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14 pages, 724 KB  
Article
Effects of a Single Oral Dose of Imepitoin on Veterinary Visit-Related Stress in Cats: An Open-Label Pilot Study
by Umut Burak Agan, Estelle Descout and Yucel Meral
Vet. Sci. 2026, 13(5), 431; https://doi.org/10.3390/vetsci13050431 (registering DOI) - 28 Apr 2026
Abstract
Stress associated with veterinary visits represents a significant concern for cats, as well as a primary challenge for both caregivers and veterinary practitioners. Based on previous in vitro and in vivo studies on imepitoin, this pilot study was conducted to explore its potential [...] Read more.
Stress associated with veterinary visits represents a significant concern for cats, as well as a primary challenge for both caregivers and veterinary practitioners. Based on previous in vitro and in vivo studies on imepitoin, this pilot study was conducted to explore its potential as an alternative treatment for stress associated with veterinary visits in cats. Cats were randomly allocated to receive imepitoin (n = 16) or placebo (n = 16) and were then evaluated using pre- and post-treatment physiological parameters, including heart rate (HR), respiratory rate (RR), rectal temperature (RT), salivary cortisol and behavioural scores derived from the cat stress score (CSS) and cat examination response scale (CERS). Despite higher baseline HR in the imepitoin group, a greater reduction in HR from pre- to post-treatment was observed compared to placebo. RR decreased, and RT slightly increased over time, regardless of treatment. A differential pre–post change in cortisol was observed between groups, with a significant decrease in the imepitoin group. Behavioural scores demonstrated improvement in the imepitoin-treated group; however, observer bias inherent in the open-label design, together with the use of a single investigator for both treatment administration and outcome assessment, limits the interpretability of the behavioural findings. These exploratory observations suggest a potential role for imepitoin in mitigating clinic-associated stress in cats; however, confirmation in larger, well-controlled, blinded, and methodologically robust studies is required before any clinical application can be considered. Full article
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19 pages, 1360 KB  
Systematic Review
The Effects of Carnosine on Cognitive Function and Mental Health—A Systematic Review and Meta-Analysis
by Yung-Fang Hsiao, Zhongqi Fan, Yueh-Yin Fan and Mei Chung
Nutrients 2026, 18(9), 1385; https://doi.org/10.3390/nu18091385 (registering DOI) - 28 Apr 2026
Abstract
Introduction: Previous research has shown that L-carnosine (β-alanyl-L-histidine) can reduce cognitive decline and improve mental health outcomes, but an updated systematic review of the effects of carnosine alone or in combination with other supplemental nutrients or bioactive compounds on these interconnected outcomes is [...] Read more.
Introduction: Previous research has shown that L-carnosine (β-alanyl-L-histidine) can reduce cognitive decline and improve mental health outcomes, but an updated systematic review of the effects of carnosine alone or in combination with other supplemental nutrients or bioactive compounds on these interconnected outcomes is lacking. Methods: We searched multiple databases from 1 January 2006 to 30 June 2025 for clinical trials evaluating the effects of all forms of carnosine (e.g., L-carnosine, zinc–L-carnosine) alone or in combination with other supplements on cognition, brain structure and function, mood, depression, or quality of life (QOL) outcomes. The Cochrane Risk of Bias (ROB) 2.0 tool was used to assess the ROB in randomized controlled trials (RCTs). When data were sufficient, random-effects meta-analyses were conducted. Strength of evidence (SoE) across studies was rated using the GRADE approach. Results: A total of 13 distinct studies (12 RCTs; 1 single-arm trial) involving healthy adults and patients with psychiatric or neurocognitive disorders were included. Studies were also heterogeneous in carnosine supplement dosage and duration. Overall 58% of included RCTs were rated ‘some concerns’ for ROB. Ten RCTs evaluated cognitive function, seven RCTs and one single-arm trial assessed mood and depression, four RCTs measured QOL, and three RCTs examined brain structure and function. Results from five RCTs found no significant differences in the majority of the cognitive function measures between L-carnosine supplement and placebo, but random-effects meta-analysis of three RCTs from a single research team found that anserine/L-carnosine supplementation significantly improved WMS-LM2 scores (pooled net change = 1.70; 95% CI 0.19, 3.2; I2 = 58.3%) but not WMS–Local Memory Immediate Recall (LM1) scores (pooled net change = 0.76; 95% CI −0.18, 1.71; I2 = 8.5%). Additionally, meta-analysis results showed that L-carnosine combined with anserine or antioxidant supplementation significantly improved the MMSE score compared to placebo (pooled net change = 0.62; 95% CI 0.23, 1.01), with small statistical heterogeneity (I2 = 21.3%). Most of the studies did not show significant effects in a wide range of mood and depression outcome measures or health-related QOL (data cannot be meta-analyzed). Conclusions: A low strength of evidence suggests that L-carnosine supplement combined with anserine or antioxidants can slow cognitive function decline among healthy elderly or patients with probable Alzheimer’s Disease or mild neurocognitive disorder. More high-quality RCTs are needed to verify these findings and to improve the certainty level of this body of evidence. Full article
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14 pages, 234 KB  
Article
Anatomical and Patient-Reported Outcomes After Non-Ablative Er:YAG Laser Therapy for Genitourinary Syndrome of Menopause: A Prospective Real-World Cohort Study
by Stephanie Kauffmann, Montserrat Girabent Farrés, Cristina Naranjo Ortiz, Laia Blanco-Ratto, Manuel Del Campo Rodríguez and Inés Ramírez-García
Healthcare 2026, 14(9), 1180; https://doi.org/10.3390/healthcare14091180 (registering DOI) - 28 Apr 2026
Abstract
Background/Objectives: This exploratory single-arm study evaluated the effects of non-ablative Erbium-doped Yttrium Aluminum Garnet (Er:YAG) laser therapy in a real-world healthcare setting. Methods: A prospective pre–post study was conducted in 47 postmenopausal women who received two sessions of non-ablative Er:YAG vaginal [...] Read more.
Background/Objectives: This exploratory single-arm study evaluated the effects of non-ablative Erbium-doped Yttrium Aluminum Garnet (Er:YAG) laser therapy in a real-world healthcare setting. Methods: A prospective pre–post study was conducted in 47 postmenopausal women who received two sessions of non-ablative Er:YAG vaginal laser therapy (IncontiLase®®/IntimaLase®®). Assessments were performed at baseline and two follow-ups (FSFI, ICIQ-SF, I-QOL, and Oxford Scale). Wilcoxon signed-rank tests and Spearman correlations were used. Results: Vaginal hiatus was significantly reduced from 2.5 cm (IQR 2.0–3.0) to 2.0 cm (IQR 1.0–3.0) (p < 0.001). Vaginal length showed a small, non-significant increase, and pelvic floor strength was unchanged. Total FSFI scores remained stable; pain showed a non-significant upward trend, and arousal decreased transiently. ICIQ-SF scores did not significantly improve, although they correlated inversely with vulvar energy at second follow-up (r = −0.424; p = 0.016). I-QOL domains showed short-term improvements in social embarrassment (p = 0.002), psychosocial impact (p = 0.002), and behavioral limitations (p = 0.013) at first follow-up. Cystocele stage improved at second follow-up (p = 0.013). Conclusions: Non-ablative Er:YAG vaginal laser therapy was associated with reduced vaginal hiatus and produced short-term improvements in select quality-of-life domains and cystocele stage, while effects on sexual function and urinary symptoms were limited. Findings remain exploratory and inform the design of future controlled studies evaluating innovative outpatient care models for GSM. Given the absence of a control group and short follow-up, these findings should be interpreted as hypothesis-generating and may be influenced by placebo or expectation effects. Full article
2 pages, 335 KB  
Correction
Correction: Mahdi et al. Melatonin Supplementation Enhances Next-Day High-Intensity Exercise Performance and Recovery in Trained Males: A Placebo-Controlled Crossover Study. Sports 2025, 13, 190
by Nourhène Mahdi, Slaheddine Delleli, Arwa Jebabli, Khouloud Ben Maaoui, Juan Del Coso, Hamdi Chtourou, Luca Paolo Ardigò and Ibrahim Ouergui
Sports 2026, 14(5), 176; https://doi.org/10.3390/sports14050176 (registering DOI) - 28 Apr 2026
Abstract
In the published paper [...] Full article
(This article belongs to the Special Issue Current Research in Applied Sports Nutrition)
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10 pages, 221 KB  
Article
Magnetic Resonance Imaging Systematically Differs from Histology in Quantifying Macrovesicular Liver Steatosis in Individuals with Morbid Obesity: A Prospective Paired MRI–Histology Study in Bariatric Surgery
by Sergio Carandina, Viola Zulian, Eric Fontas and Antonio Iannelli
Diagnostics 2026, 16(9), 1312; https://doi.org/10.3390/diagnostics16091312 - 27 Apr 2026
Abstract
Background: Liver histology remains the gold standard for assessing liver steatosis (LS); however, non-invasive methods are increasingly being explored in clinical practice. This study aimed to evaluate the agreement between magnetic resonance imaging (MRI) and liver histology in quantifying LS in patients [...] Read more.
Background: Liver histology remains the gold standard for assessing liver steatosis (LS); however, non-invasive methods are increasingly being explored in clinical practice. This study aimed to evaluate the agreement between magnetic resonance imaging (MRI) and liver histology in quantifying LS in patients with morbid obesity undergoing bariatric surgery (BS). Methods: This ancillary study is part of a prospective, double-blind, multicenter, randomized placebo-controlled trial investigating the effects of preoperative omega-3 polyunsaturated fatty acid supplementation on liver volume in morbidly obese patients undergoing BS. The parent trial yielded negative results, and randomization arm was retained as a covariate in all analyses. Patients underwent MRI within 2 days before surgery, followed by intraoperative wedge resection and TruCore needle liver biopsy. Agreement between MRI and histology was assessed using the intraclass correlation coefficient (ICC) and Cohen’s kappa coefficient (K) for both macro- and microvesicular steatosis. Results: Thirty-seven patients were enrolled; paired MRI and biopsy data were available for thirty-one (83.8%). Moderate and statistically significant agreement was observed between MRI and both TruCore (ICC: 0.52, p = 0.002; K: 0.42, p = 0.007) and wedge-resection (ICC: 0.53, p = 0.001; K: 0.29, p = 0.044) biopsies for macrovesicular steatosis. The MRI-derived values were systematically lower than histological estimates for macrovesicular steatosis (mean MRI: 23.4% vs. histology: 36.7–37.1%). No significant agreement was identified for microvesicular steatosis with either biopsy technique. Conclusions: In morbidly obese patients, MRI demonstrates only moderate agreement with liver histology for macrovesicular steatosis and is unreliable for microvesicular steatosis. The systematic underestimation of macrovesicular steatosis by MRI warrants caution when this modality is used as a standalone decision-making tool in this population. Further studies in larger and more heterogeneous cohorts are needed to better define the performance boundaries of MRI-derived fat-fraction measurement across the spectrum of obesity and metabolic liver disease. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
20 pages, 1000 KB  
Article
Effect of Multi-Antioxidant Supplement on Lipid Profile, Occupational Fatigue, Work Stress, and Hair Cortisol in Administrative Workers with and Without Obesity: A Quasi-Experimental Pilot Study
by María del Carmen López-García, Gabriel Lara-Hernández, Hamlet Avilés-Arnaut, Virginia Sánchez-Monroy, Eduardo Nateras-Molina, Ernesto Fragoso-Paniagua, Ericka Flores-Berrios and Elvia Pérez-Soto
Healthcare 2026, 14(9), 1166; https://doi.org/10.3390/healthcare14091166 - 27 Apr 2026
Abstract
Background/Objectives: Work stress (WS), occupational fatigue (OF), and Burnout syndrome (BS) among administrative workers are associated with negative psychosocial and metabolic effects. Although antioxidant-rich nutritional strategies have been proposed to help manage stress, evidence from real-world occupational settings is still limited. This [...] Read more.
Background/Objectives: Work stress (WS), occupational fatigue (OF), and Burnout syndrome (BS) among administrative workers are associated with negative psychosocial and metabolic effects. Although antioxidant-rich nutritional strategies have been proposed to help manage stress, evidence from real-world occupational settings is still limited. This study evaluated the total antioxidant capacity (TAC) of a multi-antioxidant dietary supplement 2.0 (DS2.0; apple polyphenols, [APP], astaxanthin [AXT], and fucoxanthin [FXT]; 387:12:1 ratio) and explored its association with metabolic parameters, OF, psychosocial outcomes, and hair cortisol concentration (HCC) in administrative workers with and without obesity. Methods: A quasi-experimental pilot study was conducted among 22 workers, who received DS2.0 (52.13 mg/day, n = 17) or a placebo (n = 5) for 30 days. TAC was analytically assessed using standardized assays. Metabolic outcomes (lipid profile, fasting plasma glucose), psychosocial variables (SOFI-SM, CESQT/SBI, and IMSS tests), and HCC (competitive immunoassay) were evaluated before and after supplementation. Statistical analyses included within-group pre–post comparisons, independent-sample tests, and effect size estimation. Results: DS2.0 demonstrated high TAC. Supplementation was associated with reductions in total lipids, total cholesterol, and non-HDL cholesterol, as well as decreases in OF, BS, and WS scores. HCC decreased in the overall sample (217.19 vs. 31.64 pg/mg; p = 0.000) and among workers with obesity (276.80 vs. 34.13 pg/mg; p = 0.002). Stress-related symptoms, including sleep deprivation, exhaustion, appetite changes, difficulty waking, and palpitations, also improved (p ≤ 0.05). Conclusions: An antioxidant-rich DS2.0 supplement may be associated with psychosocial and stress-related biomarkers; however, these exploratory findings require confirmation in larger randomized controlled trials. Trial registration: ISRCTN 12762846. Full article
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22 pages, 3260 KB  
Article
Comparative Clinical Evaluation of Chamomile, Sage, and Ginger Mouthwashes in Reducing Plaque and Gingival Inflammation
by Ioana Elena Lile, Anda Olivia Jesamine Samoilă, Carolina Cojocariu, Gianina Tapalagă, Neli-Kinga Oláh, Otilia Lavinia Stana, Adelina Berari and Diana Marian
Antibiotics 2026, 15(5), 433; https://doi.org/10.3390/antibiotics15050433 (registering DOI) - 27 Apr 2026
Abstract
Background: Despite mechanical hygiene, plaque-related illnesses like gingivitis and periodontitis affect over 3.5 billion people globally. Natural mouthwashes are becoming increasingly popular as consumers shift toward plant-based alternatives to chlorhexidine, which may have drawbacks that limit long-term acceptability. This study aimed to evaluate [...] Read more.
Background: Despite mechanical hygiene, plaque-related illnesses like gingivitis and periodontitis affect over 3.5 billion people globally. Natural mouthwashes are becoming increasingly popular as consumers shift toward plant-based alternatives to chlorhexidine, which may have drawbacks that limit long-term acceptability. This study aimed to evaluate the short-term clinical potential of three herbal mouthwashes—Matricaria chamomilla (chamomile), Salvia officinalis (sage), and Zingiber officinale (ginger)—in reducing dental plaque and clinical signs of gingival inflammation in young adults. (2) Materials and Methods. A randomised controlled clinical trial was conducted on 175 systemically healthy participants, allocated equally into five groups (three herbal groups, placebo, and chlorhexidine). Each herbal group used a 2% aqueous infusion three times daily for twelve weeks. The 2% aqueous infusion concentration was selected based on commonly reported concentrations in previous phytotherapeutic and clinical studies evaluating herbal mouthwashes, balancing potential efficacy with safety and tolerability. The plant materials were sourced from certified suppliers, and standardized dried plant parts were used under controlled preparation conditions. Clinical assessments were performed at baseline (T0), week 1 (T1), week 5 (T2), and week 9 (T3), corresponding to the beginning of each evaluation interval within the 12-week study, using the Silness–Löe Plaque Index and the modified Löe–Silness Gingival Index. Data were analyzed using repeated-measures ANOVA with Bonferroni post hoc correction. (3) Results. Repeated-measures ANOVA revealed a significant main effect of time for both plaque accumulation and gingival index scores. For the Silness–Löe Plaque Index, a marked time-dependent reduction was observed across the active treatment groups (p < 0.001; η2p = 0.56), with a significant time × group interaction (p < 0.001; η2p = 0.49). Similarly, the modified Löe–Silness Gingival Index showed a significant reduction over time (p < 0.001; η2p = 0.22), with a significant interaction effect between time and mouthwash type (p < 0.001; η2p = 0.17). No statistically significant differences were found among the three herbal mouthwashes in post hoc Bonferroni comparisons (all p > 0.05), whereas all active treatments showed significantly better outcomes compared with the placebo. (4) Discussion. All three rinses showed similar clinical effects on plaque and gingival scores. However, without mechanistic assays, no claims can be made about comparable antibacterial or anti-inflammatory activity. Compared with conventional antiseptics such as chlorhexidine, herbal rinses offer important advantages in terms of biocompatibility, safety, and tolerability, with no staining, taste alteration, or mucosal irritation reported. At T3, the correlation between plaque and gingival indices was weak (Spearman’s ρ = 0.18, p = 0.09), suggesting limited linear association; this finding should be interpreted cautiously, as the low end-range values and limited variability of both indices at this time point may have masked a true association. This exploratory observation raises, but does not confirm, the possibility that factors other than plaque reduction may contribute to gingival improvement. (5) Conclusions. Significant reductions in dental plaque and clinical signs of gingival inflammation were observed following regular use of chamomile, sage, and ginger mouthwashes for twelve weeks. All herbal formulations exhibit similar clinical results. Longer-term controlled trials incorporating microbiological and phytochemical analyses are recommended to validate these findings further. Full article
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26 pages, 1500 KB  
Article
Curcumin Supplementation Reduces Inflammation, Neutrophil-to-Lymphocyte Ratio (NLR), and Antioxidant Status in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial
by Metha Yaikwawong, Khanittha Kamdee and Somlak Chuengsamarn
Int. J. Mol. Sci. 2026, 27(9), 3854; https://doi.org/10.3390/ijms27093854 (registering DOI) - 27 Apr 2026
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and curcumin—a polyphenolic compound derived from Curcuma longa—has shown potential anti-inflammatory and antioxidant effects. This randomized, double-blind, placebo-controlled trial evaluated the effects of 1500 [...] Read more.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and curcumin—a polyphenolic compound derived from Curcuma longa—has shown potential anti-inflammatory and antioxidant effects. This randomized, double-blind, placebo-controlled trial evaluated the effects of 1500 mg/day curcumin supplementation for 12 months in 114 adults with T2DM, with assessments including fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, IL-1β, TNF-α), high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), antioxidant markers (SOD, GPx, TAS), and malondialdehyde (MDA). Curcumin supplementation was associated with significant reductions in pro-inflammatory cytokines (p < 0.001), hs-CRP and NLR (p < 0.05), and with improved antioxidant status as shown by increased TAS, SOD, and GPx together with reduced MDA levels (p < 0.001). Additionally, improvements in metabolic parameters were observed, including lower FPG (112.0 mg/dL vs. 134.5 mg/dL; p < 0.001), HbA1c (6.10% vs. 6.40%; p < 0.05), and HOMA-IR (4.88 vs. 6.71; p < 0.001). Overall, the findings suggest that long-term curcumin supplementation may contribute to improved inflammatory, antioxidant, and glycemic profiles in obese individuals with T2DM; however, further multi-center studies are needed to confirm these observations and clarify their clinical relevance. Full article
(This article belongs to the Special Issue The Role of Natural Products in Inflammation)
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24 pages, 1720 KB  
Article
Efficacy and Safety of Vilaprisan in the Treatment of Uterine Fibroids: Data from ASTEROID 5, a Phase 3 Multicenter Randomized Controlled Trial
by K. Gemzell-Danielsson, C.-H. Cho, P. Vadász, R. Wenzl, L. Dong, T. Faustmann, E. Groettrup-Wolfers, K. Laapas, S. Parke, C. Haberland and C. Seitz
J. Clin. Med. 2026, 15(9), 3246; https://doi.org/10.3390/jcm15093246 - 24 Apr 2026
Viewed by 73
Abstract
Background/Objectives: Vilaprisan and ulipristal acetate (UPA) have demonstrated efficacy in treating uterine fibroids (UFs). However, a direct comparison of vilaprisan and UPA has been restricted, to date, to a small phase 2 study. Here, we compare the efficacy of vilaprisan and UPA [...] Read more.
Background/Objectives: Vilaprisan and ulipristal acetate (UPA) have demonstrated efficacy in treating uterine fibroids (UFs). However, a direct comparison of vilaprisan and UPA has been restricted, to date, to a small phase 2 study. Here, we compare the efficacy of vilaprisan and UPA in reducing heavy menstrual bleeding and inducing amenorrhea in women with symptomatic UFs. Methods: ASTEROID 5 (NCT03240523) was planned as a randomized, active-controlled, multicenter phase 3 study comparing three vilaprisan 2 mg/day regimens against the approved regimen of UPA 5 mg/day for the treatment of symptomatic UFs. Participants were initially randomized 1:1:1:1 to one of four treatment arms: VPR-3/1 (vilaprisan for a 3-month treatment period [TP] followed by one menstrual bleeding episode); VPR-6/2 (vilaprisan for a 6-month TP followed by two menstrual bleeding episodes); VPR-3/2 (vilaprisan plus matching UPA placebo for a 3-month TP followed by two menstrual bleeding episodes); and UPA-3/2 (UPA plus matching vilaprisan placebo for a 3-month TP followed by two menstrual bleeding episodes). Results: Treatment was received as planned by 271 (95.4%), 266 (94.0%), 90 (90.0%) and 89 (89.9%) women in the VPR-3/1, VPR-6/2, VPR-3/2, and UPA-3/2 groups, respectively; 109 women in the VPR-3/1 (n = 44, 15.5%) and VPR-6/2 (n = 65, 23.0%) groups and none in the VPR-3/2 and UPA-3/2 groups completed treatment. Vilaprisan (total VPR group) demonstrated non-inferiority but not superiority versus UPA in inducing amenorrhea (82.9% [520/627] vs. 74.2% [66/89]; difference: 8.8% [95% confidence interval: −0.78, 18.34]; p = 0.0553), whereas vilaprisan (VPR-3/1 arm) showed superiority versus UPA in reducing total menstrual blood loss (least squares mean total MBL: 44.2 mL vs. 80.3 mL; difference: −36.1 mL; p = 0.0010). Conclusions: Vilaprisan (VPR-3/1 regimen) was superior to UPA in reducing total MBL, and it was non-inferior (total VPR group) to UPA in inducing amenorrhea. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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26 pages, 1594 KB  
Article
Comparative Evaluation of Hydrogel Dip-Coating on Cone and Pyramid Microneedle Arrays Fabricated by LCD 3D Printing
by Feria Hasanpour, Oliwia Kordyl, Zuzanna Styrna, Barbara Jadach, Tomasz Osmałek, Ferhan Ayaydin, Mária Budai-Szűcs, Anita Kovács and Szilvia Berkó
Pharmaceutics 2026, 18(5), 518; https://doi.org/10.3390/pharmaceutics18050518 (registering DOI) - 24 Apr 2026
Viewed by 320
Abstract
Background: Additive manufacturing provides a rapid and flexible alternative to conventional micromolding for producing microneedle systems. This study evaluates the potential of a cost-effective LCD 3D printer for fabricating microneedle arrays (MNAs) and investigates how the geometry of MNAs and the formulation [...] Read more.
Background: Additive manufacturing provides a rapid and flexible alternative to conventional micromolding for producing microneedle systems. This study evaluates the potential of a cost-effective LCD 3D printer for fabricating microneedle arrays (MNAs) and investigates how the geometry of MNAs and the formulation of hydrogel influence the performance of lidocaine-coated arrays. Methods: Conical and pyramidal MNAs, along with a reservoir plate, were designed and manufactured. Lidocaine-loaded and placebo hydrogels with two different polymer concentrations were prepared for dip-coating using both single and multilayer applications. Mechanical resistance and insertion efficiency were evaluated under controlled compression. The physicochemical behavior of the hydrogels were characterized, including pH, spreadability, adhesiveness, and rheological behavior. The uniformity of the coating was analyzed using 3D confocal microscopy. Drug loading was quantified by HPLC, drug release was studied using Franz diffusion cells, and skin penetration was confirmed by 3D confocal imaging and Raman mapping. Results: Conical microneedles exhibited high mechanical integrity, showing only a 2% reduction in height compared to 4% for pyramidal MNAs. Stronger drug signals were achieved in deeper skin layers with the conical geometry, indicating enhanced penetration, while pyramidal MNAs provided slightly higher lidocaine loading due to their larger lateral surface. Hydrogels with higher polymer content produced more stable, uniform coatings, particularly when applied in three layers. Rapid drug release was observed, with over 70% of the drug delivered within minutes. Conclusions: LCD 3D printing offers a cost-effective approach for fabricating MNAs with suitable structural stability and sharpness. The optimized hydrogel formulation ensured uniform coverage, as well as maximal and consistence penetration, making this platform a promising candidate for the dermal delivery of other potent drugs. Full article
(This article belongs to the Special Issue Microneedles for Transdermal Delivery and Diagnostic Applications)
24 pages, 3409 KB  
Article
Effects of a Novel Prebiotic and Postbiotic Dietary Supplement on Gut Microbiota, Intestinal Barrier Markers, and Inflammation in Healthy Dogs
by Chuandi Yi, Céline S. Nicolas, Ziqi Sun, Qin Wang, Tianyu Dong and Yi Wu
Vet. Sci. 2026, 13(5), 417; https://doi.org/10.3390/vetsci13050417 (registering DOI) - 24 Apr 2026
Viewed by 191
Abstract
Although prebiotics and postbiotics support gastrointestinal health, evidence for their combined effects in dogs remains limited. This study evaluated a novel prebiotic and postbiotic supplement in healthy dogs undergoing a dietary transition. Thirty-six healthy adult dogs were randomly assigned to control group (CON, [...] Read more.
Although prebiotics and postbiotics support gastrointestinal health, evidence for their combined effects in dogs remains limited. This study evaluated a novel prebiotic and postbiotic supplement in healthy dogs undergoing a dietary transition. Thirty-six healthy adult dogs were randomly assigned to control group (CON, high-protein basal diet with placebo chew) or treatment group (TRT, the same basal diet with chew containing prebiotics [baobab fruit pulp and acacia gum] and postbiotics [inactivated Lactobacillus acidophilus and selected yeast fractions]) for a 28-day formal trial following a 7-day adaptation period. The primary outcomes evaluated included clinical fecal scores, specific biomarkers of intestinal barrier function and inflammation, fecal short-chain fatty acids, and microbiota structure. Following the 7-day adaptation, formal trial baseline, fecal scores were already within the healthy range and remained optimal without differing between groups throughout the study. Compared with CON, the TRT group showed lower fecal calprotectin and serum diamine oxidase levels, and higher fecal butyrate (p < 0.05). Metagenomic analysis revealed increased abundances of Bacteroidota, Oscillospiraceae, Prevotellaceae, and Prevotella in TRT (p < 0.05). Overall, in healthy dogs, this supplementation was associated with favorable microbiota modulation and modulated biomarkers of intestinal barrier and inflammation within normal ranges, without altering clinical fecal endpoints. Full article
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14 pages, 259 KB  
Article
There Is No Role for Extracorporeal Shock Wave Therapy in Chronic Insertional Achilles Tendinopathy: A Comparative Study with Conservative Treatment
by İbrahim Ulusoy, Mehmet Yılmaz, Mehmet Fırat Tantekin, İsmail Güzel and Aybars Kıvrak
J. Am. Podiatr. Med. Assoc. 2026, 116(3), 24; https://doi.org/10.3390/japma116030024 - 24 Apr 2026
Viewed by 103
Abstract
Background: Chronic insertional Achilles tendinopathy (CIAT) is a type of tendinopathy resistant to conventional conservative treatments. The efficacy of extracorporeal shock wave therapy (ESWT) remains controversial. This study aims to evaluate the effects of ESWT on pain management and functional improvement in CIAT [...] Read more.
Background: Chronic insertional Achilles tendinopathy (CIAT) is a type of tendinopathy resistant to conventional conservative treatments. The efficacy of extracorporeal shock wave therapy (ESWT) remains controversial. This study aims to evaluate the effects of ESWT on pain management and functional improvement in CIAT patients and compare it with physical and medical treatments Methods: In this retrospective study, 372 patients diagnosed with CIAT between 2019 and 2023 were evaluated. The patients were divided into two groups: those who received only physical/medical therapy (Group 1) and those who underwent a combination of ESWT and physical/medical therapy (Group 2). Clinical outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) score and the Visual Analog Scale (VAS) scores. The severity of the disease was determined through magnetic resonance imaging (MRI). Group comparisons were conducted using the independent samples t-test and Fisher’s exact test, while changes over time were assessed with repeated measures ANOVA. Correlation analyses were evaluated using Pearson and Spearman correlation coefficients. Results: Significant improvement in AOFAS and VAS scores was observed in both groups by the third month (p < 0.01). However, at 6 and 12 months, ESWT did not demonstrate superiority over physical/medical treatment. Correlation analysis showed a positive relationship between baseline AOFAS scores and functional improvement, while higher initial VAS scores correlated with greater post-treatment pain reduction. Cardiovascular risk factors negatively impacted both functional recovery and pain reduction (p < 0.05). Although patient satisfaction was higher in the ESWT group, the difference was not statistically significant. Conclusions: ESWT may provide short-term pain relief and functional improvement in CIAT but does not offer a long-term advantage over physical/medical treatment. The placebo effect may contribute to early positive outcomes. These findings do not support ESWT as a routine treatment for CIAT. Full article
16 pages, 1319 KB  
Systematic Review
PD-L1-Guided Chemo-Immunotherapy in Advanced Triple-Negative Breast Cancer: A Meta-Analysis of Survival Benefits and Toxicity Profiles
by Lingshan Nan, Xi Zuo, Xiaohui Yin, Haiming Li, Yue Wang, Xiaomin Wang, Dong Chen and Ganlin Zhang
Cancers 2026, 18(9), 1352; https://doi.org/10.3390/cancers18091352 - 23 Apr 2026
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Abstract
Importance: Triple-negative breast cancer (TNBC) is characterized by high tumor mutation burden and frequent programmed cell death ligand 1 (PD-L1) expression, making immune checkpoint inhibitors (ICIs) a promising therapeutic approach. However, randomized trials of chemoimmunotherapy (Chemo-IO) in locally recurrent unresectable or metastatic TNBC [...] Read more.
Importance: Triple-negative breast cancer (TNBC) is characterized by high tumor mutation burden and frequent programmed cell death ligand 1 (PD-L1) expression, making immune checkpoint inhibitors (ICIs) a promising therapeutic approach. However, randomized trials of chemoimmunotherapy (Chemo-IO) in locally recurrent unresectable or metastatic TNBC have shown inconsistent results, necessitating a clearer understanding of efficacy and patient selection. Objective: The aim of this study was to evaluate the efficacy and safety of chemotherapy combined with immunotherapy vs. chemotherapy alone in patients with locally recurrent unresectable or metastatic triple-negative breast cancer and to identify beneficiary populations to guide optimal treatment selection. Data Sources: PubMed, Embase, and the Cochrane Library were searched from database inception through 23 August 2025. Study Selection: Randomized clinical trials (RCTs) comparing chemotherapy combined with ICIs vs. chemotherapy with placebo or control in patients with locally recurrent unresectable or metastatic TNBC were selected. Data Extraction and Synthesis: Two investigators independently performed data extraction and assessed risk of bias using the Cochrane Risk of Bias 2 tool (RoB 2). Heterogeneity was evaluated using the I2 statistic. Data were synthesized using random-effects meta-analysis models to calculate hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for dichotomous outcomes according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Results: Seven RCTs comprising 3485 patients (2085 in the Chemo-IO group, 1400 in the control group) were included. The median age across trials ranged from 52 to 57 years. Chemo-IO significantly improved PFS (HR, 0.82 [95% CI, 0.76–0.89]; p < 0.01) and OS (HR = 0.88; 95% CI: 0.81–0.96; p = 0.004) in the intention-to-treat (ITT) population, with PFS benefit particularly evident in PD-L1-positive patients (HR = 0.68, 95% CI: 0.59–0.79). However, OS improvement in the PD-L1-positive subgroup was not statistically significant. CBR did not differ significantly in the intention-to-treat population (RR, 1.11 [95% CI, 0.99–1.25]; p =  0.08) but was higher in PD-L1-positive patients (RR, 1.15 [95% CI, 1.01–1.31]; p = 0.04). Safety analyses revealed no significant differences in overall AE (RR, 1.01 [95% CI, 0.99–1.02]; p = 0.35), TEAE (RR, 1.01 [95% CI, 0.99–1.03]; p = 0.19), or grade ≥ 3 TEAE (RR, 1.00; [95% CI, 0.93–1.07]; p =  0.98). However, serious AE (RR, 1.32 [95% CI, 1.11–1.57]; p = 0.001) and irAE (RR, 1.86 [95% CI, 1.41–2.45]; p <  0.01) were more frequent with Chemo-IO. Conclusions and Relevance: Chemotherapy combined with immunotherapy significantly improved PFS and OS in patients with locally recurrent unresectable or metastatic TNBC, without substantially increasing chemotherapy-related toxicities. However, the OS benefit in PD-L1-positive patients was not statistically significant, and the combined regimen was associated with higher rates of serious and immune-related adverse events. These findings support the use of Chemo-IO as a treatment option, highlighting the importance of PD-L1 status and careful monitoring of immune-mediated toxicities in clinical practice. Full article
(This article belongs to the Section Cancer Therapy)
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27 pages, 3724 KB  
Article
Effects of Combined Caffeine and Rhodiola rosea Supplementation on Repeated Aerial Duel Performance and Neck Neuromuscular Function in Soccer Players
by Yue Dou, Ziyi Feng, Hengquan Xu, Hexin Ma, Yuewei Jiang, Xinping Lyu, Bolin Han, Shuning Liu, Chang Liu and Dingmeng Ren
Nutrients 2026, 18(9), 1339; https://doi.org/10.3390/nu18091339 - 23 Apr 2026
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Abstract
Background: Soccer aerial duels require rapid take-off, repeated-performance maintenance, and effective head–neck control under physically demanding conditions. This study examined the effects of caffeine (CAF), Rhodiola rosea (RHO), and their combination on repeated aerial duel performance and neck neuromuscular function in male collegiate [...] Read more.
Background: Soccer aerial duels require rapid take-off, repeated-performance maintenance, and effective head–neck control under physically demanding conditions. This study examined the effects of caffeine (CAF), Rhodiola rosea (RHO), and their combination on repeated aerial duel performance and neck neuromuscular function in male collegiate soccer players. Methods: Ninety-six players were randomly assigned, in a double-blind, placebo-controlled, parallel design, to placebo control (CTR), RHO, CAF, or RHO + CAF groups (n = 24 each) for 4 weeks. CAF was acutely administered at 3 mg·kg−1 before testing, whereas RHO was chronically supplemented at 2.4 g·day−1. Outcome measures included countermovement jump height, early take-off impulse, repeated heading contact height, ball exit velocity, heading duel success rate, neck maximal voluntary isometric contraction, and session rating of perceived exertion (session-RPE). Results: Significant group × time or group × repetition effects were observed for CMJ height (p = 0.0034), early take-off impulse (p = 0.0007), and post-intervention repeated heading contact height (p < 0.0001), with additional significant effects across heading-specific, neck strength, duel-success, and perceived-load outcomes. CAF was mainly associated with improved take-off-related explosive performance and duel success, whereas RHO was mainly associated with lower perceived exertion and better maintenance of heading contact height during the later repeated trials. Combined RHO + CAF supplementation produced the broadest pattern of benefits across explosive output, ball-contact performance, duel success, and multidirectional neck strength. Conclusions: These findings suggest that, in male collegiate soccer players, CAF and RHO may contribute differently to repeated aerial duel-related performance, and their combination may offer broader sport-specific benefits under repeated high-intensity demands. Full article
(This article belongs to the Section Sports Nutrition)
16 pages, 912 KB  
Article
Benefits of Regular Intake of Glucolacto-Oligosaccharides on Gut Health in Adults with Low Defecation Frequency: A Randomized, Double-Blind, Placebo-Controlled Study
by Yuichi Yoshizawa, Junya Ishida, Atsushi Shimonaka, Satoshi Hanamura, Akika Nagira, Mami Minakata, Akiko Koizumi, Aoi Fujieda, Hiroki Negishi, Shigenori Kanemura, Seiya Makino and Kenichi Hojo
Microorganisms 2026, 14(5), 955; https://doi.org/10.3390/microorganisms14050955 - 23 Apr 2026
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Abstract
The significance of less abundant genera within the gut microbiota, such as Parabacteroides, remains largely unexplored. Despite its low levels, Parabacteroides is highly conserved and potentially beneficial across populations. This trial aimed to evaluate whether a four-week intake of glucolacto-oligosaccharides (GLO), previously [...] Read more.
The significance of less abundant genera within the gut microbiota, such as Parabacteroides, remains largely unexplored. Despite its low levels, Parabacteroides is highly conserved and potentially beneficial across populations. This trial aimed to evaluate whether a four-week intake of glucolacto-oligosaccharides (GLO), previously reported as an enhancer of Parabacteroides, improves defecation frequency as the primary outcome. It also assessed holistic gut health and underlying microbiota-based mechanisms. In this randomized, double-blind, placebo-controlled trial, 50 healthy Japanese participants with a defecation frequency of five or fewer times per week were enrolled. The mean (±SE) weekly defecation frequency in the GLO group was 3.2 ± 0.2 at baseline, increasing to 5.8 ± 0.6 at week 4, whereas that in the placebo group was 3.4 ± 0.3 at baseline, increasing to 4.4 ± 0.3 at week 4. The time-dependent weekly defecation frequency was significantly higher in the GLO group than in the placebo group (p = 0.029). Changes in the relative abundance of the genus Parabacteroides significantly increased in the GLO group compared with in the placebo group. Changes in fecal bile acid composition were also confirmed in the GLO group compared with the placebo group, which was thought to be due to the unique features of Parabacteroides. Furthermore, changes in alpha diversity indices were significantly higher in the GLO group than in the placebo group (Simpson, p = 0.041; Pielou, p = 0.022). Additional analysis demonstrated that the increase in alpha diversity in the GLO group was significantly correlated with the increase in the relative abundance of Parabacteroides (p = 0.006), which tended to be associated with decreases in serum gamma-glutamyltransferase (p = 0.089) and serum triglyceride (p = 0.075) levels. These data suggest that GLO intake improved defecation status, selectively increased Parabacteroides, and harmonized the gut environment. Full article
(This article belongs to the Section Gut Microbiota)
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