Background & objectives: There has been more than 100 per cent increase in incidence of stroke in low- and middle-income countries including India from 1970-1979 to 2000-2008. Lack of reliable reporting mechanisms, heterogeneity in methodology, study population, and small sample size in existing epidemiological studies, make an accurate estimation of stroke burden in India challenging. We conducted a systematic review of epidemiologic studies on stroke conducted in India to document the magnitude of stroke. Methods: All population-based, cross-sectional studies and cohort studies from India which reported the stroke incidence rate or cumulative stroke incidence and/or the prevalence of stroke in participants from any age group were included. Electronic databases (Ovid, PubMed, Medline, Embase and IndMED) were searched and studies published during 1960 to 2015 were included. A total of 3079 independent titles were identified for screening, of which 10 population-based cross-sectional studies were considered eligible for inclusion. Given the heterogeneity of the studies, meta-analysis was not carried out. Results: The cumulative incidence of stroke ranged from 105 to 152/100,000 persons per year, and the crude prevalence of stroke ranged from 44.29 to 559/100,000 persons in different parts of the country during the past decade. These values were higher than those of high-income countries. Interpretation & conclusions: A paucity of good-quality epidemiological studies on stroke in India emphasizes the need for a coordinated effort at both the State and national level to study the burden of stroke in India. Future investment in the population-based epidemiological studies on stroke would lead to better preventive measures against stroke and better rehabilitation measures for stroke-related disabilities in the country.

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Background & objectives: Depression among adolescents is a rising problem globally. There is a need to understand the factors associated with depression among adolescents. This study was conducted to ascertain the prevalence of depressive disorders and associated factors among schoolgoing adolescents in government and private schools in Chandigarh, India. Methods: A cross-sectional study was conducted among 542 randomly selected schoolgoing adolescents (13-18 yr), from eight schools by multistage sampling technique. Depression was assessed using Patient Health Questionnaire-9 (PHQ-9) and associated factors by pretested semistructured interview schedule. Multivariate analysis was done to identify significant associated factors. Results: Two-fifth (40%) of adolescents had depressive disorders, 7.6 per cent major depressive disorders and 32.5 per cent other depressive disorders. In terms of severity, 29.7 per cent had mild depression, 15.5 per cent had moderate depression, 3.7 per cent had moderately severe depression and 1.1 per cent had severe depression. Significant associated factors included being in a government school, studying in class X^th and XII^th, rural locality, physical abuse by family members, alcohol use and smoking by father, lack of supportive environment in school, spending less time in studies, lower level of participation in cultural activities and having a boy/girlfriend. Significant predictors on binary logistic regression analysis were being in class X^th [odds ratio (OR)=5.3] and lack of self-satisfaction with own academic performance (OR=5.1). Interpretation & conclusions: Our study showed that a significant proportion of schoolgoing adolescents suffered from depression. The presence of depression was associated with a large number of modifiable risk factors. There is a need to modify the home as well as school environment to reduce the risk of depression.

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Background & objectives: With improved survival of childhood cancer patients, the number of long-term cancer survivors is increasing. Some studies have assessed the long-term morbidity after childhood cancer treatment in the developing countries. This study was conducted to assess the spectrum of late effects of cancer treatment in paediatric cancer survivors. Methods: Evaluation of the first 300 patients who completed five years of follow up in the after treatment completion clinic was done. Details of primary diagnosis, treatment received and current clinical status were noted. The spectrum of late effects was ascertained by appropriate investigations. Results: Haematological malignancies comprised 25 per cent of total cases. Most common primary diagnosis comprised acute lymphoblastic leukaemia, retinoblastoma and Hodgkin's lymphoma. The median age at evaluation and follow up was 14 and 8.5 yr, respectively. Twenty three per cent (69) of the survivors had a minimal disability (growth retardation or underweight), 13 per cent (39) had moderate disabilities needing medical attention (hepatitis B surface antigen positive, myocardial dysfunction, azoospermia and hypothyroidism), while two per cent had major/life-threatening disabilities (mental retardation, liver disease and mortality). Eleven patients relapsed on follow up, of those five patients expired. Two second malignancies were recorded during the period of follow up. Interpretation & conclusions: Late effects were of concern; however, severe disability (Grade 3-5) was seen in only two per cent survivors. Lifelong follow up of childhood cancer survivors is required to assess cancer-related morbidity, occurrence of a secondary neoplasm, to facilitate timely diagnosis and to implement remedial or preventive interventions to optimize health outcomes. Awareness towards the existence of late effects of cancer therapy is required among parents, patients and health professionals.

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Background & objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which affects females more than males. Gender affects the manifestations of SLE and men with lupus show more severe symptoms and worse prognosis. This study was aimed to compare clinical and immunological features in female and male lupus patients in Iran. Methods: Demographic, clinical and laboratory data from 78 women and 20 men with lupus were collected. Autoantibodies (against nRNP, Sm, SSA, SSB, Ro-52, CENP, Jo-1, Scl-70, nucleosome, anti-dsDNA, histone and Rib-p protein) were determined using immunoblotting technique. Results: Men with lupus had less anti-SSA (21.1 vs 48.1%) and anti-Ro52 (10.5 vs 44.3%) antibodies when compared to women and none of the male patients had anti-SSB antibodies. Kidney damage was more frequent in men (68.4% in men vs 36.7% in women). In men with kidney involvement, anti-dsDNA increased significantly (84.6 vs 20.0%) in comparison to males without nephritis. Anti-SSA (7.7 vs 50.0%) and anti-nRNP (0.0 vs 33.8%) on the other hand, decreased. Women with renal involvement had no anti-SSB antibodies. Interpretation & conclusions: In male patients, SLE appeared with more severe features, and kidney damage was more frequent in males. The frequency of some autoantibodies was different between females and males. In males with kidney damage anti-dsDNA increased significantly, while anti-SSA and anti-nRNP decreased. Anti-SSB was not detected in males and females with nephritis.

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Folate has been studied in relation to many diseases, especially cancer. Although it has been postulated to exert a dual effect on development of cancer, its role remains to be clearly defined. Its effect on cancer is the result of gene-nutrient interaction between the genes in folate metabolic pathway and dietary folate availability; mutations in genes of folate metabolism have been shown to alter individual susceptibility to certain childhood cancers as well as response to cancer chemotherapy. Although mandatory fortification of food items with folate has been initiated in some countries, many countries are yet to adopt this due to concerns about undesired adverse effects of high folate levels on health, especially cancer. However, initial reports suggest that folate fortification has led to reduction in incidence of certain childhood cancers such as neuroblastoma, wilms tumour and leukaemias. Despite studies showing folate depletion during antifolate chemotherapy and higher toxicity of chemotherapy in folate-depleted individuals, folate supplementation during cancer chemotherapy is not routinely recommended. Studies investigating the precise effect of folate supplementation during chemotherapy on both short- and long-term outcomes of cancer are needed to arrive at a consensus guideline.

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Background & objectives: Tumour protein p53 (TP53) is a stress sensitive transcription factor responsible for the control of cell survival and death to prevent from tumour formation. In vitro and animal studies have indicated that TP53 also responds to metabolic changes and influences metabolic pathways. This study was undertaken to determine the serum level of TP53 and its correlations with clinical and biochemical parameters in type 2 diabetes mellitus (T2DM) patients in comparison to non-diabetic control individuals. Methods: An observational study was conducted between December 2009 and November 2013 to evaluate TP53 serum level using ELISA. Cases (n=225) were defined as patients who were diagnosed with T2DM. Non-diabetic controls (n=255) were matched by age and sex. Multivariable modelling using logistic regression examined associations between clinical characteristics and TP53 level or T2DM predication was performed. Results: Serum TP53 level was significantly higher in T2DM patients as compared to non-diabetic healthy controls (1.69 vs 2.07 ng/ml, P<0.001). In T2DM patients, the level of TP53 increased with the age, duration of diabetes and waist-to-hip ratio (WHR) value. A logistic regression analysis revealed that increased serum TP53 level was significantly associated with family history of diabetes, age and WHR. Moreover, TP53, triglyceride and body mass index could be used to predict T2DM. Interpretation & conclusions: Our results suggest that TP53 may be linked with T2DM. The fluctuations of serum TP53 level may reflect metabolic and oxidative stress associated with chronic hyperglycaemia. Further studies need to be done to confirm these findings.

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Background & objectives: A knowledge-based, logically-linked online telepsychiatric decision support system for diagnosis and treatment of mental disorders was developed and validated. We evaluated diagnostic accuracy and reliability of the application at remote sites when used by non-psychiatrists who underwent a brief training in its use through video-conferencing. Methods: The study was conducted at a nodal telepsychiatry centre, and three geographically remote peripheral centres. The diagnostic tool of application had a screening followed by detailed criteria-wise diagnostic modules for 18 psychiatric disorders. A total of 100 consecutive consenting adult outpatients attending remote telepsychiatry centres were included. To assess inter-rater reliability, patients were interviewed face to face by non-specialists at remote sites using the application (active interviewer) and simultaneously on online application via video-conferencing by a passive assessor at nodal centre. Another interviewer at the nodal centre rated the patient using Mini-International Neuropsychiatric Interview (MINI) for diagnostic validation. Results: Screening sub-module had high sensitivity (80-100%), low positive predictive values (PPV) (0.10-0.71) but high negative predictive value (NPV) (0.97-1) for most disorders. For the diagnostic sub-modules, Cohen's kappa was >0.4 for all disorders, with kappa of 0.7-1.0 for most disorders. PPV and NPV were high for most disorders. Inter-rater agreement analysis revealed kappa >0.6 for all disorders. Interpretation & conclusions: Diagnostic tool showed acceptable to good validity and reliability when used by non-specialists at remote sites. Our findings show that diagnostic tool of the telepsychiatry application has potential to empower non-psychiatrist doctors and paramedics to diagnose psychiatric disorders accurately and reliably in remote sites.

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Background & objectives: Acetylcholinesterase (AChE) inhibitors represent a major class of drugs which provide symptomatic relief and improvement in cognitive function in Alzheimer's disease (AD). In this study, cubebin, a dibenzylbutyrolactone lignan, was isolated from Piper cubeba and investigated for its AChE inhibitory activity in an attempt to explore its potential for memory-enhancing activities in mice. Methods: Molecular docking of cubebin was carried out followed by in vitro AChE activity. Mice were treated with cubebin (25 & 50 mg/kg; i.p.), for three days and memory impairment was induced by scopolamine (3 mg/kg; i.p.). Memory function was evaluated by Morris water maze (MWM) test. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain. Results: Molecular docking study revealed that cubebin was well bound within the binding site of the AChE enzyme showing interactions such as π-π stacking and hydrogen bonding with residues present therein. Cubebin inhibited AChE enzyme in an in vitro assay with IC₅₀value of 992 μM. Scopolamine administration caused a significant impairment of learning and memory in mice, as indicated by a marked decrease in MWM performance. Scopolamine administration also produced a significant enhancement of brain AChE activity and oxidative stress in mice brain. Pre-treatment of cubebin (25 and 50 mg/kg; i.p.) significantly prevented scopolamine-induced learning and memory deficits along with attenuation of scopolamine-induced rise in brain AChE activity and oxidative stress level. Interpretation & conclusions: Cubebin showed promising protective activity in scopolamine-induced spatial memory impairment in mice. This could be attributed to its brain AChE inhibition and antioxidant activity.

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Background & objectives: Balaghat district in Central India is a highly malarious district where both Plasmodium falciparum and P. vivax are prevalent. In this district, the persistence of malaria was on an increase and not responsive to intervention measures even though there was no drug resistance. This study was undertaken by conducting mass screening to determine the prevalence of malaria among particularly vulnerable tribe of Balaghat, for developing evidence-based intervention measures for malaria control in hard to reach areas. Methods: This prospective study was carried out during 2013-2014 by conducting mass survey of the population in 10 villages of Birsa community health centre (CHC) and 12 villages of Baihar CHC. Finger-pricked blood smears were collected from all consenting individuals with or without fever for microscopic examination. Results: In the febrile group, the slide positivity rate (SPR) and slide falciparum rate (SFR) were 32.4 and 28.9 per cent, respectively, with 89.4 per cent P. falciparum, while in the afebrile individuals also, the SPR and SFR were high (29 and 26%, respectively), but these were significantly lower than that of febrile group. The gametocyte carriers were significantly higher (odds ratio 1.67, 95% confidence interval 1.25-2.25, P=0.0004) in afebrile patients when compared with febrile group. Vector incrimination showed the presence of four sporozoite-positive Anopheles culicifacies out of 1953 assayed. Interpretation & conclusions: Plasmodium falciparum malaria was high in young children (up to 8 years) as compared to the adult in both afebrile and febrile group in Balaghat district. High prevalence of gametocyte was observed in all age groups among the afebrile cases. The identification of afebrile malaria parasitaemia is an important challenge for the malaria elimination initiatives. A strong malaria surveillance system is fundamental to both programme design and implementation.

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Background & objectives: Japanese encephalitis (JE) is a major public health problem in India because of high mortality rate and residual neuropsychiatric damage in the survivors. The present study was undertaken to investigate JE positivity amongst patients admitted with acute encephalitis syndrome (AES) in upper Assam districts and different parameters with their changing trends related to it. Methods: It was a hospital-based prospective cross-sectional study conducted from January 2012 to December 2014. A total of 1707 consecutive non-repetitive hospitalized patients, satisfying the clinical case definition of AES as per the WHO guidelines, were included in the study. Cerebrospinal fluid (CSF) and serum samples were tested for JEV-specific IgM antibodies. Results: Of the 1707 patients admitted, 696 (40.77 %) were diagnosed as JE with male-to-female ratio 1.7:1 and adult to paediatric ratio 2.2:1. Fever (100%), change in mental status (100%), headache (80.02%), neck rigidity (52.01%), unconsciousness (48.99%), seizure (37.64%) and paralysis (11.06%) were the major clinical findings. The majority of cases (94%) were from rural areas. There was a significant association of JE cases with rainy season of the year i.e., June to August (P<0.001). Overall, 14.94 per cent deaths were reported in JE positive cases. Interpretation & conclusions: A higher occurrence of JE was observed in above 15 yr age group. Cases were mainly from rural areas, and there was clustering of cases in rainy season.

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Background & objectives: Cannabis is a widely used illicit drug and its use is often associated with co-occurring psychiatric disorders. This systematic review was aimed to provide information on the published Indian studies on co-occurring cannabis use disorders and psychiatric disorders. Methods: An electronic search of available Indian literature using relevant search terms was carried out in May 2015 and 52 articles in English language published from India were included in the current review. Results: Studies on cannabis and associated psychotic disorders (n=16) chiefly described acute episodes with predominant positive symptoms, following cannabis use. Some studies (n=6) observed an overall increased prevalence of all psychiatric disorders and symptoms owing to cannabis use, while others (n=14) elaborated on high rates of substance use in those with psychiatric disorders. The effect of cannabis use on cognitive function was the focus of some of the Indian studies (n=7). All these studies barring one had all male subjects, and a single study described the service delivery model for those with dual diagnosis disorders in India. Most of the research used cross-sectional observational design and focussed on treatment-seeking population. Interpretation & conclusions: A review of Indian literature on cannabis use and its association with psychiatric disorders indicates a high co-prevalence of psychotic disorders, especially in vulnerable individuals as well as high rates of co-occurrence of other psychiatric comorbidities. However, there is limited focus on exploring the aetiological association between cannabis use and psychiatric disorders; understanding the neurobiology of this association and management-related issues.

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The presence of common physical comorbidities, their demographic and clinical correlates and impact on functioning was assessed in 100 patients with schizophrenia. The patients had a mean age of 35.12±10.7 yr with mean duration of illness of 8.3±0.58 years. Seventy per cent were detected to have a comorbid physical condition. Common conditions included hypertension (21%), diabetes mellitus (15%) and anaemia (12%). Increasing age, being female, being married, longer duration of illness and longer duration of treatment were associated with higher risk of having a comorbid physical illness. Further studies need to be done with a large sample to confirm these findings.

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Background & objectives: Diabetes is a global disease burden. Various stem cell types are being explored to serve as an alternative source of islets. This study was conducted to evaluate the ability of in-house developed human embryonic stem (hES) cells-derived pancreatic progenitors to ameliorate diabetic symptoms in mice. Methods: Pancreatic progenitors were packed in macro-capsules and transplanted into six male Swiss mice and four mice were taken as controls. Thirty days post-transplantation, diabetes was induced by streptozotocin treatment. Mice were then followed up for >100 days and body weight and blood glucose levels were regularly monitored. Results: Control mice lost weight, maintained high glucose levels and did not survive beyond 40 days, whereas transplanted group maintained body weight and four of the six mice had lowered blood glucose levels. About five-fold increase was observed in human C-peptide levels in the recipients of progenitor transplants as compared to diabetic control. Interpretation & conclusions: The beneficial effect of transplanted cells was not long-lasting. Further studies are required to critically evaluate and compare the potential of endogenous pluripotent stem cells and hES cells-derived progenitors before moving from bench to the bedside.

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Background & objectives: A rapid and simple alternative method is needed to replace the laborious, time-consuming Salmonella serotyping. The objective of the present study was to improve and simplify a previously reported multiplex polymerase chain reaction (PCR)-based method and to create an online server to enable rapid determination of serovars. Methods: A method of multiplex PCR-based genome typing (MPGT) was standardized using 59 Salmonella isolates of 31 serovars. Several previously reported primers were modified to obtain a more accurate performance. The screen was separated into four different multiplex reactions distinguishable on standard electrophoresis. A blind study was subsequently performed with 81 isolates of 10 serovars most prevalent in India. Whole genome information from 440 Salmonella isolates was used to confirm the usefulness of this method and concurrence of in silico predictions and PCR results were investigated. A public server (http://www.mpgt-salmonella.res.in) was established for data storage and determination of closest previously observed Salmonella isolates based on obtained MPGT patterns. Results: The 16 target genes amplified showed variability in their presence in strains from different serotypes. Hence, identical amplification patterns suggested genetic relatedness of strains and usually identical serological behaviour. The observed absence/presence patterns of genes were converted to an MPGT code. Altogether, 83 different codes were predicted in silico based on the whole genome information of 440 strains. Results confirmed that major serovars usually displayed unique MPGT codes. Interpretation & conclusions: The multiplex PCR assay resulted in specific binary codes for isolates from each of the 31 Salmonella serovars tested. The online server allowed the user to compare obtained PCR results with stored previous patterns. Simplicity, speed and cost-effectiveness make this tool useful for quick outbreak management.

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Background & objectives: It has been shown that joint damage due to subclinical synovitis progresses despite apparent clinical remission in rheumatoid arthritis (RA). Hence, finding more objective methods to investigate subclinical synovitis has become a current issue. Ultrasonography (US) has been among the most investigated methods. This study was conducted to detect whether there was subclinical inflammation in RA patients in clinical remission by power Doppler ultrasonography (PDUS) and to evaluate the effects of this inflammation on upper extremity function. Methods: Forty five RA patients fulfilled the remission criteria of disease activity score 28 using erythrocyte sedimentation rate (DAS28-ESR), were enrolled in the study. Bilateral wrist, 2^nd and 3^th metacarpophalangeal and proximal interphalangeal joints and 2^nd and 5^th metatarsophalangeal joints were examined by PDUS. Upper extremity function was assessed with Michigan Hand Outcomes Questionnaire (MHQ) and handgrip strength. The pain was evaluated by visual analogue scale (VAS). Results: In 29 of 45 RA patients in clinical remission, synovitis was detected by PDUS at least in one joint. VAS and DAS28-ESR scores were significantly lower and total MHQ, some subgroup scores of MHQ (overall hand function, activity of daily living and work performance) and grip strength of the dominant hand were higher in patients with PD signal negativity. Interpretation & conclusions: PDUS showed a crucial role in determining the subclinical synovitis. Subclinical synovitis negatively affects the upper extremity function. Ultrasound-defined remission may be considered for good functional status and real remission in patients with RA.

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