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17 pages, 882 KB  
Article
Vigorous Physical Activity Mitigates Susceptibility to Obesity Associated with Risk Genotypes of FTO and MC4R, and SREBF1 Is Hypermethylated: A Cross-Sectional Pilot Study
by Jenni Chambers, Mary Erazo Bastidas, Clare M. P. Roscoe, Corinna Chidley, Aaisha Makkar and Aparna Duggirala
Epigenomes 2026, 10(2), 42; https://doi.org/10.3390/epigenomes10020042 (registering DOI) - 21 Jun 2026
Abstract
Aim: The aim of this study was to correlate single-nucleotide polymorphisms (SNPs) in the FTO and MC4R genes with body composition (BC) in populations with various levels of physical activity, and to investigate associations of SREBF1 methylation with the level of physical activity [...] Read more.
Aim: The aim of this study was to correlate single-nucleotide polymorphisms (SNPs) in the FTO and MC4R genes with body composition (BC) in populations with various levels of physical activity, and to investigate associations of SREBF1 methylation with the level of physical activity (PA) and BC. Methods: Fifty-six participants aged 18–65 years old with no underlying medical conditions were included in the study and were classified into sedentary/light PA (SLPA), moderate PA (MPA) and vigorous PA (VPA) groups using the International PA questionnaire (IPAQ). Anthropometric measures such as age, gender, body mass index (BMI) and body fat percentage (BFP) were recorded at the time of recruitment. Venous blood samples were collected during participant recruitment and DNA was extracted. Genotyping assays were performed for SNPs in FTO (rs9939609) and MC4R (rs17782313) using Taqman® RT qPCR and TaqMan Genotyper software 1.7.1. Methylation analysis assay for CpG sites in the SREBF1 gene was performed on 56 samples using PyroMark® Q48 Autoprep (Qiagen,Venlo, Netherlands). The results were statistically analysed to identify any associations between FTO/MC4R genotypes and the level of PA, and between SREBF1 methylation status and the level of PA. This is the first study to investigate links between PA and quantitative methylation of SREBF1. Results: According to IPAQ guidance, the 56 participants were classified into SLPA n = 14, MPA n = 11 and VPA n = 31. The correlation analysis revealed that the FTO rs9939609 ‘A’ risk allele had a significant negative association with BFP in the VPA group (p = 0.0387); the MC4R rs17782313 ‘C’ risk allele had a significant positive association with BMI in the VPA group (p = 0.0256). In the SREBF1 pyrosequencing analysis, higher levels of methylation were observed in the VPA group (p = 0.07). Conclusions: We concluded that SNPs associated with obesity identified in FTO rs9939609 and MC4R rs17782313 could help to predict the molecular effects of PA. A high frequency of FTO risk variants in the cohort was observed and the VPA group could help maintain a healthy BFP. Full article
(This article belongs to the Special Issue Epigenetic Signatures in Metabolic Health and Cancer)
42 pages, 603 KB  
Review
A Healthy Lifestyle Can Slow Immune System Aging and Reduce Age-Related Chronic Inflammation: A Narrative Review
by Marta Cąkała-Jakimowicz, Anna Domaszewska-Szostek and Monika Puzianowska-Kuźnicka
Int. J. Mol. Sci. 2026, 27(12), 5605; https://doi.org/10.3390/ijms27125605 (registering DOI) - 21 Jun 2026
Abstract
Age-related decline in immune system function is characterized by reduced numbers of naïve lymphocytes, the accumulation of senescent cells, impaired function of all immune cell types, and chronic low-grade inflammation (inflammaging). These alterations contribute to increased susceptibility to infections and malignancies, as well [...] Read more.
Age-related decline in immune system function is characterized by reduced numbers of naïve lymphocytes, the accumulation of senescent cells, impaired function of all immune cell types, and chronic low-grade inflammation (inflammaging). These alterations contribute to increased susceptibility to infections and malignancies, as well as to autoimmunity and other age-associated diseases. This article reviews current evidence on lifestyle interventions that may mitigate immune aging. Lifestyle-related strategies, including regular physical activity, nutritional interventions (e.g., different diets, caloric restriction, and other fasting-related approaches), stress reduction, and vaccination, are discussed as key modulators of immune function and systemic inflammation. Notably, vitamin D supplementation has been shown to reduce the incidence of autoimmune diseases by 22%. In comparison, caloric restriction has led to a decrease in CRP and TNF-α by 40% and 50%, respectively. Emerging complementary approaches, such as mind–body practices and controlled cold exposure, show promise, though current evidence remains limited and inconsistent. Therefore, integrated lifestyle strategies may slow aging-related immune decline and support healthy aging. However, longitudinal trials are required to define the optimal intervention parameters, population-specific thresholds, and the long-term durability of immune rejuvenation. Full article
(This article belongs to the Special Issue Understanding Aging in Health and Disease)
17 pages, 9183 KB  
Review
Reframing Telomere Biology in Exercise Science: From Descriptive Metrics to Redox–Metabolic Mechanisms for Precision Healthy Aging (2000–2025)
by Kun-Ho Lee, Kwon-Jae Song and Yun-A Shin
Biomedicines 2026, 14(6), 1396; https://doi.org/10.3390/biomedicines14061396 (registering DOI) - 21 Jun 2026
Abstract
Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains [...] Read more.
Background/Objectives: Telomeres are critical biomarkers of biological aging, with shortened leukocyte telomere length strongly linked to all-cause mortality and age-related disease risk. Although exercise modulates telomere dynamics, the field’s evolution from descriptive measurements to mechanistic inquiries involving redox biology and epigenetics remains incompletely mapped. This study systematically characterized the global research landscape of telomere–exercise science over 25 years to establish a strategic evidence base for precision exercise prescription. Methods: A bibliometric analysis was conducted on 858 publications from the Web of Science Core Collection (2000–2025). CiteSpace and VOSviewer were used for keyword co-occurrence analysis, strategic thematic mapping, and citation burst detection to visualize global research trends and identify emerging frontiers. Results: Annual publication volume grew from 2 (2000) to 71 (2025), with a compound annual growth rate of 15.4%. China emerged as one of the leading global contributors. Thematic analysis revealed a paradigm shift from descriptive leukocyte telomere length studies toward mechanistic investigations of oxidative stress, mitochondrial homeostasis, and epigenetic clocks. Keyword network analysis confirmed oxidative stress and inflammation as central hubs, mediating telomere protection via redox regulation and non-canonical telomerase functions. Conclusions: Exercise preserves telomere integrity primarily through redox–mitochondrial homeostasis, hormesis-driven antioxidant upregulation, and non-canonical telomerase activation. For aging populations and individuals at metabolic risk, aerobic training and high-intensity interval training (HIIT) are recommended as first-line non-pharmacological interventions for healthspan extension. Leukocyte telomere length and telomerase activity should be integrated as biomarkers in preventive medicine practice. Future large-scale randomized controlled trials incorporating multi-omics approaches and sex-stratified analyses are warranted to establish individualized dose–response guidelines for precision exercise prescription. Full article
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15 pages, 2632 KB  
Article
Vitamin D Status and Atherogenic Lipid Profiles, Including Lipoprotein(a), in Elite Athletes
by Vincent Groesser, Astrid Most, Jamschid Sedighi, Priyanka Böttger, Samuel Sossalla and Pascal Bauer
Nutrients 2026, 18(12), 2013; https://doi.org/10.3390/nu18122013 (registering DOI) - 21 Jun 2026
Abstract
Background/Objectives: Vitamin D has been implicated in lipid metabolism, but data regarding its association with atherogenic lipoproteins in elite athletes remain limited. Elite athletes represent a unique research model to investigate these associations with reduced confounding from obesity, chronic disease, smoking, and physical [...] Read more.
Background/Objectives: Vitamin D has been implicated in lipid metabolism, but data regarding its association with atherogenic lipoproteins in elite athletes remain limited. Elite athletes represent a unique research model to investigate these associations with reduced confounding from obesity, chronic disease, smoking, and physical inactivity. Methods: This cross-sectional study included 773 male professional athletes from mixed sports disciplines (mean age 25.5 ± 5.0 years). Serum 25-hydroxyvitamin D [25(OH)D] concentrations and lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and lipoprotein(a) [Lp(a)], were assessed. Associations were analyzed using correlation analyses, subgroup comparisons according to predefined 25(OH)D categories (<30, 30–50, and >50 ng/mL), and multivariable linear regression models adjusted for age, body mass index, season, and training-related variables. Results: Higher serum 25(OH)D concentrations were independently associated with lower LDL-C (p = 0.028), triglyceride (p = 0.002), and Lp(a) concentrations (p = 0.036), whereas no independent association was observed with HDL-C (p = 0.559). Athletes with 25(OH)D concentrations ≥30 ng/mL demonstrated lower LDL-C, triglyceride, and Lp(a) levels compared with athletes below this threshold (all p < 0.05). Higher vitamin D status was additionally associated with greater peak exercise performance (4.29 ± 1.15 vs. 3.36 ± 0.68 W/kg; p < 0.001). Conclusions: Higher 25(OH)D concentrations were independently associated with a more favorable lipid profile in elite athletes, including lower LDL-C, triglyceride, and Lp(a) concentrations. Prospective studies are warranted to further investigate the relationship between vitamin D status and lipid metabolism in athletic populations. Full article
(This article belongs to the Special Issue Advanced Nutritional Strategies for Cardio-Renal-Metabolic Health)
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16 pages, 845 KB  
Article
Association Between Triglyceride/High-Density Lipoprotein Ratio and Premature Coronary Artery Disease in Young Saudi Population: A Case–Control Study
by Thamir Al-khlaiwi, Ayman Alsaleh, Hessah Alshammari, Sara Abou Al-Saud, Manan Alhakbany, Abdulmalik Alqahtani, Aliah Alshanwani, Sarah Mazi and Muhammad Iqbal
Diagnostics 2026, 16(12), 1922; https://doi.org/10.3390/diagnostics16121922 (registering DOI) - 21 Jun 2026
Abstract
Background/Objectives: Limited research has evaluated the association between the triglyceride-to-high-density lipoprotein (TG/HDL) ratio and premature coronary artery disease (PCAD), particularly in Saudi Arabia. Therefore, this study aimed to investigate the association of the TG/HDL ratio with PCAD and to assess its sensitivity [...] Read more.
Background/Objectives: Limited research has evaluated the association between the triglyceride-to-high-density lipoprotein (TG/HDL) ratio and premature coronary artery disease (PCAD), particularly in Saudi Arabia. Therefore, this study aimed to investigate the association of the TG/HDL ratio with PCAD and to assess its sensitivity and specificity in a young Saudi population. Methods: This comparative retrospective case–control study utilized data collected from patients’ electronic medical records at King Saud University Medical City (KSUMC) between 2015 and 2023. The vessel score and Gensini score were used to evaluate the severity of coronary occlusion. The study population was divided into two groups: (1) a healthy control group consisting of blood bank donors, selected to exclude individuals with chronic diseases such as metabolic disorders and hypertension, with no evidence of coronary artery disease and aged ≤50 years (as confirmed by a cardiologist to rule out cardiovascular disease); and (2) patients with PCAD, aged ≤51 years, who underwent selective coronary angiography using the standard hospital procedure (right femoral artery approach). Coronary angiographic images were evaluated using right and left oblique views with cranial and caudal angulations. Results: A total of 898 subjects were included in the study, comprising 440 healthy controls and 458 patients with PCAD. Higher HbA1c levels were significantly associated with PCAD (adjusted OR = 13.03, 95% CI [7.32, 23.18], p < 0.001). Importantly, the TG/HDL ratio, the primary biomarker of interest, remained significantly associated with PCAD after full adjustment. Each unit increase in the TG/HDL ratio was associated with more than a threefold increase in the odds of PCAD (adjusted OR = 3.39, 95% CI [2.22, 5.16], p < 0.001), independent of age, sex, BMI, HbA1c, smoking, and total cholesterol levels. Among females, the TG/HDL ratio demonstrated an area under the curve (AUC) of 0.796, with an optimal cut-off value of 0.91, yielding 77.8% sensitivity and 71.4% specificity. Among males, the TG/HDL ratio yielded an AUC of 0.786, with a higher optimal cut-off value of 1.09 providing 73.4% sensitivity and 65.4% specificity. Conclusions: Our study indicates that the TG/HDL ratio and HbA1c are significantly associated with PCAD in young Saudi male and female populations, demonstrating good sensitivity and specificity. Females exhibited a lower cut-off value than males. Smoking and elevated cholesterol levels were also identified as prominent risk factors. However, the TG/HDL ratio did not distinguish between moderate and severe coronary stenosis, as assessed by the Gensini score. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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33 pages, 2359 KB  
Review
Snappers Reproductive Biology: An Ecological and Aquacultural Approach
by Josué López-Cardiel, Eduardo Ramírez-Ayala, Juan Manuel Martínez-Brown, Adrián Tintos-Gómez and Leonardo Ibarra-Castro
Fishes 2026, 11(6), 366; https://doi.org/10.3390/fishes11060366 (registering DOI) - 20 Jun 2026
Abstract
Reproductive biology is fundamental for understanding fish population dynamics and for guiding fisheries management and aquaculture practices. Key reproductive and fishery-related variables such as catch size, age at maturity, spawning season, aggregation behavior, and the implementation of seasonal closures are critical to ensuring [...] Read more.
Reproductive biology is fundamental for understanding fish population dynamics and for guiding fisheries management and aquaculture practices. Key reproductive and fishery-related variables such as catch size, age at maturity, spawning season, aggregation behavior, and the implementation of seasonal closures are critical to ensuring fish population sustainability. Snappers have been targeted for commercial aquaculture development due to their plasticity and ability to adapt to captive conditions. In Mexico, reproductive biology information on snappers remains fragmented and largely species-specific along both Pacific and Gulf coasts. This review reveals a lack of integrated perspective on snappers’ reproductive biology and identifies key knowledge gaps that may limit the development of effective conservation measures and aquaculture strategies. The absence of species-specific regulations for many snapper species along the Mexican Pacific coast reflects limited biological information and restricts the development of effective management policies. Increasing catch rates may indicate overexploitation, highlighting the need for targeted research to address existing information gaps and support effective conservation strategies for snapper populations. This review synthesizes available information on snapper reproductive biology and discusses how these traits can inform broodstock management, spawning control, and seed production in snappers from the Mexican coastal regions. Full article
(This article belongs to the Section Biology and Ecology)
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17 pages, 1410 KB  
Article
Preoperative OCT Biomarkers as Predictors of Postoperative Functional Outcome Assessed by Microperimetry After Inverted ILM Flap Surgery
by Ovidiu Samoilă, Anca Mădălina Sere, Lăcrămioara Samoilă and Daniel-Corneliu Leucuța
Diagnostics 2026, 16(12), 1919; https://doi.org/10.3390/diagnostics16121919 (registering DOI) - 20 Jun 2026
Abstract
Background/Objectives: A macular hole represents a significant surgical condition in an increasingly aging population. Advances in surgical techniques, particularly pars plana vitrectomy with inverted internal limiting membrane (ILM) flap, have established high anatomical closure rates exceeding 90%. The prognostic factors influencing visual [...] Read more.
Background/Objectives: A macular hole represents a significant surgical condition in an increasingly aging population. Advances in surgical techniques, particularly pars plana vitrectomy with inverted internal limiting membrane (ILM) flap, have established high anatomical closure rates exceeding 90%. The prognostic factors influencing visual recovery remain incompletely understood, and it is unclear which patients can be expected to achieve optimal functional outcomes. Methods: This retrospective longitudinal study included 35 eyes of 32 patients followed for 3–12 months. Preoperative OCT parameters (minimum linear diameter, basal diameter, and hole height) and derived indices were correlated with functional outcomes, including best-corrected visual acuity (BCVA) and microperimetry, stratified as central macular sensitivity (CMS) and sensitivity at 4° and 20°. Postoperative ellipsoid zone (EZ) and external limiting membrane (ELM) integrity were also analyzed. Predictive performance was assessed using root mean square error (RMSE) and coefficient of determination (R2). A linear regression model based on BCVA served as baseline, while Extreme Gradient Boosting (XGBoost) models incorporating OCT features were developed. Feature importance was evaluated using Shapley Additive Explanations (SHAP). Results: Overall closure rate was 100%, including 91.4% Type 1 and 8.6% Type 2 closure. Models incorporating OCT parameters outperformed BCVA-based models (lower RMSE, and higher R2). Minimum linear diameter and hole height were the strongest predictors of postoperative outcomes. Microperimetry detected functional improvement beyond BCVA and correlated with EZ and ELM restoration. Conclusions: Preoperative macular hole morphology represents a key determinant of postoperative functional recovery. These structural parameters provide meaningful prognostic value beyond visual acuity alone, supporting the role of combined OCT and microperimetric assessment in predicting surgical outcomes. Full article
(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, 4th Edition)
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19 pages, 1712 KB  
Article
Public Knowledge, Attitudes, and Perceptions of Antimicrobial Resistance in Brazil: Insights from a Nationwide Online Survey
by Victória Ribeiro Silvestre, Gustavo Guimarães Fernandes Viana, Isha Agrawal, Andréia Gonçalves Arruda, Gabriel Augusto Marques Rossi, Carlo Spanu, Fábio Sossai Possebon and Juliano Gonçalves Pereira
Antibiotics 2026, 15(6), 624; https://doi.org/10.3390/antibiotics15060624 (registering DOI) - 20 Jun 2026
Abstract
Background: Antimicrobial resistance (AMR) poses an escalating threat to global health, agriculture, and the environment, demanding urgent multisectoral action under the One Health framework. Despite global awareness efforts, understanding of AMR among the general population remains insufficient, particularly in low- and middle-income countries [...] Read more.
Background: Antimicrobial resistance (AMR) poses an escalating threat to global health, agriculture, and the environment, demanding urgent multisectoral action under the One Health framework. Despite global awareness efforts, understanding of AMR among the general population remains insufficient, particularly in low- and middle-income countries such as Brazil. This study aimed to evaluate the knowledge, attitudes, and perceptions (KAP) of the Brazilian population regarding AMR. Methods: An online questionnaire was distributed through social media platforms between April and August 2025, resulting in 945 valid responses after data cleaning. Quasi-Poisson models were applied to identify demographic predictors of KAP scores while logistic regression models were used to assess the association between KAP scores and antibiotic use-related practices. Results: Education level was the strongest predictor of higher KAP scores, whereas age and gender showed inconsistent influence. Only 40.3% of respondents correctly identified antibiotics among commonly used medicines, and 25.9% reported proper disposal of antibiotic packaging. More than half (54.2%) were willing to pay more for antibiotic-free products, although only 26.7% had ever noticed such labeling. Network analysis of open-ended responses indicated that concerns about potential health risks and AMR awareness were the primary motivators for purchasing antibiotic-free products. Conclusions: These findings reveal significant gaps in public understanding of antibiotic use and resistance in Brazil, emphasizing the urgent need for targeted educational initiatives, improved public communication, and behavioral interventions to support antimicrobial stewardship and sustainable antibiotic use. Full article
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23 pages, 2929 KB  
Article
Examining Sex Differences Across the Lifespan on the Mobile Half-Version of the Connors Continuous Performance Test
by Spenser Barry, Jordan Price, Chris Beasley and Len Lecci
Sexes 2026, 7(2), 31; https://doi.org/10.3390/sexes7020031 (registering DOI) - 20 Jun 2026
Abstract
Concussions exert a massive cost on our economic and healthcare systems. Many of the most commonly employed neurocognitive measures in concussion assessment have been shown to be psychometrically problematic. Additionally, norms are established from largely male populations. The present study investigates the use [...] Read more.
Concussions exert a massive cost on our economic and healthcare systems. Many of the most commonly employed neurocognitive measures in concussion assessment have been shown to be psychometrically problematic. Additionally, norms are established from largely male populations. The present study investigates the use of a validated and reliable measure of concussion sequelae, the mobile half-version of the Connors Continuous Performance Test 3rd Edition (CCPT-3), on a representative population to study the influence of sex and age on normative values collected at baseline. Baseline data were analyzed from 71,976 participants across a wide range of academic and athletic contexts, as well as healthcare settings. Multiple regressions examined the influence of sex as a function of age in different developmental groups: children, adolescents, young adults, adults, and older adults. Sex effects emerged during childhood, peaked during adolescence, and decreased in adulthood. Females showed better accuracy (fewer commission and omission errors), whereas males had faster response speeds (hit-rate RT). Effect sizes were generally in the small to very small range (sex effect sizes ranged from Cohen’s d = 0.02 to 0.39). The findings highlight the importance of accounting for sex and age in cognitive test performance and underscore the impact of correcting for even small effects when working with large samples. Full article
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22 pages, 4552 KB  
Article
Exploratory Ecology of Reintroduced Elk in Virginia
by Braiden A. Quinlan, Heather N. Abernathy, David M. Kalb, Jacalyn P. Rosenberger, Emily D. Thorne, William Mark Ford and Michael J. Cherry
Animals 2026, 16(12), 1917; https://doi.org/10.3390/ani16121917 (registering DOI) - 20 Jun 2026
Abstract
Reintroductions of extirpated species are an important tool in wildlife conservation. Understanding how reintroduced populations acclimatize to novel environments can lend insight into social learning that in turn is valuable for assessing reintroduction success and maximizing efficacy of subsequent efforts. During 2012, 2013, [...] Read more.
Reintroductions of extirpated species are an important tool in wildlife conservation. Understanding how reintroduced populations acclimatize to novel environments can lend insight into social learning that in turn is valuable for assessing reintroduction success and maximizing efficacy of subsequent efforts. During 2012, 2013, and 2014, the Virginia Department of Wildlife Resources implemented soft releases of elk (Cervus canadensis) translocated to southwestern Virginia from eastern Kentucky. We investigated home range establishment and post-release movements of these reintroduced elk (n = 60). We found adults moved farther from the release site than either yearlings or calves (F = 6.93, p = 0.001). Elk released in 2012 and 2013 took similar amounts of time to establish home ranges (median 181 days, range 108–214 days; and median 189 days, range 147–209 days, respectively), but individuals released in 2013 remained closer to the release site (x¯ = 605.5 m, SD = 335.7 m, closer) presumably by joining established social groups. However, the 2014 cohort generally took longer to establish home ranges (median: 231 days; range: 56–258 days) and moved farthest from the release site (x¯ = 1360.2 m, SD = 293.9 m, farther than 2012 individuals) possibly due to the larger cohort size and resulting intraspecific competition, or the earlier release date that year. Our findings suggest the number of consecutively released cohorts, the timing of the release, and the composition of age classes for released individuals are important considerations for reintroductions. Full article
(This article belongs to the Special Issue Strategies for Monitoring and Managing Wild Ungulate Populations)
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16 pages, 973 KB  
Article
Efficacy and Tolerability of Pazopanib in Elderly Patients with Advanced Soft Tissue Sarcoma: A Multicentre Real-World Study from Turkey
by Mehmet Mutlu Kidi, Harun Muğlu, Mustafa Karaağaç, Sinan Koca, Oguz Kara, Ahmet Bilici and Ertugrul Bayram
J. Clin. Med. 2026, 15(12), 4803; https://doi.org/10.3390/jcm15124803 (registering DOI) - 20 Jun 2026
Abstract
Background: Soft tissue sarcomas (STS) disproportionately affect older adults, yet patients aged ≥65 years remain markedly underrepresented in pivotal trials, limiting evidence on pazopanib in this population. We aimed to characterise the real-world efficacy and safety of pazopanib in elderly patients with [...] Read more.
Background: Soft tissue sarcomas (STS) disproportionately affect older adults, yet patients aged ≥65 years remain markedly underrepresented in pivotal trials, limiting evidence on pazopanib in this population. We aimed to characterise the real-world efficacy and safety of pazopanib in elderly patients with advanced STS. Methods: This multicentre retrospective cohort study included consecutive patients aged ≥65 years with locally advanced unresectable or metastatic STS who received pazopanib between July 2010 and June 2022 at four tertiary Turkish oncology centres. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS) and the safety profile. Results: A total of 109 patients (median age, 70 years; 50.5% female; 48.6% with Eastern Cooperative Oncology Group [ECOG] performance status ≥ 2) were analysed. The objective response rate was 11.0% (95% CI, 5.8–18.4), and the disease control rate was 45.9%. Median PFS was 4.11 months (95% CI, 3.25–4.47), and median OS was 7.85 months (95% CI, 6.91–9.00) over a median follow-up of 17.6 months. PFS showed a borderline difference across age tertiles (log-rank p = 0.078), whereas a marked monotonic OS gradient was observed (9.00, 7.86, and 5.71 months for ages 65–69, 70–74, and ≥75 years, respectively; p < 0.001). In age-stratified multivariable Cox analysis, ECOG ≥ 2 (adjusted hazard ratio [aHR], 1.68; 95% CI, 1.01–2.80; p = 0.045) and female sex (aHR, 1.66; 95% CI, 1.02–2.72; p = 0.043) were independently associated with shorter OS. Grade ≥ 3 treatment-emergent adverse events occurred in 27.5% of patients, most commonly hypertension. Because only the single most clinically prominent treatment-emergent adverse event per patient was recorded, these figures represent a conservative, non-cumulative estimate of toxicity. No treatment-related deaths occurred. Conclusions: Pazopanib retains clinically meaningful activity in unselected patients aged ≥65 years with advanced STS. Performance status, rather than chronological age, is the dominant predictor of overall survival and should guide treatment decisions in this population. Full article
(This article belongs to the Special Issue Sarcoma—Clinical Updates: 2nd Edition)
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26 pages, 1339 KB  
Article
Data-Informed and Accessibility-Oriented Motion Graphics for Depression-Related Health Communication in Aging Populations
by Cong Mo, Khachakrit Liamthaisong and Jantima Polpinij
Healthcare 2026, 14(12), 1785; https://doi.org/10.3390/healthcare14121785 (registering DOI) - 20 Jun 2026
Abstract
Background/Objectives: Short-form motion graphics are increasingly used in digital health communication. However, limited research has examined their accessibility, interaction quality, and usability for older adults. This study explores the design and evaluation of short-form motion graphics as human–computer interaction systems for depression-related [...] Read more.
Background/Objectives: Short-form motion graphics are increasingly used in digital health communication. However, limited research has examined their accessibility, interaction quality, and usability for older adults. This study explores the design and evaluation of short-form motion graphics as human–computer interaction systems for depression-related health communication in aging populations. Methods: A data-informed and human-centered approach was adopted, integrating clustering-based analysis, expert evaluation, and user-based assessment. Short-form motion graphics videos and user-generated comments were analyzed to identify design-related themes associated with accessible digital health communication. These insights informed the development of motion graphics prototypes. The evaluation involved independent expert groups and 200 older adult participants. Cognitive load and usability were assessed using a structured questionnaire. Results: The clustering analysis showed moderate cluster separation and provided an exploratory source of design insights. Expert evaluation highlighted the importance of visual clarity, structured content organization, and appropriate motion pacing. User evaluation yielded a mean usability score of 3.95 and a mean cognitive load score of 3.72, indicating generally positive perceptions of the developed motion graphics among participants. Conclusions: The findings suggest that combining data-informed analysis, expert review, and user evaluation may be useful for designing and assessing digital health communication systems for older adults. As this study was exploratory and did not include a control group, the findings should be interpreted within the context of the study and should not be considered evidence of causal relationships. Full article
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17 pages, 2322 KB  
Article
Polypharmacy and Drug Interaction Risk in Children and Adolescents with Congenital Heart Defects: Insights from a Nationwide Survey
by Kim Sarah Fritz, Paul C. Helm, Dominik Tobias, Janina Semmler, Jannos Siaplaouras, Christian Apitz and Constanze Pfitzer
J. Clin. Med. 2026, 15(12), 4802; https://doi.org/10.3390/jcm15124802 (registering DOI) - 20 Jun 2026
Abstract
Background: Congenital heart defects (CHD) are the most common congenital malformations and often require complex, lifelong pharmacotherapy. In pediatric CHD populations, multidrug regimens targeting cardiac function and comorbidities predispose patients to polypharmacy. At the molecular level, concomitant drug use increases the risk [...] Read more.
Background: Congenital heart defects (CHD) are the most common congenital malformations and often require complex, lifelong pharmacotherapy. In pediatric CHD populations, multidrug regimens targeting cardiac function and comorbidities predispose patients to polypharmacy. At the molecular level, concomitant drug use increases the risk of pharmacokinetic and pharmacodynamic interactions. Methods: This study aimed to characterize medication patterns and assess polypharmacy and potential drug–drug interactions in patients with CHD. A cross-sectional online survey was conducted in collaboration with the German National Register for Congenital Heart Defects (NRCHD) between November and December 2021. Patients aged 6–17 years with CHD were eligible for inclusion. Participants reported their current medications in open-ended questions. Drugs were categorized into pharmacological classes, and common drug combinations were evaluated for potential interactions. Results: Of 894 participants included in the analysis, 372 reported current medication use. Among these, 179 (48.1%) met criteria for polypharmacy (≥2 drugs). Polypharmacy was more frequent in patients with higher disease severity and comorbidity burden. Several drug combinations showed potential for clinically relevant pharmacokinetic and pharmacodynamic interactions, including mechanisms involving renal electrolyte handling, altered protein binding, cytochrome P450-mediated metabolism, and additive pharmacodynamic effects. Conclusions: Children with CHD are exposed to complex multidrug regimens with a considerable interaction risk, underscoring the need for systematic medication review and mechanistically informed pharmacological management in pediatric CHD care. Full article
(This article belongs to the Section Cardiology)
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17 pages, 1522 KB  
Article
Endothelial Dysfunction and Early Renal Injury Biomarkers in Hypertensive Patients After COVID-19
by Gulomjon Kholov, Nilufar Akhmedova, Ulugbek Ochilov, Gulruh Khayrullayeva and Otabek Yuldashev
COVID 2026, 6(6), 106; https://doi.org/10.3390/covid6060106 (registering DOI) - 20 Jun 2026
Abstract
Background: Endothelial dysfunction and renal injury are emerging as a common feature of long COVID, especially in those with hypertension. It is not yet well characterised whether SARS-CoV-2 infection exacerbates podocyte dysfunction, fibrotic signalling and renal hemodynamic remodelling, over and above the effects [...] Read more.
Background: Endothelial dysfunction and renal injury are emerging as a common feature of long COVID, especially in those with hypertension. It is not yet well characterised whether SARS-CoV-2 infection exacerbates podocyte dysfunction, fibrotic signalling and renal hemodynamic remodelling, over and above the effects of hypertension alone and there are no reliable early biomarkers in this population. Methods: We conducted a comparative cross-sectional study with prospective 6-month treatment response follow-up in 120 adult patients (aged 30–60 years) with essential hypertension (Stage I, II or III; n = 40 per stage), at Bukhara Regional Multidisciplinary Hospital. Each stage subgroup was further divided into post-COVID (3–6 months after recovery; n = 20) and non-COVID (n = 20) strata. Patients with diabetes, known chronic kidney disease, previous myocardial infarction or stroke and other major comorbidities were excluded. Serum cystatin-C, creatinine, aldosterone, TGF-β1 and VEGF-A; urinary nephrin and microalbumin; cystatin-C-derived eGFR (CKD-EPI) and oral protein-loaded renal functional reserve (RFR); and renal Doppler indices (Vps, Ved, RI, PI) of the main, segmental and interlobar arteries were assessed before and after 6 months of guideline-based renin–angiotensin–aldosterone system (RAAS) blockade (enalapril 5–10 mg or azilsartan 40–80 mg, ±eplerenone). Comparisons were made by Student’s t-test—associations by Pearson correlation. Results: At baseline, post-COVID hypertensive patients exhibited consistently higher endothelial–podocyte injury markers than non-COVID counterparts. Urinary nephrin was elevated across all stages (Stage I: 126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01; Stage III: 203.3 ± 11.2 vs. 164.5 ± 9.7 pg/mL, p < 0.05), as were VEGF-A (Stage III: 286.1 ± 16.4 vs. 223.2 ± 12.6 pg/mL, p < 0.01) and TGF-β1 (Stage III: 186.4 ± 10.1 pg/mL, 1.3-fold higher; p < 0.01). The detection of microalbuminuria was 100% in Stage III post-COVID patients and 85% in non-COVID controls. The post-COVID groups had selective loss of renal functional reserve (7.8 ± 1.1% in Stage III compared to 12.5 ± 1.6% in non-COVID controls, p < 0.001). Nephrinuria correlated strongly with RFR (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001) and aldosterone (r = 0.613, p < 0.001). Six months of RAAS blockade reduced nephrinuria, microalbuminuria and TGF-β1 in both arms but the magnitude of biomarker reduction appeared smaller in the post-COVID group, particularly in Stage III. Conclusions: Long COVID appears to be associated with persistent endothelial dysfunction and podocyte injury in hypertensive patients. These results indicate that nephrinuria, VEGF-A, TGF-β1 and renal functional reserve are potential exploratory markers of endothelial and renal abnormalities in hypertensive patients following COVID-19. Before clinical utility can be determined, larger studies with multivariable modelling, diagnostic-performance analyses and correction for multiple testing are needed. The differences in biomarker response between groups observed in this study need to be confirmed in larger prospective studies with multivariable modelling and formal interaction analyses. Full article
(This article belongs to the Special Issue Endothelial Dysfunction in Long COVID)
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14 pages, 531 KB  
Article
Association of Triglyceride-Glucose Index with Negative Clinical Outcomes in Geriatric Patients with Chronic Heart Failure
by Li Tian, Xuan Qiu, Qiqi Cheng, Jun Shen and Suqing Wang
J. Clin. Med. 2026, 15(12), 4794; https://doi.org/10.3390/jcm15124794 (registering DOI) - 20 Jun 2026
Abstract
Objectives: To determine the prognostic value of the triglyceride-glucose (TyG) index, which serves as a surrogate for insulin resistance, for heart failure rehospitalization and all-cause mortality in older adults with chronic heart failure, and to evaluate its clinical utility in risk stratification [...] Read more.
Objectives: To determine the prognostic value of the triglyceride-glucose (TyG) index, which serves as a surrogate for insulin resistance, for heart failure rehospitalization and all-cause mortality in older adults with chronic heart failure, and to evaluate its clinical utility in risk stratification and nursing care. Methods: In this single-center retrospective cohort study, 786 patients aged ≥65 years with chronic heart failure hospitalized at a tertiary referral hospital in Central China (January 2022–January 2025) were included and divided into low vs. high TyG index groups based on the median. Baseline data were extracted from medical records. Follow-up ended in December 2025. Associations between TyG index and adverse outcomes were examined using Kaplan–Meier curves, restricted cubic spline (RCS) regression, and multivariable Cox proportional hazards models. Results: The median TyG index was 8.35. In unadjusted analyses, the high-TyG group had significantly greater cumulative risks of heart failure rehospitalization (p < 0.001) and all-cause mortality (p = 0.028). After multivariable adjustment, the TyG index remained independently associated with heart failure rehospitalization (hazard ratio [HR]= 1.63), whereas its association with all-cause mortality was attenuated and no longer significant. Restricted cubic spline analysis revealed a nonlinear dose–response relationship between the TyG index and heart failure rehospitalization, and a linear relationship with all-cause mortality. Conclusions: In elderly patients with chronic heart failure, the TyG index independently predicted heart failure rehospitalization and demonstrated a nonlinear dose–response relationship; its independent association with all-cause mortality was not significant after full adjustment. The index may nonetheless aid in risk stratification and individualized nursing in this population. Full article
(This article belongs to the Section Geriatric Medicine)
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