In the study village, although there was desire to have sons, a girl child is not ignored. The value of having a girl in the family was appreciated. There was no gender discrimination in giving nutrition and health care. However the workload in girls was found to be marginally higher than in boys. The educational status of girls was lower than that of boys in terms of school enrollment and attendance. But menarche, was not an important cause of the lower educational status of girls. In the sociocultural context of the study village the priority in a girl's life during school going age was marriage. Soon after attaining puberty in a girl's life during school going age was marriage, not education and this perhaps reveals the lesser importance given to a girl's education by the community. CONCLUSION: The need of the hour is to improve her educational status by changing the attitude of the community so that a girl child's priority in her school age is not marriage but education.

Tuberculin reactivity in healthy school children in Pondicherry.

Five hundred healthy school children in the age group 5-9 years underwent tuberculin testing. Seventy nine per cent of the study population had a BCG scar. 9.2% children were found to be suffering from malnutrition, using the Quetlet's Index and 7.8% were found to be malnourished by weight for age method. 18.6% of the children were tuberculin positive (induration > or = 10 mm) and the prevalence of tuberculin positivity increased with age. The numbers of tuberculin reactors or the mean tuberculin reaction were not affected by malnutrition. BCG scar status neither affected the mean tuberculin size nor the number of tuberculin reactors.

Acute pulmonary edema as a complication of anti-snake venom therapy.

Polyvalent Anti-snake Venom (ASV) is a life-saving antivenin for severe envenomation due to snake bite in India. ASV infusion is occasionally associated with severe allergic reactions, i.e. anaphylaxis and death. We report a rare instance of non-cardiogenic pulmonary edema due to ASV infusion in an eleven years old boy.

Hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition in children associated with immunodeficiency, life threatening infections and malignancy. Infection associated hemophagocytosis responds well to appropriate antimicrobioal therapy and rarely to steroids when the infective agent is suspected to be of viral origin.

Perinephric abscess due to Aspergillus fumigatus.

Invasive aspergillosis is rare in healthy children. Severe systemic complications due to aspergillosis may be seen in AIDS patients with severe neutropenia and macrophage dysfunction.

Enteric fever: a changing perspective.

All the cases of enteric fever admitted between 1988-1992 were studied. There was a gradual rise in the number of admitted cases. Central nervous system (CNS) complications like encephalopathy (14.9%), meningitis (8.8%), seizures (8.5%) and cerebellitis (3.4%) were noted more during 1991 and 1992. Other complications like myocarditis (4.6%), hepatitis (9.5%) and gastrointestinal bleeding were noted in increasing numbers during 1991-1992. Multidrug resistant (MDRT) cases were 46.3% in 1991 and 33.5% in 1992. There was a significant difference in the time taken for defervescence (a gradual rise) between the years but between the individual drugs there was no such significant difference. Deaths were noted only in 1991 and 1992 in cases of MDRT with complications. There has been an increase in resistance of S. typhi to commonly used drugs like ampicillin, chloramphenicol and cotrimoxazole. S. typhi resistant to ciprofloxacin was cultured in 2 cases each from 1990-1992. Further, the time taken for defervescence with ciprofloxacin also showed a gradual rise from 3.5 days in 1990 to 6.2 days in 1992. Nevertheless, ciprofloxacin is still the drug of choice for treatment of complicated cases of MDRT.

Empyema in infancy and childhood.

A study of 108 cases of empyema during 18 months period showed the incidence of empyema to be 2.17%. Staph. aureus (17.6%) was the common causative organism. Response to a combination of cloxacillin and gentamicin was better than that of crystalline penicillin and gentamicin. Only 30.3% cases needed intercostal drainage for more than 2 weeks. Almost 43% cases could be discharged by 3-4 weeks after hospitalisation and 38.1% by 30-57 days. The mortality rate was 12.1%. Among the survivors, excluding 8 children who left against medical advice, all had complete recovery excepting one child in whom AFB was isolated and who developed bronchiectasis and recurrent hemoptysis, inspite of antituberculous treatment. Age of the child, antibiotic combination given and nutritional status appear to be the main factors influencing the recovery and prognosis.

Role of Glasgow Coma Scale in pediatric nontraumatic coma.

OBJECTIVE: To assess the relationship between Modified Glasgow Coma Scale (MGCS), its components and survival in children with acute coma. DESIGN: Prospective observational study. SETTING: Tertiary care referral hospital. PATIENTS: Consecutive children (n = 270) with acute nontraumatic coma between 2 months to 12 years. METHODOLOGY: MGCS and brainstem reflexes were assessed at 6 hourly intervals for 72 hours from the time of admission. The lowest score of the MGCS and worst brain stem reflexes were used for the analysis. MAIN OUTCOME MEASURE: Survival. RESULTS: Total score (Spearman rank correlation coefficient IRI = O.577, ocular response (IRI = O.641), motor response (IRI = O.729), verbal response (lRI = 0.608), brain stem response (lRI = O.843) were all found to be associated with adverse outcome. Multivariate regression analysis revealed that ocular response and motor response were individually predictive of short-term outcome. CONCLUSION: A score incorporating the brain stem reflexes, ocular response and motor response in the assessment and prognostication of comatose patients needs to be evaluated.

Typhoid fever below five years.

During a seven year period (1981-87), 53 cases of typhoid fever in children below five years were seen. This accounted for 13.5% of all typhoid admission in pediatrics during the above period. Predominant symptoms were fever (100%), vomiting (52.8%), diarrhea (30.2%) and anorexia (24.5%). Chills and rigor associated with fever was noticed in 38% of the children. Salmonella typhi was isolated from blood in 22 of 53 (41.7%) cases. A significant finding on peripheral smear was eosinopenia (86.8%). Complications like endotoxic shock, enteric encephalopathy and gastrointestinal hemorrhage were noticed in only few cases (7.6%). There were no deaths.