50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences.

India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India-including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups-providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry from gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover ~1.5 Gb (or 50%) of the introgressing Neanderthal and ~0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.

Prevalence of DSM-5 mild and major neurocognitive disorder in India: Results from the LASI-DAD.

INTRODUCTION: India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. METHODS: The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) (N = 4,096) is a nationally representative cohort study in India using multistage area probability sampling methods. Using neuropsychological testing and informant reports, we defined DSM-5 mild and major neurocognitive disorder, reported its prevalence, and evaluated criterion and construct validity of the algorithm using clinician-adjudicated Clinical Dementia Ratings (CDR)®. RESULTS: The prevalence of mild and major neurocognitive disorder, weighted to the population, is 17.6% and 7.2%. Demographic gradients with respect to age and education conform to hypothesized patterns. Among N = 2,390 participants with a clinician-adjudicated CDR, CDR ratings and DSM-5 classification agreed for N = 2,139 (89.5%) participants. DISCUSSION: The prevalence of dementia in India is higher than previously recognized. These findings, coupled with a growing number of older adults in the coming decades in India, have important implications for society, public health, and families. We are aware of no previous Indian population-representative estimates of mild cognitive impairment, a group which will be increasingly important in coming years to identify for potential therapeutic treatment.

Region-based analysis with functional annotation identifies genes associated with cognitive function in South Asians from India.

The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been identified from studies conducted in European Ancestry (EA) but are unknown in South Asians. Using whole-genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD), we performed a gene-based analysis of 84 genes previously associated with AD in EA. We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. For each gene, we examined missense/loss-of-function (LoF) variants and brain-specific promoter/enhancer variants, separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores) using the variant-Set Test for Association using Annotation infoRmation (STAAR). In the missense/LoF analysis without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes had an association with at least one measure of cognitive function (FDR q<0.1). APOE was associated with four measures of cognitive function, PICALM was associated with HMSE score, and TSPOAP1 was associated with executive function. The most strongly associated variants in each gene were rs429358 (APOE ε4), rs779406084 (PICALM), and rs9913145 (TSPOAP1). rs779406084 is a rare missense mutation that is more prevalent in LASI-DAD than in EA (minor allele frequency=0.075% vs. 0.0015%); the other two are common variants. No genes in the brain-specific promoter/enhancer analysis met criteria for significance. Results with and without annotation weights were similar. Missense/LoF variants in some genes previously associated with AD in EA are associated with measures of cognitive function in South Asians from India. Analyzing genome sequence data allows identification of potential novel causal variants enriched in South Asians.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nation-wide survey.

Introduction: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over two years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. Methods: We used data from the Real-Time Insights of COVID-19 in India (RTI COVID-India) cohort study (N=3,662). We used covariate-adjusted linear regression models with generalized estimating equations to assess associations between mental health (PHQ-4 score) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender, and rural/urban residence. Results: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly and independently associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.041 SD units; 95% Confidence Interval 0.030 - 0.053), government stringency index (0.060 SD units; 0.048 - 0.072), self-reported major financial impacts (0.45 SD units; 0.41-0.49), and COVID-19 infection in the household (0.11 SD units; 0.07-0.16). Conclusion: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-age and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Cohort Profile: Real-Time Insights of COVID-19 in India (RTI COVID-India).

BACKGROUND: The coronavirus disease (COVID) pandemic caused disruption globally and was particularly distressing in low- and middle-income countries such as India. This study aimed to provide population representative estimates of COVID-related outcomes in India over time and characterize how COVID-related changes and impacts differ by key socioeconomic groups across the life course. METHODS: The sample was leveraged from an existing nationally representative study on cognition and dementia in India: Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). The wave-1 of LASI-DAD enrolled 4096 older adults aged 60 years and older in 3316 households from 18 states and union territories of India. Out of the 3316 LASI-DAD households, 2704 with valid phone numbers were contacted and invited to participate in the Real-Time Insights COVID-19 in India (RTI COVID-India) study. RTI COVID-India was a bi-monthly phone survey that provided insight into the individual's knowledge, attitudes, and behaviour towards COVID-19 and changes in the household's economic and health conditions throughout the pandemic. The survey was started in May 2020 and 9 rounds of data have been collected. FINDINGS TILL DATE: Out of the 2704 LASI-DAD households with valid phone numbers, 1766 households participated in the RTI COVID-India survey at least once. Participants were in the age range of 18-102 years, 49% were female, 66% resided in rural area. Across all rounds, there was a higher report of infection among respondents aged 60-69 years. There was a greater prevalence of COVID-19 diagnosis reported in urban (23.0%) compared to rural areas (9.8%). Respondents with higher education had a greater prevalence of COVID-19 diagnosis compared to those with lower or no formal education. Highest prevalence of COVID-19 diagnosis was reported from high economic status compared to middle and low economic status households. Comparing education gradients in experiencing COVID-19 symptoms and being diagnosed, we observe an opposite pattern: respondents with no formal schooling reported the highest level of experiencing COVID-19 symptoms, whereas the greatest proportion of the respondents with secondary school or higher education reported being diagnosed with COVID-19. FUTURE PLANS: The study group will analyse the data collected showing the real-time changes throughout the pandemic and will make the data widely available for researchers to conduct further studies.

Estimating the Prevalence of Dementia in India Using a Semi-Supervised Machine Learning Approach.

INTRODUCTION: Accurate estimation of dementia prevalence is essential for making effective public and social care policy to support individuals and families suffering from the disease. The purpose of this paper is to estimate the prevalence of dementia in India using a semi-supervised machine learning approach based on a large nationally representative sample. METHODS: The sample of this study is adults 60 years or older in the wave 1 (2017-2019) of the Longitudinal Aging Study in India (LASI). A subsample in LASI received extensive cognitive assessment and clinical consensus ratings and therefore has diagnoses of dementia. A semi-supervised machine learning model was developed to predict the status of dementia for LASI participants without diagnoses. After obtaining the predictions, sampling weights and age standardization to the World Health Organization (WHO) standard population were applied to generate the estimate for prevalence of dementia in India. RESULTS: The prevalence of dementia for those aged 60 years and older in India was 8.44% (95% CI: 7.89%-9.01%). The age-standardized prevalence was estimated to be 8.94% (95% CI: 8.36%-9.55%). The prevalence of dementia was greater for those who were older, were females, received no education, and lived in rural areas. DISCUSSION: The prevalence of dementia in India may be higher than prior estimates derived from local studies. These prevalence estimates provide the information necessary for making long-term planning of public and social care policy. The semi-supervised machine learning approach adopted in this paper may also be useful for other large population aging studies that have a similar data structure.

Mycoplasma pneumoniae among Hospitalized Patients with Acute Respiratory Tract Infections in an Indian Tertiary Care Hospital: an Underreported Health Problem.

The epidemiology of Mycoplasma pneumoniae (Mp) is poorly understood in India. The present study was conducted to identify the prevalence of Mp in a large set of patients with acute respiratory tract infections (ARI) in an Indian tertiary hospital. During 2015-2020, we tested throat swab specimens from patients with the clinical diagnosis of ARI (n = 1,098) by a real-time PCR and compared the demographic, clinical, laboratory, and outcome data of Mp-positive and Mp-negative patients. During the study period, 5% (55/1,098) of the tested samples were positive for Mp by PCR. School-aged children and young adults represented 36% (20/55) of the cases and 47.3% (26/55) of the cases were registered during the summer and monsoon. Among the Mp-positive patients, 61.8% (34/55) had underlying conditions; the most common were malignancy (n = 12; 21.8%) and hypertension (n = 6; 10.9%). Fever (98.2% versus 84.9%; P = 0.006), and pharyngitis (27.3% versus 16.3%; P = 0.034) were significantly common in the Mp-positive group than Mp-negative group. Among the Mp-positive group, 20% (11/55) of patients were admitted to an intensive care unit and a total of 7/55 (12.7%) patients received ventilatory support. The mortality in the Mp-positive cohort was 13.3%. The study provides baseline data regarding Mp prevalence and clinical characteristics. The application of molecular assays for diagnosing this pathogen among hospitalized patients with ARI could reduce inappropriate empirical antibiotic treatment and improve patient outcomes. Further large-scale studies are required to avoid the underdiagnosis of Mp infections in India and such studies should address some research gaps, such as macrolide resistance and molecular typing. IMPORTANCE M. pneumoniae (Mp) is a significant pathogen causing atypical pneumonia but by far these infections are underreported clinical entities in India. In the present study, we report the prevalence of Mp and describe the demographic and baseline clinical data of Mp-positive cases in an Indian tertiary care hospital. Our study may improve the clinician's awareness of this important agent of respiratory infection therefore timely and accurate diagnostic tools can be applied for patient management decisions and outcomes.

Performance of the Informant Questionnaire on Cognitive Decline for the Elderly (IQCODE) in a nationally representative study in India: the LASI-DAD study.

BACKGROUND: Low and middle-income countries like India anticipate rapid population aging and increases in dementia burden. In India, dementia screening scales originally developed in other contexts need to be assessed for feasibility and validity, given the number of different languages and varying levels of literacy and education. METHOD: Using data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (N = 4,028), we characterize the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We described patterns and correlates of missingness, evaluated the psychometric properties of the scale, and assessed criterion validity against the Hindi Mental State Examination (HMSE) using linear regression. RESULTS: Several IQCODE items had high levels of missingness, which was associated with urbanicity, respondent's gender, and informant's generation (same vs. younger generation). Full IQCODE scores showed strong criterion validity against the HMSE; each 1-point increase in IQCODE score was associated with a 3.03-point lower score on the HMSE, controlling for age, gender, and urbanicity. The statistically significant association between IQCODE and HMSE was stronger in urban than rural settings (p-value for interaction = 0.04). Associations between IQCODE and HMSE remained unchanged after removing the three items with the highest levels of differential missingness (remembering addresses and telephone numbers, ability to work with familiar machines, ability to learn to use new gadget or machine). CONCLUSION: Findings raise questions about the value of including items with high proportions of missingness, which may signal cultural irrelevance, while removing them did not affect criterion validity.

Blood Circulatory Level of Seven Sirtuins in Alzheimer's Disease: Potent Biomarker Based on Translational Research.

Alzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changes. This study evaluated serum levels of all seven sirtuin (SIRT1-SIRT7) proteins in three study groups: AD, mild cognitive impairment (MCI) and geriatric control (GC) by surface plasmon resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteins. Out of seven sirtuins, serum SIRT1, SIRT3 and SIRT6 levels (mean ± SD) were significantly decreased in AD (1.65 ± 0.56, 3.15 ± 0.28, 3.36 ± 0.32 ng/µl), compared to MCI (2.17 ± 0.39, 3.60 ± 0.51, 3.73 ± 0.48 ng/µl) and GC (2.84 ± 0.47, 4.55 ± 0.48, 4.65 ± 0.55 ng/µl). ROC analysis showed the cut-off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in the case of other SIRTs between the study groups. This study reveals an inverse relation of serum SIRT1, SIRT3 and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.

Circulatory GSK-3ß: Blood-Based Biomarker and Therapeutic Target for Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the progressive brain disorder which degenerates brain cells connection and causes memory loss. Although AD is irreversible, it is not impossible to arrest or slow down the progression of the disease. However, this would only be possible if the disease is diagnosed at an early stage, and early diagnosis requires clear understanding of the pathogenesis at molecular level. Overactivity of GSK-3ß and p53 accounts for tau hyperphosphorylation and the formation of amyloid-ß plaques. OBJECTIVE: Here, we explored GSK-3ß and p53 as blood-based biomarkers for early detection of AD. METHODS: The levels of GSK-3ß, p53, and their phosphorylated states were measured using surface plasmon resonance and verified using western blot in serum from AD, mild cognitive impairment (MCI), and geriatric-control (GC) subjects. The neurotoxic SH-SY5Y cell line was treated with antioxidant Emblica Officinalis (EO) for rescue effect. RESULTS: GSK-3ß, p53, and their phosphorylated states were significantly over expressed (p > 0.001) in AD and MCI compared to GC and can differentiate AD and MCI from GC. The expression level of GSK-3ß and p53 proteins were found to be downregulated in a dose-dependent manner after the treatment with EO in amyloid-b-induced neurotoxic cells. CONCLUSION: These proteins can serve as potential blood markers for the diagnosis of AD and EO can suppress their level. This work has translational value and clinical utility in the future.

Frailty, Disability, and Mortality in a Rural Community-Dwelling Elderly Cohort from Northern India.

INTRODUCTION: With increasing proportion of the elderly in the world, detecting and preventing frailty assumes importance to improve the quality of life and health. The study aimed to estimate the prevalence of frailty, disability and its determinants and their relation with mortality among community dwelling elderly cohort. MATERIALS AND METHODS: The study was conducted in a cohort in rural Haryana, India, and was followed till October 2018. Frailty was assessed using the Edmonton Frailty Scale and disability was assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) scale by trained physicians. RESULTS: The prevalence of frailty was found to be 47.3% (95% confidence interval [CI]: 44.0-50.8). The median WHODAS-2 score was found to be 10.4 (2.1-29.2). Those who were older (odds ratio [OR] - 2.5; 95% CI: 1.8-3.4), women (OR - 3.3; 95% CI: 2.2-4.9) and those with chronic disease (OR 2.3; 95% CI: 1.7-3.1) had higher rates of frailty. The adjusted hazard ratio of death among frail people was 4.7 (2.3-9.7). CONCLUSION: In this study we found the frailty is associated with the mortality among community dwelling elderly. Thus early identification of the frailty and its determinants may help us to reduce the mortality related to this.

The changing perspective of clinical trial designs.

Maintaining health and well-being of the population is a universal priority. Governments around the globe are therefore seeking greater efficiency and better outcomes from researches being held. Although large randomized trials or systematic review of several large trials provides the highest level of evidence, the intricate cost, time, and difficulties of conventional trials have led to questions about their sustainability commanding search for alternative approaches. Demands for improved competences in medical research have led to mounting interest in newer clinical trial designs. This article provides an insight into newer clinical trial designs, including cluster trials, adaptive designs, the master protocols along with their strengths, weaknesses, and which trials design should be opted for in different clinical scenarios.

Incidence, risk factors, and viral etiology of community-acquired acute lower respiratory tract infection among older adults in rural north India.

BACKGROUND: There are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries. METHODS: We established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls. RESULTS: We followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively. CONCLUSION: In this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

Serum sestrins: potential predictive molecule in human sarcopenia.

BACKGROUND: The aging trajectory from a state of robustness and good health proceeds from sarcopenia to frailty followed by disability and death due to decline in skeletal muscle mass and function. Sarcopenia is now formally recognized as a muscle disease with an ICD-10-MC diagnosis code. The autophagic response seems to be affected in the skeletal muscle during aging contributing to sarcopenia. Sestrins (Sesns) proteins play a critical role in autophagy induction under cellular stress conditions. AIMS: The study aims to identify sarcopenia in older adults using Asian Working group guidelines (AWGS) to determine clinically relevant cut-off levels for diagnosis and their association with antioxidant protein Sesns. METHODS: The study recruited 102 older adults attending Geriatric medicine OPD AIIMS, New Delhi, India. The level of serum Sesns were evaluated by Surface Plasmon Resonance (SPR) and validated by immunoblotting. Fifty older adults were diagnosed as sarcopenics according to AWGS. RESULTS: Sesn 1 (p = 0.0448) and Sesn 2 (p < 0.0001) levels were significantly reduced in sarcopenic compared to non-sarcopenic. ROC analysis showed a better cut-off of Sesn 2; 10.104 ng/µL with 92% sensitivity and 84% specificity. Even after adjusting the values with respect to confounding factors, Sesn levels remained significantly reduced in sarcopenics (p < 0.030). DISCUSSION: The level of Sesn 2 showed positive co-relation with the characteristics of sarcopenia. This study first time reported the concentration of serum sestrin in sarcopenic older adults. CONCLUSION: It can be concluded that sarcopenia can be diagnosed at the early stage by using the serum sestrin scale as one of the potential biomarker.

Distribution of Virulence Genes and Sequence-Based Types Among Legionella pneumophila Isolated From the Water Systems of a Tertiary Care Hospital in India.

Background: Legionnaires' disease (LD) is a potentially fatal pneumonia predominantly caused by infection due to Legionella pneumophila although more than 50 other Legionella species are described. Water systems contaminated with Legionella spp. are the implicated sources of Legionnaires' disease. In this study, we aimed to assess Legionella contamination in the water sources of a tertiary care hospital and to determine the virulence properties and molecular characteristics of L. pneumophila environmental isolates. Methods: During May 2015 through August 2018, a total of 201 hospital water samples were tested for L. pneumophila by standardized culture procedures; environmental isolates were examined for the presence of two virulence genes: Legionella vir homolog (lvh) and repeats in structural toxin (rtxA) by PCR. The genotyping of isolates was performed by sequence-based typing (SBT) according to the protocol of the European Study Group for Legionella Infections (ESGLI). Results:L. pneumophila was isolated from 38/201 (18.9%) water samples; among the 46 isolates, the lvh locus was present in 45 (97.8%), the rtxA locus was found in 45 (97.8%), and both loci were found in 44 (95.7%) isolates. A total of 23 sequence types (STs) were identified among the 44 isolates (index of discrimination [IOD] of 0.929), and 11/23 (47.8%) STs were new to the ESGLI database. Conclusions: The study results showed genetic diversity in L. pneumophila isolates from the hospital environment along with a high percentage of pathogenicity loci. Besides, certain STs may have an increased ability to cause legionellosis, thus requires specific infection control and prevention strategies whenever identified.

Legionella pneumophila in Patients with Pneumonia at a Referral Hospital, New Delhi, India, 2015-2020.

Legionnaires' disease (LD) is an established cause of pneumonia, and the disease remains largely underdiagnosed. Even though LD has been reported from many parts of the world, only sporadic cases have been reported in India. During February 2015-January 2020, we enrolled 597 patients with radiographically confirmed pneumonia and tested respiratory secretions for Legionella spp. by using real-time PCR, and culture. A commercial urinary antigen test (UAT) was also used to detect the Legionella pneumophila (Lp) serogroup 1 antigen in urine. An LD case was defined as a patient with pneumonia and positive results for Legionella spp. infections determined by real-time PCR (from any respiratory specimen) or culture or UAT. Demographic data, risk factors, clinical, radiological, and outcome data of Lp-positive and Lp-negative patients were compared using logistic regression. Over the study period, 14 (2.3%) patients were positive for Legionella spp. infections by real-time PCR and UAT; eight (57%) were admitted to the intensive care unit, and four (28.6%) in-hospital deaths occurred. Bivariate analysis showed that renal disease, neurological conditions, confusion, leukocytosis, and requirement of oxygen support were more common in the Lp-positive group than in the Lp-negative group. However, multivariate analysis failed to confirm most of these differences; renal disease was the only independent variable remaining significant. All test methods have intrinsic limitations in identifying Legionella; therefore, more than one testing method should be used. Application of molecular assays including real-time PCR has great value because of its high sensitivity, specificity, and rapid diagnostic potency. Increased awareness and improved diagnostic testing could facilitate early detection of cases, pathogen-directed therapy, and improved outcomes for patients.

Healthcare policies and programmes for older persons: Exploring awareness among stakeholders.

BACKGROUND: Human rights are for all, regardless of age. The older adults are seen as vulnerable because biological, psychological and social ageing predispose the ageing person to frailty, infirmity, and in many cases dependency, setting the older person apart from the rest of the population in need of special protection and rights. Although the implementation of legislation, policies, and a package of integrated programmes and projects to cater to the needs of older persons had helped them to uplift their status, more has to be done to stem the increase of the reach of laws in a more fruitful manner. AIM: To develop a colloquial structured Healthcare Policies & Programmes Awareness Questionnaire and assess the awareness about the government healthcare provisions and benefits available for senior citizens among health professionals, older patients, and their caregivers. METHODS: This study was conducted in two phases, the development of the questionnaire consisting of relevant healthcare national policies and programmes followed by a cross sectional pilot study on 335 participants. RESULTS: The level of awareness was only 45.6% among health professionals followed by 26.4% & 22.2% of awareness among the caregivers and the older adults respectively. CONCLUSION: There is a huge gap between the healthcare providers and healthcare takers knowledge due to which the preventive and promotive care of older adults is poor in our country. There is a need to strengthen institutions and mechanism that can more systematically promote interaction between researchers, policymakers and other stakeholders who can influence the uptake of the research findings in a synergistic manner.

Serum FOXO3A: A ray of hope for early diagnosis of Alzheimer's disease.

Diagnosis of Alzheimer's disease (AD) is often difficult because of distinct and subjective clinical features, especially in the early stage. FOXO3a protein present in the cognitive centre of brain in inferior temporal region and parahippocampus. FOXO3a can be a potential novel target against AD. AD, Mild Cognitive impairment (MCI) and Geriatric Control (GC) were recruited after diagnosis by clinical assessment, MRI, TauPET and FDG-PET. We have quantified serum FOXO3a by surface plasmon resonance (SPR) and compare with TauPET between of AD, MCI patients and GC. Serum FOXO3A was significantly lower in AD (1.42 ± 0.09 ng/µl) compare to MCI (1.61 ± 0.14 ng/µl) and GC (1.89 ± 0.07 ng/µl). However, the Tau was higher in AD both in serum and also in PET scan. Serum pTau was significantly over-expressed in AD (0.176 ± 0.03 ng/µl), compare to other groups; MCI (0.16 ± 0.014 ng/µl) and GC (0.15 ± 0.024 ng/µl). Serum FOXO3A could significantly differentiate AD vs MCI, MCI vs GC and AD vs GC. However, Tau protein could only differentiate AD vs GC but not MCI vs GC. Serum FOXO3A may serve as novel blood marker for early detection for AD and target for therapeutic intervention.

Hindi Version of Addenbrooke's Cognitive Examination III: Distinguishing Cognitive Impairment Among Older Indians at the Lower Cut-Offs.

BACKGROUND: Screening and diagnostic tests provide an objective measure of cognitive performance and also aid in distinguishing mild cognitive impairment (MCI) from major neurocognitive disorder (MNCD). Further, when such tests are culturally and educationally unbiased, it strengthens their diagnostic utility. This study aimed to validate the Hindi version of Addenbrooke's Cognitive Examination III (ACE-III) in Indian older adults and compare its validity with the Hindi Mini-Mental State Examination (HMSE). METHODS: A sample of 412 consenting older adults visiting a memory clinic was recruited into the study. They were categorized into three groups: healthy controls (n=222), MCI (n=70), and MNCD (n=120). The complete clinical protocol was followed. Hindi ACE-III and HMSE were administered and were statistically analyzed. RESULTS: The optimal cut-off values to detect MCI and MNCD with ACE-III were 71 and 62 (AUC: 0.849 and 0.884), respectively, which were slightly higher than with HMSE (AUC: 0.822, 0.861). Education- and age-stratified cut-offs were also computed. CONCLUSION: Hindi ACE-III has good discriminating power at lower cut-offs than the standard scores in differentiating between MCI and MNCD.