OBJECTIVE: This study explores the relationship between CRFs, BBB integrity, and WMH burden.
DESIGN, SETTING, AND PARTICIPANTS: The study included 155 participants from the Biomarkers and Cognition Study, Singapore (BIOCIS). CRFs were assessed through blood tests for glucose and lipid profiles, and blood pressure measurements. WMH volumes were quantified using MRI.
MEASUREMENTS: BBB integrity was evaluated using a Transendothelial Electrical Resistance (TEER) assay with human brain microvascular endothelial cells (hBMEC) exposed to participant plasma.
RESULTS: Plasma from individuals with a higher WMH burden was associated with increased BBB disruption in hBMEC. Higher systolic and diastolic blood pressure, as well as body mass index, were correlated with greater BBB disruption. Regression analyses revealed that elevated blood glucose and lipid levels were linked to increased BBB disruption. Both periventricular and subcortical WMH burdens were associated with increased BBB disruption.
CONCLUSION: This study highlights a relationship between CRFs, BBB disruption, and WMH burden, suggesting that CRFs may impair BBB integrity and contribute to WMH and cognitive decline in cSVD.
METHODS: An online cross-sectional survey that assessed PA avoidance, two types of weight stigma, and PA level was completed in late 2023 by 884 Taiwanese young adults aged between 20 and 40 years (63.9% females). Multinomial logistic regression and structural equation modeling (SEM) were used to assess the associations between variables and perform the mediation analysis.
RESULTS: Cognitive behavioral symptoms and negative consequences related to gaming disorder were more common among participants with lower PA than those with moderate to high PA. Individuals at risk of gaming disorder exhibited higher level of PA avoidance, internalized weight stigma, and perceived weight stigma. The SEM found a direct association between gaming disorder and PA, which was negatively mediated by PA avoidance. However, this direct effect was not present when the association was negatively mediated by serial mediations of weight stigma and PA avoidance.
DISCUSSION AND CONCLUSIONS: Higher gaming disorder was associated with higher levels of PA, but this association may not be present when taking into account the mediation effect of weight stigma and PA avoidance. The findings suggest complex relationships and further research is needed to examine individual differences and relationships among clinical groups.
METHODS: Using Web of Science and PubMed databases, systematic reviews and meta-analyses comparing outcomes of biceps tenodesis and tenotomy were identified. Abstracts were evaluated for the nine most severe types of spin as described by Yavchitz et al. and appraised using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews). Study characteristics were extracted, including adherence to PRISMA guidelines,funding status, and impact metrics such as journal impact factor, total number of citations, and average annual citations.
RESULTS: A total of 16 studies were included, with spin detected in 81.3% of the abstracts. Type three spin was the most frequent (56.3%), followed by types six (43.8%), five (37.5%), nine (25.0%), two (12.5%), and four (6.3%). Spin types one, seven, and eight were not observed. AMSTAR 2 appraised 75% of the studies as 'low' quality, and 25% as 'critically low' quality. All studies had at least one critical flaw, with item 15 (investigation of publication bias) being the most frequent (93.8%). A strong positive correlation was found between AMSTAR 2 scores and citation counts (r = 0.821, p
OBJECTIVE: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.
METHODS: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.
RESULTS: Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.
INTERPRETATION: This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing. ANN NEUROL 2025.
METHODOLOGY: A multicenter, prospective study of consecutive adults with IBS who underwent a hydrogen breath test (HBT) (glucose, 75 g; lactose, 25 g; or fructose, 25 g) was conducted. The proportion of patients who tested positive for glucose, fructose and lactose HBT were evaluated. The symptom severity, psychology, and quality of life of subjects with SIBO were compared with those having LM and/or FM. Independent factors associated with severe IBS (IBS-symptom severity scale: IBS-SSS > 300) were explored.
RESULTS: A total of 116 subjects were included (median age 56 years, male 35.3%). Of these, 23.3% (27/116), 85.7% (24/28), and 44.4% (16/36) of them tested positive for glucose, lactose, and fructose HBT, respectively. Among those with a positive HBT (n = 65), patients with SIBO were more likely to have the diarrhea-predominant subtype of IBS (77.8% vs. 47.4%, p = 0.014). Severe IBS was associated with SIBO, compared with LM/FM (SIBO: 36.4% vs. LM: 9.1%/FM 13.3%, p = 0.016). With multivariate analysis, SIBO (OR 5.25, p = 0.028) and depression (OR 5.59, p = 0.030) were independently associated with severe IBS.
CONCLUSION: Although LM and FM commonly co-exist in IBS, their clinical relevance appears to be less significant than that of SIBO. The connection between SIBO with depression reinforces the importance of the microbiome-gut-brain axis in IBS.
METHODS: The systematic review protocol was registered on PROSPERO on July 26, 2023 (CRD42023445166). The research articles related to the immunogenicity, efficacy, or safety of malaria or TB vaccines that were published between January 1, 2012, and August 31, 2023, were searched on three databases: Web of Science (WoS), PubMed, and ClinicalTrials.gov.
RESULTS: A total of 2342 articles were obtained, 50 of which met the inclusion criteria. 28 (56%) articles reported on malaria vaccine attributes, while 22 (44%) articles reported on TB vaccines. In both cases, the major challenges in sub-Saharan African clinical trials were immunogenicity and efficacy, rather than safety.
CONCLUSION: Factors such as population characteristics, pathogen genetic diversity, vaccine nature, strategy, and formulation were associated with slow progress of the malaria and TB vaccine candidates in sub-Saharan African clinical trials.
OBJECTIVE: This study aims to review the external and internal load performed by soccer referees in high-level competitions, to identify changes in these indicators over different periods as the competition progresses, and to analyze the standards for dividing speed zones and heart rate zones.
METHODS: Web of Science, PubMed, Scopus, and EBSCOhost were thoroughly searched. Grey literature sources and Google Scholar were also consulted, with a focus on analysing and comparing the physical demands of soccer referees at different phases of high-level matches.
RESULTS: A total of 14 manuscripts were included in this review. Studies revealed that the total distance (TD) covered by referees during a full match ranged from 9 to 12 km. High-intensity running (HIR) constituted 2.0-18.7% of TD, accounting for approximately 38% of total time (TT). Referees reached 80-100% of their maximal heart rate during matches. The standards for dividing speed zones and heart rate zones varied among the selected studies.
DISCUSSION: This systematic review aimed to provide a comprehensive overview of referees' physical demands (e.g., TD, HIR, and HR) to offer practitioners valuable biological data for training and competition preparation. The lack of uniform criteria for dividing speed and heart rate zones limits data collection, thereby affecting the reporting of distances covered at different exercise intensities.