Balkan Medical Journal最新文献

Background: The fetal liver is perfused by the umbilical vein (UV) and the main portal vein (MPV), both of which are crucial for nutrient delivery. The configuration of the umbilicoportal anastomosis may influence MPV blood flow and potentially affect fetal liver perfusion in fetuses with fetal growth restriction (FGR).

Aims: To evaluate absolute and normalized UV and MPV blood flows in fetuses with normal growth and FGR, and to investigate the effect of umbilicoportal anastomosis type on MPV flow.

Study design: This prospective case-control study included 108 appropriate-for-gestational-age (AGA) fetuses and 43 FGR fetuses between 18 and 37 weeks of gestation, evaluated over nine months.

Methods: Ultrasound was used to measure UV and MPV diameters, while Doppler ultrasound assessed time-averaged maximum velocities. Flow volumes were calculated as time-averaged maximum velocity volume and normalized to estimated fetal weight (TAMXVVN) and abdominal circumference. Anastomoses were categorized as T-, X-, or H-shaped. Z-scores were derived from AGA nomograms.

Results: Compared with AGA fetuses, FGR fetuses exhibited significantly smaller UV diameters, lower absolute UV flow, UV-TAMXVVN, and UVTAMXVV/ AC (p < 0.05), but higher MPV-TAMXVVN (p < 0.05), suggesting compensatory redistribution. Both UV and MPV flows showed strong correlations with gestational age (r > 0.7, p < 0.001). UV-TAMXVVN Z-scores decreased with gestation, whereas MPV-TAMXVVN Z-scores increased until 32 weeks before plateauing. Blood flow parameters did not differ significantly across anastomosis types in either group.

Conclusion: FGR fetuses demonstrate reduced UV perfusion with compensatory increases in MPV flow. The type of umbilicoportal anastomosis does not significantly affect MPV blood flow.

Background: Hyperuricemia and gout are common metabolic disorders that show substantial disparities in prevalence and management across different socioeconomic status.

Aims: To investigate the association between social determinants of health (SDOH) and mortality risk in adults with hyperuricemia and/or gout, to assess whether the interaction between SDOH and gout/hyperuricemia status influences mortality risk.

Study design: A retrospective cohort study.

Methods: We analyzed 6,560 United States (US) adults (mean age 58 years, 60.02% men) with hyperuricemia and/or gout from the 1999-2018 National Health and Nutrition Examination Survey. The primary study outcomes were all-cause and cardiovascular mortality. A control group of 6,560 adults without hyperuricemia or gout was measured using propensity-score matching based on age, sex, and race. SDOH was measured using a composite score (range 0-8) created from eight socioeconomic indicators: education, employment, food security, family income-to-poverty ratio, marital status, health insurance coverage, insurance type, and home ownership.

Results: Over a median follow-up of 101 months, 1,335 (14.76%) deaths occurred among participants with hyperuricemia and/or gout, including 496 (5.33%) cardiovascular deaths. Relative to adults with hyperuricemia and/or gout who had an SDOH score of 7-8, the hazard ratios (95% confidence intervals) for those with SDOH scores of 5-6, 3-4, and ≤ 2 were 1.48 (1.21-1.81), 1.85 (1.49-2.28), and 2.38 (1.82-3.11), respectively, for all-cause mortality, and 1.62 (1.16-2.25), 1.65 (1.18-2.31), and 2.10 (1.24-3.54), respectively, for cardiovascular mortality. Restricted cubic spline analyses demonstrated an inverse relationship between SDOH and both mortality outcomes. Subgroup analysis indicated that the association between SDOH and mortality risk was stronger among participants younger than 60 years. Interaction analyses showed that hyperuricemia/gout status did not significantly modify the association between SDOH and mortality.

Conclusion: Cumulative social disadvantage, indicated by a lower SDOH score, independently predicted higher mortality risk in US adults with hyperuricemia and/or gout, with the most pronounced effects observed in individuals under 60 years. Notably, the unfavorable cardiovascular effects associated with SDOH appeared more evident in adults without hyperuricemia or gout than in those with these conditions.

Background: Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in KMT2A. Although several large international cohorts have helped define its broad clinical spectrum, data from underrepresented populations remain limited.

Aims: To characterize the molecular and phenotypic spectrum of Turkish patients with WDSTS and compare these findings with previously published cohorts.

Study design: Multicenter retrospective cohort study.

Methods: Sixteen individuals from 15 unrelated families were recruited across Türkiye. Clinical information was obtained through medical records and systematic phenotyping. Molecular analyses included next-generation sequencing or targeted variant testing, and the variants were classified according to the American College of Medical Genetics and Genomics guidelines.

Results: Fifteen distinct KMT2A variants were identified, including nine novel alleles. Most variants were predicted to result in loss of function; only one was a missense substitution. Neurodevelopmental involvement was prominent, with developmental and speech delays, intellectual disability, and behavioral comorbidities such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Endocrine evaluation revealed growth hormone deficiency in approximately half of the tested patients. Ophthalmologic, cardiac, and dental abnormalities, including delayed tooth eruption, further expanded the known phenotype. Additional systemic features included skeletal, genitourinary, and immunological findings. Comparison with previously reported cohorts displayed no statistically significant genotype-phenotype correlations, although truncating variants appeared to be associated with more pronounced neurodevelopmental and behavioral manifestations.

Conclusion: This report presents the largest Turkish WDSTS cohort to date, expands the known KMT2A variant spectrum with nine novel alleles, and highlights several underreported clinical features. Beyond its immediate clinical relevance, the study further supports KMT2A as a key chromatin regulator and an "umbrella gene" within the chromatinopathy spectrum. Growing recognition of these disorders underscores the need for systematic, multidisciplinary surveillance and contributes to the expanding global understanding of their shared pathogenic mechanisms.

Background: Carotid atherosclerosis (CAS) is a key cause of ischemic stroke that is strongly associated with increased risks of cardiovascular disease and vascular death, hence the urgent need to develop therapeutic strategies targeting carotid atherosclerotic plaques that would reduce the overall risk of cerebrovascular events.

Aims: This study performs single-cell sequencing to dissect the cellular subpopulations in CAS. Molecular docking is used to uncover the potential therapeutic targets, consequently providing a theoretical basis for the CAS treatment strategies.

Study design: Integrated single-cell, spatial transcriptomic and molecular docking analysis.

Methods: The single-cell sequencing data were retrieved from the Gene Expression Omnibus. Enrichment analyses were performed to characterize the cellular subpopulation functions. Accordingly, cell-cell communication networks were mapped to uncover the inter-subgroup interactions. Molecular docking was also employed to identify the potential therapeutic targets.

Results: In this study, we identified the multiple cellular subpopulations that are associated with CAS. These CAS-related subpopulations engage in intercellular communication via distinct signaling pathways. Cannabidiol exhibits strong binding affinities for the macrophage, endothelial, and vascular smooth muscle cell markers. Spatial transcriptomics revealed that ACTC1, AKR1C2, and FABP4 exhibit region-specific expression patterns within the plaque.

Conclusion: Dissecting the diverse cellular subpopulations in CAS and elucidating their functions and mechanisms, this study integrates single-cell sequencing, molecular docking, and spatial transcriptomics to offer fresh insights into CAS therapy.