Tag: nevin manimala

Endocrine. 2025 Feb 2. doi: 10.1007/s12020-025-04176-0. Online ahead of print.

ABSTRACT

PURPOSE: Hyperprolactinemia in children and adolescents can result from various etiologies, including pituitary masses. Understanding the underlying causes, clinical presentation, and outcomes is essential for effective management.

METHOD: A retrospective cohort study was conducted, analyzing clinical data from patients diagnosed with hyperprolactinemia secondary to pituitary masses. The study included patients aged under 18 years, who were diagnosed between January 2018 and September 2024. Patients were classified into two groups: those with prolactinoma and those with non-prolactinoma causes, including non-functioning pituitary adenomas (NFPAs) and craniopharyngiomas. Serum prolactin levels, imaging studies, and treatment responses were assessed.

RESULTS: A total of 33 patients with hyperprolactinemia attributed to pituitary masses were identified. The diagnoses among the patients were as follows: 54.5% had prolactinomas, 24.2% had NFPAs, and 21.2% had craniopharyngiomas. The age at diagnosis ranged from 8.4-17.9 years. In the prolactinoma group, the mean age at diagnosis was 15.6 ± 2.1 years, while in the non-prolactinoma group, it was 13.5 ± 2.9 years, and a statistically significant difference was observed (p = 0.024). The median prolactin level was 258 ng/mL (range: 30.5-14,35 0 ng/mL). According to the diagnoses, the median prolactin level was 491.5 ng/mL (range: 249-14,350 ng/mL) for prolactinomas, 45.6 ng/mL (range: 30.5-68.5 ng/mL) for NFPAs, and 61 ng/mL (range: 44-72 ng/mL) for craniopharyngiomas. Menstrual irregularities, headaches, and galactorrhea were the most commonly reported complaints. Overweight/obesity was present in 39.3% of the entire cohort, while patients with prolactinomas demonstrated a significant reduction in BMI SDS following cabergoline treatment. Cabergoline treatment achieved a 100% success rate in patients with prolactinomas.

CONCLUSION: We observed a higher prevalence of hyperprolactinemia due to NFPAs and craniopharyngiomas compared to previous reports. Notably, obesity was prevalent among patients and demonstrated a favorable response to cabergoline therapy. These findings emphasize the necessity for future studies, particularly larger prospective trials incorporating genetic analyses, to enhance our understanding of the characteristics and treatment outcomes of pediatric hyperprolactinemia.

PMID:39893604 | DOI:10.1007/s12020-025-04176-0

J Assoc Physicians India. 2025 Jan;73(1):e8-e13. doi: 10.59556/japi.73.0772.

ABSTRACT

OBJECTIVE: Denosumab, a human monoclonal antibody that exhibits strong affinity and specificity for the receptor activator of nuclear factor-kappa B ligand (RANK-L), is essential in regulating bone turnover. Its inhibition of RANK-L decreases bone resorption by preventing the development, function, and survival of osteoclasts. The objective of the study was to evaluate and compare the efficacy and safety of biosimilar denosumab with the reference product, Prolia (denosumab), in Indian women suffering from postmenopausal osteoporosis.

METHODS: This phase III study was a prospective, active-controlled, randomized, double-blind trial that included postmenopausal women diagnosed with osteoporosis. Participants were randomly allocated in a 2:1 ratio to receive either the biosimilar denosumab (Treatment A) or the reference denosumab (Prolia®; Treatment B). All participants also received daily supplementation of 500 international units (IU) of vitamin D3 and 1000 mg calcium. The primary outcomes measured were the bone mineral density (BMD) percentage change at the lumbar spine and the neck of femur, while the secondary endpoint assessed changes in biomarkers from baseline at months 6 and 12.

RESULTS: The lumbar spine BMD percentage change for group A vs group B from baseline to month 6 was 5.69 ± 0.88 (p < 0.0001) vs 5.08 ± 1.19 (p < 0.0001), and at 12 months was 7.26 ± 1.05 (p < 0.0001) vs 7.31 ± 1.40 (p < 0.0001), demonstrating equivalent efficacy. Both treatment groups showed statistically significant improvement in femoral neck BMD at 12 months. No statistically significant difference was noted in the ln-transformed primary pharmacokinetic parameters, including C-max, AUC0-120d, and AUC0-∞.

CONCLUSION: Biosimilar denosumab was comparable to reference denosumab with respect to its efficacy, safety, pharmacokinetics (PK), pharmacodynamics, and immunogenicity in women with postmenopausal osteoporosis. Thus, biosimilar denosumab is expected to improve the quality of life in osteoporotic patients at affordable prices.

PMID:39893524 | DOI:10.59556/japi.73.0772

Crit Rev Clin Lab Sci. 2025 Feb 1:1-30. doi: 10.1080/10408363.2025.2453152. Online ahead of print.

ABSTRACT

Monitoring individuals’ laboratory data is essential for assessing their health status, evaluating the effectiveness of treatments, predicting disease prognosis and detecting subclinical conditions. Currently, monitoring is performed intermittently, measuring serum, plasma, whole blood, urine and occasionally other body fluids at predefined time intervals. The ideal monitoring approach entails continuous measurement of concentration and activity of biomolecules in all body fluids, including solid tissues. This can be achieved through the use of biosensors strategically placed at various locations on the human body where measurements are required for monitoring. High-tech wearable biosensors provide an ideal, noninvasive, and esthetically pleasing solution for monitoring individuals’ laboratory data. However, despite significant advances in wearable biosensor technology, the measurement capacities and the number of different analytes that are continuously monitored in patients are not yet at the desired level. In this review, we conducted a literature search and examined: (i) an overview of the background of monitoring for personalized laboratory medicine, (ii) the body fluids and analytes used for monitoring individuals, (iii) the different types of biosensors and methods used for measuring the concentration and activity of biomolecules, and (iv) the statistical algorithms used for personalized data analysis and interpretation in monitoring and evaluation.

PMID:39893518 | DOI:10.1080/10408363.2025.2453152

J Anim Breed Genet. 2025 Feb 1. doi: 10.1111/jbg.12929. Online ahead of print.

ABSTRACT

The aims of the present study were to perform single-step genomic predictions in the dual-purpose German Black Pied cattle (DSN) breed considering a DSN specific SNP chip (DSN_200 K), and to use the corresponding estimated breeding values (EBV) in ongoing optimum genetic contribution (OGC) selection. All results were compared with the application of the commercial Illumina BovineSNP50 BeadChip (50 K). The traits of interest in the present study (due to the differing breeding history of these traits in the past) included 305-day lactation protein percentage (Pro%) of 9029 DSN cows, fat-to-protein ratio (FPR) from the first test-day of 8773 DSN cows, and stature (STAT) measured in cm of 4409 DSN cows. The DSN cows represented the calving years 2008-2019. Genotyping of 2797 DSN animals was conducted using both the DSN_200 K and the 50 K. From the genotyped animals, a subset of 1800 cows had phenotypic records for all three traits FPR, Pro% and STAT. Heritabilities from the single-step genetic parameter estimations were quite large for Pro% (0.69) and STAT (0.78), but small for FPR (0.11). The choice of the SNP chip only had minor effects on variance components, heritabilities and EBVs. Furthermore, genetic parameters were very similar from genetic-statistical models additionally considering a linear regression on pedigree-based inbreeding coefficients. OGC selection was applied to a pool of 1125 pre-selected bull sires (BS) and bull dams (BD). A more relaxed genetic relationship constraint was associated with favourable effects on the average EBVs for Pro%, FPR and STAT, and a declining number of selected BS. The gains in genetic merit were marginal when relaxing the constraint at 0.06 for the genetic relationships or higher. The same associations were found for an overall breeding index (I-DSN), considering the three traits with equal weights. Consequently, we suggested OGC applications with a genetic relationship constraint of 0.06, which contributed to genetic gain in I-DSN of 17.9%, and to increased diversity due to an increased number of BS, when compared to the current practical elite animal selection scheme. A large number of finally selected BS and BD was identical when either using EBV from the DSN_200 K or from the 50 K. From such perspective, we only see marginal extra value for the specific DSN SNP-chip application.

PMID:39893511 | DOI:10.1111/jbg.12929

Hereditas. 2025 Feb 1;162(1):12. doi: 10.1186/s41065-025-00376-w.

ABSTRACT

BACKGROUND: With the development of the economy, the number of obese patients has been increasing annually worldwide. The proportion of asthma patients associated with obesity is also gradually rising. However, the pathogenesis of obesity-related asthma remains incompletely understood, and conventional pharmacological treatments generally show limited efficacy.

OBJECTIVE: This study aims to explore the causal relationship between obesity and allergic asthma, elucidate the pathogenesis of obesity-related asthma, and identify the plasma proteins involved in its development, providing new insights for clinical interventions.

METHODS: In this study, we employed a two-step approach for mediation Mendelian randomization (MR) analysis, utilizing stringent selection criteria to identify instrumental variables (IVs). This approach was used to assess the causal impact of obesity on allergic asthma and to validate the plasma proteins identified as mediating factors. We further explored the functions and enriched pathways of the mediating proteins using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, we conducted drug-targeted MR analysis to evaluate the potential of each mediator plasma proteins as a drug target gene. If significant heterogeneity remained among the IVs, we applied the weighted median method as the primary analytical tool. Otherwise, we utilized the inverse variance weighted (IVW) method as the main analytical approach. Additionally, we conducted various sensitivity analyses and statistical tests to further illustrate the robustness of the observed associations.

RESULTS: The research findings indicate a causal relationship between obesity and allergic asthma. Plasma proteins such as TPST1, ROR1, and DAPK1 mediate this relationship, with TPST1 accounting for over 10% of the mediation effect. GO and KEGG analyses show that the genes corresponding to these mediator proteins are primarily enriched in pathways related to responses to stimuli, carbohydrate synthesis and metabolism, regulation of certain protein activities, and synaptic connections. The drug-targeted MR analysis suggests that SIGLEC12, BOLA1, HOMER2, and TPST1 all have the potential to be drug target genes.

CONCLUSION: This study suggests that obese patients defined by BMI may promote the development of allergic asthma by influencing the expression of plasma proteins such as TPST1, ROR1, and DAPK1. Furthermore, some of these plasma proteins, including TPST1, could potentially serve as therapeutic targets for treating allergic asthma in these patients. However, further research is needed to explore their therapeutic potential and the mechanisms underlying their effects.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:39893495 | DOI:10.1186/s41065-025-00376-w

BMC Womens Health. 2025 Feb 1;25(1):45. doi: 10.1186/s12905-025-03578-6.

ABSTRACT

INTRODUCTION: The conflict between work and family responsibilities has created many challenges for working women in Iran. This study aimed to examine the effect of work-family conflict (WFC), subjective socio-economic status (SSS), and physical activity (PA) and quality of working life (QWL) on the quality of life (QOL) of working women in Kermanshah, Iran.

METHODS: This cross-sectional study was conducted with 392 working women in Kermanshah, the most populous city in western Iran. The data gathering tool was a six-part questionnaire, including demographic checklist, PA scale, a question on SSS, WFC scale, QWL questionnaire, and QOL questionnaire. Data were analyzed by SPSS and AMOS software.

RESULTS: The majority of participants (69.4%) were inactive or had low levels of PA during their leisure times. The highest positive correlation was observed between QWL and QOL (r = 0.309, p-value < 0.001). The highest direct effect among the variables belonged to the SSS on QWL (β = 0.41, p-value = 0.001) and QOL (β = 0.20, p-value < 0.001). Furthermore, the analysis of indirect effects indicated that QWL played a mediating role between SSS and QOL (β = 0.092, p-value < 0.001).

CONCLUSION: The findings of this study revealed that variables such as SSS, PA, and QWL had significant direct effects on QOL. However, WFC had no significant effect on QOL. Moreover, QWL had a significant positive mediating role between SSS and QOL.

PMID:39893490 | DOI:10.1186/s12905-025-03578-6

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