Alzheimer's disease (AD) is the most common neurodegenerative cortical dementia. It starts with memory loss, spatial disorientation in people above the age of 65 yr with a preference to females. Its incidence is expected to increase threefold by 2050. It affects almost one out of ten persons above the age of 65 years. Majority of patients are sporadic, but a very small percentage is autosomal dominant. The pathomechanisms postulated include amyloid cascade hypothesis according to which mutation in amyloid precursor protein causes Aβ aggregation. The next hypothesis is signal transducer and activation of transcription 3 (STAT3) causing aberration in intracellular signalling pathways. Senile plaques and neurofibrillary tangles are other important pathological changes reported. It is observed that dementia research has not yielded the expected result world over, and therefore, the pitfalls with reference to known facts about diagnosis, clinical features, pathogenic mechanisms, assessment of progression, biomarkers, treatment and prevention, as well as brief information on our experiments with relatively inexpensive methods of differentiating the most common types of dementia AD and frontotemporal dementia are discussed.

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Background & objectives: Hospital-acquired infections (HAIs) are a major challenge to patient safety and have serious public health implications by changing the quality of life of patients and sometimes causing disability or even death. The true burden of HAI remains unknown, particularly in developing countries. The objective of this study was to estimate point prevalence of HAI and study the associated risk factors in a tertiary care hospital in Pune, India. Methods: A series of four cross-sectional point prevalence surveys were carried out between March and August 2014. Data of each patient admitted were collected using a structured data entry form. Centers for Disease Control and Prevention guidelines were used to identify and diagnose patients with HAI. Results: Overall prevalence of HAI was 3.76 per cent. Surgical Intensive Care Unit (ICU) (25%), medical ICU (20%), burns ward (20%) and paediatric ward (12.17%) were identified to have significant association with HAI. Prolonged hospital stay [odds ratio (OR=2.81), mechanical ventilation (OR=18.57), use of urinary catheter (OR=7.89) and exposure to central air-conditioning (OR=8.59) had higher odds of acquiring HAI (P<0.05). Interpretation & conclusions: HAI prevalence showed a progressive reduction over successive rounds of survey. Conscious effort needs to be taken by all concerned to reduce the duration of hospital stay. Use of medical devices should be minimized and used judiciously. Healthcare infection control should be a priority of every healthcare provider. Such surveys should be done in different healthcare settings to plan a response to reducing HAI.

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Background & objectives: Magnetic resonance imaging (MRI) is frequently done for the evaluation of chronic low backache (CLBA), however, its significance in Indian patients has not been evaluated. We report here the MRI findings in patients with CLBA and their sensitivity and specificity with clinical evidence of radiculopathy and localized CLBA as well as correlate these with pain severity and disability. Methods: Seventy two patients with CLBA aged 20-70 yr without trauma, infection, tumour, metastasis and vascular malformation were included in the study. Their demographic characteristics, lifestyle, education and employment were noted. Lumbosacral MRI was carried out and 19 MRI parameters at six levels (D12-L1-L5-S1) were noted. The severity of pain was assessed by Numeric Rating Scale (NRS, 0-10) and disability by Oswestry Disability Index (ODI). Results: MRI was abnormal in all patients, the most common being disc desiccation (90.3%) followed by facet joint arthropathy (FJA; 75%) and nerve root compression (NRC; 72.2%). Endplate changes and high-intensity zone were noted in 58 and 50 per cent of patients, respectively. One-third patients with FJA, however, were below 30 yr of age. NRC on MRI had 61.3 per cent sensitivity and 10 per cent specificity with clinical radiculopathy. FJA had 60.7 per cent sensitivity and 15.9 per cent specificity with localized CLBA. None of the MRI parameters and MRI sum score correlated with NRS and ODI. On multivariate analysis, NRS was independent predictor of ODI (odds ratio 0.58, 95% confidence interval 0.35-0.98, P=0.04). Interpretation & conclusions: In patients with CLBA, NRC on MRI showed poor specificity with corresponding clinical radiculopathy and FJA with localized backache. None of the MRI abnormality correlated with the severity of pain or disability.

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Background & objectives: Indian data have been largely missing from genome-wide databases that provide information on genetic variations in different populations. This hinders association studies for complex disorders in India. This study was aimed to determine whether the complex genetic structure and endogamy among Indians could potentially influence the design of case-control studies for autoimmune disorders in the south Indian population. Methods: A total of 12 single nucleotide variations (SNVs) related to genes associated with autoimmune disorders were genotyped in 370 healthy individuals belonging to six different caste groups in southern India. Allele frequencies were estimated; genetic divergence and phylogenetic relationship within the various caste groups and other HapMap populations were ascertained. Results: Allele frequencies for all genotyped SNVs did not vary significantly among the different groups studied. Wright's F_STwas 0.001 per cent among study population and 0.38 per cent when compared with Gujarati in Houston (GIH) population on HapMap data. The analysis of molecular variance results showed a 97 per cent variation attributable to differences within the study population and <1 per cent variation due to differences between castes. Phylogenetic analysis showed a separation of Dravidian population from other HapMap populations and particularly from GIH population. Interpretation & conclusions: Despite the complex genetic origins of the Indian population, our study indicated a low level of genetic differentiation among Dravidian language-speaking people of south India. Case-control studies of association among Dravidians of south India may not require stratification based on language and caste.

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People with epilepsy have increased risk of premature death, and their life expectancy may reduce by 2-10 yr. Population- and hospital-based studies have shown that the excess mortality in epilepsy is not entirely explained by deaths directly attributable to epilepsy such as accidents and drowning during a seizure. It is also significantly contributed by deaths from other causes such as cardiac deaths, deaths due to malignancies and other causes. It had recently been recognized that sudden unexpected deaths in epilepsy (SUDEP) contributed to a small yet important proportion of mortality in epilepsy. SUDEPs are deaths (witnessed or unwitnessed) unrelated to trauma, drowning or status epilepticus and not attributable to any specific medical conditions. Several factors related to epilepsy and drug therapy have been found to be associated with higher risk of SUDEP.

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Background & objectives: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. Methods: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. Results: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. Interpretation & conclusions: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

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Coronary artery disease (CAD) is a multifactorial disease whose prevalence remains unabated especially in developing countries. Both lifestyle factors and genetic predisposition contribute to this disorder. Though notable achievements have been made in the medical, interventional and surgical management of CAD, the need for its prevention is more important. Among other modalities, this calls for defining evidence-based new biomarkers, which on their own or in combination with other known biomarkers may predict the risk of CAD to enable institution of appropriate preventive strategies. In the present communication, we have discussed the usefulness of shortening of telomeres as a potential biomarker of CAD. Clinical research evidence in favour of telomere shortening in CAD is well documented in different ethnic populations of the world. Establishing a well-standardized and accurate method of evaluating telomere length is essential before its routine use in preventive cardiology.

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Background & objectives: Violence against women cutting across diverse socio-economic classes is an under-recognized human rights violation in the world. This analysis was undertaken to examine the prevalence along with predictors of intimate partner violence (IPV) and its association with HIV/AIDS and sexually transmitted infections (STIs) in Indian ever-married women. Methods: The data obtained from 2005 to 2006 third round of National Family Health Survey-3 (NFHS-3) were used in this study. Analyses were conducted on ever-married women by linking individual women data including violence information and HIV test results. Results: The analyses indicated all forms of violence to be prevalent in India. The prevalence of lifetime IPV reported was 35.3 per cent. Multivariate analysis using logistic regression identified younger age of women, higher number of children, low level of education of women as well as her partner, working status of women, higher spousal age, rural residence, alcohol consumption by husband, childhood witness of violence among parents, nuclear household and lower standard of living to be positively associated with the experience of IPV by the women (P<0.05). HIV-positive status of women, as well as women from high HIV prevalent State, were at increased odds of IPV (P<0.05). Interpretation & conclusions: Significantly higher reporting of HIV/STIs by women experiencing IPV hints at new pathways that link violence and HIV. Further, our analysis showed a high prevalence of IPV in India.

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Background & objectives: Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians. Methods: Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results: From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were observed in 40.3 per cent females, who were significantly older (P<0.001), had lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3, 16.2 and 13 per cent women with menstrual abnormalities were in peri-/post-menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively. Age, CD4 count at diagnosis and 25(OH)D were best predictors of male hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI. Interpretation & conclusions: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females.

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Background & objectives: Clostridium difficile is the primary cause of hospital-acquired colitis in patients receiving antibiotics. The pathogenicity of the organism is mainly due to the production of toxins. This study was conducted to investigate the presence of toxigenic C. difficile in the faecal samples of hospitalized patients suspected to have C. difficile infection (CDI) and corroborating the findings with their clinical and demographic data. Methods: Diarrhoeic samples obtained from 1110 hospitalized patients were cultured for C. difficile and the isolates confirmed by phenotypic and molecular methods. Toxigenicity of the isolates was determined using enzyme-linked immunosorbent assay for toxins A and B. Details of patients included in the study were noted and analyzed. Results: Of the 1110 patients (mean age 39±19.6 yr), 63.9 per cent were males and 36.1 per cent were females. The major antibiotics received by the patients were nitazoxanide (23.9%), penicillins/penicillin combinations (19.0%), quinolones including fluoroquinolones (13.1%), carbapenems (11.5%), glycopeptides (11.0%) and cephalosporins (8.4%). The clinical symptoms predominantly present were watery diarrhoea (56.4%), fever (40.0%) and abdominal pain (35.3%). The underlying diseases were gastrointestinal disorders (52.6%), followed by cancers (13.2%), surgical conditions (8.3%), and hepatic disorders (8.0%). Of the 174 C. difficile isolates, 54.6 per cent were toxigenic. Toxigenic C. difficile was present in all patients with surgical conditions, 65.2 per cent with cancers and 57.1 per cent with gastrointestinal disorders. Interpretation & conclusions: C. difficile was found to be an important cause of gastrointestinal infections in hospitalized patients with underlying diseases and on antibiotics. Clinical conditions of the patients correlating with toxigenic culture can be an important tool for establishing CDI diagnosis.

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Background & objectives: Type-1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA) share similar pathological features but differ in age of onset and progression. There is a scarcity of information on differences in CD4+ T-cell responses, particularly, cytokine secretion, between the two forms of autoimmune diabetes. Here proliferative potential and concentration of pro- and anti-inflammatory cytokines secreted by peripheral blood mononuclear cells (PBMCs) of T1DM and LADA patients were compared, after in vitro stimulation with β-cell autoantigens. Methods: A total of 19 patients with LADA, 37 with T1DM and 20 healthy controls were compared on the basis of lymphocyte proliferation and secretion of pro- and anti-inflammatory cytokines belonging to different T-helper types after in vitro stimulation of PBMCs with insulin and glutamic acid decarboxylase 65 (GAD65). Results: Following insulin stimulation, LADA group secreted higher concentration of interleukin-17 (IL-17) (P=0.02) and had higher proportion of interferon gamma (IFN-γ) secretors (P<0.001) than T1DM group. Post-GAD65 stimulation, higher proportion of LADA patients secreted IL-23 than T1DM group (P=0.02). Proportion of responders , as well as levels of secreted IL-10, were significantly higher in LADA than T1DM group, following stimulation with both insulin (P=0.01) and GAD65 (P=0.03). A significant positive correlation was observed between body mass index and IL-17 levels (r=0.41, P=0.04) and fasting plasma C-peptide with IL-10 levels (r=0.37, P=0.04). Interpretation & conclusions: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.

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Background & objectives: Persons with schizophrenia use various coping strategies to adapt to distressing symptoms as well as to deal with daily stressors. Efforts have been made to explore alternative frameworks of coping using Ways of Coping Checklist (WCC) in persons with schizophrenia. This study aimed to re-analyze (factor analysis) the revised-WCC in Indian patients with residual schizophrenia. The secondary aim of the study was to evaluate the relationship of new framework of coping with psychopathology, disability and quality of life (QOL). Methods: Using a cross-sectional design, 103 patients with residual schizophrenia were assessed on WCC. A principal component analysis with varimax rotation was carried out to determine the factor structure of WCC. Results: Factor analysis yielded six factors which explained 51.6 per cent of the total variance and had acceptable-to-good internal consistency. Based on the type of items loaded, the six factors were named as follows: active and growth-oriented coping, accepting and fantasizing, reflective and confrontative coping, detachment, seeking social support and negative emotional coping. Patients most often used coping strategy of seeking social support, followed by 'accepting and fantasizing' and 'active and growth-oriented coping'. Correlation analysis showed that those who more often used 'active and growth-oriented coping' had less negative symptoms, lower level of disability and higher spiritual and overall QOL. Interpretation & conclusions: The factor structure of revised-WCC was different among patients with schizophrenia when compared with individuals without mental illness, living in the community. It was evident that use of certain adaptive coping strategies was associated with better QOL and lower level of psychopathology. Our findings provided a framework of coping in patients with residual schizophrenia and suggested that promotion of certain coping strategies might be useful in improving the QOL and reduction of psychopathology in patients with schizophrenia.

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Background & objectives: Metabolic syndrome (MetS) increases the likelihood of developing coronary artery disease (CAD), and inflammation is involved in the pathogenesis of both these conditions. The present work was conducted to examine the relative expression of 18 key inflammatory genes associated with MetS and incident CAD in a representative group of patients. Methods: A total of 178 male patients, including 57 with CAD and 121 without CAD, were enrolled in the study. The participants without CAD were characterized for the presence of MetS using modified criteria specific for Asian Indians, which included a lower cut-off for waist circumference (≥90 cm for men). The expression of 18 inflammatory genes was evaluated in peripheral whole blood by quantitative polymerase chain reaction method. Results: Of the 121 participants without CAD, 53 (43.8%) had three or more risk factors (MetS group), 50 (41.3%) had one or two risk factors (non-MetS group), while 18 (14.8%) did not have any risk factors (control group). High nuclear factor-kappa B (NF-κB) expression levels and low interleukin-10 (IL-10) levels were observed in MetS patients. Linear association was seen between NF-κB and vascular endothelial growth factor A (VEGFA) expression and with increase in MetS components. Comparison of gene expression pattern between CAD and MetS revealed significantly higher expression of leukotriene genes - arachidonate 5-lipoxygenase (ALOX5), arachidonate 5-lipoxygenase activating protein (ALOX5 AP), leukotriene A4 hydrolase (LTA4H) and leukotriene C4 synthase (LTC4S), and lower expression of NF-κB, interleukin 1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1/CCL2) and signal transducer and activator of transcription 3 (STAT3) genes in CAD. There was linear increase in expression of LTA4H, LTC4S, IL-8 and VEGFA genes across the four groups, namely from controls, non-MetS, MetS and CAD. Interpretation & conclusions: A distinct gene expression pattern was seen in MetS and CAD implying a well-orchestrated inflammatory and immune activity. Specifically, NF-κB might be playing an active role in MetS, allowing further expansion of the inflammatory process with resolution of inflammation in full-blown CAD, wherein other gene players such as leukotrienes may dominate.

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Background & objectives: Multiple sclerosis (MS) is common in some ethnic groups. Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive cytokine that may be an important regulator in MS disease pathogenesis. IL-10 promoter includes several single nucleotide polymorphisms and the level of IL-10 expression is related to these polymorphisms. Furthermore, loci within the histocompatibility regions are responsible for susceptibility to MS. The aim of this study was to investigate the association of IL-10 gene promoter polymorphisms and HLA-DRB1*15 allele frequencies with MS susceptibility in an Iranian population. Methods: In this study 336 MS patients and 454 healthy controls were included. Genomic DNA was purified from peripheral blood samples by a standard protocol. Genotyping was performed by the sequence-specific primer polymerase chain reaction method. Results: IL-10 −1082 G/G and IL-10 −819 C/C genotypes were more frequent in MS patients than healthy individuals. DRB1^*15 allele showed a higher frequency among MS patients compared to controls. Interpretation & conclusions: The IL-10 and HLA-DRB1*15 polymorphisms were associated with the susceptibility to MS in Iranian patients. Our results suggest that gene-gene interaction of IL-10 polymorphisms and HLA-DRB1*15 alleles may be important factors in the development of MS.

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Background & objectives: Central nervous system (CNS) infection caused by Mycobacterium tuberculosis (MTB) is the most severe form of extrapulmonary tuberculosis (EPTB) due to a high level of mortality and morbidity. Limited studies are available on CNS-TB animal model development. The present study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients. Methods: Groups of mice were infected by the intravenous route with MTB C3 strain isolated from the CSF of CNS-TB patients. Brain and lung tissue were evaluated for bacterial burden, histopathology and surrogate markers of TB infection at 30 and 50 days post-infection. Results: Mice infected intravenously with MTB C3 strains showed progressive development of CNS disease with high bacillary burden in lungs at the initial stage (30 days), which eventually disseminated to the brain at a later stage (50 days). Similarly, high mortality (60%) was associated in mice infected with C3 strain compared to control. Interpretation & conclusions: The study showed development of a novel murine model of CNS-TB using the C3 strain of MTB that replicated events of extrapulmonary dissemination. The developed model would be helpful in understanding the pathogenesis of CNS-TB infection for the development of improved therapeutic interventions in future.

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