Nevin Manimala

Biol Trace Elem Res. 2025 Nov 27. doi: 10.1007/s12011-025-04918-1. Online ahead of print.

ABSTRACT

A large number of South American camelids (SAC) presented to a veterinary clinic are diagnosed with anemia. While various causes are known, such as infections with Haemonchus contortus, chronic inflammation, neoplasia, gastric ulcers, or deficiencies, little is known about the role of the trace elements copper and iron in SAC. In this retrospective study, the laboratory diagnostic data, in particular the red and white blood count, as well as the findings of the initial clinical examination of 181 alpacas presented at the University of Veterinary Medicine Hannover, Hannover, Germany in the period from January 2020 to September 2023 were therefore analyzed. In addition, iron, copper, transferrin, and ceruloplasmin were determined in the serum collected during the initial examination. The statistical analysis revealed significant correlations between the serum iron content and various degrees of anemia, and also between serum copper content and various degrees of anemia. These observations confirm the need to characterize the iron metabolism of SAC more precisely to improve differentiation between different causes of anemia.

PMID:41307871 | DOI:10.1007/s12011-025-04918-1

Drugs Real World Outcomes. 2025 Nov 27. doi: 10.1007/s40801-025-00526-6. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperuricemia is a common comorbidity in patients with cardiovascular diseases and chronic kidney disease, often requiring long-term urate-lowering therapy. Febuxostat, a xanthine oxidase inhibitor, has raised cardiovascular safety concerns. Dotinurad, a selective urate reabsorption inhibitor, has emerged as a potential alternative, but clinical evidence in patients with Stage B/C heart failure remains limited.

METHODS: This single-center retrospective study evaluated 30 patients with Stage B (n = 10) and C (n = 20) heart failure and hyperuricemia who were switched from febuxostat (10, 20, or 40 mg) to dotinurad (0.5, 1.0, or 2.0 mg, respectively), based on the prior febuxostat dose. Laboratory and urinary parameters were assessed at baseline and at follow-up (median 65 days [56-84] after switching).

RESULTS: In Stage B heart failure, serum uric acid showed a non-significant trend toward reduction (5.8 [4.4-6.3] to 5.3 [4.8-7.5] mg/dL, p = 0.09), whereas in Stage C heart failure, serum uric acid increased significantly (5.1 [4.6-6.6] to 5.4 [4.8-6.8] mg/dL, p = 0.02). The proportion of patients achieving serum uric acid ≤ 6.0 mg/dL was maintained (Stage B: 60.0 to 50.0%; Stage C: 70.0 to 75.0%). Urinary uric acid excretion increased, while urinary pH remained stable in both groups. The uricosuric effect of dotinurad was evident with or without concomitant use of sodium-glucose cotransporter 2 inhibitors. No adverse events, including cardiovascular events, urolithiasis, or gout flares, were observed.

CONCLUSIONS: Switching from febuxostat to dotinurad may be effective and safe over the short term in patients with Stage B/C heart failure and hyperuricemia.

PMID:41307868 | DOI:10.1007/s40801-025-00526-6

Dig Dis Sci. 2025 Nov 27. doi: 10.1007/s10620-025-09584-w. Online ahead of print.

ABSTRACT

PURPOSE: We aim to test the hypothesis that “primary early surgery (i.e., within 2 years from symptoms onset) in chronic calcific pancreatitis (CCP) has better durable long-term Quality of Life (QOL) than patients undergoing late surgery (> 2 years from symptom onset)” using the SF-36 questionnaire.

METHODS: This is a prospective observational study conducted between 2016 and 2025. 162 patients with large-duct CCP (MPD diameter ≥ 6 mm) underwent either Frey’s procedure or lateral pancreatico-jejunostomy (LPJ). 62/162 patients on regular follow -up were included in the study. The 62 patients were grouped into primary early surgery group (PESG) and late surgery group (LSG). After long term (> 3 year) of follow-up, patient’s responses regarding QOL were recorded using the SF-36 questionnaire and compared. The primary outcome measures were pain, physical functioning and role limitations due to physical health and the other components on the SF-36 were taken as secondary outcome measures.

RESULTS: 27/62 cases were in LSG and 35/62 belonged to PESG. Mann-Whitney U test was used to make group comparisons. 7 out of 8 components namely Pain, Physical Functioning, Role Limitations Due to Physical Health, Role Limitations Due to Emotional Problems, Energy/ Fatigue, Emotional Well-Being, Social Functioning had statistically significant difference favoring better QOL in PESG.

CONCLUSION: Primary early surgery has a positive impact on long-term QOL in patients with CCP. However, future RCTs will help to draw solid conclusions to support or refute our observations.

PMID:41307862 | DOI:10.1007/s10620-025-09584-w

J Assist Reprod Genet. 2025 Nov 27. doi: 10.1007/s10815-025-03731-y. Online ahead of print.

ABSTRACT

PURPOSE: Sperm mature as they transit through the epididymis, during which they gain progressive motility and the capability to fertilize oocytes. Autophagy plays a significant role in the regulation of testicular spermiogenesis. Autophagy-related gene 5 (Atg5) is recognized as a crucial regulator of autophagy progression. However, the role of Atg5 in regulating epididymal sperm maturation has yet to be elucidated.

METHODS: To investigate the function of Atg5 in regulating epididymal sperm maturation, Atg5 conditional knockout mice were generated using Cre/LoxP technology, and sperm quality and fertility were assessed. Comprehensive quantitative analyses and bioinformatics evaluations of the proteome in segments 4-5 of the caput epididymis and sperm from the cauda epididymis were conducted.

RESULTS: Atg5 deletion reduced autophagy in the caput epididymis but did not significantly affect sperm motility. Quantitative proteomics via data-independent acquisition (DIA) and subsequent bioinformatics analysis revealed significant alterations in the expression of several sperm proteins. Among these, the upregulated proteins were strongly associated with Atg5-independent surrogate autophagy, while the downregulated proteins were linked to sperm maturation. Additionally, qRT-PCR assays demonstrated that seven genes closely related to autophagy and sperm quality were differentially expressed in the 4-5 segments of the caput epididymis.

CONCLUSIONS: Atg5 affects protein expression and abundance in both the caput epididymis (segments 4-5) and cauda epididymal sperm, without statistically significant effects on sperm motility or male fertility. However, the potential impact of autophagy inhibition on sperm maturation may arise under challenging survival conditions by influencing the expression of sperm proteins.

PMID:41307852 | DOI:10.1007/s10815-025-03731-y

Discov Oncol. 2025 Nov 27. doi: 10.1007/s12672-025-04173-9. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition with increasing evidence of comorbidity with breast cancer (BRCA). While epidemiological studies suggest an association, the underlying genetic mechanisms remain largely unexplored.

METHODS: We conducted a comprehensive genome-wide investigation to explore the shared genetic basis between IBD (including CD and UC) and breast cancer. Summary statistics from large-scale GWAS were analyzed using linkage disequilibrium score regression (LDSC), GNOVA, stratified LDSC (S-LDSC), MAGMA, PLACO, and summary-data-based Mendelian randomization (SMR). Tissue-specific enrichment was evaluated using GTEx data, and functional annotation was performed using FUMA.

RESULTS: We identified significant genetic correlations between IBD and breast cancer at the genome-wide level. Subsequent pleiotropy analyses detected 83 genome-wide significant pleiotropic SNPs and 24 shared risk loci, including 9p24.1 and 10q21.2, involving key immune-regulatory genes such as JAK2, CD274, and ZNF365. MAGMA and FUMA revealed enrichment of shared genes in immune pathways such as cytokine signaling, JAK-STAT signaling, and antigen presentation. Tissue-specific analyses indicated significant expression of pleiotropic genes in the colon, terminal ileum, and breast. SMR analysis further supported the transcriptional regulatory role of genes like P4HA2, ZNF365, SLC22A4, and SLC22A5 in both diseases.

CONCLUSION: This study presents the first systematic genetic evidence of a shared immunogenetic basis between IBD and breast cancer. The identification of pleiotropic loci and candidate drug targets provides novel insights into inflammation-associated tumorigenesis and lays the groundwork for future cross-disease prevention and therapeutic strategies.

PMID:41307839 | DOI:10.1007/s12672-025-04173-9

Discov Ment Health. 2025 Nov 27;5(1):189. doi: 10.1007/s44192-025-00324-0.

ABSTRACT

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder that imposes significant physical, psychological, and social burdens on patients and their family caregivers. Family caregivers play a crucial role in patient care, but often experience substantial caregiving burden and psychological distress. Telenursing, as an emerging approach in healthcare, offers an accessible and cost-effective method for providing education and support to caregivers. This study aims to evaluate the effectiveness of telenursing in care education for family caregivers of patients with psoriasis.

METHODS: A single-site, open-label randomized clinical trial with two parallel groups (intervention and control) will be conducted at the dermatology clinic of Razi Hospital, Tehran University of Medical Sciences, between June 2025 and November 2025. Seventy family caregivers of patients with psoriasis who meet the inclusion criteria will be recruited and randomly assigned (38 per group) to either a telenursing-based care education program (intervention) or usual education (control). The intervention will last six weeks, including four weeks of structured online education via WhatsApp and Skyroom, followed by two weeks of follow-up. Primary outcomes (psychological well-being and caregiving burden) and the secondary outcome (caregiver self-efficacy) will be assessed at baseline and post-intervention using validated questionnaires. Statistical analyses will be conducted using SPSS software V.23, with a significance level of p < 0.05.

DISCUSSION AND CONCLUSION: This trial will evaluate whether a structured telenursing program can improve psychological well-being and caregiver self-efficacy while reducing caregiving burden among family caregivers of patients with psoriasis. The findings may inform scalable nurse-led telehealth strategies to support caregivers in chronic dermatological conditions. Trial registration IRCT20240319061338N2, registered on 17 January 2025 in the Iranian Registry of Clinical Trials (IRCT) ( http://www.irct.ir/ ).

PMID:41307833 | DOI:10.1007/s44192-025-00324-0

Drug Saf. 2025 Nov 27. doi: 10.1007/s40264-025-01629-3. Online ahead of print.

ABSTRACT

BACKGROUND: Sulfonylureas (SU) are widely used for diabetes management in older adults but can cause hypoglycemia, which may be worsened by drug interactions. We applied high-throughput data mining to identify medications that could increase hypoglycemia risk when taken with SU.

METHODS: Using Medicare, MarketScan, and Optum Clinformatics (2003-2022), we identified patients aged ≥ 65 years who experienced a severe hypoglycemic event after at least 90 days on SU. We evaluated all medications dispensed in the 90 days before the event using a case-crossover (CCO) design. We adjusted for time-varying confounding and direct effect of the evaluated medications (precipitant) using a case-case time-control (CCTC) approach and metformin as control. We computed odds ratios (ORs) for its association with hypoglycemia. The false discovery rate (FDR) was controlled at 0.05 to adjust for multiple testing. To reduce confounding from other diabetes medications, we analyzed non-diabetes and diabetes medications separately.

RESULTS: Among 1607 candidate drugs received before experiencing hypoglycemia, 86 non-diabetes medications showed a CCO OR ≥ 1.00. With metformin as control, sulfamethoxazole/trimethoprim (CCTC OR 1.76, p < 0.01, FDR q < 0.01) and metronidazole (CCTC OR 2.17, p < 0.01, FDR q = 0.04) were associated with severe hypoglycemia. Among 10 diabetes medications, insulin showed increased association (CCO OR 1.22, p < 0.01); however, once adjusted for the drug’s direct effects, CCTC OR was 1.03 (p = 0.47, FDR q = 0.47).

CONCLUSIONS: Using a high-throughput data mining approach, we identified two antibiotics (sulfamethoxazole/trimethoprim and metronidazole) that may increase hypoglycemia risk in older adults on sulfonylureas. Given the exploratory nature of this study, these findings warrant further investigation.

PMID:41307830 | DOI:10.1007/s40264-025-01629-3

Arch Osteoporos. 2025 Nov 27;20(1):148. doi: 10.1007/s11657-025-01623-3.

ABSTRACT

In 744 adults from Pune (Western India) and nearby villages, osteoporosis prevalence was higher in rural women than urban (43% vs 18%). Advancing age, location, height, tobacco use and sunlight were key determinants. These findings emphasize urgent need for preventive and management strategies in rural population to reduce osteoporosis burden.

BACKGROUND: About 150 million older adults (age > 60y) live in India presently, representing ~ 14% of the global older population. The population is expected to reach 324 million by 2050, leading to higher healthcare burden from conditions like osteoporosis. However, there is limited knowledge about bone health and its determinants in middle-aged rural and urban Indian adults.

METHODS: This study included 744 adults (398 women) aged > 40y from urban and rural areas of Pune, India. We assessed areal bone mineral density (aBMD) at lumbar spine and femur using dual energy x-ray absorptiometry and volumetric bone parameters by peripheral quantitative computed tomography. Socio-economic-status and lifestyle factors (diet, physical activity, tobacco use, sunlight) were evaluated. Differences in bone parameters were analysed and multiple linear regression was used to identify predictors of bone health.

RESULTS: Significant differences observed in anthropometry and lifestyle factors in urban and rural population. Rural men and women had lower aBMD than urban, with osteoporosis more common in rural women (43%) than urban (18%), and in women compared to men (31% vs 8%). In both sexes, bone outcomes were influenced by anthropometric, residential, and lifestyle factors. Height and rural residence predicted bone density and geometry in men, while in women, age, height, rural residence, tobacco intake, and sunlight exposure were key determinants CONCLUSION: Rural population showed poor bone health. Bone health in both sexes was influence by age, height, rural residence, lifestyle factors like tobacco use and sunlight exposure. Strategies targeting lifestyle modification may help improving bone health among Indians.

PMID:41307825 | DOI:10.1007/s11657-025-01623-3

J Thromb Thrombolysis. 2025 Nov 27. doi: 10.1007/s11239-025-03215-x. Online ahead of print.

ABSTRACT

Several risk assessment models (RAMs) guide standardized prophylaxis to prevent venous thromboembolism (VTE) in trauma patients. The Caprini, Trauma Embolic Scoring System (TESS), and Greenfield Risk Assessment Profile (RAP) have been validated individually, but their predictive powers have not been directly compared in the general trauma population. This study evaluated the discriminatory ability of these three RAMs in trauma patients at an ACS-verified Level I Trauma Center. A retrospective review was performed of adult trauma patients in a single institution over one year. Demographic and clinical data were used to calculate Caprini, TESS, and RAP scores. The primary outcome was inpatient VTE. Logistic regression models – both combined and separate – generated receiver operating characteristic (ROC) curves for each score. Caprini served as the reference for comparing discriminatory ability. Among 1,276 patients, 33 (2.6%) developed inpatient VTE. Caprini, TESS, and RAP scores predicted VTE with odds ratios of 1.07 (95% CI 1.04-1.10), 1.39 (95% CI 1.23-1.56), and 1.20 (95% CI 1.12-1.29), respectively. ROC c-statistics were similar: Caprini 0.75 (95% CI 0.68-0.82), TESS 0.73 (95% CI 0.64-0.83), and RAP 0.70 (95% CI 0.60-0.79). Caprini, TESS, and RAP RAMs showed comparable moderate discriminatory ability (c-statistic > 0.70) in predicting inpatient VTE among trauma patients. No model was superior, suggesting any of these RAMs may guide standardized VTE prophylaxis in this population.

PMID:41307791 | DOI:10.1007/s11239-025-03215-x

Neuroinformatics. 2025 Nov 27;23(4):57. doi: 10.1007/s12021-025-09756-z.

ABSTRACT

Modelling real-world networks allows investigating the structure and the dynamics of such networks, which led to significant developments in various scientific fields. One of the most used models in these investigations is the Watts-Strogatz, with a structure composed of high clustering and short path lengths known as small-world networks. This model proposes an interesting gradient between regular and random networks, but its generating process, which relies on a single rewiring probability parameter, is hard to access and to manipulate. In order to study the mechanics of the Watts-Strogatz model, the present work proposes a new method based on deep neural networks that could estimate its probability p. To illustrate its applicability, neuroimaging and phenotypic resting-state fMRI data were used from patients with ADHD and typical development children, obtained from the ADHD-200 database. The neural network efficiently estimated the probability parameter, resulting in small-world graphs for functional brain connectivity with a mean ± s.e.m. p distribution of 0.804 ± 0.003. Despite no difference was found considering the gender or diagnosis of participants, the generalized linear model revealed age as a significant predictor of p (mean ± s.e.m.: 4.410 ± 0.877; p < 0.001), indicating a great effect of neurodevelopment on the brain network’s structure. The proposed approach is promising in estimating the probability of the Watts-Strogatz model, and its application has the potential to improve investigations of network connectivity with a relatively efficient and simple framework.

PMID:41307783 | DOI:10.1007/s12021-025-09756-z