Tag: nevin manimala

Alzheimers Res Ther. 2025 Feb 1;17(1):35. doi: 10.1186/s13195-025-01682-1.

ABSTRACT

BACKGROUND: Recent studies suggest that opioid receptor signaling may differentially affect Alzheimer’s disease (AD) pathology and the relevant behavioral dysfunctions. However, the precise roles and mechanisms of opioid receptor subtypes in AD pathologies are still unclear with major controversies.

METHODS: We compared the delta-opioid receptor (DOR)- and mu-opioid receptor (MOR)-mediated effects on AD-associated cognitive deficits, pathologies, neuroinflammations, cell death using transgenic APP/PS1 mouse model and BV2 cell line at behavioral, molecular, and cellular levels. Unpaired t-test and one/two way analysis for variance (ANOVA) were used to analyze statistical significance of the data.

RESULTS: We show a distinct role of DOR and its major difference with MOR in AD injury in an APP/PS1 mouse model. DOR activation by UFP-512, but not MOR activation by DAMGO, attenuated cognitive impairment, reduced beta-amyloid (Aβ) production and aggregation, as well as protected the neurons from apoptosis in APP/PS1 mice. DOR and MOR also differentially modulated microglia in APP/PS1 mice and in vitro AD cell model with a DOR-mediated inhibition on the excessive activation of microglia and the release of pro-inflammatory cytokines in AD pathologies. Gene expression profiling further revealed that the alternations in DOR/MOR are closely associated with microglial homeostatic signatures and high mobility group protein B1 (HMGB1) in AD. DOR activation inhibited HMGB1 secretion and its translocation from nuclear to cytoplasm. Our in-vitro studies further confirmed that DOR overexpression mitigated microglial inflammatory response and rescued neurons from AD injury via HMGB1-NF-κB signaling pathway.

CONCLUSIONS: These novel findings uncover previously unappreciated roles of DOR in neuroprotection against AD injury via modulating microglia-related inflammatory responses.

PMID:39893485 | DOI:10.1186/s13195-025-01682-1

BMC Infect Dis. 2025 Feb 1;25(1):152. doi: 10.1186/s12879-025-10442-3.

ABSTRACT

BACKGROUND: Influenza is a seasonal infection with a huge impact on morbidity and mortality in older adults, for whom vaccination is recommended. New influenza vaccines for this population have been introduced in Spain in the past 5 years, and a number of cost-effectiveness analyses (CEA) have been published to aid healthcare decision-making. The objective of this study was to assess possible sources of uncertainty in the CEAs of influenza vaccines for the older adults in Spain.

METHODS: A systematic review was performed to identify Spanish CEAs published since 2016. Potential sources of structural, methodologic and parametric uncertainty in CEA results were systematically analysed using the TRansparent Uncertainty ASsessmenT (TRUST) Tool, quality assessment checklists, and the WHO guidance on economic evaluations of influenza vaccine strategies. The primary sources of efficacy/effectiveness were analysed in depth to ascertain whether they could support the conclusions of the respective CEAs.

RESULTS: Seven CEAs were included. Overall, they were designed and performed in accordance with the applicable guidelines; however, some critical sources of uncertainty were detected, mainly: (1) the choice and use of efficacy/effectiveness data (real-world single season studies, meta-analyses including studies with high risk of bias and/or high heterogeneity with biased interpretation); (2) use of fewer than 5 seasons to estimate influenza burden; (3) generalized use of influenza-like illness data to estimate effectiveness and burden, among others.

CONCLUSIONS: Seemingly well-designed studies may conceal important sources of uncertainty that affect the results. This must be taken into account when interpreting results to support decision-making.

PMID:39893473 | DOI:10.1186/s12879-025-10442-3

Harm Reduct J. 2025 Feb 1;22(1):13. doi: 10.1186/s12954-025-01159-2.

ABSTRACT

BACKGROUND: Drug-related harm is a significant public health concern in the UK, particularly among underserved groups such as gay, bisexual, and other men who have sex with men (GBMSM). This study explores the role of night-time venues (for example night clubs or sex-on-premises venues) in promoting harm reduction strategies for GBMSM who use drugs, highlighting unique challenges within these spaces.

METHODS: The study used a mixed-methods approach, including an online survey (n = 53) and semi-structured interviews (n = 8). Participants included GBMSM with lived experience of substance use in night-time venues, as well as those providing support to this population. Data was collected through a Likert-scale survey and thematic analysis of qualitative responses.

RESULTS: Findings reveal dissatisfaction among survey respondents about the level of support for harm reduction provided by night-time venues, which are perceived as inconsistent in their approach towards substance use. The study also identifies economic and legal barriers faced by venues that prevent the endorsement of harm reduction techniques.

CONCLUSIONS: Addressing these barriers could transform night-time venues into effective sites for harm reduction, particularly by targeting “afters” culture (the phenomenon where club-goers will return to a residential setting and continue substance use for prolonged periods ‘after’ the night-time venue closes or the event ends) and promoting safer practices. This research suggests that coordinated efforts with local government and policy reform are crucial to fostering safer environments for GBMSM.

PMID:39893472 | DOI:10.1186/s12954-025-01159-2

Hereditas. 2025 Feb 1;162(1):14. doi: 10.1186/s41065-025-00373-z.

ABSTRACT

BACKGROUND: Previous observational studies have reported an association between chronic obstructive pulmonary disease (COPD) and osteoporosis (OP). The aim of this study is to investigate the causal relationship between COPD and OP by two-sample Mendelian randomization (MR) analysis. The current status of cross-sectional research between COPD and OP in the past decade was explored through bibliometrics.

METHODS: Single nucleotide polymorphisms (SNPs) that have been found to be strongly associated with COPD were used as instrumental variables (IVs) in MR Analysis. The primary outcome of the study was BMD measurement at five specific anatomical sites, namely the whole body, femoral neck, lumbar spine, forearm, and heel. These BMD measurements were derived primarily from a genome-wide association study (GWAS) and summary statistics from the International Genetic Factors Consortium for Osteoporosis (GEFOS). The main analysis method was inverse variance weighting (IVW). Multiple sensitivity analyses were performed to assess the robustness and reliability of the current MR Results. Further confirmatory MR Analysis between COPD and OP was applied. In bibliometrics. Publications were extracted from the Web of Science core collection publications related to osteoporosis and sarcopenia published between January 2014 and October 2024; Bibliometrics and visualization were performed by Microsoft Office Excel, Citespace, and R (Bibliometrix).

RESULTS: The MR Findings suggest that there is no causal relationship between COPD and BMD at five specific anatomical sites. The results of the primary IVW MR Analysis were generally supported by our sensitivity MR Analysis. We performed MR Analysis for the validation of COPD and OP (IVW OR: 1.019; 95%CI: 0.898-1.564; p = 0.768) also did not support a causal relationship between COPD and BMD. A total of 471 articles written by 1119 organizations from 42 countries/regions by 3331 authors and published in 238 journals were identified in the bibliometric analysis. China is the leading country in terms of the number of publications. China Medical University contributed the most publications. The International Journal of Chronic Obstructive Pulmonary Disease has the highest publication in this field.

CONCLUSIONS: In conclusion, This MR Study found no causal relationship between COPD and OP, suggesting that the observed associations may be due to common genetic effects or environmental confounders. The global research trends in this field in the past decade were summarized through bibliometric analysis, and care became the focus of future research on the relationship between copd and OP.

PMID:39893471 | DOI:10.1186/s41065-025-00373-z

J Health Popul Nutr. 2025 Feb 1;44(1):24. doi: 10.1186/s41043-025-00770-0.

ABSTRACT

BACKGROUND: Even though maternal nutrition has improved, food taboos and poor dietary practices during pregnancy can still lead to nutrient deficiencies, increasing the risk of complications for both mothers and children. Therefore, this study aimed to generate pooled evidence from across different countries in Sub-Saharan Africa to inform effective prevention actions. This meta-analysis aims to determine the pooled prevalence of food taboo practices and identify associated factors among pregnant women in Sub-Saharan Africa.

METHODS: This study systematically reviewed relevant articles and reports from databases including Embase, MEDLINE, Science Direct, PubMed, Google, and Google Scholar. The Newcastle-Ottawa Scale assessed article quality. Data extraction and analysis were done using Excel and STATA 17, respectively. Heterogeneity was assessed using Cochran’s Q test and the I² statistic, with a random effects model employed for meta-analysis. Publication bias was evaluated and addressed using Duval and Tweedie’s Trim and Fill analysis.

RESULTS: A total of fifty-eight studies with 20,262 pregnant women were included in this meta-analysis. The pooled proportion of food taboo practices reported by the 58 studies was 41% (95% CI: 34, 48%). In the subgroup analysis, the pooled proportion of food taboo practices for studies conducted in urban areas was 40% (95% CI: 32, 48%), while it was 43% (95% CI: 32, 56%) among rural residents. Factors associated with food taboo practices among pregnant women included being unable to read and write (AOR = 2.64%; 95% CI: 1.79-3.90; I² = 56.9%), not receiving antenatal care follow-up (AOR = 3.73%; 95% CI: 2.83-3.90; I² = 55.1%), and poor maternal nutrition knowledge (AOR = 3.33%; 95% CI: 1.56-7.09; I² = 84.3%).

CONCLUSION: According to this review, over two out of every five pregnant mothers practiced food taboos in the region. The educational status of the mother, antenatal care follow-up, and maternal nutrition knowledge were factors affecting food taboo practices among pregnant women. Therefore, emphasis should be given to the uptake of antenatal care follow-up to improve maternal nutrition knowledge and nutritional status.

PMID:39893470 | DOI:10.1186/s41043-025-00770-0

Trials. 2025 Feb 1;26(1):37. doi: 10.1186/s13063-025-08749-2.

ABSTRACT

BACKGROUND: The euglycemic clamp test stands as the best method for assessing the pharmacokinetic and pharmacodynamic properties of long-acting insulin. However, despite its widespread use, there remains a notable absence of an established gold standard for evaluating the test’s quality. Existing recommendations from regulatory agencies lack specific threshold values, particularly concerning long-acting insulin. This study aimed to determine the evaluation criteria for assessing the quality of the long-acting insulin euglycemic glucose clamp test and to improve the overall quality of this testing method.

METHODS: Fifty-three healthy volunteers were administered a single dose of insulin degludec (0.4 IU/kg) and underwent a 24-h euglycemic clamp test. Blood samples were collected to evaluate the pharmacokinetics and pharmacodynamics of insulin degludec. Volunteers were separated into group A (coefficient of variation in blood glucose [CVBG] ≤ 3.5%) and group B (CVBG > 3.5%). The quality difference of the clamp test between the groups was assessed using various quality control indices. Volunteers were also categorized into group C (C-peptide reduction rate < 50%) and group D (C-peptide reduction rate ≥ 50%). The clamp test quality, pharmacokinetics, and pharmacodynamics of groups C and D were compared.

RESULTS: According to CVBG, group A had a mean CVBG of 2.95%, group B had a mean CVBG of 4.15%, and group A had a significantly lower CVBG than group B (p < 0.001). CVBG was positively correlated with other quality control indicators, such as the percentage of glucose excursion from the target range (GEFTR), duration of GEFTR, and area under the curve (AUC) of GEFTR. According to the reduction of C-peptide levels: group D had significantly higher C-peptide reduction than group C (p < 0.001). Groups C and D had CVBG < 3.5%. The quality of groups C and groups D was evaluated by the quality control indicators of the clamp test. Only the AUC of GEFTR was statistically different between Groups C and D (p = 0.043, < 0.05), and there was no statistical difference in other indicators between the two groups.

CONCLUSIONS: CVBG could be used as a standard for evaluating the quality of long-acting insulin euglycemic glucose clamp test, and the test quality was superior with a CVBG ≤ 3.5%. A C-peptide reduction ratio ≥ 50% indicated sufficient endogenous insulin inhibition; however, when the glucose fluctuation is small (CVBG is maintained at a low level) during the clamp test, even if the clamp test quality is slightly different, it is not sufficient to interfere with endogenous insulin secretion.

PMID:39893469 | DOI:10.1186/s13063-025-08749-2

AIDS Res Ther. 2025 Feb 1;22(1):9. doi: 10.1186/s12981-024-00690-9.

ABSTRACT

BACKGROUND: In January 2021, the United States (US) Food and Drug Administration (FDA) approved the first long-acting injectable antiretroviral therapy (LAI ART) regimen for the treatment of HIV providing an alternative to daily oral regimens. We analyzed electronic health records (EHRs) to provide real-world evidence of demographic and clinical characteristics associated with the receipt of LAI ART among people with HIV (PWH).

METHODS: Leveraging EHRs from a large clinical research network in the Southern US – OneFlorida + linked with Medicaid (updated to 08/2022) – we identified a cohort of PWH who have been prescribed at least one dose of LAI ART since January 2021 and characterized their demographics, clinical characteristics, and HIV care outcomes.

RESULTS: A total of 233 LAI ART recipients were identified: 56.7% female, 45.1% aged 30 to 44, 51.3% non-Hispanic Black, 78.1% on Medicaid and 4.7% on private insurance. Approximately three-quarters of injections (71.2%) were received within 37 days of the previous dose, and 84.4% were received within 67 days. About 8% of LAI ART recipients did not have optimal care engagement the year before LAI ART initiation; one in five recipients had a diagnosis of alcohol or substance use disorder in lifetime. All achieved viral suppression (< 50 copies/mL) before starting LAI ART. Of a subset of patients with HIV viral load test records, only 1 record of virologic failure (viral load > 200 copies/ml) was observed after the initiation of LAI ART.

DISCUSSION: There has been an increasing trend of LAI ART initiation since approval. People with suboptimal care engagement and with substance use disorder in lifetime were not excluded from LAI ART treatment.

PMID:39893464 | DOI:10.1186/s12981-024-00690-9

Malar J. 2025 Feb 1;24(1):32. doi: 10.1186/s12936-025-05273-1.

ABSTRACT

BACKGROUND: Malaria burden remains high in some Peruvian regions, especially in the Northeast Amazon rainforest state of Loreto and the tropical coastal state of Tumbes. Novel non-invasive diagnostic tools for malaria are being developed, and formative research in malaria-endemic areas with community members and health professionals who would potentially use these devices is vital for this process. This study aimed to examine the acceptability and feasibility of four new non-invasive malaria diagnostic tools in development in two regions of Peru with significant malaria burden.

METHODS: The research team conducted focus group discussions and key informant interviews in Spanish to assess acceptability and ascertain questions and concerns regarding the non-invasive diagnostic tools. Focus group discussions included a range of community members (pregnant women, parents), professionals (health, education), and community leaders in Loreto. Vector control authorities and health professionals from Loreto, Tumbes, and Lima participated as key informants.

RESULTS: Participants were initially enthusiastic about all non-invasive diagnostic tools. However, as discussions proceeded, high enthusiasm remained for two devices that were easy to use, acceptable for the communities they were intended for, feasible to carry in remote areas, and did not require new supplies nor generate waste: the skin scan and the skin odour test. The breath and saliva tests were considered less hygienic. They were less acceptable to community members and health professionals due to concerns of disease transmission and other environmental and cultural concerns. Health professionals felt the finger scan test and the skin odour test would help triage community members in endemic sites and would be valuable in remote regions with difficult access to health facilities or laboratories.

CONCLUSIONS: Novel non-invasive malaria diagnostic tools can be valuable in malaria-endemic settings. As manufacturers evaluate the efficacy and effectiveness of these non-invasive diagnostic tools, international recommendations should be created to ensure their agile integration into national malaria programmes.

PMID:39893463 | DOI:10.1186/s12936-025-05273-1

J Med Internet Res. 2025 Jan 31;27:e65967. doi: 10.2196/65967.

ABSTRACT

BACKGROUND: Health systems are increasingly offering patient portals as tools for patients to access their health information with the goal of improving engagement in care. However, understanding health care providers’ perspectives on patient portal implementation is crucial.

OBJECTIVE: This study aimed to understand health care providers’ experiences of implementing the MyChart patient portal, perspectives about its impact on patient care, clinical practice, and workload, and opportunities for improvement.

METHODS: Using an explanatory sequential mixed methods approach, we conducted a web-based questionnaire and semistructured individual interviews with health care providers at a large Canadian community hospital, 6 months after MyChart was first offered to patients. We explored perspectives about the impact of MyChart on clinical practice, workload, and patient care. Data were analyzed using descriptive statistics and thematic analysis.

RESULTS: In total, 261 health care providers completed the web-based questionnaire, and 15 also participated in interviews. Participants agreed that patients should have access to their health information through MyChart and identified its benefits such as patients gaining a greater understanding of their own health, which could improve patient safety (160/255, 62%). While many health care providers agreed that MyChart supported better patient care (108/258, 42%), there was limited understanding of features available to patients and expectations for integrating MyChart into clinical routines. Concerns were raised about the potential negative impacts of MyChart on patient-provider relationships because sensitive notes or results could be inappropriately interpreted (109/251, 43%), and a potential increase in workload if additional portal features were introduced. Suggested opportunities for improvement included support for both patients and health care providers to learn about MyChart and establishing guidelines for health care providers on how to communicate information available in MyChart to patients.

CONCLUSIONS: While health care providers acknowledged that MyChart improved patients’ access to health information, its implementation introduced some friction and concerns. To reduce the risk of these challenges, health systems can benefit from engaging health care providers early to identify effective patient portal implementation strategies.

PMID:39888658 | DOI:10.2196/65967

JAMA Netw Open. 2025 Jan 2;8(1):e2457341. doi: 10.1001/jamanetworkopen.2024.57341.

ABSTRACT

IMPORTANCE: Ultraprocessed foods (UPF), characterized as shelf-stable but nutritionally imbalanced foods, pose a public health crisis worldwide. In adults, UPF consumption is associated with increased obesity risk, but findings among children are inconsistent.

OBJECTIVES: To examine the associations among UPF intake, anthropometric adiposity indicators, and obesity status in Canadian children.

DESIGN, SETTING, AND PARTICIPANTS: In the CHILD Cohort Study, one of the largest prospective, multicenter, population-based pregnancy cohorts in Canada, diet was assessed during the 3-year visit (September 2011 to June 2016), and anthropometric measurements were assessed at the 5-year visit (December 2013 to April 2018). Data analysis was performed between July 1, 2023, and June 30, 2024.

EXPOSURE: Diet intake was assessed using a semiquantitative food frequency questionnaire at 3 years of age. UPFs were identified using the NOVA classification system.

MAIN OUTCOMES AND MEASURES: Anthropometric adiposity indicators were measured at 5 years of age and used to calculate age- and sex-standardized z scores for body mass index (BMI), waist to height ratio, and subscapular and triceps skinfold thicknesses, and obesity, which was defined using BMI z score cutoffs. Multivariable-adjusted regression analyses were used to examine the associations of UPF with adiposity and obesity development, accounting for parental, birth, and early-childhood factors.

RESULTS: Among 2217 participants included in this study, median age at the outcome assessment was 5.0 (IQR, 5.0-5.1) years, and 1175 (53.0%) were males. At 3 years of age, UPF contributed 45.0% of total daily energy intake. UPF energy contribution was higher in males vs females (46.0% vs 43.9%; P < .001). Among all participants, higher UPF intake at 3 years of age was associated with higher anthropometric adiposity indicators at 5 years of age, primarily driven by males. In males, every 10% UPF energy increase was associated with higher adiposity indicator z scores for BMI (β, 0.08; 95% CI, 0.03-0.14), waist to height ratio (β, 0.07; 95% CI, 0.01-0.12), and subscapular (β, 0.12; 95% CI, 0.06-0.18) and triceps (β, 0.09; 95% CI, 0.03-0.15) skinfold thickness and higher odds of living with overweight or obesity (odds ratio, 1.19; 95% CI, 1.03-1.36). No significant associations were observed among females.

CONCLUSIONS AND RELEVANCE: In this cohort study of Canadian children, high UPF consumption during early childhood was associated with obesity development, primarily in males. These findings can inform targeted public health initiatives for early childhood centers and caregiver education programs to reduce UPF intake and prevent obesity.

PMID:39888617 | DOI:10.1001/jamanetworkopen.2024.57341