Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, and corresponds to the most common cause of dementia worldwide. Although not fully understood, the pathophysiology of AD is largely represented by the neurotoxic events triggered by the beta-amyloid cascade and by cytoskeletal abnormalities subsequent to the hyperphosphorylation of microtubule-associated Tau protein in neurons. These processes lead respectively to the formation of neuritic plaques and neurofibrillary tangles, which are the pathological hallmarks of the disease. Clinical benefits of the available pharmacological treatment for AD with antidementia drugs (namely cholinesterase inhibitors and memantine) are unquestionable, although limited to a temporary, symptomatic support to cognitive and related functions. Over the past decade, substantial funding and research have been dedicated to the search and development of new pharmaceutical compounds with disease-modifying properties. The rationale of such approach is that by tackling key pathological processes in AD it may be possible to attenuate or even change its natural history. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and Tau pathology in AD, focusing on pharmaceutical compounds undergoing phase 2 and phase 3 randomized controlled trials.

Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In addition to preventing myocardial infarction (MI), stroke, and death, primary prevention with statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians.

Background & objectives: There are very few studies that have investigated the muscle strength and endurance of upper limbs (UL) in chronic obstructive pulmonary disease (COPD). We undertook this study to measure and compare the skeletal muscle strength and endurance of UL in COPD patients and age matched healthy controls and to study the association between lung function parameters and UL muscle strength and endurance. Methods: Forty one COPD patients and 45 height and weight matched healthy subjects of the same age group were studied. UL skeletal muscle strength and endurance were measured using the hand grip dynamometer test. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV ₁ ), forced expiratory flow during 25-75% FVC (FEF _25-75% ) and peak expiratory flow rate (PEFR) were measured. The handgrip muscle strength and endurance between the two groups were compared and correlations between FVC and FEV ₁ with muscle strength and endurance were analyzed. Results: The mean handgrip strength and mean muscle endurance in COPD patients were significantly lesser than the normal subjects in both males and females (P<0.001). There was significant positive correlation between muscle strength and FVC in males (r ² =0.32, P<0.05); and between muscle strength and FEV ₁ in females (r ² =0.20, P<0.05). Interpretation & conclusion: The study showed that the handgrip muscle strength decreases as the FVC and FEV ₁ decrease in patients with COPD. Identifying those patients who have reduced strength and endurance will allow early interventions targeted at improving the quality of life of the patient.

Background & objectives: Socio-economic status is associated with increased morbidity in patients with asthma. The aim of the present study was to assess the association between socio-economic status and family history of asthma in adult asthma patients. Methods: The study included 200 adults with asthma and 400 non-asthmatic controls. Socio-economic status was determined based on income. Regression analysis was used to estimate odd ratios in relation to socio-economic class, using age, gender, family history of asthma and smoking habits. Results: The highest occurrence of having any family history of asthma was observed in the high class group (88.2%), followed by upper middle class (79.5%), lower middle class (60%) and the lowest in the low class group (34%). Having any family history of asthma was an important risk factor in both univariate and multivariate analyses in lower middle class, upper middle class and high class, but not in the low class group. Interpretation and conclusions: The results indicated a positive association between having a family history of asthma and higher socio-economic status. Further studies on a large representative sample need to be conducted to confirm these findings.

Background & objectives: The population of elderly is growing globally and so are the physical illnesses and psychiatric morbidity. This study was planned to assess the prevalence and patterns of psychiatric morbidity amongst rural older adults in Lucknow, north India. Methods: A survey was conducted in subjects aged 60 yr and above to identify the cases of psychiatric morbidity in rural population from randomly selected two revenue blocks of Lucknow district, Uttar Pradesh, India. All subjects were screened through Hindi Mental Status Examination (HMSE) and Survey Psychiatric Assessment Schedule (SPAS) to identify for the suspected cases of cognitive and the psychiatric disorders, respectively. The subjects screened positive on HMSE and SPAS were assessed in detail on Cambridge Mental Disorder of the Elderly Examination-Revised (CAMDEX-R) and Schedule for Clinical Assessment in Neuropsychiatry (SCAN), to diagnose cognitive disorders and psychiatric disorders (other than the cognitive), respectively on the basis of International Classification of Diseases-10 (ICD-10) diagnostic guidelines. Results: The overall prevalence of psychiatric morbidity in rural older adults was found to be 23.7 per cent (95% CI=21.89-25.53). Mood (affective) disorders were the commonest (7.6%, 95% CI=6.51-8.80), followed by mild cognitive impairment (4.6%, 95% CI=3.72-5.53), mental and behavioural disorders due to substance use (4.0%, 95% CI=3.17-4.87) and dementia (2.8%) [Alzheimer's disease (2.4%, 95% CI=1.81-3.16) and vascular (0.4%, 95% CI=0.16-0.73)]. Interpretation & conclusions: Overall prevalence of psychiatric morbidity amongst rural elderly in this study was found to be less in comparison to those reported in earlier studies from India. However, prevalence pattern of different disorders was found to be similar. Therefore, it appears that a stringent methodology, refined case criteria for diagnosis and assessment by trained professionals restrict false diagnosis.

Background & objectives: The relationship between obesity and self perception, particularly in children and young adults has important implications for physical and psychosocial health and well-being. A better understanding of this relationship could help target psychology services and public health strategies more effectively. The aim of the present study was to assess the effect of body mass index (BMI) on physical self concept and cognition of the first year medical undergraduate students in a medical college in north India. The relationship between physical self concept and academic performance and presence of any gender differences were also examined. Methods: The study was carried out on 18-21 yr old first year M.B.B.S. students of Maulana Azad Medical College, New Delhi, India. Physical self concept was assessed using short version of Physical Self Description Questionnaire (PSDQ-S) which is a psychometrically strong instrument for measuring multiple dimensions of physical self-concept. Cognition was assessed by P300 evoked potentials and academic performance was evaluated on the basis of marks obtained in anatomy, physiology and biochemistry subjects. Results: There was no association between BMI and physical self-concept or between BMI and cognition. Gender differences on physical self-concept were also insignificant. No correlation was seen between physical self-concept and academic performance. Interpretation & conclusion: The present results suggest that negative consequences of high body mass index on physical self-concept and cognition are not seen in young adults. It may be that academic achievement nullifies the effect on physical self-concept and the effect on cognition accumulates as the age progresses, therefore, appears later in life.

Background & objectives : Microbial infections in the normally sterile environment of the middle ear cavity in patients with otitis media trigger expression of Toll-like receptors (TLRs), cytokines, and nitric oxide. We evaluated the expression levels of TLR-1, -2, -4, -5, -6, and -9, interleukin (IL)-6, -8, -10, and -12, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and nitric oxide (NO), in paediatric patients with otitis media with effusion (OME). Methods: The levels of TLR, cytokine, and nitric oxide synthase (NOS) mRNAs in middle ear effusion were assessed by real-time polymerase chain reaction in 96 children with OME, 24 prone and 72 not prone to otitis. The level of expression of each mRNA was compared in the otitis-prone and non-otitis-prone groups, in patients with and without bacteria, and by frequency of ventilation tube insertion. Results: The expression of TLR-1, -2, -4, -5, -6, and -9; IL-6, -8, -10, and -12; IFN-γ; TNF-α; and NOS mRNAs in the effusion fluid of both the otitis-prone and non-otitis-prone groups were measured. The expression levels of TLR-2, -4, -6, and -9 mRNA were significantly lower in the otitis-prone than in the non-otitis-prone group (P<0.05). Although higher levels of TLR, cytokine, and NOS mRNAs were generally observed in culture positive than in culture negative patients, none of these differences was statistically significant. No differences were observed in the expressions relative to the frequencies of ventilation tube insertion. Interpretation & conclusions: TLRs, cytokines, and NOS, which act cooperatively in the innate immune response, were closely associated with OME. Decreased expression of TLRs may be associated with increased susceptibility to OME.

Background & objectives: There is a concern on the quality and the usefulness of teleophthalmology images, particularly those using indigenous equipment, in making a diagnosis and treatment decisions in ophthalmology. The present study was done to compare the level of agreement and sensitivity and specificity of diagnosis and management decisions of various eye diseases by teleophthalmology using indigenous equipment, compared to the in-clinic assessment. Methods: Patients having different eye diseases were evaluated by two ophthalmologists - one ophthalmologist examined the patient in clinic setting while the other ophthalmologist made the diagnosis and management decision based on images sent by teleophthalmology. The images were taken by the ophthalmic technician using digital imaging system and fundus camera. The clinical findings and management decisions by the two ophthalmologists were masked to each others. Results: In diagnosis of anterior segment eye diseases such as cataract and corneal diseases there was good to very good agreement (kappa values of 0.68 and 0.91 for cataract and corneal diseases respectively) between in-clinic assessment and assessment by teleophthalmology. There was moderate agreement (kappa values of 0.52 and 0.48 for glaucoma and retinal diseases respectively) between in-clinic assessment and assessment by teleophthalmology for the diagnosis of glaucoma and retinal diseases. For the management decisions of patients, there was moderate level of agreement in all groups of eye diseases. Interpretation & conclusions: Teleophthalmology, using indigenous equipment was found to be effective in diagnosis and management decision of anterior segment eye diseases such as cataract and cornea, and with some modification and continuous training to the technicians could become an effective tool for screening and referral of glaucoma and retinal diseases.

Background & objectives: The reported low relapse rates after 24 months multidrug therapy (MDT) for multibacillary leprosy (MB) led to the recommendation of reducing duration of therapy to 12 months. However, only a few reports exist on long term follow up data after 12 months fixed duration therapy (FDT). The present study was done to assess the incidence of relapse in MB leprosy patients after 12 months treatment. Methods: The leprosy patients detected in field surveys during 2001-2006 in Agra district, Uttar Pradesh, India, were put on WHO-MDT and followed up for treatment completion, relapse, reactions and development of disability. The assessment was done clinically by following up the patients until January 2011. Data collected were analyzed for risk and survival analysis. Results: The incidence of relapse was found to be 1.97/100 person years of follow up. The incidence of relapse by age (34 yr vs >34 yr), sex (male vs female), delay in detection (<36 months vs >36 months) and smear status (smear +ve vs -ve) was not found to be significantly different but patients with no nerve involvement were observed to have significantly higher relapses than those with three or more nerve involvement (P<0.05). Similarly, borderline-borderline and BB with reaction (BB/BBR) patients were observed to have significantly high relapses than among those with borderline tuberculoid or BT with reaction (BT/BTR) or borderline lipromatous/lepromatous/neuritic (BL/LL/N) type of leprosy (P<0.01). Interpretation & conclusion: From the observations in the study, it can be suggested that relapses occur in 12 months FDT and almost as much as reported in 24 months FDT for MB leprosy. Although, early relapses may be due to insufficient treatment, late relapses may be due to persistent dormant mycobacteria. However, a study relating to immunological response of treatment and change in immunological profile relating to the occurrence of relapses and its clinical correlates may suggest better information on causes of relapses.

Background & objectives: There has been an extensive invasion of tuberculosis at the global level by multidrug resistant as well as extensively drug resistant organisms. Attempts to recover the pathogen in pure culture have frequently failed since the specimens are often highly contaminated and also due to use of insufficient or over-active decontamination procedures. Hence in the present study different methods of decontamination were tested to evaluate their independent efficacies for culture of Mycobacterium tuberculosis. Methods: A total of 359 samples (241 sputum, 59 urine, 50 endometrium biopsy, 9 pus samples) from clinically suspected cases of tuberculosis were subjected to four different methods of decontamination followed by inoculation in Lowenstein-Jensen medium (LJM), and bilayered medium (BLM) and Kirchner's liquid medium (KLM) to determine the influence of differential decontamination processes. Sputum scanty and positive specimens were graded and each sample was subjected to decontamination by four different techniques. Results: Treatment of specimens with 4 per cent NaOH yielded minimum recovery of pure cultures, while use of 2 per cent NaOH produced higher number of contaminants compared to other methods of decontamination. Addition of N-acetyl L-cystein (NALC) coupled with 2 per cent NaOH to the samples for decontamination provided fairly reasonable recovery, but the highest number of M. tuberculosis cultures could be obtained when the specimens were treated with tri-sodium phosphate and benzalkonium (TSPB). Among the sputum positive cases recovery of growth of M. tuberculosis was higher with greater number of bacilli present in the specimens. Regarding the influence of culture media, BLM produced not only rapid growth, but reasonably higher rate of isolation of M. tuberculosis. Interpretation & conclusions: Although use of TSPB was found to be an efficient method of decontamination for successful isolation of M. tuberculosis from contaminated samples, both NALC+ 2 per cent NaOH and TSPB also showed significant recovery of M. tuberculosis cultures in BLM that can facilitate early diagnosis and initiation of treatment.

Background & objectives: Enterococci have emerged as important nosocomial pathogens and emergence of resistance to many of the antimicrobials used for Gram-positive organisms has made the management of infections due to Enterococcus species difficult. Resistance to glycopeptide antibiotics, especially vancomycin is of special concern. This study was undertaken to perform a phenotypic and genotypic characterization of vancomycin resistant Enterococcus (VRE) isolates obtained from clinical samples in a tertiary care hospital in southern India. Methods: Susceptibility testing was performed for Enterococcus isolates collected over a period of one year (November 2008-October 2009). Minimum inhibitory concentrations (MIC) of vancomycin and teicoplanin were determined for the isolates by the agar dilution method. Genotypic characterization of VRE isolates was done by performing multiplex polymerase chain reaction (PCR) for detecting the various vancomycin resistance genes. Results: Of the 367 isolates of Enterococcus species isolated, 32 were found to be resistant to vancomycin after MIC testing. VanA was the commonest phenotype of vancomycin resistance and the commonest genotype was vanA. Among the other important findings of the study was the presence of heterogeneity in isolates of VRE with the vanA gene cluster with regards to resistance to teicoplanin and the coexistence of vanA and vanC1 gene clusters in an isolate of E. gallinarum which conferred high level glycopeptide resistance to the isolate. Interpretation & conclusions: Enterococcus species have emerged as important nosocomial pathogens in our patients with a capacity to cause a variety of infections. The vancomycin resistance among Enterococcus isolates was 8.7 per cent in our study which was high compared to other Indian studies. VanA was the commonest phenotype of glycopeptide resistance and vanA was the commonest vancomycin resistance gene. The study also demonstrates phenotypic as well as genotypic heterogeneity among isolates of VRE from clinical specimens.