Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.

Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function. METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories.

Objective: To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR). Design: In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes. Setting: We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China. Main outcomes and measures: The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach. Results: From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1-2 years, less than 1 year, and 2-3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology. Conclusion and relevance: Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Era of TB elimination: Growing need to understand diversities of Mycobacterium tuberculosis lineages!

INTRODUCTION: The mycobacterium tuberculosis complex (MTBC) has highly clonal population structure which made the organism spread globally mirroring human migration out of Africa and resulted in the formation of seven lineages. We conducted this study to determine the proportion of spoligotype lineages and drug susceptibility profile of Mycobacterium tuberculosis isolates among smear positive TB patients attending a tertiary care hospital in Mysore, Karnataka, India. METHODS: It is a descriptive study conducted at JSS Hospital a tertiary care centre at Mysore, India during 2018-19. The sputum smear positive samples were subjected to solid culture and drug susceptibility testing and spoligotyping for identification of lineages. RESULTS: Of the 100 samples which were culture positive, 94 isolates were clustered into five spoligotype international types with SIT-126 (EAI-5) being the largest cluster of 46 (46%) isolates, followed by SIT-62 (H1) with 24 (24%), SIT -26 (CAS 1-DELHI) with 20 (20%), SIT-53 (T1) with 03 (3%) and SIT-482 (BOV-1) with 01 (1%). Among the remaining six isolates, two had unique Cameroon spoligotypes and four were orphans CONCLUSION: The study finding reveals that a diverse pattern of genotypes is circulating in the region of which EAI-5, Harleem (H1) and CAS-DELHI pattern forms the majority (88%). It is evident that there is a wide range of MTB genetic lineages in circulation and further research is needed to understand the diversity across the country.

Variation in the prevalence of chronic bronchitis among smokers: a cross-sectional study.

OBJECTIVE: Given the wide variations in prevalence of chronic obstructive pulmonary disease observed between populations with similar levels of exposure to tobacco smoke, we aimed to investigate the possibility of variations in prevalence of chronic bronchitis (CB) between two geographically distinct smoking populations in rural Karnataka, India. DESIGN: The Burden of Obstructive Lung Disease (BOLD) questionnaire was administered to all men aged >30 years in a cross-sectional survey. The χ(2) and Fisher's exact tests were used to compare CB prevalence in the two populations. Logistic regression was used to analyse the impact of multiple variables on the occurrence of CB. RESULTS: Two samples of 2322 and 2182 subjects were included in the study. In non-smokers, CB prevalence did not differ between the populations. However, it was significantly different between smoking populations (44.79% vs. 2.13%, P < 0.0001). Logistic regression indicated that, in addition to smoking, region, age, occupational dust exposure and type of house were associated with higher likelihood of CB. An interaction between smoking and area of residence was found (P < 0.001) and appeared to explain the effect of region (without interaction). CONCLUSION: A significant difference in CB prevalence was observed between male populations from two areas of Karnataka state, including when stratified by smoking status. No significant difference was observed between non-smokers.

Identification of a threshold for biomass exposure index for chronic bronchitis in rural women of Mysore district, Karnataka, India.

BACKGROUND & OBJECTIVES: Exposure to air pollution due to combustion of biomass fuels remains one of the significant risk factors for chronic respiratory diseases such as chronic bronchitis. There is a need to identify the minimum threshold level of biomass index that is significantly associated with chronic bronchitis. This study was undertaken to identify a threshold for biomass exposure index in a rural women population in Mysore district, south India. METHODS: A cross-sectional survey was conducted in a representative population of Mysore and Nanjangud taluks. Eight villages each from Mysore and Nanjangud were randomly selected based on the list of villages from census 2001. A house-to-house survey was carried out by trained field workers using the Burden of Obstructive Diseases questionnaire, which evaluated the biomass smoke exposure and chronic bronchitis. All the women aged above 30 yr were included in the study. RESULTS: A total of 2011 women from Mysore and 1942 women from Nanjangud participated in the study. All women were non-smoking and used biomass fuels as the primary fuel for cooking. A threshold of biomass fuel exposure of 60 was identified on multivariate analysis in Mysore district after adjusting for age, passive smoking and working in a occupational exposure to dust, as the minimum required for a significant association with chronic bronchitis. One in every 20 women in Mysore district exposed to biomass fuel exposure index of 110 or more developed chronic bronchitis. INTERPRETATION & CONCLUSIONS: The minimum threshold of biomass exposure index of 60 is necessary to have a significant risk of developing chronic bronchitis in women. The number needed to harm to develop chronic bronchitis reduces with increasing biomass exposure index and women residing in rural Nanjangud have a higher risk for developing chronic bronchitis as compared to women in Mysore.

Association of socio-economic status with family history in adult patients with asthma.

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.

Factors affecting 30-month survival in lung cancer patients.

BACKGROUND & OBJECTIVES: Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. METHODS: Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. RESULTS: A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. INTERPRETATION & CONCLUSIONS: Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients.

Prevalence of COPD in India: a systematic review.

BACKGROUND: The increasing burden of chronic diseases is a particular risk to countries with developing health systems. Chronic obstructive pulmonary disease (COPD) is contributing to the burden of chronic diseases. Understanding the current prevalence of COPD in India is important for the production of sustainable management strategies. AIMS: To provide a systematic review of studies assessing the prevalence of COPD in India. METHODS: Database searches, journal hand searches, and scanning of reference lists were used to identify studies. Studies of general adult populations resident in India were included. Data extraction and quality assessment were carried out using pre-tested proformas. Owing to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. RESULTS: We did not identify any studies from which we could draw a rigorous estimate of the prevalence of COPD by standard definition. Reliable standard estimates of chronic bronchitis were only available for rural populations. We identified four studies that gave estimated prevalences between 6.5% and 7.7%, and others suggestive that prevalences in some environmentally atypical regions may lie outside this range. Sex and smoking status were relatively important predictors of COPD prevalence. Residential environs, age, and domestic smoke exposure are also important, but investigation of their effect was limited by study heterogeneity. CONCLUSIONS: Although limited by the number and heterogeneity of studies and their unsuitability for meta-analysis, we found the most rigorous existing estimates of the general prevalence of chronic bronchitis in rural areas to lie between 6.5% and 7.7%. These figures are unlikely to apply to all Indian subpopulations, so the general prevalence of chronic bronchitis in India remains unknown. Accurate estimates of the prevalence of chronic bronchitis/COPD from across the country are required to supplement existing data if optimal management strategies are to be devised.

Prevalence of chronic cough, chronic phlegm & associated factors in Mysore, Karnataka, India.

BACKGROUND & OBJECTIVES: Chronic cough and chronic phlegm are important indicators of respiratory morbidity, accelerated lung function decline, increased hospitalization and mortality. This study was planned to estimate the prevalence of chronic cough and phlegm in the absence of dyspneoa and wheezing and to study its associated factors in a representative population of Mysore district. METHODS: A cross-sectional survey was planned in a representative population of Mysore taluk. Eight villages were randomly selected based on the list of villages from census 2001. Trained field workers using the Burden of Obstructive Diseases questionnaire carried out a house-to-house survey. RESULTS: A total of 4333 adult subjects were enrolled in the study with 2333 males and 2000 females. The prevalence of chronic cough in the community was 2.5 per cent and that of chronic phlegm was 1.2 per cent. A significant association was observed between chronic cough and age, gender, occupation and smoking and chronic phlegm with age, gender, occupation, indoor animals and smoking. A multivariate analysis confirmed independent association of age, occupation and smoking for chronic cough and age and smoking for chronic phlegm. On sub-group analysis of males, heavy smokers had higher prevalence of chronic cough and chronic phlegm as compared to light smokers and non smokers. INTERPRETATION & CONCLUSIONS: The prevalence of chronic cough was 2.5 per cent and chronic phlegm was 1.2 per cent in the general population in Mysore which is lower than that observed in other studies. Heavy smoking was an important preventable risk factor identified in this study and efforts towards smoking cessation are crucial to achieve good respiratory health in the community.

Effect of area of residence on patterns of aeroallergen sensitization in atopic patients.

BACKGROUND: An association with sensitization to inhaled allergens and allergic rhinitis and asthma has been established. A recent study concluded that the disparity in allergen sensitization might primarily be caused by environmental factors rather than genetic differences. The primary objective was to identify potential differences in sensitization among subjects with the same ethnicity in South India who reside in different environments. METHODS: Five hundred forty-six patients presenting to a tertiary allergy center with allergic rhinitis and or asthma underwent evaluation using a structured questionnaire, skin-prick testing to common aeroallergens, and spirometry and were categorized according to area of residence. RESULTS: The most common allergens causing sensitization were house-dust mite (range, 65-70%), trees (range, 52-56%), and cockroaches (range, 39-53%). There was lower risk of sensitization to cockroach allergens for subjects <21 years old living in suburban (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.81) and rural environments (OR, 0.33; 95% CI, 0.11-0.96) compared with subjects <21 years old living in urban areas. There was higher risk of sensitization to fungi in subjects <21 years old living in suburban areas (OR, 1.51; 95% CI, 0.60-3.77) and rural environments (OR, 2.71; 95% CI, 0.98-7.48) compared with subjects <21 years old living in urban environments. CONCLUSION: Sensitization patterns are similar in different areas of residence except in younger subjects. Sensitization to fungi was higher in younger subjects from the rural area and cockroach sensitization were higher in younger subjects from urban areas. Sensitization is an important precursor of clinical allergic disease and further studies to unravel the complex gene-environment interactions of aeroallergen sensitization in different environments are needed.

Validation of a structured questionnaire for COPD and prevalence of COPD in rural area of Mysore: A pilot study.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is increasing in India and there is a need to study the prevalence of COPD, particularly in the rural areas, which may be most affected due to their lifestyle. MATERIALS AND METHODS: FIRST STAGE: Validation of the questionnaire-105 consecutive patients underwent administration of the structured questionnaire and spirometry was used as a gold standard for the diagnosis of COPD. Second stage: Adults above 40 years (n = 900) in two villages of Mysore district were administered with the validated questionnaire, Knowledge and Attitude questionnaire and Fagerstorm questionnaire, to assess nicotine dependency. RESULTS: The questionnaire was found to have a sensitivity of 62.5% and specificity of 87.6% to diagnose COPD. Of the total 900 adults surveyed (Males: 453, Females: 447), the total prevalence of COPD was 7.1%. Males had a higher prevalence (11.1%) compared to females (4.5%). The prevalence of smoking was very high among men at 71.9% and all the women were nonsmokers. The prevalence of COPD was 14.7% in smokers, 19.3% had mild to moderate nicotine dependency and 12.8% were highly dependent. Of the women exposed to regular biomass fuels, the prevalence of COPD was 3.9%, which increased to 4.8% on addition of regular passive smoking. In smoking, male gender and age were significantly associated with COPD (P < 0.05). CONCLUSION: The structured questionnaire is a useful tool for the screening of COPD in field studies. Smoking and biomass fuel exposure are important risk factors for COPD.