Search Results (55)

Background/Objectives: The prevalence of dementia among South Asians across India is high among those who are 65 years and older, yet little is known about genetic risk factors for dementia in this population. Methods: 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 on the missense/loss-of-function (LoF) and brain-specific promoter/enhancer variants of 84 genes, previously associated with AD in European Ancestry (EA). These analyses were performed 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). We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. Results: In the missense/LoF analysis, without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes were associated 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 enriched in LASI-DAD compared to EA (minor allele frequency = 0.075% vs. 0.0015%). Conclusions: 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 the identification of potential novel causal variants enriched in South Asians. Full article

Pseudomonas aeruginosa is a ubiquitous environmental bacterium that causes a variety of infections in humans and animals. Although antibiotic resistance in livestock has been extensively documented, continuous surveillance remains crucial for tracking emerging resistance trends and assessing control measures. During 2017 and 2018, 234 strains of P. aeruginosa were identified from 1063 strains of pathogenic and nonpathogenic bacteria isolated from raw milk of healthy and mastitis cows. In this study, 132 convenience P. aeruginosa isolates were recovered and tested for antimicrobial susceptibility and the presence of antimicrobial resistance genes and virulence factors. Antimicrobial susceptibility testing revealed that these P. aeruginosa isolates were resistant to three (gentamicin, tobramycin, and ceftazidime) out of eight antibiotics. Real-time PCR targeting 21 antibiotic resistance genes indicated that aminoglycoside modifying enzyme (AME) gene ant(3″)-I was most frequently identified in both antimicrobial-resistant and -susceptible P. aeruginosa isolates, followed by aac(6′)-II and aac(6′)-Ib. The β-lactamase encoding gene, bla_PDC, was mainly identified in susceptible P. aeruginosa isolates. Virulence factors screening revealed the presence of exoS, exoT, exoU, pyo, aprA, toxA, plcH, algD, lasB, lasI, lasR, rh1L, and rh1R in resistant isolates, with the detection rates ranging from 16.7% to 88.9%. Additionally, next-generation sequencing was conducted on three resistant isolates to validate these findings. This study showed the antibiotic resistance of P. aeruginosa in raw milk samples from large-scale dairy farms in Jiangsu and Shandong provinces, China. Full article

The synthesis of nanoparticles (NPs) via laser ablation synthesis in solution (LASiS) is a promising method for sustainable and efficient nanoparticle fabrication. This work investigates the transition from one-factor-at-a-time experimentation to a more efficient, multivariate approach for optimising NP production efficiency. By applying the Industry 4.0 principles, the objective is to digitise and automate laboratory processes to increase productivity and robustness. Design of Experiments (DoE) strategies, Taguchi orthogonal arrays and full-factorial design (FFD), have been employed to enhance laser ablation processes. Both models confirmed that increasing laser power led to higher colloid absorbance, with the Taguchi DoE offering rapid initial process mapping and FFD providing a higher-resolution analysis. The optimal laser repetition rate of 30 kHz was identified as a balance between pulse energy and thermal effects on the target, maximising ablation efficiency. The Taguchi model had a prediction of NP size with an R² value of 0.49, while the FFD struggled with accurate size prediction. Additionally, this study introduced a recirculation flow regime as a rapid test platform for predicting optimal conditions for continuous flow production. Using a semi-autonomous DoE platform decreased the operator involvement and increased the process selectivity. This proof-of-concept for on-the-bench NP rapid manufacturing demonstrated how efficient NP synthesis processes can be developed by clarifying the effects of varying parameters on colloid productivity, paving the way for broader industrial applications in the future. Full article

Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial infections of the urinary tract, upper respiratory tract, gastrointestinal tract, central nervous system, etc. It is possible to develop bacteremia and sepsis in immunocompromised patients. A major problem in treatment is the development of antibiotic resistance. Therefore, new preparations of natural origin are sought, such as plant extracts, which are phytocomplexes and to which it is practically impossible to develop resistance. Geum urbanum L. (Rosacea) is a perennial herb known for many biological properties. This study aimed to investigate the redox-modulating capacity and effect of ethyl acetate (EtOAc) extracts from roots (EtOAcR) and aerial parts (EtOAcAP) of the Bulgarian plant on the phenotype inhibition of the P. aeruginosa Las/RhI quorum sensing (QS) system, which primarily determines drug resistance in pathogenic bacteria, including biofilm formation, motility, and pigment production. We performed QS assays to account for the effects of the two EtOAc extracts. At sub-minimal inhibitory concentrations (sub-MICs) ranging from 1.56 to 6.25 mg/mL, the biofilm formation was inhibited 85% and 84% by EtOAcR and 62% and 39% by EtOAcAP extracts, respectively. At the same sub-MICs, the pyocyanin synthesis was inhibited by 17–27% after treatment with EtOAcAP and 26–30% with EtOAcR extracts. The motility was fully inhibited at 3.12 mg/mL and 6.25 mg/mL (sub-MICs). We investigated the inhibitory potential of lasI, lasR, rhiI, and rhiR gene expression in biofilm and pyocyanin probes with the PCR method. Interestingly, the genes were inhibited by two extracts at 3.12 mg/mL and 6.25 mg/mL. Antiradical studies, assessed by DPPH, CUPRAC, and ABTS radical scavenging methods and superoxide anion inhibition showed that EtOAcAP extract has effective antioxidant capacity. These results could help in the development of new phytocomplexes that could be applied as biocontrol agents to inhibit the phenotype of the P. aeruginosa QS system and other antibiotic-resistant pathogens. Full article

Aims. To identify the difference between adult patients with septal defects and paroxysmal atrial fibrillation (AF) and patients without a history of arrhythmia using the left atrial (LA) volume and function parameters, to reveal the parameters associated with AF development. Methods and results. In this prospective study, 81 patients with septal defects and left-to-right shunts were enrolled between 2021 and 2023 and divided into two groups: with paroxysmal AF and without AF. Left atrial function was analyzed based on the indexed left atrial volumes (LAVI and preA-LAVI), ejection fraction (LAEF), expansion index (LAEI), reservoir (LAS-r), conduit (LAS-cd) and contractile (LAS-ct) strain, and stiffness index (LASI) using a Philips CVx3D ultrasound system (Philips, Amsterdam, The Netherlands) and corresponding software. In total, 26 patients with paroxysmal atrial fibrillation (mean age: 59.6 ± 11.7 years, female: 80.8%) and 55 patients with septal defects without any history of arrhythmias (mean age: 44.8 ± 11.6 years, female: 81.8%) were included. All patients were in the NYHA class I or II at baseline. Our findings demonstrated a significant difference between all LA function parameters in the two groups. Upon univariable analysis, the LAVI, preA-LAVI, LASI, LAEF, LAEI, LAS-r, LAS-c, LAS-ct, age, cardiac index, E/A, and RV pressure were found to be associated with AF. The multivariate analysis identified LAVI (OR 1.236, 95% CI 1.022–1.494, p = 0.03), LAS-r (OR 0.723, 95% CI 0.556–0.940, p = 0.02), and LAS-ct (OR 1.518, 95% CI 1.225–1.880, p < 0.001) as independent predictors of AF development. The proposed model demonstrated high sensitivity and specificity with an adjusted classification threshold of 0.38 (AUC: 0.97, 95% CI 0.93–1.00, sensitivity 92% and specificity 92%, p < 0.001). Conclusions. The assessment of LA function using speckle-tracking echocardiography demonstrated significantly different values in the AF group among patients with congenital septal defects. This technique can therefore be implemented in routine clinical management. The key message. Atrial fibrillation development in adult patients with congenital septal defects and a left-to-right shunt is associated with the changes in left atrial function under conditions of an increased preload. Full article

Introduction: Non-communicable diseases (NCDs) represent a major global health challenge, particularly in low- and middle-income countries like India, with significant gender disparities in mortality and disease burden. This study aims to investigate these disparities, using data from national health surveys, to inform gender-specific public health strategies and align with global health goals. Methodology: The study uses data from the Longitudinal Aging Study in India (LASI) and National Family Health Surveys (NFHS-4 and NFHS-5). Result: The results from the Longitudinal Ageing Study in India (LASI) and National Family Health Surveys (NFHS-4 and NFHS-5) indicate significant demographic and health-related variations among 65,562 participants. Key findings show gender disparities in lifestyle habits such as alcohol and tobacco use, and differences in health outcomes across age, education, and socioeconomic status. Notably, an increase in NCD prevalence, particularly hypertension and diabetes, was observed from NFHS-4 to NFHS-5, highlighting evolving health challenges in India. Conclusions: The study emphasizes the importance of gender in the prevalence and management of non-communicable diseases (NCDs) in India, advocating for public health strategies that address gender differences, socio-economic factors, and urban-rural disparities to achieve health equity. Full article

Advancements in digital technologies have transformed the world by providing more opportunities and possibilities. However, elderly persons have several challenges utilizing modern technology, leading to digital exclusion, which can negatively impact sustainable development. This research attempts to address the current digital exclusion by addressing the challenges older people face considering evolving digital technologies, focusing on economic, social, and environmental sustainability. Three distinct goals are pursued in this study: to perform a detailed literature review to identify gaps in the current understanding of digital exclusion among the elderly, to identify the primary factors affecting digital exclusion in the elderly, and to analyze the patterns and trends in different countries, with a focus on differentiating between High-Income Countries (HICs) and Lower Middle-Income Countries (LMICs). The research strategies used in this study involve a combination of a literature review and a quantitative analysis of the digital exclusion data from five cohorts. This study uses statistical analysis, such as PCA, chi-square test, one-way ANOVA, and two-way ANOVA, to present a complete assessment of the digital issues that older persons experience. The expected results include the identification of factors influencing the digital divide and an enhanced awareness of how digital exclusion varies among different socio-economic and cultural settings. The data used in this study were obtained from five separate cohorts over a five-year period from 2019 to 2023. These cohorts include ELSA (UK), SHARE (Austria, Germany, France, Estonia, Bulgaria, and Romania), LASI (India), MHAS (Mexico), and ELSI (Brazil). It was discovered that the digital exclusion rate differs significantly across HICs and LMICs, with the UK having the fewest (11%) and India having the most (91%) digitally excluded people. It was discovered that three primary factors, including socio-economic status, health-related issues, and age-related limitations, are causing digital exclusion among the elderly, irrespective of the income level of the country. Further analysis showed that the country type has a significant influence on the digital exclusion rates among the elderly, and age group plays an important role in digital exclusion. Additionally, significant variations were observed in the life satisfaction of digitally excluded people within HICs and LMICs. The interaction between country type and digital exclusion also showed a major influence on the health rating. This study has a broad impact since it not only contributes to what we know academically about digital exclusion but also has practical applications for communities. By investigating the barriers that prevent older people from adopting digital technologies, this study will assist in developing better policies and community activities to help them make use of the benefits of the digital era, making societies more equitable and connected. This paper provides detailed insight into intergenerational equity, which is vital for the embedding principles of sustainable development. Furthermore, it makes a strong case for digital inclusion to be part of broader efforts (and policies) for creating sustainable societies. Full article

The effects of holding time and Si on the content, shape size and structure of Ti₂Al₂₀La phase in Al-Ti-La intermediate alloy were investigated by an X-ray diffractometer, scanning electron microscope and transmission electron microscope. The results show that the volume fraction and aspect ratio of Ti₂Al₂₀La phase in Al-Ti-La intermediate alloy decrease significantly, from 21% and 2.3 without Si addition to 4% and 2.0 with the addition of 2.3 wt.% Si at a holding time of 15 min at 750 °C, respectively. The Si element will attach to the Ti₂Al₂₀La phase and form La-Si binary phase at the grain boundary of α-Al. With the increase of holding time from 15 min to 60 min, the content of Ti₂Al₂₀La phase in the alloy gradually decreases and the size decreases significantly. Meanwhile, Al₁₁La₃ will dissolve and disappear, while the content of La-Si binary phase increases, and part of Ti₂Al₂₀La phase transforms into Ti₂(Al_20−x,Si_x)La phase. Full article

Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas aeruginosa, another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate P. aeruginosa biofilm alone or in combination with phages PB10 and PA19 was investigated. The P. aeruginosa cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP–phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group (p < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of P. aeruginosa was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene lasI. While the ZnO-NPs repressed the lasI gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells. Full article

Background: Quorum sensing (QS) controls the virulence of P. aeruginosa. This study aims to determine the anti-QS activity of aspirin alone and in combination with chitosan to reach maximum inhibition. We tested ten virulent Pseudomonas aeruginosa (P. aeruginosa) isolates and screened for N-acyl homoserine lactone (AHL) production using Agrobacterium tumefaciens as a biosensor. P. aeruginosa isolates were treated with sub-minimum inhibitory concentrations (MICs) of aspirin and chitosan–aspirin. We used broth microdilution and checkerboard titration methods to determine the MICs and the synergistic effect of these two compounds, respectively. Real-time polymerase chain reaction (PCR) was used to estimate the anti-QS activity of the aspirin–chitosan combination on the expression of lasI and rhlI genes. Results: Aspirin decreased the motility and production of AHLs, pyocyanin, and biofilm. Chitosan potentiated the inhibitory effect of aspirin. The chitosan–aspirin combination inhibited lasI and rhlI gene expression in PAO1 (ATCC 15692) by 7.12- and 0.92-fold, respectively. In clinical isolates, the expression of lasI and rhlI was decreased by 1.76 × 10²- and 1.63 × 10⁴-fold, respectively. Molecular docking analysis revealed that aspirin could fit into the active sites of the QS synthases lasI and rhlI with a high binding affinity, causing conformational changes that resulted in their inhibition. Conclusions: The chitosan–aspirin combination provides new insights into treating virulent and resistant P. aeruginosa. Full article

India is a large middle-income country and has surpassed China in overall population, comprising 20% of the global population (over 1.43 billion people). India is experiencing a major demographic shift in its aging population. Chronic diseases are common among older adults and can be persistent over the life course, lead to the onset of disability, and be costly. Among older adults in India, the existence of multiple comorbid chronic conditions (i.e., multimorbidity) is rapidly growing and represents a burgeoning public health burden. Prior research identified greater rates of multimorbidity (e.g., overweight/obesity diabetes, hypertension, cardiovascular disease, stroke, and malignancies) in minority populations in the United States (U.S.); however, limited studies have attempted to characterize multimorbidity among older adult sub-populations residing in India. To address this gap, we conducted a narrative review of studies on multimorbidity using the data from the Longitudinal Aging Study of India (LASI), the largest nationally representative longitudinal survey study of adults in India. Our definition of multimorbidity was the presence of more than two conditions in the same person. Our findings, based on 15 reviewed studies, aim to (1) characterize the definition and measurement of multimorbidity and to ascertain its prevalence in ethnically and culturally diverse sub-populations in India; (2) identify adverse outcomes associated with multimorbidity in the Indian adult population; and (3) identify gaps, opportunities, and future directions. Full article

Antimicrobial resistance poses a severe threat, particularly in developing countries where the ready availability of drugs and increased consumption lead to improper antibiotic usage, thereby causing a surge in resistance levels compared to developed areas. Despite the past success of antibiotics, their effectiveness diminishes with regular use, posing a significant threat to medical efficacy. Pseudomonas aeruginosa, an opportunistic pathogen, triggers various infection-related issues, occurring on occasions including chronic wounds, burn injuries, respiratory problems in cystic fibrosis, and corneal infections. Targeting the quorum sensing (QS) of P. aeruginosa emerges as a strategic approach to combat infections caused by this bacterium. The objective of this study was to check the effect of antimycobacterial drugs against the potential QS targets in P. aeruginosa and identify lead candidates. The antimycobacterial drugs were first examined for the toxicological and pharmacokinetic profile. By virtual screening through molecular docking, delamanid and pretomanid stood out as major candidates. The binding energies of delamanid and pretomanid with LasR were determined to be −8.3 and −10.9 kcal/mol, respectively. The detailed analysis of the complexes of lead compounds were examined through molecular dynamics simulations. The molecular simulations data validated a sustained interaction of lead drugs with target proteins (PqsR, LasI, and LasA) in a physiological environment. The negligible changes in the secondary structure of proteins in presence of hit antimycobacterial drugs further strengthened the stability of the complexes. These findings highlight the potential repurposing of delamanid and pretomanid, specifically in targeting P. aeruginosa quorum-sensing mechanisms. Full article

Investigating diet-related disease in India’s ageing population is challenging due to poor dietary assessment infrastructure and limited capacity for nutritional analyses. We developed a semi-quantitative Food Frequency Questionnaire (FFQ) to capture dietary intake among older Indian adults. Nutrient analysis of FFQ data requires linkage to a nutrient database preferably based on local food composition. However, the Indian Food Composition Tables (IFCT) provided only partial coverage for FFQ items, nutrient data for cooked foods were unavailable, and some important nutrients were missing, e.g., iodine and vitamin B12. The objective was to develop a nutrient database maximising the IFCT to allow for the analysis of FFQ data. The development of the nutrient database involved: (1) the creation of a core dataset within the Nutritics (2019) software platform comprising analytical data for matched foods in the IFCT reference database; (2) the selection of suitable matches for additional foods/beverages consumed in the FFQ informed by local dietetic expertise; (3) the import of nutrient profiles for additional foods/beverages from international food composition tables (UK, USA, and Singapore) to provide full coverage for all FFQ items; (4) the filling of nutrient data gaps in the core IFCT dataset to ensure all foods/beverages have a value for each nutrient; and (5) the generation of a conversion file for food frequencies to daily intakes (in servings and grams) to facilitate FFQ linkage with the nutrient database. The complete nutrient database provides full coverage of FFQ raw and cooked food/beverages and has the capability to analyse 53 nutrients. Overall, 53% of the FFQ items were matched to the IFCT, whilst 28% were matched from the UK (GB21-0), 15% from the USA (FNDDS), and 4% from the Singapore food tables. All FFQ items matched to the IFCT had missing nutrients mapped from matches in other databases, with GB21-0 being the first preference. For cooked FFQ items matched to the IFCT (n = 21), an appropriate cooking method was applied using established nutrient retention factors. The bespoke nutrient database developed through the integration of nutritional expertise and dietary assessment software will allow for the nutrient analysis of FFQ data. The next step is to automate the nutrient analysis process from computer-assisted FFQ data collection in Wave 2 of LASI-DAD. Full article

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women. A prospective multicenter study was conducted enrolling 169 breast cancer women treated with anthracyclines. A cardiological evaluation including an electrocardiogram and echocardiogram with an analysis of GLS, left atrial (LA) strain, and LA stiffness (LASi) was performed at baseline (T0), 3 (T1), and 6 months (T2) after starting chemotherapy. The patients were divided into two groups: patients with asymptomatic mild cardiotoxicity at T1 (with a relative reduction in GLS > 15%; Group 1) and those without (Group 2). We did not find a significant change in left ventricular ejection fraction (LVEF) at T1 and T2; we found a significant change in GLS (p-value < 0.0001) in the peak atrial longitudinal strain (PALS) and in LASi (p-value < 0.0001). Impairment of atrial function was greater in Group 1 compared to Group 2. A PALS variation > 20.8% identified patients who were most likely to develop asymptomatic mild cardiotoxicity [AUC 0.62; CI (0.51–0.73) p = 0.06, sensitivity 45%, specificity 69.5%]. Conclusions: PALS and LASi significantly change during chemotherapy in association with GLS. Atrial strain is an additional parameter that could be measured together with GLS to detect cardiotoxicity early. Full article

Pseudomonas aeruginosa is among the most ubiquitous bacteria in the natural world, exhibiting metabolic and physiological versatility, which makes it highly adaptable. Imipenem + cilastatin and tetracycline are antibiotic combinations commonly used to treat infections caused by P. aeruginosa, including serious infections such as sepsis. In the context of bacterial infections, biofilm, formed by bacterial cells surrounded by extracellular substances forming a matrix, plays a pivotal role in the resistance of P. aeruginosa to antibiotics. This study aimed to characterize a representative panel of P. aeruginosa isolates from septicemias, assessing their susceptibility to various antibiotics, specifically, imipenem + cilastatin and tetracycline, and the impact of these treatments on biofilm formation. Results from antibiotic susceptibility tests revealed sensitivity in most isolates to six antibiotics, with four showing near or equal to 100% sensitivity. However, resistance was observed in some antibiotics, albeit at minimal levels. Notably, tetracycline showed a 100% resistance phenotype, while imipenem + cilastatin predominantly displayed an intermediate phenotype (85.72%), with some resistance (38.1%). Microdilution susceptibility testing identified effective combinations against different isolates. Regarding biofilm formation, P. aeruginosa demonstrated the ability to produce biofilms. The staining of microtiter plates confirmed that specific concentrations of imipenem + cilastatin and tetracycline could inhibit biofilm production. A significant proportion of isolates exhibited resistance to aminoglycoside antibiotics because of the presence of modifying genes (aac(3)-II and aac(3)-III), reducing their effectiveness. This study also explored various resistance genes, unveiling diverse resistance mechanisms among P. aeruginosa isolates. Several virulence genes were detected, including the las quorum-sensing system genes (lasI and lasR) in a significant proportion of isolates, contributing to virulence factor activation. However, genes related to the type IV pili (T4P) system (pilB and pilA) were found in limited isolates. In conclusion, this comprehensive study sheds light on the intricate dynamics of P. aeruginosa, a remarkably adaptable bacterium with a widespread presence in the natural world. Our findings provide valuable insights into the ongoing battle against P. aeruginosa infections, highlighting the need for tailored antibiotic therapies and innovative approaches to combat biofilm-related resistance. Full article