Nevin Manimala

Dermatol Ther (Heidelb). 2025 Jul 7. doi: 10.1007/s13555-025-01468-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Therapeutic burden (TB) has been proposed as a potential predictor of treatment outcomes in both dermatological and non-dermatological diseases. This study aims to introduce the concept in the context of alopecia areata (AA) and assess its potential value in supporting therapeutic decision-making in clinical practice.

METHODS: A prospective cohort study was conducted including patients with AA who started treatment with baricitinib between January 2022 and January 2025 at a third-level hospital center. The main variable was TB, defined as the cumulative sum of previous systemic treatment cycles. An analysis was performed on whether socio-demographic or clinical factors were associated with TB.

RESULTS: Forty-four patients with AA treated with baricitinib were included. Most were women (65.90%) with a mean age of 37.70 (16.10) years. The predominant type of AA was multi-plaque (65.90%) and approximately one third (34.10%) had total/universal forms of the disease. Lower TB was statistically significantly associated with a greater reduction in Severity of Alopecia Tool (SALT) scores during the first 12 months of barictinib treatment compared with those patients with high TB (p < 0.05). This association was observed independently of all other known progression factors (duration of AA, baseline SALT, total/universal AA, female sex) (p < 0.05).

CONCLUSIONS: We present the concept of AA-adapted TB as a useful tool for categorizing patients with AA and contributing to therapeutic decision-making. Patients with AA with low TB showed a greater response to baricitinib treatment than patients who had received a greater number of systemic treatments previously.

PMID:40622665 | DOI:10.1007/s13555-025-01468-1

J Epidemiol Glob Health. 2025 Jul 7;15(1):93. doi: 10.1007/s44197-025-00433-7.

ABSTRACT

PURPOSE: Measles is a highly contagious but vaccine-preventable infectious disease. According to health authorities such as the ECDC (20240, urgent action is required to address the increasing spread of measles and insufficient vaccination coverage across the EU. The main objective of the present research is a comparative analysis of measles outbreak risk in two neighbouring countries with intensive economic relations and similar socio-economic challenges-Bulgaria and Romania. This research aims to deliver results on measles outbreak risk assessment in Bulgaria’s neighbouring countries to gain broader insight on the potential threats faced regionally and globally.

METHODS: Data from a 50-year period was collected on immunization coverage and demographic dynamics in Bulgaria and Romania. The main objective of the paper is the calculation of an annual Risk Index defined as the ratio of all susceptible individuals to the total population. A mathematical model is applied to estimate the immunization coverage and demographic parameters on an annual basis. This allows us to calculate with satisfactory precision the accumulation of susceptible persons tracing at least 20 years back in the history, needed for the calculation of an annual Risk Index.

RESULTS: The Risk Index curves for measles outbreak in Bulgaria and Romania are calculated for the period 2000 to 2023. The Risk Index curve for Bulgaria reveals a concerning increase after 2015, with particularly alarming values projected for 2017 and later. The results of the Risk Index for Romania after 2016 are also concerning. In 2023, the Risk Index for Bulgaria hits 7.55%, whereas in Romania it hits 8.1%.

CONCLUSION: Comparing the findings from the Risk Index to the real data from measles outbreaks for two neighbouring countries-with similar socio-demographic challenges-shows that the Risk Index is a good indicator for risk of measles outbreak. It can help the health authorities to forecast potential measles outbreaks – alongside vaccination coverage, demographic factors should also be considered when monitoring public health.

PMID:40622651 | DOI:10.1007/s44197-025-00433-7

Mol Biol Rep. 2025 Jul 7;52(1):676. doi: 10.1007/s11033-025-10793-9.

ABSTRACT

BACKGROUND: Indigenous cattle in India are known for their resilience to diseases, parasites, and heat stress. Belahi is a newly registered indigenous breed reared by pastoralist communities in the North Himalayan foothills (Shivalik range). It has been naturally selected for adaptability to nomadic grazing, disease resistance, and milk production. This study aimed to identify genomic selection signatures in Belahi cattle.

METHODS AND RESULTS: Genome-wide SNP data were analyzed using three intra-population statistics-Tajima’s D, Integrated Haplotype Score (iHS), and Nucleotide Diversity-which were combined into De-correlated Composite of Multiple Signals (DCMS). Additionally, Runs of Homozygosity (ROH) were used to detect regions under putative selection. DCMS identified 290 significant SNPs, while ROH revealed 8 overlapping regions. A total of 822 and 339 protein-coding genes were identified from DCMS and ROH, respectively, with 15 genes overlapping. Key genes included IL2 and IL21 (immune response) on BTA 17, and DNAJB13 (stress-related protein-folding) on BTA 15. QTL analysis revealed associations with tick resistance, susceptibility to respiratory and mycobacterial diseases, and pigmentation traits. Significant pathways included interleukin-2 receptor binding, leukocyte-mediated immunity, and peptidyl-tyrosine phosphorylation.

CONCLUSIONS: The results suggest that Belahi cattle have undergone natural selection for immunity and environmental stress tolerance due to their nomadic lifestyle. These genomic insights support the breed’s potential use in improving disease resistance and climate adaptability in cattle breeding programs.

PMID:40622616 | DOI:10.1007/s11033-025-10793-9

Cell Mol Neurobiol. 2025 Jul 7;45(1):66. doi: 10.1007/s10571-025-01583-9.

ABSTRACT

Vascular dementia (VaD) is a prevalent form of dementia caused by cerebrovascular disease, leading to cognitive impairment. While various risk factors have been identified, the role of plasma proteins in VaD etiology remains poorly understood. This study employs Mendelian randomization (MR) to investigate the causal relationship between plasma proteins and VaD risk, complemented by experimental validation. We conducted a two-sample MR analysis using summary statistics from genome-wide association studies (GWAS) on plasma proteins and VaD. Plasma protein data were derived from the deCODE Health study, encompassing 35,559 Icelandic participants and genetic associations for 4907 circulating proteins. VaD GWAS data were obtained from the FinnGen biobank, comprising 2717 VaD patients and 393,024 controls. Instrumental variables (IVs) were selected based on genome-wide significance thresholds (P < 5 × 10^-8 for plasma proteins, P < 5 × 10^-6 for VaD). The primary analysis used inverse variance weighting (IVW), supplemented by weighted median, MR-Egger, simple mode, and weighted mode methods. The Sensitivity analyses included heterogeneity tests, horizontal pleiotropy assessments, and leave-one-out analyses. Additionally, a 2-vessel occlusion (2-VO) animal model was used to validate key genes, with gene expression measured by quantitative real-time PCR (qPCR). Our initial MR analysis identified 123 plasma proteins significantly associated with VaD (P < 0.05), of which 12 maintained significance after FDR correction (FDR < 0.05). Importantly, the comprehensive pleiotropy analysis ultimately confirmed robust causal relationships for nine of these proteins with VaD. Among these, MED4 (OR = 1.819, 95% CI: 1.493-2.217, FDR < 0.001), COPS7B (OR = 1.136, 95% CI: 1.076-1.199, FDR < 0.001), CSF3 (OR = 1.262, 95% CI: 1.139-1.398, FDR < 0.001), IL26 (OR = 1.125, 95% CI: 1.066-1.186, FDR < 0.001), NRXN1 (OR = 1.125, 95% CI: 1.066-1.187, FDR < 0.001), LRRTM4 (OR = 1.418, 95% CI: 1.225-1.614, FDR < 0.001), and MAGEA3 (OR = 1.883, 95% CI: 1.403-2.529, FDR < 0.001) were identified as risk factors for VaD, with MED4 showing the strongest association. Conversely, CRYZL1 (OR = 0.387, 95% CI: 0.246-0.609, FDR < 0.001) and TMCC3 (OR = 0.327, 95% CI: 0.191-0.558, FDR < 0.001) were identified as protective factors. The Reverse MR analysis indicated no significant association between VaD and the 9 plasma proteins. In the 2-VO model, MED4 expression was significantly reduced, while NRXN1 expression was elevated compared to the sham group (P < 0.05). This study identifies several plasma proteins with a significant causal relationship with VaD, highlighting MED4 and NRXN1 as potential biomarkers and therapeutic targets. The findings were further validated in an experimental model, providing robust evidence for their roles in VaD pathogenesis. Further research is needed to elucidate the underlying mechanisms and confirm their clinical relevance.

PMID:40622612 | DOI:10.1007/s10571-025-01583-9

Clin Rheumatol. 2025 Jul 7. doi: 10.1007/s10067-025-07523-8. Online ahead of print.

ABSTRACT

BACKGROUND: Autoimmune enteropathy (AIE) and common variable immunodeficiency (CVID) can both manifest as chronic diarrhea and small intestinal villous atrophy, making their differentiation challenging.

AIMS: To explore the similarities and differences in the clinical manifestations, laboratory tests, pathological features, and long-term prognoses between these two diseases.

METHODS: This retrospective study included 26 AIE patients and 29 CVID patients with gastrointestinal (GI) involvement who were admitted to our center from June 2012 to May 2024, with all their medical records reviewed. Differences between the two diseases were evaluated via statistical tests.

RESULTS: Compared with CVID patients, AIE patients experienced a shorter duration of severe diarrhea, greater weight loss, and more severe hypoalbuminemia and electrolyte imbalances. Furthermore, CVID patients exhibited a notable history of recurrent respiratory infections; significantly lower serum levels of IgG, IgM, and IgA; a marked decrease in B-cell and CD4 + T-cell counts; and a significant inversion of the CD4 + /CD8 + ratio within peripheral blood lymphocyte subsets. Endoscopically, AIE patients are more likely to present with active inflammatory changes, such as erosions and hyperemia. On the basis of histopathological analysis of 23 AIE patients and 24 CVID patients, AIE patients presented with reduced goblet and Paneth cells, pronounced neutrophilic infiltration, and more frequent apoptotic bodies, while CVID patients demonstrated reduced plasma cells and deep crypt lymphocytosis. The diagnostic efficiency of the five pathological items in the duodenum (AUC 0.937), which includes goblet cell and Paneth cell reduction, was greater than that of the four-item combination (AUC 0.622). Long-term follow-up indicated that patients with both conditions were prone to diarrhea relapse, and CVID patients showed a slightly longer median relapse-free survival than did AIE patients.

CONCLUSIONS: Although AIE patients and CVID patients share many similarities, they exhibit significant differences. A thorough medical history, laboratory tests, and endoscopic and histopathological results provide compelling evidence for their differential diagnosis. Key Points • Both AIE and CVID with gastrointestinal involvement are immune-mediated diseases characterized by chronic diarrhea and small intestinal villi atrophy, making clinical diagnosis difficult. • AIE and CVID have different characteristics that can be used to distinguish them, especially pathological findings.

PMID:40622608 | DOI:10.1007/s10067-025-07523-8

Sleep Breath. 2025 Jul 7;29(4):233. doi: 10.1007/s11325-025-03392-2.

ABSTRACT

BACKGROUND: Sleep is essential for mental and physical health, significantly impacting overall quality of life. The Body Roundness Index (BRI) has emerged as a novel measure that captures body fat distribution more accurately than traditional indices such as BMI. Thus, aim of this study is to find the relationship between BRI and sleep quality.

METHODS: This cross-sectional study was conducted at the Nutrition and Obesity Awareness Center, Xzmat Medical City, Kurdistan Region, Iraq, from 2022 to 2024. A total of 4,813 participants aged 18-65 were recruited. BRI was calculated using standard equations incorporating height, weight, and waist circumference. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and wearable actigraphy devices. Statistical analysis was performed using SPSS version 26.0, with logistic regression models used to determine the association between BRI and sleep quality, adjusting for potential confounders.

RESULTS: Participants were categorized into BRI tertiles: T1 (< 3.19), T2 (3.20-6.01), and T3 (> 6.02). Higher BRI was associated with poorer sleep quality, shorter sleep duration, increased sleep disturbances, longer sleep latency, and greater day dysfunction due to sleepiness. Adequate sleep quality significantly decreased from 75.6% in T1 to 23.4% in T3 (p < 0.001). Logistic regression revealed that higher BRI tertiles were significantly associated with increased odds of inadequate sleep quality (OR for T3: 11.75, 95% CI: 10.13-13.60, p < 0.001) even after adjusting for confounders.

CONCLUSION: The study demonstrates a significant association between higher BRI and poorer sleep quality among Kurdish adults. These findings underscore the importance of considering body fat distribution in addressing sleep health. Public health interventions targeting weight management may also improve sleep quality and overall health in this population.

PMID:40622600 | DOI:10.1007/s11325-025-03392-2

Acta Parasitol. 2025 Jul 7;70(4):149. doi: 10.1007/s11686-025-01085-0.

ABSTRACT

PURPOSE: Paragonimiasis is a neglected tropical disease, often mistaken with common respiratory diseases, has resulted in substantial global literature. However, there is a notable lack of comprehensive literature specifically focused on paragonimiasis in Southeast Asia (SEA). To address this gap, we conducted a bibliometric assessment to provide an overview of existing literature on this disease.

METHODS: A literature search was performed in SCOPUS, with metadata analysis using the Bibliometrix package in R. Network visualization was conducted through VOSViewer 1.6.20. Additionally, country-specific socio-economic data were obtained from the World Bank and correlated with scientific productivity using Spearman’s correlation analysis, with a significant level set at p-value < 0.05.

RESULTS: This study revealed that Thailand leads in paragonimiasis research within SEA contributing the most in terms of authors, institutions, and publications, followed by Vietnam and the Philippines. Paragonimus heterotremus emerged as the most highly cited Paragonimus species in the region. Keyword co-occurrence analysis identified three key research clusters: clinical epidemiology, molecular genetics, and immunodiagnostics. The latter has gained significant attention in recent years. Among socio-economic factors, research collaborations were statistically significant in enhancing scientific productivity in paragonimiasis research across SEA.

CONCLUSION: The study underscores the importance of strengthening international collaborations to advance paragonimiasis research. It also highlights immunodiagnostics as a crucial area for future research and policy development.

PMID:40622582 | DOI:10.1007/s11686-025-01085-0

Pediatr Nephrol. 2025 Jul 7. doi: 10.1007/s00467-025-06876-1. Online ahead of print.

ABSTRACT

BACKGROUND: Prematurity has been linked to kidney dysfunction from infancy through adulthood. Children born very preterm are at particular risk due to interrupted nephrogenesis. However, early detection remains challenging, and a uniform monitoring strategy is lacking.

METHODS: This cross-sectional study involved school-aged (6-16 years) children born at ≤ 32 weeks of gestation, with no history of small for gestational age (SGA). They were further stratified by birth weight (BW): low, very low, and extremely low (LBW, VLBW, ELBW) categories. Age- and sex-matched full-term children served as controls. Anthropometry, blood pressure (BP), and kidney function were assessed, using traditional (urea; creatinine, Cr; β2-microglobulin, B2M; albuminuria) and modern biomarkers (cystatin C, CysC; symmetric dimethylarginine, SDMA). Estimated glomerular filtration rate (eGFR) based on Cr and Cr-CysC was also calculated. Statistical analysis was performed using R (version 4.3.2), with significance set at p < 0.05.

RESULTS: Eighty-one children were included: 43 preterm (77% from multiple pregnancies) and 38 controls. Compared to controls, preterm participants had higher serum cystatin C (p < 0.001) and lower Cr-CysC-eGFR (p < 0.001). They also had higher serum urea (p = 0.002), but all individual values were within the normal range. No differences were observed in BP, serum Cr, Cr-eGFR, or albuminuria. ELBW children had lower body mass index (BMI) (p = 0.048) and higher B2M (p = 0.046) than LBW peers.

CONCLUSIONS: School-aged children born very preterm may already exhibit subtle signs of kidney dysfunction, with ELBW children showing greater metabolic and renal strain. Cystatin C and Cr-CysC-eGFR appear promising biomarkers for early detection of kidney alterations in this high-risk population.

PMID:40622578 | DOI:10.1007/s00467-025-06876-1

Brain Behav. 2025 Jul;15(7):e70669. doi: 10.1002/brb3.70669.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) and depression are major global health burdens, yet their bidirectional causal relationship remains unclear.

OBJECTIVE: To explore the causal relationship between depression and TBI, and to clarify whether depression is one of the potential risk factors for TBI and whether TBI is one of the pathogenic factors for depression.

METHODS: This bidirectional two-sample Mendelian randomization (MR) analysis investigated causal relationships between depression (n = 170,756) and TBI (n = 3193) using genome-wide association study (GWAS) summary statistics. Genetic instruments were selected as single nucleotide polymorphisms (SNPs) significantly associated with exposures (depression/TBI) and outcomes (TBI/depression) at genome-wide significance (P < 5 × 10⁻⁶). The inverse variance weighted (IVW) method under fixed-effects and multiplicative random-effects models served as the primary analytical approach, with Cochran’s Q test evaluating SNP heterogeneity. To address horizontal pleiotropy, MR-Egger regression and MR-PRESSO(MR Pleiotropy RESidual Sum and Outlier)outlier correction were applied. Sensitivity analyses included weighted median, penalized weighted median, maximum likelihood estimation, and leave-one-out validation to ensure robustness. All analyses were conducted using the TwoSampleMR package in R (v4.3.2), with effect estimates reported as odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: MR analyses revealed bidirectional causal relationships between depression and TBI. In forward analyses, depression increased TBI risk across multiple IVW frameworks (fixed-effects IVW: OR = 1.137, 95% CI = 1.019-1.271, P = 0.022; multiplicative random-effects IVW: OR = 1.137, 95% CI = 1.014-1.277, P = 0.028), corroborated by maximum likelihood estimation (OR = 1.137, 95% CI = 1.017-1.274, P = 0.024). Reverse analyses demonstrated TBI’s causal effect on depression through IVW models (fixed-effects: OR = 1.083, 95% CI = 1.036-1.131, P < 0.001; multiplicative random-effects: OR = 1.083, 95% CI = 1.043-1.124,P < 0.001) and penalized weighted median methods (OR = 1.079, 95% CI = 1.018-1.145, P = 0.011). Robustness was confirmed by null heterogeneity (Cochran’s Q: forward P = 0.209, reverse P = 0.596) and absence of horizontal pleiotropy (MR-PRESSO: forward P = 0.218, reverse P = 0.672; MR-Egger intercepts: forward P = 0.661, reverse P = 0.874). All effect estimates remained stable in sensitivity analyses, supporting unconfounded causal inference.

CONCLUSION: Our MR analyses robustly demonstrate bidirectional causality: depression is a risk factor for TBI (OR = 1.137, 95% CI = 1.019-1.271), and TBI subsequently increases depression risk (OR = 1.083, 95% CI = 1.036-1.131), advocating integrated clinical monitoring.

PMID:40621715 | DOI:10.1002/brb3.70669

Med J Aust. 2025 Jul 7;223(1):46-53. doi: 10.5694/mja2.52698.

ABSTRACT

OBJECTIVES: To describe clinician-reported reasons for non-waitlisting of patients with kidney failure for deceased donor kidney transplantation, and to examine disparities affecting Aboriginal and Torres Strait Islander people.

DESIGN: Retrospective cross-sectional analysis of data from a national clinical quality registry.

PARTICIPANTS AND SETTING: Patients receiving dialysis in 26 Australian renal units as of 31 December 2020.

MAIN OUTCOME MEASURES: Rates of active waitlisting for kidney transplantation and clinician-reported reasons for non-waitlisting.

RESULTS: Thirty-six of 1832 Aboriginal and Torres Strait Islander people (2.0%) were actively waitlisted, compared with 512 of 6128 non-Indigenous people (8.4%). For Aboriginal and Torres Strait Islander patients aged < 65 years, 457 of 1204 (38%) were not waitlisted due to a permanent contraindication, 276 (23%) due to a temporary contraindication, and 232 (19%) due to incomplete work-up. Among those with a contraindication, cardiovascular disease was reported as the reason for about a quarter of people in both groups. Obesity was cited for 163 Aboriginal and Torres Strait Islander patients aged < 65 years (22%) and 30 Aboriginal and Torres Strait Islander patients aged ≥ 65 years (10%); in the non-Indigenous group, obesity was cited for 207 (26%) and 163 (9%) patients aged < 65 years and ≥ 65 years, respectively. Cancer was reported for 28 Aboriginal and Torres Strait Islander patients aged < 65 years (4%) and 86 non-Indigenous patients aged < 65 years (11%). Other reasons for non-waitlisting, reported as free text, included patient safety, smoking, age and mental health.

CONCLUSIONS: Aboriginal and Torres Strait Islander people experience inequities in waitlisting for kidney transplantation across multiple stages of a complex process. Addressing these barriers requires system-level reform and accountability to improve equity in transplantation access.

PMID:40621681 | DOI:10.5694/mja2.52698