Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (433)

Search Parameters:
Keywords = cohort-based recruitment

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
13 pages, 1729 KB  
Article
Genotypic and Phenotypic Insights on 11 Novel Variants in the ABCA4 Gene
by Saoud Al-Khuzaei, Jing Yu, Suzanne Broadgate, Morag Shanks, Penny Clouston, Robert E. MacLaren, Peter Charbel Issa, Stephanie Halford, Samantha R. De Silva and Susan M. Downes
Genes 2026, 17(7), 728; https://doi.org/10.3390/genes17070728 (registering DOI) - 23 Jun 2026
Abstract
Objectives: The aim of this study was to report novel ABCA4 variants detected in a cohort of 259 patients with ABCA4 retinopathy with the intention of improving the diagnostic accuracy for ABCA4 retinopathy and expanding its genetic spectrum. Methods: We retrospectively [...] Read more.
Objectives: The aim of this study was to report novel ABCA4 variants detected in a cohort of 259 patients with ABCA4 retinopathy with the intention of improving the diagnostic accuracy for ABCA4 retinopathy and expanding its genetic spectrum. Methods: We retrospectively reviewed 259 patients with ABCA4 retinopathy, comprising 190 patients from the Oxford Cohort and 69 patients from other centres with a clinical diagnosis of ABCA4 retinopathy who were referred for genetic testing. Patients with a phenotype consistent with ABCA4 retinopathy who had a novel ABCA4 variant were included. Phenotyping in the Oxford Cohort included clinical evaluation, retinal imaging, and electrodiagnostic testing. Genetic testing was performed using next-generation sequencing (NGS) and Sanger sequencing. In silico analysis was used to investigate the pathogenicity of novel variants. Results: Eleven novel variants were detected in 12/259 patients, with one variant detected in two unrelated patients. These variants included three missense, four truncating, three splice-site variants, and one exon deletion. The variants were distributed across eight exons and three introns of ABCA4. In silico analysis and phenotype correlation supported the potential pathogenicity of the novel variants. Phenotypes ranged from mild isolated flecks with preserved retinal architecture to extensive chorioretinal degeneration. Conclusions: Despite over 2200 ABCA4 variants being reported to date, a further 11 novel ABCA4 variants were identified in 259 patients using NGS panel-based sequencing and MLPA. The variants were located across the whole ABCA4 gene, emphasising the necessity to sequence the whole gene. Our reporting of these variants expands the known genetic spectrum of ABCA4 retinopathy, contributing to accurate diagnosis in this patient group and the identification of suitable patients for recruitment to potential therapeutic interventions. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
10 pages, 549 KB  
Article
Prevalence of Filifactor alocis and Its RTX Protein-Encoding Gene, ftxA, Among Periodontitis Patients in Sweden
by Rolf Claesson, Jessica Radu, Zeinab Razooqi, Anders Johansson and Jan Oscarsson
Pathogens 2026, 15(7), 662; https://doi.org/10.3390/pathogens15070662 (registering DOI) - 23 Jun 2026
Abstract
The oral pathogen Filifactor alocis encodes a repeats-in-toxin (RTX) protein, FtxA, that is encoded by the ftxA gene; it is present in approximately 50% of known isolated strains from various infected oral sites, including periodontitis, peri-implantitis, and root canal infections. It has been [...] Read more.
The oral pathogen Filifactor alocis encodes a repeats-in-toxin (RTX) protein, FtxA, that is encoded by the ftxA gene; it is present in approximately 50% of known isolated strains from various infected oral sites, including periodontitis, peri-implantitis, and root canal infections. It has been determined from PCR assessment of periodontally diseased cohorts in Ghana and Australia. Based on current knowledge, ftxA appears to be associated with both the progress and severity of periodontitis. This finding could potentially be linked to enhanced levels of ftxA-positive F. alocis, relative to ftxA-negative strain, and/or, in addition, a synergy between ftxA-positive strains and other periodontal pathogens. The exact mechanism remains unclear but may depend on an FtxA-mediated shifting of the host cell response toward immunosuppression. The main objective of the present work was to evaluate the prevalence and loads of F. alocis and the presence of ftxA in subgingival plaque in patients recruited for periodontal treatment in Sweden. This observational study included all samples that were received from external clinics over one full year (n = 71 patients). Our findings revealed that F. alocis was carried by 49 (69%) of the individuals, with the prevalence of ftxA amounting to 42.9% (n = 21). In 32 of the 71 samples, F. alocis could be quantitatively assessed. In this sub-population of F. alocis-positive patients, high loads of the bacterium were not related to age, and high loads were more frequently observed upon carriage of ftxA. The presence of, and co-colonization with, F. alocis with four additional periodontal pathogens was also evaluated. F. alocis was notable in that it co-colonized with all of the other species. Moreover, it was detected alongside two and even three of the other species within the same sample. Full article
15 pages, 3096 KB  
Article
Hatched Late to Be Fed? Identifying the Origin of Late-Summer Pikeperch Cohorts Using Daily Otolith Increments
by Radka Symonová, Million Tesfaye, Kateřina Soukalová, Tomáš Jůza, Zuzana Sajdlová, Vladislav Draštík and Jan Kubečka
Fishes 2026, 11(6), 372; https://doi.org/10.3390/fishes11060372 (registering DOI) - 22 Jun 2026
Viewed by 146
Abstract
Effective fisheries management depends on a clear understanding of the recruitment dynamics of young-of-year (YOY) fish. Analysis of two-decade ichthyological data from Czechia and the Netherlands revealed an unexpectedly small cohort of YOY pikeperch (Sander lucioperca) in late summer. The origin [...] Read more.
Effective fisheries management depends on a clear understanding of the recruitment dynamics of young-of-year (YOY) fish. Analysis of two-decade ichthyological data from Czechia and the Netherlands revealed an unexpectedly small cohort of YOY pikeperch (Sander lucioperca) in late summer. The origin of these individuals remained speculative. Building on the long-term patterns documented in these regions, we provide a new empirical contribution by analyzing the daily otolith increments of 29 pikeperch individuals sampled in the Lipno Reservoir (Czechia) in late August 2023. The otolith-based aging revealed that the extremely small pikeperch were not more than 35 days old, indicating they hatched at the turn of July and August. Even with the uncertainty in the exact timing of the first otolith increment formation, this approach disclosed the origin of the extremely small cohort as late-hatched individuals produced by wild late-spawning pikeperch. These extremely small, delayed pikeperch coexist with their normal, earlier-spawned conspecifics, which are often already piscivorous. Although they mostly do not survive the first winter, they still contribute to the recruitment indirectly by serving as prey for conspecifics. Our results highlight the need to revise the current understanding of pikeperch spawning phenology in the temperate zone. Full article
(This article belongs to the Special Issue Application of Otoliths in Fish Ecology and Fisheries)
Show Figures

Figure 1

25 pages, 1882 KB  
Study Protocol
Translating Knowledge into Practical Guidance for Sustainable Employment Across the Life Course of Individuals with Disabilities: Study Protocol and Cohort Profile of the Work–Life Study on Spinal Cord Injury
by Urban Schwegler, Mahesh Sarki, George Austin-Cliff, Albert Marti and Martin W. G. Brinkhof
Disabilities 2026, 6(3), 54; https://doi.org/10.3390/disabilities6030054 (registering DOI) - 18 Jun 2026
Viewed by 112
Abstract
Vocational integration (VI) services aim to support sustainable employment for persons with disabilities. However, in individuals with spinal cord injury, evidence on effective intervention targets and the evaluation of sustainable integration remains limited. The Work–Life Study aims to build an evidence base for [...] Read more.
Vocational integration (VI) services aim to support sustainable employment for persons with disabilities. However, in individuals with spinal cord injury, evidence on effective intervention targets and the evaluation of sustainable integration remains limited. The Work–Life Study aims to build an evidence base for supporting sustainable employment in Switzerland by (1) identifying typical work–life trajectories; (2) examining key work–life transitions and their predictors; (3) establishing a multi-state model for intervention targets; (4) exploring individual work–life narratives; and (5) developing guidelines for personalized VI practice. The study combines a mixed methods design with a collaborative Integrated Knowledge Translation approach, actively involving VI professionals and individuals with spinal cord injury. Participants are recruited from the Swiss Spinal Cord Injury Cohort Study (SwiSCI). Work–life history data are collected through a Biographical Survey and Biographical Interviews and analyzed alongside SwiSCI data. Guideline development includes a stakeholder meeting with representatives from the Swiss Paraplegic Group, spinal cord injury clinics, individuals with spinal cord injury, employers, and disability insurers. Of 2041 eligible SwiSCI participants, 478 (23.4%) completed the Biographical Survey (median age 57.5 years; median time since injury 19.1 years), with responders and non-responders showing comparable characteristics. Work–life data closely matched existing SwiSCI data (rho > 0.8), indicating good recall. The resulting guidelines will help VI providers coordinate rehabilitation services to optimally promote sustainable employment for individuals with spinal cord injury. Full article
Show Figures

Figure 1

14 pages, 1973 KB  
Article
Trefoil Factor 3 as a Biomarker for Peripheral Artery Disease
by Ben Li, Hamzah Khan, Farah Shaikh, Abdelrahman Zamzam, Ravel Raphael, Muzammil H. Syed, Rawand Abdin and Mohammad Qadura
Biomolecules 2026, 16(6), 892; https://doi.org/10.3390/biom16060892 - 17 Jun 2026
Viewed by 202
Abstract
Background: While trefoil factor 3 (TFF3) has been linked to cardiovascular disease, its role in peripheral artery disease (PAD) remains largely unexplored. In this prospective study, we assessed three pre-selected circulating biomarkers and found that TFF3 demonstrated the strongest association with the presence [...] Read more.
Background: While trefoil factor 3 (TFF3) has been linked to cardiovascular disease, its role in peripheral artery disease (PAD) remains largely unexplored. In this prospective study, we assessed three pre-selected circulating biomarkers and found that TFF3 demonstrated the strongest association with the presence of PAD. Building on this finding, we integrated plasma TFF3 concentrations with clinical characteristics to construct predictive models aimed at identifying individuals with PAD and estimating their risk of major adverse limb events (MALE) over a two-year follow-up period. Methods: A total of 476 individuals were prospectively recruited, including 312 patients with PAD and 164 controls without PAD. At study entry, circulating concentrations of TFF3, oncostatin M (OSM), and brain-derived neurotrophic factor (BDNF) were quantified, and all participants were subsequently monitored for a two-year period. The primary endpoint was the occurrence of MALE within two years, comprising acute limb ischemia, major amputation, or lower extremity revascularization by either open surgical or endovascular approaches. PAD diagnosis served as the secondary outcome and was established by an ankle–brachial index (ABI) ≤ 0.9 or toe–brachial index (TBI) ≤ 0.67 in the presence of reduced or absent pedal pulses. For predictive model development, the cohort was randomly divided into training (70%) and testing (30%) sets. A random forest algorithm incorporating clinical variables and plasma TFF3 levels was developed and optimized using 10-fold cross-validation. Model discrimination was quantified using the area under the receiver operating characteristic curve (AUROC). For prognostic evaluation, patients were classified into low- and high-risk groups based on the optimal ROC-derived probability threshold of 0.60, and MALE-free survival between groups was assessed using Cox proportional hazards regression. Results: Among the three candidate biomarkers evaluated, only TFF3 demonstrated a significant association with PAD. Patients with PAD exhibited higher circulating TFF3 concentrations than those without PAD (7.27 ± 3.36 vs. 5.89 ± 2.67 pg/mL; p < 0.001), whereas OSM and BDNF showed no significant differences between groups. Over the two-year follow-up period, MALE occurred in 28 patients (9%). Predictive models combining plasma TFF3 measurements with clinical variables achieved strong performance for both PAD detection and 2-year MALE risk estimation, yielding AUROCs of 0.79 and 0.85, respectively. Furthermore, patients classified as high risk by the model experienced a significantly increased hazard of MALE during follow-up (HR 1.12, 95% CI 1.10–1.19; p = 0.003). Variable importance analysis revealed that TFF3 was the most influential predictor of MALE, followed by age and smoking history. Conclusions: Combining plasma TFF3 levels with readily available clinical characteristics enabled the development of a predictive model with good discriminatory ability for both PAD diagnosis and estimation of 2-year MALE risk. Such an approach may enhance risk stratification by identifying patients at elevated risk earlier in their disease course, thereby informing decisions related to vascular testing, referral for specialist evaluation, and implementation of targeted treatment strategies. Full article
(This article belongs to the Special Issue Biomolecular Sciences and Precision Medicine in Vascular Disease)
Show Figures

Figure 1

12 pages, 2607 KB  
Article
The Role of 3D/4D Transperineal Ultrasound in Risk Stratification for Pelvic Organ Prolapse Recurrence: Native Tissue Versus Mesh Repair
by José Antonio García-Mejido, María José Nuñez-Matas, Olaya Salas-Álvarez, Alejandro Crespo-Rodriguez, Ana Fernández-Palacín and José Antonio Sainz-Bueno
J. Clin. Med. 2026, 15(12), 4627; https://doi.org/10.3390/jcm15124627 - 14 Jun 2026
Viewed by 231
Abstract
Background/Objectives: Pelvic organ prolapse (POP) management requires precise patient selection for surgical techniques to balance clinical efficacy and safety. The primary aim of this study was to evaluate the role of preoperative 3D/4D transperineal ultrasound in the risk stratification of POP recurrence. [...] Read more.
Background/Objectives: Pelvic organ prolapse (POP) management requires precise patient selection for surgical techniques to balance clinical efficacy and safety. The primary aim of this study was to evaluate the role of preoperative 3D/4D transperineal ultrasound in the risk stratification of POP recurrence. We analyzed the impact of levator ani muscle (LAM) injuries, specifically avulsion and ballooning, as identified by ultrasound, on both anatomical and subjective success rates, comparing native tissue repair versus mesh-augmented surgery. Methods: A prospective, multicenter observational study was conducted over a five-year period, January 2021 to December 2024 (recruitment), with follow-up completed in December 2025, ensuring a minimum follow-up of 12 months for all participants. The cohort included 276 women scheduled for primary surgery for symptomatic POP stage ≥ 2. Prior to intervention (116 underwent native tissue repair and 160 received mesh), all patients underwent 3D/4D transperineal ultrasound for standardized volume acquisition. Using this preoperative functional imaging technique, we measured the hiatal area and diagnosed the presence of hiatal ballooning (≥25.0 cm2) or levator muscle avulsion. Results: Ultrasound assessment revealed significant differences in surgical success based on the diagnosed baseline site-specific defects. Hiatal ballooning was the sonographic finding that demonstrated the greatest impact on risk stratification. Among patients with preoperative ballooning, mesh use significantly reduced both subjective recurrence (5.7% vs. 21.4%, p = 0.001) and objective recurrence (21.4% vs. 35.7%, p = 0.040) compared to native tissue repair. Furthermore, in women without ultrasound-documented avulsion, mesh also decreased objective recurrence (17.9% vs. 33.0%, p = 0.024). Multivariate analysis, adjusted for age, BMI, menopausal status, and parity, confirmed that, after stratifying by these preoperative ultrasound findings, a native tissue approach remains the primary independent predictor of surgical failure (OR 1.752 for objective recurrence; p = 0.041). Conclusions: In conclusion, native tissue repair was identified as the primary independent predictor of surgical failure. While 3D/4D transperineal ultrasound helps identify high-risk phenotypes such as hiatal ballooning, these sonographic findings did not maintain independent significance in the multivariate model. Therefore, ultrasound should be considered a complementary tool for surgical planning rather than a definitive predictor of recurrence. Full article
Show Figures

Figure 1

22 pages, 1095 KB  
Article
Maternal Pre-Pregnancy Body Mass Index and Its Impact on Short- and Long-Chain Fatty Acid and Microbiome Profiles of Human Breast Milk in Caucasian Women of Northeast Tennessee
by Kristy L. Thomas, Amy E. Wahlquist and William Andrew Clark
Nutrients 2026, 18(12), 1917; https://doi.org/10.3390/nu18121917 - 12 Jun 2026
Viewed by 330
Abstract
Background: Increasing evidence suggests that breast milk and its bioactive components, including short-chain fatty acids and the milk microbiome, are influenced by maternal nutrition and body mass index (BMI). Bioactive components transferred to the infant through breast milk play a pivotal role [...] Read more.
Background: Increasing evidence suggests that breast milk and its bioactive components, including short-chain fatty acids and the milk microbiome, are influenced by maternal nutrition and body mass index (BMI). Bioactive components transferred to the infant through breast milk play a pivotal role in infant growth and development and have indications in the child’s future short- and long-term health outcomes. This study aimed to assess the impact of maternal pre-pregnancy BMI (PP-BMI) on human breast milk macronutrient composition, short- and long-chain fatty acid profiles, and breast milk microbiome profiles. Approach: This was an exploratory cohort study of forty-four lactating Caucasian women, two to fourteen weeks postpartum, divided into groups based on pre-pregnancy body mass index (BMI). Study participants signed informed consent, completed health and nutritional surveys, and provided a breast milk sample. Breast milk samples were subjected to proximate analysis, microbiome identification and short- and long-chain fatty acid extraction and analysis. Results: Maternal age, maternal physical activity, infant birth weight, and time of lactation at sample collection were not significantly different between the maternal PP-BMI groups. PP-BMI was significantly different between the two maternal groups. No significant differences were found between the maternal BMI groups concerning nutritional intake. No differences in breast milk microbiomes were observed in alpha diversity and beta diversity between the maternal PP-BMI groups. For long-chain fatty analysis in breast milk samples, myristic acid was significantly higher in the PP-BMI overweight/obese group while stearic acid was significantly higher in the PP-BMI normal-weight group. Butyric, valeric, and isocaproic acid concentrations in HBM were significantly higher in the PP-BMI normal-weight group and lower or undetectable in the PP-BMI overweight/obese group. Conclusions: Data from this exploratory cohort study indicate that maternal diet and pre-pregnancy BMI may be associated with differences in selected HBM fatty acids. There were no significant differences in microbiomes for alpha and beta diversity in breast milk between maternal PP-BMI groups; however, lower relative abundance was observed in the breast milk of the PP-BMI overweight/obese group. These findings should be interpreted in the context of the study’s limitations, including convenience recruitment from a Facebook group, the modest sample size, and restriction to Caucasian women from a single geographic region. Full article
Show Figures

Figure 1

10 pages, 213 KB  
Article
A Greek Case–Control Replication Study of IKZF1 rs4132601 and CDKN2A rs3731217 in Childhood Acute Lymphoblastic Leukemia
by Ioannis Kyriakidis, Spyridoula D. Katsarou, Maria I. Zervou, Nikolaos Katzilakis, Maria Stratigaki, Iordanis Pelagiadis and Eftichia Stiakaki
Genes 2026, 17(6), 682; https://doi.org/10.3390/genes17060682 - 10 Jun 2026
Viewed by 259
Abstract
Background/Objectives: Inherited variants in IKZF1 and CDKN2A/2B are among the most consistently reported germline susceptibility markers for childhood acute lymphoblastic leukemia (ALL). Nonetheless, effect sizes differ across ancestry groups, age ranges, and immunophenotypic subtypes, making well-characterized population-specific replication studies valuable for refining ancestry-specific [...] Read more.
Background/Objectives: Inherited variants in IKZF1 and CDKN2A/2B are among the most consistently reported germline susceptibility markers for childhood acute lymphoblastic leukemia (ALL). Nonetheless, effect sizes differ across ancestry groups, age ranges, and immunophenotypic subtypes, making well-characterized population-specific replication studies valuable for refining ancestry-specific evidence. This study examined two sentinel variants with historical relevance, IKZF1 rs4132601 and CDKN2A rs3731217, within a pediatric Greek cohort. Methods: A case–control study with retrospective case ascertainment and control recruitment through routine pediatric visits was conducted, comprising 50 children and adolescents with ALL and 91 healthy controls from Crete, Greece. Constitutional DNA was isolated from peripheral blood samples collected during remission in cases, while controls provided peripheral blood for targeted germline genotyping. Genotyping was performed using PCR-restriction fragment length polymorphism analysis. We evaluated Hardy–Weinberg equilibrium and genotype and allele distributions and analyzed the data using logistic regression models. Results: Control minor allele frequencies were broadly compatible with public European reference data. Neither IKZF1 rs4132601 nor CDKN2A rs3731217 showed a significant association with susceptibility to childhood ALL under either genotype-based or additive models. Results remained consistent after excluding T-cell ALL cases. Exploratory genotype-phenotype analyses did not reveal robust associations with clinical or molecular features. Conclusions: In this first Greek pediatric assessment of IKZF1 rs4132601 and CDKN2A rs3731217, no significant association with ALL susceptibility was observed. Within the constraints of limited statistical power, these negative findings provide population-specific evidence, refine regional allele-frequency and effect-size estimates, highlight the limitations of relying on single historical sentinel single-nucleotide polymorphisms (SNPs), and support future ancestry-informed and polygenic approaches in southeastern European cohorts. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Show Figures

Graphical abstract

11 pages, 508 KB  
Article
Blood-Based Epigenetic Aging Signatures in D3GHR Carriers: An Exploratory Pilot Study of Metabolic Adaptation and Aging-Related Pathways
by Ori Berger, Maayan Insler, Ghadeer Falah, Gil Ben David, Lital Sharvit, Shmuel Springer, Ran Talisman and Gil Atzmon
Int. J. Mol. Sci. 2026, 27(12), 5181; https://doi.org/10.3390/ijms27125181 - 8 Jun 2026
Viewed by 213
Abstract
The exon 3 deletion polymorphism in the growth hormone receptor gene (d3GHR) is associated with altered GH signaling and longevity-related phenotypes, yet its relationship with blood-based epigenetic aging remains unclear. We analyzed whole-blood DNA from 21 unrelated adults recruited at Laniado Medical Center [...] Read more.
The exon 3 deletion polymorphism in the growth hormone receptor gene (d3GHR) is associated with altered GH signaling and longevity-related phenotypes, yet its relationship with blood-based epigenetic aging remains unclear. We analyzed whole-blood DNA from 21 unrelated adults recruited at Laniado Medical Center to determine whether the d3GHR genotype was associated with differential DNA methylation in skin-aging-related genes and altered age acceleration across established DNA methylation clocks. Genome-wide methylation was profiled using the Infinium MethylationEPIC v2.0 array, focusing on 1098 CpG sites linked to wrinkling, pigmentation, and extracellular matrix remodeling. No significant single-CpG methylation differences were detected within the targeted panel. However, two promoter-proximal differentially methylated regions (DMRs) were identified near CYP1A1 (FWER = 0.014) and ACAT2 (FWER = 0.026). Notably, only the pan-tissue Horvath clock showed a significant genotype effect, with marked age acceleration in d3/d3 carriers (mean Δ ≈ +14.5 years, p = 0.0179) that persisted after adjustment for chronological age. In contrast, second-generation clocks such as PhenoAge showed a non-significant trend toward deceleration. These findings suggest a preliminary association between d3GHR genotype, clock-specific epigenetic age acceleration and promoter-level methylation signatures near metabolic and stress-response genes. The observed Horvath acceleration may reflect systemic metabolic or immune adaptation rather than direct structural senescence in core skin-aging gene programs in blood. Given the very small d3/d3 subgroup, these findings should be interpreted strictly as exploratory pilot observations and cannot establish reproducible genotype-specific effects without validation in larger independent cohorts. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Health and Aging-Related Diseases)
Show Figures

Figure 1

13 pages, 937 KB  
Article
Validation of Blood-Based Biomarkers After Mild Traumatic Brain Injury with GCS 15 in a Singapore Emergency Department: An Observational Study
by Win Sen Kuan, Ying Wei Yau, Desiree Xin Ying Lim, Chew Kiat Yeoh, Nicole Mun Teng Cheung, Hannah Xin Yi Lim and Mui Teng Chua
Medicina 2026, 62(6), 1095; https://doi.org/10.3390/medicina62061095 - 5 Jun 2026
Viewed by 280
Abstract
Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin [...] Read more.
Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) have emerged as possible adjuncts to head CT in evaluating mild TBI (mTBI). We aim to validate the performance of the Abbott Alinity i TBI test (UCH-L1 and GFAP) compared to head CT in an Asian cohort with mTBI and GCS 15. Materials and Methods: This prospective observational study was conducted at a tertiary academic medical center from 2 December 2024 to 19 March 2025. Patients aged 21 years and above who sustained head injury within 12 h of ED attendance had GCS of 15 and required head CT as per attending physician were eligible. Plasma was separated from whole blood within 10 min of collection and immediately stored at −20 °C. UCH-L1 and GFAP levels were analyzed in batches within 28 days of recruitment at the hospital central laboratory using the Alinity i TBI test. Results: Among 120 patients enrolled, there was predominance of males (55.8%, 67/120) and Chinese ethnicity (75.8%, 91/120). The median age was 73 (interquartile range [IQR] 56 to 79) years. Overall incidence of positive head CT was 9.2% (11/120); all 11 patients had positive Alinity i TBI tests. The sensitivity and negative predictive value of the biomarkers in our cohort were both 100% (95% confidence intervals [CIs] 71.5% to 100% and 78.2% to 100%, respectively), specificity 13.8% (95% CI 7.9% to 21.7%) and positive predictive value 10.5% (95%CI 5.4% to 18%). Exploratory post hoc analysis suggested that GFAP alone, at the prespecified assay threshold, was associated with modestly higher specificity [21.1% (95% CI 13.9% to 30.0%)] in this cohort. Conclusions: The Alinity i TBI test can safely rule out intracranial injury in patients with mTBI and GCS 15 presenting within 12 h of injury. However, specificity was low, limiting its ability to reduce head CT use in its current form. Exploratory post hoc analyses of the individual biomarkers, particularly GFAP alone, should be interpreted cautiously. Future studies should focus on optimizing specificity while maintaining a high degree of sensitivity. Full article
Show Figures

Figure 1

11 pages, 1718 KB  
Review
Current Clinical Trials to Treat Anxiety Disorders in the Elderly: A Registry-Based Review
by Gunnar P. H. Dietz and Matthias W. Riepe
Pharmaceuticals 2026, 19(6), 891; https://doi.org/10.3390/ph19060891 - 4 Jun 2026
Viewed by 318
Abstract
Background/Objectives: Anxiety disorders in people over 65 y of age are common. Treatment of those disorders is often based on studies involving much younger patients. Experience shows that those treatments are regularly ineffective in the elderly, due to differences in physiology and [...] Read more.
Background/Objectives: Anxiety disorders in people over 65 y of age are common. Treatment of those disorders is often based on studies involving much younger patients. Experience shows that those treatments are regularly ineffective in the elderly, due to differences in physiology and the disparate etiology of the disease. Here, we examine current trends in research to generate data for evidence-based approaches to treat anxiety disorders in the elderly. Our objective was to evaluate the scope, methodological characteristics, and therapeutic focus of current clinical trials for anxiety disorders in the elderly, and to determine whether the existing evidence pipeline is likely to meet the substantial unmet need for effective and well-tolerated treatments. Methods: We searched clinicaltrials.gov for studies addressing “Anxiety disorder” and related readouts and selected those studies that included patients older than 65 y, and that had anxiety measures as primary or secondary endpoints. Results: We find that over 99% of clinical “anxiety” trials exclude patients older than 65 y. Sixty-six trials fulfilled our inclusion criteria. Trials specifically recruiting the elderly are a rare exception. Unexpectedly, only 10 “anxiety” trials are sponsored by the pharmaceutical industry, despite the potential rewards in such investments. Discussion and Conclusions: Although most clinical trials are registered in clinicaltrials.gov., our work is limited by the fact that not all clinical trials carried out world-wide are included in that database. Our findings indicate that ongoing clinical research supporting evidence-based recommendations for the treatment of anxiety in the elderly is scarce. Detailed secondary analysis of clinical trial results for the efficacy and safety of anxiolytics in various age cohorts may at least be a useful instrument for hypothesis generation, to trigger additional clinical research specifically designed to address anxiety treatment in the elderly. Full article
(This article belongs to the Section Pharmacology)
Show Figures

Figure 1

13 pages, 263 KB  
Article
Evaluation of Classical and New Clinical Criteria for Diagnosing Familial Hypercholesterolemia in Childhood
by Raffaele Buganza, Giulia Massini, Cecilia Nobili, Martina Ferrandino, Maria Donata Di Taranto, Luisa de Sanctis and Ornella Guardamagna
Cardiogenetics 2026, 16(2), 12; https://doi.org/10.3390/cardiogenetics16020012 - 3 Jun 2026
Viewed by 246
Abstract
Background: Heterozygous familial hypercholesterolemia (HeFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased cardiovascular risk, making early diagnosis essential; however, the diagnostic performance of pediatric criteria is heterogeneous. This study evaluated the effectiveness of different diagnostic criteria and scoring systems to [...] Read more.
Background: Heterozygous familial hypercholesterolemia (HeFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased cardiovascular risk, making early diagnosis essential; however, the diagnostic performance of pediatric criteria is heterogeneous. This study evaluated the effectiveness of different diagnostic criteria and scoring systems to select children for genetic testing. Materials and methods: A total of 214 pediatric subjects with suspected HeFH were included, recruited from patients followed at a tertiary care center, based on LDL-C levels ≥ 95th age- and sex-specific percentile in both the proband and one biological parent. All subjects underwent genetic analysis of the main FH-associated genes (LDLR, APOB, PCSK9). The following diagnostic criteria and scoring systems were retrospectively evaluated and compared with genetic findings: Simon Broome Register (SBR), Dutch Lipid Clinic Network (DLCN), European Atherosclerosis Society (EAS), American Heart Association (AHA), Familial Hypercholesterolemia Canada Network (FH-CAN), Japanese Atherosclerosis Society (JAS), Lipid TransPort Disorders Italian Genetic Network for Italian pediatric patients (LIPIGEN-FH-PED), and the Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS). Results: Pathogenic variants were identified in 91.8% of subjects. Approaches using lower LDL-C thresholds minimized the loss of variant-positive individuals (particularly JAS and FH-PeDS, with a missed diagnoses rate of 1.6%), whereas more restrictive definitions excluded a substantial proportion of affected patients (10.5% SBR, 56.3% DLCN, 6.3% EAS, 6.3% AHA, 7.4% FH-CAN, and 6.3% LIPIGEN-FH-PED). The mutation detection rate (MDR) was >91% for all examined criteria. Conclusions: Several current diagnostic criteria may underestimate the true number of children carrying FH-associated variants. Less selective criteria enable the identification of a greater number of FH-positive individuals while maintaining a high MDR, thus supporting the prioritization of identifying as many affected children as possible in the pediatric setting. This cohort reflects a tertiary referral population rather than the general population; therefore, further studies are needed to evaluate the applicability of our findings to broader public health contexts and screening settings. Full article
(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
13 pages, 757 KB  
Article
Assessment of Adverse Events Using the Therapy–Disability–Neurology (TDN) Grading System in a Cohort of Aneurysmal Subarachnoid Hemorrhage Patients: A Single-Center Retrospective Cohort Study
by Vincens Kälin, Alexis Paul Romain Terrapon, Anna Maria Zeitlberger, Gareth Ambler, Svenja Maschke, Ahmed El-Garci, Sara Bonasia, Oliver Bozinov, Marian Christoph Neidert and Isabel Charlotte Hostettler
Brain Sci. 2026, 16(6), 599; https://doi.org/10.3390/brainsci16060599 - 31 May 2026
Viewed by 220
Abstract
Background/Objectives: Adverse events (AE) associated with neurosurgical interventions can cause neurological deficits and impaired functional outcomes. The Therapy–Disability–Neurology (TDN) grade classifies AE severity based on treatment requirements, disability, and neurological deficits, but has not been validated in aneurysmal subarachnoid hemorrhage (aSAH). We aimed [...] Read more.
Background/Objectives: Adverse events (AE) associated with neurosurgical interventions can cause neurological deficits and impaired functional outcomes. The Therapy–Disability–Neurology (TDN) grade classifies AE severity based on treatment requirements, disability, and neurological deficits, but has not been validated in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to validate the TDN grade in predicting functional outcomes and length of hospital stay (LOS) in aSAH patients, treated surgically and/or endovascularly. Methods: We conducted a single-center retrospective cohort study of a prospectively collected database of aSAH patients. Patients were recruited between 2009 and 2022. The TDN grade was retrospectively applied. Primary outcome variables were functional outcomes, assessed using the Glasgow Outcome Scale (GOS, selected for comparability with prior aSAH outcome literature), at discharge and last follow-up, and LOS. Results: We included 355 patients: mean age was 57.2 (12.9 SD) and 235 (66.1%) were female. The TDN grade showed a moderate positive correlation with length of hospital stay (rho = 0.4, p < 0.001). Negative correlations were observed with functional outcomes at discharge (GOS: rho = −0.56, p < 0.0001) and at last follow-up (GOS: rho = −0.58, p < 0.0001). The TDN grade demonstrated good discrimination for unfavorable outcome at last follow-up (AUC = 0.82) and good discrimination for employment status (AUC = 0.71). Patients with AEs stayed 7.63 days longer on average (p < 0.001). Conclusions: The TDN grade predicted hospital stay and functional outcomes in aSAH patients treated surgically and/or endovascularly, demonstrating good discrimination for unfavorable outcomes and employment status. These findings extend the grade’s applicability to both treatment- and disease-related complications and support its potential utility as a standardized tool for prognostication and resource planning. Results should be interpreted in light of the single-center retrospective design and selection bias. Full article
Show Figures

Figure 1

16 pages, 1319 KB  
Article
Assessing Cognitive Deterioration After COVID-19 Infection (The ACDC Study): An Exploratory Multimodal Neuroimaging Study
by Jonathan McLaughlin and Gordon Waiter
J. Clin. Med. 2026, 15(11), 4241; https://doi.org/10.3390/jcm15114241 - 30 May 2026
Viewed by 211
Abstract
Background: Cognitive difficulties are common after SARS-CoV-2 infection, yet their neurobiological underpinnings remain uncertain. Cognitive symptoms in post-COVID-19 condition (PCC) are often characterised by attentional and executive dysfunction, although the relationship between subjective symptoms and objective neurobiological changes remains uncertain. Methods: Adults previously [...] Read more.
Background: Cognitive difficulties are common after SARS-CoV-2 infection, yet their neurobiological underpinnings remain uncertain. Cognitive symptoms in post-COVID-19 condition (PCC) are often characterised by attentional and executive dysfunction, although the relationship between subjective symptoms and objective neurobiological changes remains uncertain. Methods: Adults previously hospitalised with COVID-19 who reported persistent cognitive symptoms underwent neuropsychological testing and 3 T MRI. The protocol included high-resolution volumetric imaging, diffusion-based tractography, and magnetic resonance spectroscopy (MRS) of frontal white matter. Data were compared with age- and sex-matched controls from a pre-COVID-19 cohort and against pooled normative MRS datasets. Analyses adjusted for intracranial volume, sex, and time since infection, with false-discovery-rate correction. This study was exploratory and hypothesis-generating in design. Results: Thirty participants were recruited; twenty-nine completed MRI acquisition. Participants (mean age 58 years; 62% female; approximately two years post-infection) demonstrated selective impairments in attention, working memory, and verbal fluency. No widespread volumetric or white-matter differences were identified, although reduced posterior hypothalamic volume and altered occipito-parietal connectivity were observed. MRS demonstrated reduced N-acetylaspartate and elevated choline, myo-inositol, and glutamate-glutamine ratios relative to normative reference ranges. No significant associations were observed between imaging measures and cognitive or symptoms outcomes after correction. Conclusions: PCC is characterised by circumscribed cognitive changes and subtle neural differences, but these objective changes do not closely align with subjective symptom severity. This mismatch shares phenotypic features with functional cognitive disorder and suggests that post-COVID-19 “brain fog” is not driven by structural or neurochemical changes alone. Instead, it potentially reflects a combination of mild neurobiological effects and functional cognitive processes. Together, these findings highlight the importance of considering both brain-based and functional contributors to persistent cognitive complaints after SARS-CoV-2 infection. Full article
(This article belongs to the Section Clinical Neurology)
Show Figures

Figure 1

13 pages, 239 KB  
Article
Association Between Dipstick Hematuria and Elevated Albuminuria in a Hospital-Based Population with Diverse Chronic Conditions
by Cheewaporn Tanintheerakul, Rungnapa Peerakam, Pharisa Nanthawong, Suwatsin Kittikunnathum and Piyawan Bunpo
Diagnostics 2026, 16(11), 1678; https://doi.org/10.3390/diagnostics16111678 - 29 May 2026
Viewed by 214
Abstract
Background/Objective: Albuminuria is an early marker of kidney damage and cardiovascular risk. However, data on its prevalence and association with urine dipstick parameters in heterogeneous, hospital-based populations remain limited. The objective of this study was to determine the prevalence of elevated albuminuria [...] Read more.
Background/Objective: Albuminuria is an early marker of kidney damage and cardiovascular risk. However, data on its prevalence and association with urine dipstick parameters in heterogeneous, hospital-based populations remain limited. The objective of this study was to determine the prevalence of elevated albuminuria measured by the urine albumin-to-creatinine ratio (UACR) in a diverse patient population and evaluate associations with semi-quantitative urine dipstick parameters. Methods: This cross-sectional study included 393 adults recruited from a tertiary-care hospital setting, comprising individuals undergoing clinical evaluation and routine health assessments. Given the hospital-based recruitment and enrichment with chronic conditions, the study population represents a high-risk cohort rather than the general population. Spot urine samples were analyzed for the UACR and dipstick parameters. Elevated albuminuria was defined as a UACR ≥ 30 mg/g. Associations were assessed using chi-square tests and multivariate logistic regression, with adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Elevated albuminuria was observed in 64% of participants. This high prevalence likely reflects the underlying clinical characteristics of the study population, including a substantial burden of chronic kidney disease and other comorbidities, and should not be interpreted as representative of population-level prevalence. Chronic kidney disease was independently associated with elevated albuminuria (aOR 3.14, 95% CI 1.12–8.86, p = 0.030), as was male sex (aOR 1.54, 95% CI 1.01–2.34, p = 0.045). Dipstick-positive blood was significantly associated with elevated albuminuria (85% vs. 60% in those without dipstick blood positivity, p = 0.005). Dipstick albumin strongly correlated with the UACR (p < 0.001), although 22% of individuals with negative dipstick albumin still had an elevated UACR. Other urine dipstick parameters were not significantly associated with elevated albuminuria. Conclusions: In this high-risk, hospital-based cohort, elevated albuminuria was common and associated with kidney disease and male sex. Dipstick blood positivity is significantly associated with albuminuria and may warrant further investigation. However, reliance on dipstick testing alone may underestimate disease burden, supporting the need for broader implementation of UACR-based screening strategies. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
Show Figures

Graphical abstract

Back to TopTop