Nanophotonic waveguide-based sensing of circulating cell-free mitochondrial DNA: implications for personalized medicine.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) has emerged as a promising biomarker, with potential implications for disease diagnosis. Changes in mtDNA, such as deletions, mutations or variations in the number of copies, have been associated with mitochondrial disorders, heart diseases, cancer and age-related non-communicable diseases. Previous methods, such as polymerase chain reaction-based approaches, next-generation sequencing and imaging-based techniques, have shown improved accuracy in identifying rare mtDNA variants or mutations, but they have limitations. This article explains the basic principles and benefits of using planar optical waveguide-based detection devices, which represent an advanced approach in the field of sensing.

Phage therapy: an alternative treatment modality for MDR bacterial infections.

The increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects of modern medicine. Recognising the urgency of this issue, the World Health Organisation has prioritised the development of novel antimicrobials to combat ESKAPEE pathogens. Comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli, such pathogens represent a spectrum of high to critical drug resistance, accounting for a significant proportion of hospital-acquired infections worldwide. In response to the waning efficacy of antibiotics against these resilient pathogens, phage therapy (PT) has emerged as a promising therapeutic strategy. This review provides a comprehensive summary of clinical research on PT and explores the translational journey of phages from laboratory settings to clinical applications. It examines recent advancements in pre-clinical and clinical developments, highlighting the potential of phages and their proteins, alone or in combination with antibiotics. Furthermore, this review underlines the importance of establishing safe and approved routes of phage administration to patients. In conclusion, the evolving landscape of phage therapy offers a beacon of hope in the fight against MDR bacterial infections, emphasising the imperative for continued research, innovation and regulatory diligence to realise its full potential in clinical practice.

Investigating the Presence of Rotavirus in Wastewater Samples of Bhopal Region, India, by Utilizing Droplet Digital Polymerase Chain Reaction.

INTRODUCTION: Rotavirus-induced viral gastroenteritis outbreaks result in over two million hospitalizations globally yearly. Wastewater-based epidemiology (WBE) has emerged as a crucial tool for detecting and monitoring viral outbreaks. The adoption of WBE has been instrumental in the early detection and surveillance of such viral outbreaks, providing a non-invasive method to assess public health. OBJECTIVE: This study aims to utilize droplet digital polymerase chain reaction (ddPCR) technology to detect and quantify Rotavirus in wastewater samples collected from the Bhopal region of India, thereby contributing to the understanding and management of viral gastroenteritis outbreaks through environmental surveillance. METHODS: In this study, we used ddPCR to detect and quantify Rotavirus in wastewater samples collected from the Bhopal region of India. We monitored its viral presence in municipal sewage treatment plants bi-weekly using an advanced ddPCR assay. Targeting the rotavirus non-structural protein 3 (NSP-3) region with custom primers and TaqMan probes, we detected virus concentration employing polyethylene glycol (PEG). Following RNA isolation, complementary DNA (cDNA) synthesis, and ddPCR analysis, our novel method eliminated standard curve dependence, propelling virus research and treatment forward. RESULTS: Out of the 42 samples collected, a 16.60% positivity rate was observed, indicating a moderate presence of Rotavirus in Bhopal. The wastewater treatment plants (WWTP) attached to a hospital exhibited a 42.85% positivity rate, indicating the need for targeted monitoring. Leveraging ddPCR, precise quantification of rotavirus concentrations (ranging from 0.75 to 28.9 copies/µL) facilitated understanding and supported effective remediation. CONCLUSIONS:  This study emphasizes the importance of vigilant wastewater surveillance, especially in WWTPs with higher rotavirus prevalence. The significance of ddPCR in comparison to conventional and real-time PCR lies in its superior sensitivity and specificity in detecting and quantifying positive samples. Furthermore, it can identify positive samples even in the smallest quantities without the need for a standard curve to evaluate. This makes ddPCR a valuable tool for accurate and precise detection and quantification of samples.

Deciphering the complex interplay of risk factors in type 2 diabetes mellitus: A comprehensive review.

The complex and multidimensional landscape of type 2 diabetes mellitus (T2D) is a major global concern. Despite several years of extensive research, the precise underlying causes of T2D remain elusive, but evidence suggests that it is influenced by a myriad of interconnected risk factors such as epigenetics, genetics, gut microbiome, environmental factors, organelle stress, and dietary habits. The number of factors influencing the pathogenesis is increasing day by day which worsens the scenario; meanwhile, the interconnections shoot up the frame. By gaining deeper insights into the contributing factors, we may pave the way for the development of personalized medicine, which could unlock more precise and impactful treatment pathways for individuals with T2D. This review summarizes the state of knowledge about T2D pathogenesis, focusing on the interplay between various risk factors and their implications for future therapeutic strategies. Understanding these factors could lead to tailored treatments targeting specific risk factors and inform prevention efforts on a population level, ultimately improving outcomes for individuals with T2D and reducing its burden globally.

Effect of the Built Environment on the Cumulative Incidence of Acute Diarrheal Diseases: A Community-Based Cohort Study From Underprivileged Areas of Bhopal, India.

Background Diarrhea is a major public health problem in under-five children worldwide. Various sociodemographic, environmental, and behavioral factors play a role in the occurrence of diarrheal disease in children under the age of five. This study aims to estimate the cumulative incidence of acute diarrheal diseases during a one-year study period and examine its association with the built environment factors among children under the age of five in selected underprivileged areas of Bhopal. Methodology We conducted this study in Bhopal, a city in central India. We surveyed the underprivileged dwellers of Vajpayee Nagar, Sanjay Nagar, and Mother India Colony of Bhopal city. This is a prospective cohort study with a one-year follow-up period to examine the cumulative incidence of acute diarrheal diseases among under-five-year-old children in the study area. Data were analyzed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results Data were collected from February 2021 to February 2022. A total of 658 families of eligible children were contacted to participate in the study. After excluding 38 participants for various reasons (denied consent: 3; lost to follow-up: 32; moved out of the study area: 3), data were finally analyzed for 620 participants. In the study among the under-five-year-old children, the cumulative incidence of acute diarrheal diseases was 23.8% (148 out of 620). In our study, lower age (adjusted odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.99, p = 0.041) and non-availability of flush latrine in the house (adjusted OR = 4.95, 95% CI = 1.80-13.59, p = 0.002) were statistically associated with a higher incidence of acute diarrheal disease among the study population. Conclusions In our investigation, we observed a cumulative incidence of diarrhea at 23.8% (148 out of 620) among the underprivileged under-five population residing in Bhopal, India. This incidence exhibited significant associations with younger age and the absence of in-house flush latrines.

Cardiovascular disease risk assessment through sensing the circulating microbiome with perovskite quantum dots leveraging deep learning models for bacterial species selection.

Perovskite quantum dots (PQDs) are novel nanomaterials wherein perovskites are used to formulate quantum dots (QDs). The present study utilizes the excellent fluorescence quantum yields of these nanomaterials to detect 16S rRNA of circulating microbiome for risk assessment of cardiovascular diseases (CVDs). A long short-term memory (LSTM) deep learning model was used to find the association of the circulating bacterial species with CVD risk, which showed the abundance of three different bacterial species (Bauldia litoralis (BL), Hymenobacter properus (HYM), and Virgisporangium myanmarense (VIG)). The observations suggested that the developed nano-sensor provides high sensitivity, selectivity, and applicability. The observed sensitivities for Bauldia litoralis, Hymenobacter properus, and Virgisporangium myanmarense were 0.606, 0.300, and 0.281 fg, respectively. The developed sensor eliminates the need for labelling, amplification, quantification, and biochemical assessments, which are more labour-intensive, time-consuming, and less reliable. Due to the rapid detection time, user-friendly nature, and stability, the proposed method has a significant advantage in facilitating point-of-care testing of CVDs in the future. This may also facilitate easy integration of the approach into various healthcare settings, making it accessible and valuable for resource-constrained environments.

Holistic One Health Surveillance Framework: Synergizing Environmental, Animal, and Human Determinants for Enhanced Infectious Disease Management.

Recent pandemics, including the COVID-19 outbreak, have brought up growing concerns about transmission of zoonotic diseases from animals to humans. This highlights the requirement for a novel approach to discern and address the escalating health threats. The One Health paradigm has been developed as a responsive strategy to confront forthcoming outbreaks through early warning, highlighting the interconnectedness of humans, animals, and their environment. The system employs several innovative methods such as the use of advanced technology, global collaboration, and data-driven decision-making to come up with an extraordinary solution for improving worldwide disease responses. This Review deliberates environmental, animal, and human factors that influence disease risk, analyzes the challenges and advantages inherent in using the One Health surveillance system, and demonstrates how these can be empowered by Big Data and Artificial Intelligence. The Holistic One Health Surveillance Framework presented herein holds the potential to revolutionize our capacity to monitor, understand, and mitigate the impact of infectious diseases on global populations.

Investigating the presence of dioxins in drinking water: implications for public health.

The presence of highly toxic dioxins, specifically polychlorinated dibenzo-p-dioxins (PCDDs), in drinking water is a matter of great concern due to their long-lasting nature and harmful effects. In this study, we detected three out of the five dioxin congeners: 2, 3, 7, 8-tetrachlorodibenzodioxin (TCDD), 1, 2, 3, 7, 8-pentachlorodibenzo-p-dioxin (PeCDD), and octachlorodibenzo-p-dioxin (OCDD). The investigation revealed that three dioxins were present in water samples of winter season, while TCDD and OCDD were found in the summer season. The geometric mean concentrations of PCDDs were 229.9 ng/L (winter) and 108.4 ng/L (summer), exceeded the maximum contaminant level of 30 pg/L set by the USEPA in surface water. The estimated daily intake of PCDDs for residents through drinking water was 273.97 ng-WHO2005-TEQ/kg/days during winter and 78.875 ng-WHO2005-TEQ/kg/days during summer. Our study emphasizes the urgent need for further research on persistent organic pollutants in drinking water to safeguard public health and community well-being.

Smart carbon-based sensors for the detection of non-coding RNAs associated with exposure to micro(nano)plastics: an artificial intelligence perspective.

Micro(nano)plastics (MNPs) are pervasive environmental pollutants that individuals eventually consume. Despite this, little is known about MNP's impact on public health. In this article, we assess the evidence for potentially harmful consequences of MNPs in the human body, concentrating on molecular toxicity and exposure routes. Since MNPs are present in various consumer products, foodstuffs, and the air we breathe, exposure can occur through ingestion, inhalation, and skin contact. MNPs exposure can cause mitochondrial oxidative stress, inflammatory lesions, and epigenetic modifications, releasing specific non-coding RNAs in circulation, which can be detected to diagnose non-communicable diseases. This article examines the most fascinating smart carbon-based nanobiosensors for detecting circulating non-coding RNAs (lncRNAs and microRNAs). Carbon-based smart nanomaterials offer many advantages over traditional methods, such as ease of use, sensitivity, specificity, and efficiency, for capturing non-coding RNAs. In particular, the synthetic methods, conjugation chemistries, doping, and in silico approach for the characterization of synthesized carbon nanodots and their adaptability to identify and measure non-coding RNAs associated with MNPs exposure is discussed. Furthermore, the article provides insights into the use of artificial intelligence tools for designing smart carbon nanomaterials.

Prevalence of work-related musculoskeletal disorders and quality of life assessment among garment workers in Tiruppur district, Tamil Nadu.

Objectives. The garment industry is a labour-intensive industry, with workers susceptible to musculoskeletal problems, especially those employed in smaller units that lack adequate occupational health provisions. This study aims to determine the prevalence of work-related musculoskeletal disorders (WMSDs) among workers in both large and small garment units and assess their quality of life (QoL). Methods. The study surveyed 746 garment workers, comprising 372 from large units and 374 from small units. Data were collected through the Nordic musculoskeletal questionnaire and the World Health Organization Quality of Life (WHOQOL)-BREF questionnaire, with posture analysis conducted using the rapid upper limb assessment (RULA) and rapid entire body assessment (REBA) scales. Results. The results showed that 32% of workers in large-scale garment units and 43.9% in small-scale garment units reported musculoskeletal symptoms. The occurrence of musculoskeletal disorders (MSDs) was significantly associated with increasing age, smoking, alcohol consumption, job duration, working in shifts and moonlighting. Conclusion. The workers in the garment industry, particularly of small units, are highly susceptible to WMSDs.

Survival Analysis for Cohort of Bhopal Gas Disaster Victims during 1985-2015.

Context: After the gas tragedy on the night of December 2/3, 1984, at Bhopal, the Indian Council of Medical Research (ICMR) started following up on four population cohorts with different levels of post-disaster mortality from December 3-6, 1984. Aims: The present study was undertaken to estimate the survival time of the cohort, and investigate the risk of mortality based on exposure, gender, and median age. Settings and Design: Survival analysis is generally used to evaluate factors associated with the time to an event of failure or death among any covered population. Methods and Materials: To know the cause of death and mortality rate, a retrospective cohort analysis was conducted on the outcomes of 92,320 individuals with an exposed and non-exposed group from 1985 to 2015 in Bhopal, India. Statistical Analysis Used: Basic survival analysis method, Kaplan-Meier method, and Cox proportional hazard regression model were used to analyze the mortality risk. Results: During the past 30 years, the survivability was 87.25%, and the mortality rate was 7.2% for the cohort population of Bhopal gas survivors. Cox regression analysis showed that exposed, males, and individuals above 21 years (at the time of the disaster) were at higher risk of mortality from 1985 to 2015. Conclusions: During the initial two phases, the mortality was higher in the exposed group, but over time, their survival turned out to be the same in both groups.

Design and Fabrication of a Nanobiosensor for the Detection of Cell-Free Circulating miRNAS-LncRNAS-mRNAS Triad Grid.

The increased understanding of the competitive endogenous RNA (ceRNA) network in the onset and development of breast cancers has suggested their use as promising disease biomarkers. Keeping these RNAs as molecular targets, we designed and developed an optical nanobiosensor for specific detection of the miRNAs-LncRNAs-mRNAs triad grid in circulation. The sensor was formulated using three quantum dots (QDs), i.e., QD-705, QD-525, and GQDs. These QDs were surface-activated and modified with a target-specific probe. The results suggested the significant ability of the developed nanobiosensor to identify target RNAs in both isolated and plasma samples. Apart from the higher specificity and applicability, the assessment of the detection limit showed that the sensor could detect the target up to 1 fg concentration. After appropriate validation, the developed nanobiosensor might prove beneficial to characterizing and detecting aberrant disease-specific cell-free circulating miRNAs-lncRNAs-mRNAs.

Molecular surveillance of dengue virus in field-collected Aedes mosquitoes from Bhopal, central India: evidence of circulation of a new lineage of serotype 2.

Introduction: Dengue fever is hyperendemic in several Southeast and South Asian countries, including India, with all four serotypes (DENV 1-4) circulating at different periods and in different locations. Sustainable and improved virological and entomological surveillance is the only tool to prevent dengue and other vector-borne diseases. Objectives: The present study has been carried out to detect and characterize the circulating dengue virus (DENV) in field-collected Aedes mosquitoes in Bhopal, Central India. Methods: Aedes mosquitoes were collected from 29 localities within Bhopal city during October 2020 to September 2022. DENV infection was assessed in the individual head and thorax regions of Aedes mosquitoes using reverse transcriptase PCR. Positive samples were sequenced, and the circulating serotypes and genotypes were determined using phylogenetic analysis. Results: DENV RNA was detected in 7 Aedes aegypti and 1 Aedes albopictus, with infection rates of 0.59 and 0.14%, respectively. Phylogenetic analysis revealed all the isolates belonged to DENV serotype 2 and distinctly clustered with the non-Indian lineage (cosmopolitan genotype 4a), which was not recorded from the study area earlier. The time to most common recent ancestor (TMRCA) of these sequences was 7.4 years old, with the highest posterior density (HPD) of 3.5-12.2 years, indicating that this new lineage emerged during the year 2014. This is the first report on the DENV incrimination in both Ae. aegypti and Ae. albopictus mosquitoes collected from Bhopal, Central India. Conclusion: The observed emergence of the non-Indian lineage of DENV-2 in Bhopal, which again is a first report from the area, coincides with the gradual increase in DENV cases in Bhopal since 2014. This study emphasizes the importance of DENV surveillance and risk assessment in this strategically important part of the country to decipher its outbreak and severe disease-causing potential.

Evaluation of Cytogenetic Alterations in Patients of Chronic Kidney Disease.

Introduction: In recent years, there has been a rise in chronic kidney disease (CKD), and it has been estimated that by 2040, CKD will be the fifth most common cause of death globally. In addition to diabetes, hypertension, obesity, hyperlipidemia, and nonalcoholic fatty liver disease commonly associated with CKD, exposure to various toxins as a result of pollution or industrial disasters is also discussed as a cause for multi-organ pathology including kidneys. Although few cytogenetic studies were undertaken to assess the genetic damage in survivors of the disaster, no studies are available on the cytogenetic damage of toxic-gas exposed population having CKD. Therefore, the present multi-group cross-sectional study was undertaken to assess the independent role of CKD as well as toxic gas exposure on cytogenetics. Methods: The cytogenetic alterations were evaluated through chromosomal aberration analysis and micronuclei assay. The study included 608 study participants divided into four groups on the basis of history of exposure to the leaked gas and presence or absence of CKD. Results: The results of the study showed no statistically significant difference in cytogenetic damage between gas-exposed and non-exposed patients of CKD, whereas significantly higher cytogenetic damage was observed among gas-exposed participants having CKD compared to gas-exposed participants free from CKD, suggesting that cytogenetic changes could be due to CKD itself. Conclusions: Thus, to conclude, the cytogenetic alterations observed in the study can be partly attributed to the disease itself.

Prevalence of chronic kidney disease among severely gas-exposed survivors in Bhopal, India.

Background The survivors of the 1984 Bhopal gas disaster frequently express concern of them being at higher risk of developing chronic kidney disease (CKD) as a consequence of the long-term health effects of gas exposure. We aimed to estimate the prevalence of CKD among the survivors of severely gas-exposed cohort assembled in 1985 after the Bhopal gas disaster to study the long-term health consequences of gas exposure. Methods We did this cross-sectional study with a sample size of 215 systematically selected participants among the severely gas-exposed survivors in Bhopal to estimate the prevalence of CKD. Sociodemographic and relevant past medical history of the participants was obtained using a semi-structured questionnaire and their blood and urine samples were collected. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Those found with reduced e-GFR and proteinuria, suggestive of CKD, were further surveyed after 3 months to differentiate CKD from acute renal damage. Results The prevalence of CKD among the severely gas-exposed cohort survivors in Bhopal was 16.7%. Multiple logistic regression analysis revealed that body mass index and level of education were significant predictors of CKD. Conclusion The prevalence of CKD among the severely exposed survivors of Bhopal was at par with the national prevalence, putting at rest the apprehension of gas-exposed survivors of being at higher risk of developing CKD.

Dermatological Symptoms among Polyester Dyeing and Printing Workers in Mumbai.

Background: Textile is one of the important sectors in the Indian economy. The use of synthetic chemicals is maximum during the wet processing technique, which consists of dyeing, printing and finishing. Aims and Objectives: This study was conducted to find out the prevalence of occupational dermatological symptoms among the workers employed in the dyeing and printing unit of the textile industry. Materials and Methods: A cross-sectional study, with a sample of 242 workers, was conducted in three different dyeing and printing factories. The workers were interviewed using a semi-structured questionnaire adapted from the Nordic Occupational Skin Questionnaire. Results: The prevalence of dermatological symptoms on the hands was found to be 51.7%. The various pattern of lesions included redness in 0.4% to itching in 26% of dyeing and printing workers. Those working for >5 years had 2.21 times higher risk as compared to those working for ≤5 years Odds Ratio (OR): 2.21; 95% Confidence Interval (CI): 1.19-4.11). Similarly, those working in the dyeing section were at 2.94 times higher risk as compared to those working in the printing section (OR: 2.94; 95% CI: 1.58-5.47). Conclusion: The workers working in the printing and dyeing industry were at risk of developing skin lesions, which can partly be attributed to reactive chemicals used and partly to poor handling practices of the workers.

Beneficial role of kaempferol and its derivatives from different plant sources on respiratory diseases in experimental models.

Respiratory illnesses impose a significant health burden and cause deaths worldwide. Despite many advanced strategies to improve patient outcomes, they are often less effective. There is still considerable room for improvement in the treatment of various respiratory diseases. In recent years, alternative medicinal agents derived from food plants have shown better beneficial effects against a wide variety of disease models, including cancer. In this regard, kaempferol (KMF) and its derivatives are the most commonly found dietary flavonols. They have been found to exhibit protective effects on multiple chronic diseases like diabetes, fibrosis, and so on. A few recent articles have reviewed the pharmacological actions of KMF in cancer, central nervous system diseases, and chronic inflammatory diseases. However, there is no comprehensive review that exists regarding the beneficial effects of KMF and its derivatives on both malignant- and non-malignant respiratory diseases. Many experimental studies reveal that KMF and its derivatives are helpful in managing a wide range of respiratory diseases, including acute lung injury, fibrosis, asthma, cancer, and chronic obstructive pulmonary disease, and their underlying molecular mechanisms. In addition, we also discussed the chemistry and sources, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, methods to enhance bioavailability, as well as our perspective on future research with KMF and its derivatives.

A Comparative Study of Work Stress among Working Females Getting Paid and Working Women Unpaid (Housewives) During Pregnancy.

Introduction: The potential impact of employment on pregnancy is an important issue as several occupational factors have been reported to be associated with adverse pregnancy outcomes through increased work stress. The current study was undertaken among pregnant women to understand the difference in pregnancy-related stress among pregnant working women getting paid (WWP) and working women unpaid (WWU) (housewives) and to assess workplace stress among working WWP. Methods: A total of 426 study participants which included 213 participants in each group were recruited from a tertiary care hospital in Chennai. All the study participants were interviewed using an A-Z scale to understand pregnancy-related stress while WWP were also interviewed using Workplace Stress Questionnaire (WSQ). Results: It was observed that the mean score of WWP was significantly higher than the mean scores of WWU (t = 94.63; df = 1, P = 0.000). Those WWP who were working for >8 h daily had higher scores as compared to those working for ≤8 h. Conclusion: The study shows that the WWP had work stress in addition to background pregnancy-related stress.

Assessment of multidrug-resistant profile, multi-locus sequence typing and efflux pump activity in Salmonella Typhimurium isolated from hospital sewage.

Salmonella enterica serovar Typhimurium is becoming a leading cause of gastroenteritis and mortality. The use of antibiotics has increased natural resistance of S. Typhimurium to antibiotics. This study aims to isolate and characterize multi-drug-resistant (MDR) Salmonella strains from hospital sewage samples in Bhopal City, central India. The MDR isolates were characterized by molecular identification, antimicrobial resistance patterns, multi-locus sequence typing, and efflux pump activity. Specific genes (hilA, stn, invA, typh, and iroB) were used to confirm S. Typhimurium isolates. The Kirbey-Bauer method was employed to profile antimicrobial resistance using 20 antibiotics. Multi-locus sequence typing confirmed S. Typhimurium using seven housekeeping genes (aroC, dnaN, hemD, hisD, purE, sucA, and thr). Out of five strains, only four were confirmed as S. Typhimurium during MLST analysis. Efflux pump activity was determined using the ethidium bromide (EtBr) cartwheel test. Of the 160 isolates, 38 were presumptively confirmed as S. Typhimurium based on biochemical characterization, and only five MDR Salmonella strains were selected for their resistance against most antibiotics. Efflux pump activity revealed that five out of the four MDR isolates did not retain EtBr inside the cells, indicating pronounced efflux activity. Additionally, the isolated strains showed a specific correlation between the antimicrobial phenotypes and genotypes. The results of this study provide a better understanding of the characterization of S. Typhimurium serotype in Bhopal City. Future studies should focus on understanding changing antimicrobial resistance patterns, pathogenicity, and the genetic background of Salmonella serotypes. Further surveillance activities for antimicrobial-resistant Salmonella in different environmental sources should be prioritized.