Nevin Manimala

Front Biosci (Landmark Ed). 2024 Dec 3;29(12):408. doi: 10.31083/j.fbl2912408.

ABSTRACT

BACKGROUND: There is a growing interest in exploring the biological characteristics of nanoparticles and exploring their potential applications. However, there is still a lack of research into the potential genotoxicity of fullerene derivatives and their impact on gene expression in human cells. In this study, we investigated the effects of a water-soluble fullerene derivative, C60[C6H4SCH2COOK]5H (F1), on human embryonic lung fibroblasts (HELF).

METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to study the cytotoxicity of F1; reactive oxygen species (ROS) level was determined with 2,7-DCFH-DA; gene expression level was evaluated by reverse transcription polymerase chain reaction (RT-PCR); protein expression level was determined by flow cytofluorometry; fluorescence microscopy was used for visualization; Mann-Whitney statistical U-test was used for data processing. The differences were considered significant at p < 0.01.

RESULTS: F1 at a concentration of 0.3 mg/mL causes a short-term (up to 1 hour) increase in the number of double-strand breaks and oxidative DNA damage in HELF. Within 1 to 24 hours, F1 penetrates through the cell and nuclear membrane of HELF and localizes in the nucleus. In this case, the response of cells to DNA damage is activated: the functional activity of DNA repair genes, antioxidant and anti-apoptotic genes is increased within 24 hours. Due to the processes of activation of cell division and inhibition of apoptosis, an increase in the population of HELF cells in the presence of the fullerene derivative F1 is observed. F1 has a stabilizing effect on cell nuclei under the action of 1 Gy radiation.

CONCLUSIONS: An increase in antioxidant protection, activation of repair genes, anti-apoptotic genes, progression of the cell cycle, and a decrease in the level of oxidative damage, and DNA breaks in cells indicates the cytoprotective properties of F1.

PMID:39735985 | DOI:10.31083/j.fbl2912408

J Integr Neurosci. 2024 Dec 4;23(12):211. doi: 10.31083/j.jin2312211.

ABSTRACT

BACKGROUND: Heat shock proteins (HSPs) play a critical role in the molecular mechanisms of ischemic stroke (IS). A possible role for HSP40 family proteins in atherosclerosis progression has already been revealed; however, to date, molecular genetic studies on the involvement of genes encoding proteins of the HSP40 family in IS have not yet been carried out.

AIM: We sought to determine whether nine single nucleotide polymorphisms (SNPs) in genes encoding HSP40 family proteins (DNAJB1, DNAJB2, DNAJA1, DNAJA2, DNAJA3 and DNAJC7) are associated with the risk and clinical features of IS.

METHODS: Using TaqMan-based polymerase chain reaction (PCR) and the MassArray-4 system, DNA samples of 2551 Russians – 1306 IS patients and 1245 healthy individuals – were genotyped.

RESULTS: SNP rs2034598 DNAJA2 decreased the risk of IS exclusively in male patients (odds ratio = 0.81, 95% confidence interval 0.78-0.98, p = 0.028); rs7189628 DNAJA2 increased the brain infarct size (p = 0.04); and rs6500605 DNAJA3 lowered the age of onset of IS (p = 0.03). SNPs rs10448231 DNAJA1, rs7189628 DNAJA2, rs4926222 DNAJB1 and rs2034598 DNAJA2 were involved in the strongest epistatic interactions linked to IS; SNP rs10448231 DNAJA1 is characterised by the most essential mono-effect (2.96% of IS entropy); all of the top SNP-SNP interaction models included the pairwise combination rs7189628 DNAJA2×rs4926222 DNAJB1, which was found to be a key factor determining susceptibility to IS. In interactions with the studied SNPs, smoking was found to have multidirectional effects (synergism, antagonism or additive effect) and the strongest mono-effect (3.47% of IS entropy), exceeding the mono-effects of rs6500605 DNAJA3, rs10448231 DNAJA1, rs2034598 DNAJA2, rs7189628 DNAJA2 and rs4926222 DNAJB1, involved in the best G×E models and determining 0.03%-0.73% of IS entropy.

CONCLUSIONS: We are the first to discover polymorphisms in genes encoding HSP40 family proteins as a major risk factor for IS and its clinical manifestations. The comprehensive bioinformatics analysis revealed molecular mechanisms, underscoring their significance in the pathogenesis of IS, primarily reflecting the regulation of heat stress, proteostasis and cellular signalling.

PMID:39735968 | DOI:10.31083/j.jin2312211

J Integr Neurosci. 2024 Dec 27;23(12):225. doi: 10.31083/j.jin2312225.

ABSTRACT

BACKGROUND: Recently, there has been a surge in virtual reality (VR)-based training for upper limb (UL) rehabilitation, which has yielded mixed results. Therefore, we aimed to explore the effects of conventional therapy combined with VR-based training on UL dysfunction during post-stroke rehabilitation.

METHODS: Studies published in English before May 2023 were retrieved from PubMed, Embase, and the Cochrane Library. We also included randomized controlled trials that compared the use of conventional therapy and VR-based training with conventional therapy alone in post-stroke rehabilitation. The meta-analysis was performed using Review Manager Software (version 5.3; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark) and Stata/MP 17.0 (StataCorp, LLC, College Station, TX, USA). Univariate and multivariate meta-regression analyses were performed to investigate the effects of stroke duration, VR characteristics, and type of conventional therapy on VR-based training.

RESULTS: In total, 27 randomized controlled trials were included, which enrolled 1354 patients. Our results showed that conventional therapy plus VR-based training is better than conventional therapy alone in UL motor impairment recovery measured using Fugl-Meyer Upper Extremity (standardized mean difference [SMD] = 0.32, 95% confidence interval [CI]: 0.07-0.57, Z = 2.52, p = 0.01). Meta-regression showed that stroke duration had independent effects on Fugl-Meyer Upper Extremity scores of VR-based training in rehabilitation (p = 0.041). Furthermore, in subgroup analysis based on stroke duration, stroke duration >6 months was statistically significant (SMD = 0.20, 95% CI: 0.01-0.39, Z = 2.06, p = 0.04). No relevant publication bias (p = 0.1303), and no significant difference in activity limitation assessed using the Box-Block Test (mean difference [MD] = 2.79, 95% CI: -0.63-6.20, Z = 1.60, p = 0.11) was observed. Regarding the functional independence measured using the Functional Independence Measure scale, studies presented no significant difference between the experimental and control groups (MD = 1.15, 95% CI: -1.84-4.14, Z = 0.76, p = 0.45).

CONCLUSIONS: Conventional therapy plus VR-based training is superior to conventional therapy alone in promoting the recovery of UL motor function after stroke. Therefore, VR-based training may be a potential option for improving UL motor function. The study was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/), registration number: CRD42023472709.

PMID:39735963 | DOI:10.31083/j.jin2312225

CJC Open. 2024 Oct 3;6(12):1443-1452. doi: 10.1016/j.cjco.2024.09.012. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Patients with heart failure (HF) can experience a poor quality-of-life (QOL), recurring hospitalizations, and progressive disease symptoms. Patient-reported outcome measures (PROMs) integrate patients’ voices into clinical care, by assessing patient symptoms, function, and QOL. In 2022, PROMs were incorporated into the electronic health record system (Epic) at a large academic hospital in Toronto, Ontario, Canada. The purpose of this study was to use implementation-science frameworks to systematically evaluate the uptake and integration of PROMs into clinical HF care.

METHODS: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework guided this mixed-methods, 1-year, quality-improvement project. Data sources included the following: clinician use of PROMs; patient-level data on completed PROMs; and semistructured interviews with clinicians. The PROM was the Kansas City Cardiomyopathy Questionnaire-12, which captures 4 domains related to HF-symptom frequency, physical limitations, social limitations, and QOL (KCCQ-12 is used as an example case of PROMs in general). Quantitative data were analyzed using descriptive statistics; qualitative data were analyzed using behaviour-change frameworks and latent content analysis.

RESULTS: Over the course of 1 year, more patients were assigned to PROMs, a higher proportion of patients completed PROMs, and approximately 80% of patients had high scores on the questionnaire. Clinicians experience barriers-related to attention and decision processes, the environmental context, and their professional role-to integrating PROMs into practice. Suggested changes to improve PROM uptake include adding language licenses for PROM translations, reducing cognitive load for clinicians who are assigning and interpreting PROMs in the Epic system, and championing modelling of use of PROMs in practice.

CONCLUSIONS: This study demonstrates the benefit of using implementation science frameworks, to evaluate the implementation of PROMs in practice and provide actionable recommendations to health systems.

PMID:39735955 | PMC:PMC11681351 | DOI:10.1016/j.cjco.2024.09.012

Prostate Cancer. 2024 Dec 22;2024:4406057. doi: 10.1155/proc/4406057. eCollection 2024.

ABSTRACT

Prostate cancer is the most common noncutaneous malignancy among men worldwide, including in Sudan, where it represents a significant public health challenge. CD147, a transmembrane glycoprotein implicated in tumor progression, invasion, and metastasis, has shown potential as a prognostic biomarker in various cancers. This retrospective case-control study aimed to evaluate CD147 expression in prostate adenocarcinoma among Sudanese men and its association with tumor grade. A total of 80 paraffin-embedded tissue samples, including 40 cases of prostate adenocarcinoma and 40 benign prostatic hyperplasia (BPH) controls, were analyzed using immunohistochemistry. CD147 expression was observed in 22.5% of adenocarcinoma cases compared to 7% of controls; however, the association was not statistically significant (p=0.07). Low-grade tumors were predominant in the cohort, consistent with early-stage diagnoses. The findings revealed no clear link between CD147 expression and tumor grade, diverging from prior studies that associate CD147 with advanced tumor stages. The nonsignificant results may be attributed to the small sample size, emphasizing the need for future research with larger, more diverse cohorts, advanced molecular techniques, and functional studies to better elucidate the role of CD147 in prostate cancer pathogenesis and its potential as a therapeutic target.

PMID:39735939 | PMC:PMC11682863 | DOI:10.1155/proc/4406057

Front Toxicol. 2024 Dec 13;6:1494977. doi: 10.3389/ftox.2024.1494977. eCollection 2024.

ABSTRACT

Bivalve are exposed to a wide range of contaminants, some of which may be toxic to human health. The aim of this study was to detect essential and non-essential elements such as Na, Ca, Mg, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Pb, Hg, Be and Co in water, sediments, and Mytilus galloprovincialis and Tapes decussatus from Faro Lake. It is a lake of marine origin located on the northern coast of Messina (Sicily), where shellfish farming has been practiced for many years. Metals were analysed by a single quadrupole inductively coupled plasma mass spectrometer (ICP-MS), except for Hg, which was quantified using a direct mercury analyser (DMA-80). The study evaluated the nutritional intake of elements through the ingestion of clams and mussels and the potential health risks to consumers. The lead levels found in M. galloprovincialis were below the LOQ, while in T. decussatus the concentrations were below the limit indicated by European Regulation 915/2023. Statistical analysis was carried out on M. galloprovincialis and T. decussatus samples using SPSS 27 and the data showed highly significant differences between the two species (p < 0.001). Cadmium (Cd) and mercury (Hg) concentrations were also below the legal limit in all samples analyzed. This study has shown that clams and mussels are a source of sodium (Na) with a Recommended Dietary Allowance (RDA) of 36% in M. galloprovincialis and 77% in T. decussatus. The percentages obtained for calcium (Ca) and magnesium (Mg) were 17%-19% and 18%-8%, respectively. The RDA of chromium (Cr) was of 191% for M. galloprovincialis and of 405% for T. decussatus. The Fe percentages were 92% and 169% for M. galloprovincialis and T. decussatus, respectively. The concentrations of the other metals observed in the two bivalve species of Lake Faro were generally lower than the Tolerable Weekly Intake (TWI) values estimated as a risk to human health.

PMID:39735886 | PMC:PMC11671395 | DOI:10.3389/ftox.2024.1494977

Indian J Orthop. 2024 Nov 5;59(1):69-76. doi: 10.1007/s43465-024-01225-0. eCollection 2025 Jan.

ABSTRACT

PURPOSE: There is paucity of guidelines with inadequate data available about the extent and prevention of bone and joint disease in beta-thalassemic patients in Indian population. This study aims to determine bone and joint involvement in beta-thalassemic patients. It evaluates serum biochemical parameters of bone formation and resorption and correlates with the symptomatology in these patients. The study also determines their daily physical activity and find a correlation if any with bone mineral density.

METHODS: The study was carried out on 40 regularly transfused beta thalassemic patients between 5 and 18 years of age under regular follow-up at our centre from June 2012 to June 2014. All patients were interviewed as per a well-structured proforma for symptoms relating to bone and joint disease as described by the patient/parents in past 1 year and physical activity by QAPACE questionnaire. Venous blood samples were drawn under aseptic conditions and used for estimation of biochemical parameters (calcium, phosphorus, alkaline phosphatase, vitamin D, parathyroid hormone and serum ferritin). Enrolled subjects were scanned for bone mineral density (BMD) at femur neck, trochanter and Ward’s angle using dual-energy X-ray absorptiometry.

RESULTS: A total of 40 patients were enrolled in the study (Male:Female = 80:20). Half the patients (n = 20) had symptoms pertaining to bone and joint disease. The most common symptom was leg pain (42.50%), followed by backache (22.50%). Asymptomatic patients had greater mean serum vitamin D as compared to the symptomatic patients (22.2 vs 15.08 ng/ml) (p = 0.225). Five patients were detected to have osteopenia, all above 10 years of age. The mean BMD in symptomatic patients at femur neck, trochanter and ward’s angle was 0.781, 0.639 and 0.735 g/cm², respectively, as compared to 0.754, 0.635 and 0.722 g/cm² in asymptomatic patients. The difference was not statistically significant. Patients with low BMD had lower mean pre-transfusion Hb (< 9 g/dl) (p = 0.01). Eighty percent of osteopenic patients had sedentary lifestyle as compared to 44% of patients with normal BMD. Bone mineral density did not have any correlation with vitamin D levels, serum ferritin and type of chelation therapy.

CONCLUSION: Pre-transfusion hemoglobin of more than 9 gm/dL has a protective role in maintaining good bone health and bone mineral density. Engaging thalassemia patients in physical activity has a positive effect on bone mineral density. Low vitamin D levels contribute to symptoms of bone and joint involvement in thalassemia and the same needs to be determined and supplemented.

PMID:39735876 | PMC:PMC11680515 | DOI:10.1007/s43465-024-01225-0

Indian J Orthop. 2024 Nov 30;59(1):108-114. doi: 10.1007/s43465-024-01292-3. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: Ultracongruent (UC) total knee replacement (TKR) designs, serving as alternatives to posterior stabilized (PS) and cruciate retaining (CR) designs, lack conclusive evidence regarding posterior femoral rollback. This study aimed to compare intraoperative posterior femoral rollback and maximal knee flexion between UC and PS inserts, addressing the paucity of literature on femoral rollback achieved with UC designs in total knee replacement.

METHODS: A consecutive cohort of 20 patients undergoing robotic-assisted primary total knee replacement, posterior femoral rollback and maximal intraoperative knee flexion were assessed. Robotic imaging at varying flexion angles (0°, 45°, 90°, and 120°) was conducted after implanting femoral and tibial components with Ultracongruent and Posterior-Stabilized trial inserts. Femoral contact on the tibia was estimated as a percentage of the sagittal dimension of the tibial component with 0 representing the anterior edge and 100 representing the posterior edge of the tibial component.

RESULTS: In extension, UC inserts exhibited a statistically significant posterior contact point versus PS inserts (56.3 + 4.3 vs 53.5 + 5.3, p = 0.003). Between 0 and 45° flexion, 13 of 20 UC inserts showed a paradoxical anterior translation exceeding 5%, unlike the PS group. At 90° flexion, both displayed consistent posterior femoral rollback, with PS inserts having a more posterior contact point (63.5 + 6.2 vs 67.2 + 5.1, p = .008). At 120° flexion, rollback was similar (70.1 + 8.4 vs 71.3 + 8.4, p = 0.128). Mean maximal flexion was 130° (SD = 6.87) and 133° (SD = 6.72) for UC and PS inserts, respectively (p = 0.0001).

CONCLUSIONS: The study indicates UC inserts achieve comparable posterior femoral rollback in deep flexion, supporting their alternative use, despite minor intraoperative flexion differences. However, paradoxical anterior translation in mid-flexion with UC inserts warrants further investigation into wear and clinical outcomes.

PMID:39735874 | PMC:PMC11680524 | DOI:10.1007/s43465-024-01292-3

Front Public Health. 2024 Dec 13;12:1466780. doi: 10.3389/fpubh.2024.1466780. eCollection 2024.

ABSTRACT

INTRODUCTION: Antimicrobial resistance (AMR) is a global problem and is especially threatening for low-and-middle income countries like Bangladesh. The COSTAR (Community-led Solutions to Antimicrobial Resistance) project includes a Randomised Control Trial (RCT) which aims to evaluate the effectiveness of the Community Dialog Approach (CDA) to improve levels of correct and appropriate knowledge and reported practice about antibiotics, antibiotic use, and antibiotic resistance (ABR) from a One Health perspective, among adult community members in 5 selected sub-districts of Cumilla. The CDA is a community engagement approach involving community members in active discussions also known as Community Dialogs (CD), run by local facilitators. The dialogs promote collective action to produce sustainable social change. The trial’s process evaluation will evaluate fidelity, dose, adaptation, reach, mechanisms of impact and the process of knowledge diffusion using the MRC framework for the evaluation of complex interventions.

METHODS AND ANALYSIS: The process evaluation will be implemented in the catchment areas of 25 selected community clinics (CCs) in the intervention group. The key actors involved in the process evaluation are participants from master trainers and trainers training; community dialog facilitators; supervisors; community dialog participants and non-participants; and local and national level government stakeholders. Qualitative and quantitative data will be collected through Focus Group Discussion (FGDs); Case Studies; Key Informant Interview (KIIs); CD observations; monitoring forms; quarterly feedback from facilitators and supervisors, and pre-and-post-test questionnaires administered during the training of facilitators. All qualitative data will be coded using a priori coding framework in NVIVO 14. Quantitative data will be analysed using descriptive statistics.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Bangladesh Medical Research Council (BMRC): BMRC/NREC/2019-2022/427 and from the University of Leeds Faculty of Medicine and Health ethics board: MREC 20-034. All results will be disseminated through a one pager summary; infographics; peer-reviewed journal articles and national and international conferences.

CLINICAL TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN93756764, identifier ISRCTN93756764.

PMID:39735768 | PMC:PMC11672119 | DOI:10.3389/fpubh.2024.1466780

Front Public Health. 2024 Dec 13;12:1450826. doi: 10.3389/fpubh.2024.1450826. eCollection 2024.

ABSTRACT

OBJECTIVE: Anxiety is a serious psychiatric illness in older adult people. Activities of daily living and social participation are important factors influencing anxiety in older adult people. Using social participation as a mediating variable, this study explored the influence of activities of daily living on anxiety in older adult people to provide scientific evidence for improving the psychological health of older adult people.

METHODS: A multistage stratified random sampling method was used in this study to recruit older adult people. T tests and variance analysis were used for single factor analysis, and a multiple linear regression model was used for multifactor analysis. Pearson correlation analysis was used to study the correlation between activities of daily living and social participation and anxiety. The Process program was used to perform the bootstrap test.

RESULTS: The mean anxiety score of the interviewed older adult individuals was 3.028 ± 4.606 points, and 28.66% of the older adult individuals had anxiety. There was a statistically significant difference in the anxiety scores of older adult people across sex, age, marital status, education level, and health insurance status (p < 0.05). After controlling for other variables, each one-point increase in the activities of daily living score significantly increased the anxiety score by 0.122 points (𝛽=0.122, p < 0.001), and each one-point increase in the social participation score significantly decreased the anxiety score by 0.058 points (𝛽= – 0.058, p < 0.001). According to the results of the mediating effect analysis, there was a significant positive relationship between activities of daily living and anxiety, and the total effect was established (𝛽=0.1719, p < 0.001). After controlling for social participation, there was a significant direct effect of activities of daily living on anxiety in older adult people (𝛽=0.1255, p < 0.001). A partial mediating effect of social participation on the relationship between activities of daily living and anxiety in older adult people was found. The indirect effect of social participation was 26.99%.

CONCLUSION: Activities of daily living and social participation are important factors affecting anxiety in older adult people. Health education should be increased to enhance the physical activity of older adult people to improve their activities of daily living, create a good atmosphere for their social participation, improve their motivation for and continuity of social participation.

PMID:39735764 | PMC:PMC11671491 | DOI:10.3389/fpubh.2024.1450826