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12 pages, 598 KB  
Article
Laboratory-Based Surveillance and Genetic Diversity of Enteric Adenovirus Among Children in Argentina, 2022–2024
by Juan Ignacio Degiuseppe, Paula Mabel Moron, Christian Barrios Mathieur and Argentinean Surveillance Network for Viral Gastroenteritis
Trop. Med. Infect. Dis. 2026, 11(2), 35; https://doi.org/10.3390/tropicalmed11020035 (registering DOI) - 25 Jan 2026
Abstract
Enteric adenoviruses are recognized causes of pediatric acute gastroenteritis, yet national-level data on their epidemiology and genetic diversity in Argentina remain limited. This study aimed to describe the laboratory-based surveillance of enteric adenoviruses and to characterize the circulating genotypes among children during the [...] Read more.
Enteric adenoviruses are recognized causes of pediatric acute gastroenteritis, yet national-level data on their epidemiology and genetic diversity in Argentina remain limited. This study aimed to describe the laboratory-based surveillance of enteric adenoviruses and to characterize the circulating genotypes among children during the 2022–2024 period. Data were obtained from the Argentine National Health Surveillance System, including weekly aggregated reports of adenovirus testing results from clinical laboratories nationwide. Detection frequencies were analyzed by year, age group, clinical setting, geographic region, and epidemiological week. Molecular characterization was performed using partial hexon gene sequencing. A total of 22,826 stool samples were tested, of which 1530 (6.7%) were positive for adenovirus, with no significant differences in positivity across years. Detection rates were highest among children under 1 year of age and were consistently greater in outpatient and emergency department settings compared with hospitalized patients. No clear seasonal pattern was observed. Genotyping revealed a predominance of HAdV-F41, with sporadic detection of non-enteric adenovirus types. These findings provide the first nationwide overview of enteric adenovirus circulation and genetic diversity in Argentina, highlighting stable transmission patterns and supporting the value of sustained laboratory surveillance to better characterize viral gastroenteritis etiology in the post-rotavirus vaccination era. Full article
(This article belongs to the Special Issue Viral Enteropathogens in Pediatric Populations)
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23 pages, 2066 KB  
Article
Intelligent Attention-Driven Deep Learning for Hip Disease Diagnosis: Fusing Multimodal Imaging and Clinical Text for Enhanced Precision and Early Detection
by Jinming Zhang, He Gong, Pengling Ren, Shuyu Liu, Zhengbin Jia, Lizhen Wang and Yubo Fan
Medicina 2026, 62(2), 250; https://doi.org/10.3390/medicina62020250 (registering DOI) - 24 Jan 2026
Abstract
Background: Hip joint disorders exhibit diverse and overlapping radiological features, complicating early diagnosis and limiting the diagnostic value of single-modality imaging. Isolated imaging or clinical data may therefore inadequately represent disease-specific pathological characteristics. Methods: This retrospective study included 605 hip joints [...] Read more.
Background: Hip joint disorders exhibit diverse and overlapping radiological features, complicating early diagnosis and limiting the diagnostic value of single-modality imaging. Isolated imaging or clinical data may therefore inadequately represent disease-specific pathological characteristics. Methods: This retrospective study included 605 hip joints from Center A (2018–2024), comprising normal hips, osteoarthritis, osteonecrosis of the femoral head (ONFH), and femoroacetabular impingement (FAI). An independent cohort of 24 hips from Center B (2024–2025) was used for external validation. A multimodal deep learning framework was developed to jointly analyze radiographs, CT volumes, and clinical texts. Features were extracted using ResNet50, 3D-ResNet50, and a pretrained BERT model, followed by attention-based fusion for four-class classification. Results: The combined Clinical+X-ray+CT model achieved an AUC of 0.949 on the internal test set, outperforming all single-modality models. Improvements were consistently observed in accuracy, sensitivity, specificity, and decision curve analysis. Grad-CAM visualizations confirmed that the model attended to clinically relevant anatomical regions. Conclusions: Attention-based multimodal feature fusion substantially improves diagnostic performance for hip joint diseases, providing an interpretable and clinically applicable framework for early detection and precise classification in orthopedic imaging. Full article
(This article belongs to the Special Issue Artificial Intelligence in Medicine: Shaping the Future of Healthcare)
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9 pages, 2680 KB  
Article
Evaluating Three Techniques for Coronoid Process and Anterior Capsule Fixation: A Biomechanical Study
by Arsh N. Patel, Briana M. Pompa-Hogan, Tori N. Kinamon, Arsalaan Sayyed, Natalia A. Pluta, James K. Aden and Taylor J. Bates
Trauma Care 2026, 6(1), 1; https://doi.org/10.3390/traumacare6010001 (registering DOI) - 24 Jan 2026
Abstract
Background: To compare the biomechanical strength of three fixation techniques for the elbow anterior capsule and coronoid process using a synthetic ulna model. We hypothesize that a cortical suture button would be equivalent to the bone tunnel model but inferior to a screw-post [...] Read more.
Background: To compare the biomechanical strength of three fixation techniques for the elbow anterior capsule and coronoid process using a synthetic ulna model. We hypothesize that a cortical suture button would be equivalent to the bone tunnel model but inferior to a screw-post construct. Methods: A biomechanical study was conducted using a composite ulna bone model to simulate coronoid process fixation with three techniques: traditional trans-osseous bone tunnel repair, suspensory fixation using a cortical button, and a screw-post construct using a 3.5 mm cortical screw. All constructs were assembled using high-strength suture. Each specimen underwent axial loading on an Instron machine until failure, defined as loss of fixation through the dorsal cortex. Peak ultimate strength was recorded. Statistical analysis was performed using one-way ANOVA and Tukey’s HSD test. Results: The suture button construct demonstrated the highest mean ultimate strength at 490.3 ± 125.2 N, significantly greater than both the bone tunnel (328.8 ± 86.4 N, p < 0.01) and screw-post constructs (273.4 ± 54.5 N, p < 0.001). While the bone tunnel construct exhibited a 20.3% higher strength than the screw-post construct, this difference was not statistically significant (p = 0.13). The screw-post construct showed the least variability in strength to failure but the lowest overall strength. The suture button demonstrated the greatest mechanical strength but also the most variability. Conclusions: Suspensory fixation using a titanium cortical suture button provides significantly greater mechanical strength compared to traditional bone tunnel and screw-post techniques in a synthetic ulna model. While variability was greatest with the suture button construct, its superior load-bearing capacity suggests potential advantages in stabilizing the elbow through anterior capsule and coronoid fracture repair. These findings support further clinical investigation of suture button fixation as a viable technique in complex elbow injuries. Full article
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13 pages, 785 KB  
Article
Questionnaire-Based Survey on Risk Factors and Prevalence of Major Vector-Borne Diseases in the Aegean Region of Türkiye
by Serdar Pasa, Kerem Ural, Hasan Erdogan, Songul Erdogan, Ilia Tsachev, Mehmet Gultekin and Tahir Ozalp
Vet. Sci. 2026, 13(2), 114; https://doi.org/10.3390/vetsci13020114 (registering DOI) - 24 Jan 2026
Abstract
This study aims to investigate the prevalence and risk factors associated with canine vector-borne diseases (CVBDs) in the Aegean Region of Türkiye. Using a questionnaire-based approach, this study intends to fill the gaps in existing knowledge regarding the prevalence and determinants of these [...] Read more.
This study aims to investigate the prevalence and risk factors associated with canine vector-borne diseases (CVBDs) in the Aegean Region of Türkiye. Using a questionnaire-based approach, this study intends to fill the gaps in existing knowledge regarding the prevalence and determinants of these infections. A retrospective analysis of 781 dogs presented to Aydın Adnan Menderes University Small Animal Clinic from 2019 to 2024 was conducted. Among these, 205 dogs were confirmed to have at least one CVBD using rapid diagnostic tests (SNAP 4DX PLUS and SNAP Leishmania) with confirmatory methods. Data on dog demographics, lifestyle, and environmental exposure were collected using structured questionnaires. Prevalence rates were calculated based on the at-risk population, and logistic regression determined associations between risk factors and disease occurrence. Overall CVBD prevalence was 26.3%, with Ehrlichiosis (9.9%) and Leishmaniasis (7.4%) being the most common infections. Co-infections were present in 8.3% of cases. Geographical factors significantly influenced infection rates, particularly in Aydın compared to İzmir and Muğla, while demographics like age, breed size, gender, and outdoor activity had no significant impact. This highlights the necessity for region-specific control measures and the need for consistent adherence to preventive protocols to mitigate CVBD prevalence in high-risk areas. Full article
(This article belongs to the Section Veterinary Internal Medicine)
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17 pages, 1908 KB  
Article
Manual Dexterity Rehabilitation in Parkinson’s Disease and Paranoid Schizophrenia: A Controlled Study
by Tatiana Balint, Alina-Mihaela Cristuta, Adina Camelia Slicaru, Ilie Onu, Daniel Andrei Iordan and Ana Onu
Life 2026, 16(2), 196; https://doi.org/10.3390/life16020196 (registering DOI) - 24 Jan 2026
Abstract
Background: Manual dexterity (MD) impairment is a frequent and disabling feature in patients with Parkinson’s disease (PD) and paranoid schizophrenia (PS), significantly affecting functional independence and activities of daily living. However, rehabilitation strategies specifically targeting fine motor control remain insufficiently integrated into routine [...] Read more.
Background: Manual dexterity (MD) impairment is a frequent and disabling feature in patients with Parkinson’s disease (PD) and paranoid schizophrenia (PS), significantly affecting functional independence and activities of daily living. However, rehabilitation strategies specifically targeting fine motor control remain insufficiently integrated into routine physiotherapy (PT). Objective: This study investigated the effects of a structured, progressive PT program incorporating targeted MD training on upper limb function in patients with PD and PS. Methods: A prospective, exploratory, interventional study was conducted in 30 patients, allocated to either an experimental group (EG, n = 20) or a control group (CG, n = 10). Participants had PD (Hoehn and Yahr stages II–III) or chronic, clinically stable PS. MD was assessed using the Purdue Pegboard Test, Coin Rotation Task, and Kapandji opposition score. The EG completed a four-phase, 40-week dexterity-oriented rehabilitation program, while the CG received standard disease-specific PT. Between-group differences in change scores were analyzed using one-way ANOVA. Results: The EG showed significantly greater improvements than the CG in thumb opposition, psychomotor processing speed, and unilateral and bilateral fine motor performance (p < 0.001 for all), with large to very large effect sizes (η2 = 0.45–0.76). No significant between-group differences were observed for complex sequential assembly tasks. Conclusions: Integrating targeted MD training into structured PT programs significantly improves fine motor performance in patients with PD and PS, supporting its inclusion in rehabilitation protocols for residential and outpatient care settings. Full article
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14 pages, 613 KB  
Article
Aneuploidy Patterns and Chaotic Embryos in IVF: Age-Stratified Analysis and Re-Biopsy Outcomes from a Romanian Cohort
by Anca Huniadi, Petronela Naghi, Iona Zaha, Adelin Marcu, Liana Stefan, Liliana Sachelarie and Ioana Cristina Rotar
Medicina 2026, 62(2), 247; https://doi.org/10.3390/medicina62020247 (registering DOI) - 24 Jan 2026
Abstract
Background and Objectives: Aneuploidy is the leading cause of implantation failure and miscarriage, with prevalence increasing with maternal age. Embryos classified as chaotic, characterized by the presence of five or more chromosomal abnormalities, and those with complex aneuploidies, defined by two to [...] Read more.
Background and Objectives: Aneuploidy is the leading cause of implantation failure and miscarriage, with prevalence increasing with maternal age. Embryos classified as chaotic, characterized by the presence of five or more chromosomal abnormalities, and those with complex aneuploidies, defined by two to four abnormalities, represent a controversial category in preimplantation genetic testing for aneuploidy (PGT-A), as the potential for misclassification remains a significant concern. Materials and Methods: We performed a retrospective study at the Calla IVF Center, Oradea, analyzing 230 blastocysts grouped by maternal age (25–30, 31–35, 36–40, and 41–50 years). A trophoblast biopsy was performed on days 5–7, and the samples were analyzed by next-generation sequencing (NGS). Embryos were classified as euploid, aneuploid, mosaic, or chaotic. The 19 embryos initially diagnosed as chaotic were thawed and subjected to re-biopsy. Statistical analysis included descriptive statistics (chi-square tests and ANOVA) and multivariable regression models, with p < 0.05 as the criterion for statistical significance. Results: Aneuploidy increased with maternal age, from 29.6% in women aged 25–30 years to 68.7% in those aged 41–50 (p = 0.002). Poor-quality blastocysts exhibited higher aneuploidy rates (72.4%) than good-quality embryos (34.6%; p = 0.004). Chaotic embryos comprised 8.3% of the cohort. Upon re-biopsy, none were confirmed as euploid; all remained abnormal and were reassigned to aneuploid, mosaic, or persistently chaotic categories. This finding suggests that apparent euploid results reported elsewhere may reflect technical variability and sampling limitations in PGT-A rather than accurate chromosomal normalization. Conclusions: The prevalence of aneuploid embryos showed a progressive increase with advancing maternal age. Chaotic embryos are heterogeneous, and re-biopsy may help refine the interpretation of complex PGT-A profiles, supporting its role as a diagnostic and quality control tool rather than a strategy to identify euploid embryos. Our study offers novel insights through age-stratified analysis, the integration of morphology with genetics in a Romanian IVF cohort, and a detailed evaluation of chaotic embryos, providing clinical recommendations for patient counseling and embryo selection. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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18 pages, 1241 KB  
Article
Coffee Cascara as a Source of Natural Antimicrobials: Chemical Characterization and Activity Against ESKAPE Pathogens
by Merike Vaher and Olga Bragina
Molecules 2026, 31(3), 403; https://doi.org/10.3390/molecules31030403 (registering DOI) - 24 Jan 2026
Abstract
Coffee cascara is a byproduct of coffee production traditionally used for infusions and animal feed. In this study, aqueous extracts of cascara from three different sources (Cas1–Cas3) were analyzed for their polyphenol and flavonoid content, as well as the concentrations of key individual [...] Read more.
Coffee cascara is a byproduct of coffee production traditionally used for infusions and animal feed. In this study, aqueous extracts of cascara from three different sources (Cas1–Cas3) were analyzed for their polyphenol and flavonoid content, as well as the concentrations of key individual bioactive compounds including caffeine, trigonelline, chlorogenic acid, and protocatechuic acid. Among the tested samples, Cas1 exhibited the highest total polyphenol (802.2 mg GAE/L) and flavonoid (134.7 mg QE/L) contents. The antibacterial activity of these extracts and an artificial mixture of the four compounds were evaluated against ESKAPE pathogens. Cas1 exhibited the most promising antibacterial effect, with minimal bactericidal concentration (MBC) values as low as 0.03 mg/mL for S. aureus and A. baumannii, and 0.26 mg/mL for P. aeruginosa. The artificial mixture, despite containing higher concentrations of the major compounds, exhibited reduced efficacy (MBC of 0.04 mg/mL for S. aureus and 0.15 mg/mL for A. baumannii, respectively), highlighting the superior activity of the native extracts. These results indicate that cascara extracts possess strong antibacterial activity, which correlates with their content of bioactive compounds, mainly polyphenols and alkaloids. The pronounced efficacy of the native extracts compared to the artificial mixture suggests that minor constituents in cascara may synergistically contribute to antibacterial effects. The present study highlights the potential of cascara aqueous extracts as natural multi-component antimicrobial agents, particularly against clinically relevant pathogens such as A. baumannii. Full article
(This article belongs to the Special Issue Biological Evaluation of Plant Extracts)
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25 pages, 24853 KB  
Article
Mesenchymal Stem Cell Therapy Modulates Peripheral–Central Immune Interactions and Attenuates Neuroinflammation-Driven Cognitive Dysfunction
by Gunel Ayyubova, Shahla Huseynova, Nigar Mustafayeva, Leyla Yildirim, Seher Ismayilova, Tarana Gasimova and Sabina Aliyeva
Int. J. Mol. Sci. 2026, 27(3), 1182; https://doi.org/10.3390/ijms27031182 (registering DOI) - 24 Jan 2026
Abstract
Peripheral inflammation is increasingly recognized as a critical driver of sustained neuroinflammation and cognitive dysfunction in neurodegenerative and inflammation-associated disorders. Systemic inflammatory mediators can compromise blood–brain barrier integrity, activate glial cells, and initiate maladaptive neuroimmune cascades that disrupt hippocampal–prefrontal circuits underlying learning and [...] Read more.
Peripheral inflammation is increasingly recognized as a critical driver of sustained neuroinflammation and cognitive dysfunction in neurodegenerative and inflammation-associated disorders. Systemic inflammatory mediators can compromise blood–brain barrier integrity, activate glial cells, and initiate maladaptive neuroimmune cascades that disrupt hippocampal–prefrontal circuits underlying learning and memory. Here, we investigated whether early systemic administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) mitigates inflammation-driven cognitive deficits in a chronic lipopolysaccharide (LPS) mouse model. Adult mice received daily LPS injections for seven days to induce persistent systemic and central inflammation, which was confirmed by serum and hippocampal cytokine analyses in a separate cohort at the time of MSC administration, followed by intravenous MSC treatment immediately after cessation of the inflammatory insult. Behavioral testing revealed significant impairments in spatial working memory, recognition memory, and associative learning. These deficits were accompanied by pronounced microglial activation, immune cell accumulation, astrocytosis, and a shift toward a pro-inflammatory cytokine milieu with suppression of IL-10 in the hippocampal CA1 region and medial prefrontal cortex. Early MSC treatment attenuated glial reactivity, reduced pro-inflammatory cytokines, restored IL-10 expression, and partially rescued cognitive performance. Collectively, these findings identify a post-inflammatory therapeutic window in which early MSC-based immunomodulation can rebalance neuroimmune signaling and limit inflammation-induced hippocampal–prefrontal circuit dysfunction, highlighting a clinically relevant strategy for targeting cognitive impairment associated with chronic systemic inflammation. Full article
(This article belongs to the Special Issue Therapeutics and Pathophysiology of Cognitive Dysfunction)
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30 pages, 1606 KB  
Systematic Review
Mass Screening Strategies for Celiac Disease in Apparently Healthy Children and Adolescents: A Systematic Review
by Alexandra Mpakosi, Vasileios Cholevas, Andreas G. Tsantes, Argyro Pastrikou, Aikaterini Fragkiadaki, Sofia Zhgabi, Vasiliki Mougiou, Nicoletta Iacovidou and Rozeta Sokou
Medicina 2026, 62(2), 246; https://doi.org/10.3390/medicina62020246 (registering DOI) - 24 Jan 2026
Abstract
Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of [...] Read more.
Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of life and preventing serious complications later in life. However, it is impossible to identify asymptomatic children and adolescents without screening. In this systematic review, we attempted to identify different mass screening programs that have been reported for CD in apparently healthy children and adolescents across the world, to highlight the advantages and disadvantages of such strategies, and to collect and synthesize data from these studies reporting the prevalence of CD. In addition, where data were available, we also attempted to evaluate the diagnostic accuracy of the tests used, their cost-effectiveness, the reported clinical benefits, and follow-up data from individuals identified through screening. Materials and Methods: Electronic databases, including PubMed and Scopus, were systematically searched. Initially, a total of 316 studies were retrieved. Finally, 55 studies met all inclusion criteria and were included in this review. The included studies were published between 1996 and 2023. Results: The reported age of participants ranged from 6 months to 23 years. Confirmation of CD by biopsy was reported in all but six studies. According to the studies that provided data, the (tTG IgA) seroprevalence of CD in apparently healthy children and adolescents, detected through different mass screening methods around the world, ranged from 0.20% (Turkey) to 3.11% (Italy). In addition, the prevalence of biopsy-confirmed CD ranged from 0.036% (Vietnam) to 3% (Sweden and Spain). Studies from 17 countries reported mass screening strategies based on finger-prick rapid tests. All rapid tests detected CD antibodies, except two, which detected HLA DQ2/DQ8 haplotypes. Rapid tests appeared to be no less sensitive and specific than other screening tests for CD and were probably less expensive, but further studies are needed for more reliable conclusions. Of the 55 studies in the review, only 10 reported follow-up data. After 3 months of a gluten-free diet, the general condition of the patients improved; after 6 months, tTG IgA and EMA IgA levels decreased and hemoglobin values increased; while after 1 year, tTG IgG levels also decreased, symptoms subsided, the children’s weight and height increased, school performance improved, episodes of upper respiratory tract infections decreased, and thyreoperoxidase antibodies that were positive at screening became negative. Conclusions: Mass screening for CD in asymptomatic children and adolescents is a challenge. Future research should provide more answers regarding the most appropriate target age, the frequency of screening, the optimal screening method, the cost-effectiveness, the clinical utility, and the long-term impact of mass screening on patients’ quality of life. Full article
(This article belongs to the Section Pediatrics)
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16 pages, 1338 KB  
Article
Biofilm Formation in Aspergillus fumigatus: A Comparative Study of Strains from Different Origins
by Marta Cano-Pérez, Juan de Dios Caballero Pérez, Elia Gómez García de la Pedrosa and Alicia Gómez-López
Microorganisms 2026, 14(2), 272; https://doi.org/10.3390/microorganisms14020272 (registering DOI) - 24 Jan 2026
Abstract
One of the most notable aspects of Aspergillus fumigatus, and related to its dynamic adaptation, is its ability to form biofilm and produce a wide variety of secondary metabolites. The aim of this study is to advance the characterization of biofilms generated by [...] Read more.
One of the most notable aspects of Aspergillus fumigatus, and related to its dynamic adaptation, is its ability to form biofilm and produce a wide variety of secondary metabolites. The aim of this study is to advance the characterization of biofilms generated by different A. fumigatus strains across their developmental stages and analytically evaluate their structure and composition and their relationship with secondary metabolism activation. An in vitro biofilm model was standardized to investigate structural and analytical differences among strains isolated from distinct clinical settings and associated with different pathologies. We found that all tested strains could form biofilms; however, the characteristics of these structures—including total biomass, cellular viability and overall structure—varied markedly among strains under the evaluated conditions. Strains isolated from cystic fibrosis patients exhibited distinct behaviors in most conducted assays compared to other strains. These findings provide new insights into the variability of biofilm composition and may contribute to a better understanding of the role of biofilms in fungal pathogenesis, persistence and treatment resistance. Full article
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22 pages, 706 KB  
Article
Clinical Effectiveness of a Novel Caffeine Nano-Cream for Cellulite Reduction: A Randomised Double-Blind Trial
by Thellie Ponto, Christofori M. R. R. Nastiti, Giuseppe Luna, Vânia R. Leite-Silva, Brioni R. Moore, Anthony Wright and Heather A. E. Benson
Pharmaceutics 2026, 18(2), 151; https://doi.org/10.3390/pharmaceutics18020151 (registering DOI) - 24 Jan 2026
Abstract
Background: Caffeine (CAF), whether extracted from plants or synthesised as a chemical compound, is considered the safest among other xanthine alkaloids. Novel nano-cream formulations have been successfully developed and evaluated to increase the potential of caffeine as a skin cosmeceutical, targeting the [...] Read more.
Background: Caffeine (CAF), whether extracted from plants or synthesised as a chemical compound, is considered the safest among other xanthine alkaloids. Novel nano-cream formulations have been successfully developed and evaluated to increase the potential of caffeine as a skin cosmeceutical, targeting the minimisation of cellulite appearance. Methods: Nano-cream formulations were prepared through a process of hot-temperature emulsification, in a variety of homogeniser combinations. Results: When chemical penetration enhancers (CPEs) (lanolin, transcutol, and propylene glycol), either alone or in combination, were incorporated into the nano-cream formulations, the permeation of CAF through skin increased. All nano-cream formulations achieved sustained delivery of CAF into and through the skin over 8 h (IVPT). Quantification of CAF from skin tissues was achieved using high-performance liquid chromatography (HPLC). The nano-cream formulation containing lanolin (LAN) showed the highest CAF permeation (8.829 ± 1.472 µg/cm2/h) through the skin compared to CAF in an aqueous solution (2.533 ± 0.480 µg/cm2/h) and a commercial CAF cellulite product with the same CAF concentration (2.827 ± 0.555 µg/cm2/h). Therefore, 2% CAF nano-cream formulation containing LAN was chosen for clinical testing. A double-blind, randomised, placebo-controlled paired trial was conducted, in which each volunteer applied active and placebo creams to the upper thighs twice daily for 12 weeks. The effect of the cream on skin appearance was monitored over 12 weeks. The primary outcome measures were reduced cellulite scores from 3.96 (95% CI: 3.16–4.76) to 2.50 (95% CI: 1.70–3.30) (active) compared with placebo from 3.88 (95% CI: 3.08–4.67) to 2.83 (95% CI: 2.03–3.63). The effect sizes (E.S.) indicated a moderate effect for the active CAF nano-cream formulation (E.S. = 0.475), while the placebo (E.S. = 0.286) had a small effect. Conclusion: We concluded that our optimised 2% CAF nano-cream formulation containing LAN offered an effective formulation strategy for enhancing skin penetration in the IVPT study. The LAN nano-cream formulation demonstrated efficacy and tolerability, both objectively and subjectively, in a human clinical trial. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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17 pages, 3526 KB  
Article
Spectral Precision: The Added Value of Dual-Energy CT for Axillary Lymph Node Characterization in Breast Cancer
by Susanna Guerrini, Giulio Bagnacci, Paola Morrone, Cecilia Zampieri, Chiara Esposito, Iacopo Capitoni, Nunzia Di Meglio, Armando Perrella, Francesco Gentili, Alessandro Neri, Donato Casella and Maria Antonietta Mazzei
Cancers 2026, 18(3), 363; https://doi.org/10.3390/cancers18030363 - 23 Jan 2026
Abstract
Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, [...] Read more.
Background/Objectives: To develop and validate a predictive model that combines morphological features and dual-energy CT (DECT) parameters to non-invasively distinguish metastatic from benign axillary lymph nodes in patients with breast cancer (BC). Methods: In this retrospective study, 117 patients (median age, 65 years; 111 women and 6 men) who underwent DECT followed by axillary lymphadenectomy between April 2015 and July 2023, were analyzed. A total of 375 lymph nodes (180 metastatic, 195 benign) were evaluated. Two radiologists recorded morphological criteria (adipose hilum status, cortical appearance, extranodal extension, and short-axis diameter) and placed regions of interest to measure dual-energy parameters: attenuation at 40 and 70 keV, iodine concentration, water concentration and spectral slope. Normalized iodine concentration was calculated using the aorta as reference. Univariate analysis identified variables associated with metastasis. Multivariate logistic regression with cross-validation was used to construct two models: one based solely on morphological features and one integrating water concentration. Results: On univariate testing, all DECT parameters and morphological criteria differed significantly between metastatic and benign nodes (p < 0.01). In multivariate analysis, water concentration emerged as the only independent DECT predictor (odds ratio = 0.97; p = 0.002) alongside cortical abnormality, absence of adipose hilum, extranodal extension and short-axis diameter. The morphologic model achieved an area under the receiver operating characteristic curve (AUC) of 0.871. Increasing water concentration increased the AUC to 0.883 (ΔAUC = 0.012; p = 0.63, not significant), with internal cross-validation confirming stable performance. Conclusions: A model combining standard morphologic criteria with water concentration quantification on DECT accurately differentiates metastatic from benign axillary nodes in BC patients. Although iodine-based metrics remain valuable indicators of perfusion, water concentration offers additional tissue composition information. Future multicenter prospective studies with standardized imaging protocols are warranted to refine parameter thresholds and validate this approach for routine clinical use. Full article
14 pages, 3401 KB  
Article
Selective Complement Inhibition in Anti-p200 Pemphigoid: Immune Infiltrate Profiles and Therapeutic Implications Compared to Bullous Pemphigoid
by Shirin Emtenani, Tina Rastegar Lari, Charlotte Kiehne, Nina van Beek, Maike M. Holtsche and Enno Schmidt
Biomolecules 2026, 16(2), 182; https://doi.org/10.3390/biom16020182 - 23 Jan 2026
Abstract
Anti-p200 pemphigoid is an autoimmune blistering disease (AIBD) caused by autoantibodies against laminin β4 and/or γ1, and clinically resembles bullous pemphigoid (BP) as well as the inflammatory variant of epidermolysis bullosa acquisita (EBA). All three diseases show IgG and/or C3 deposition along the [...] Read more.
Anti-p200 pemphigoid is an autoimmune blistering disease (AIBD) caused by autoantibodies against laminin β4 and/or γ1, and clinically resembles bullous pemphigoid (BP) as well as the inflammatory variant of epidermolysis bullosa acquisita (EBA). All three diseases show IgG and/or C3 deposition along the cutaneous basement membrane zone (BMZ). Although complement activation is central to BP and EBA pathogenesis, its role in anti-p200 pemphigoid remains unclear. To investigate this, we analyzed inflammatory infiltrates in lesional and perilesional skin from anti-p200 pemphigoid patients (n = 11), revealing a neutrophil-predominant pattern, with mixed neutrophil–eosinophil infiltrates in 81% of cases, which contrasted with the eosinophil-rich infiltrates typical of BP. Infiltrating neutrophils expressed C5aR1 and C5aR2. Complement fixation test (CFT) of patient sera demonstrated C3c deposition at the BMZ in 40% (20/50) of anti-p200 pemphigoid cases and 87% (13/15) of BP cases. Patients in both cohorts could be stratified into high, mild, and non-complement-fixating groups. Pharmacological inhibition of C1s (sutimlimab), C3 (compstatin), C5 (tesidolumab), or C5aR1 (avacopan) significantly blocked C3c or C5 deposition in vitro. These findings indicate that selective blockade of the classical, alternative, or terminal complement pathways effectively prevents BMZ complement deposition, highlighting pathway-specific complement inhibition as a potential therapeutic strategy for anti-p200 pemphigoid. Full article
24 pages, 4164 KB  
Article
Antimicrobial Activity of Acidifying Hyaluronic Acid–Starch Microfiber Dressings Against Clinical Isolates from Chronic Wounds
by Ivana Stará, Petra Moťková, Markéta Vydržalová, Marcela Pejchalová, Ladislav Burgert, Radim Hrdina, Marek Bouška, Martin Adam, Karel Královec and Iveta Brožková
J. Funct. Biomater. 2026, 17(2), 58; https://doi.org/10.3390/jfb17020058 - 23 Jan 2026
Abstract
Hyaluronic acid (HA) is a natural biopolymer widely used in wound dressings for its supportive role in the healing process. In this study, we investigated the occurrence of microorganisms in chronic wounds and evaluated the antimicrobial activity of newly synthesized HA–Starch-based materials enriched [...] Read more.
Hyaluronic acid (HA) is a natural biopolymer widely used in wound dressings for its supportive role in the healing process. In this study, we investigated the occurrence of microorganisms in chronic wounds and evaluated the antimicrobial activity of newly synthesized HA–Starch-based materials enriched with acidifying agents. Microbial isolates obtained from chronic wounds were tested for susceptibility using the agar diffusion method. The prepared materials exhibited significant antimicrobial activity against both reference strains and multidrug-resistant clinical isolates. Further characterization by scanning electron microscopy and elemental analysis confirmed uniform microfiber morphology and the expected elemental composition of the fibers. Cytotoxicity assessments performed using the xCELLigence system demonstrated the potential safety of developed materials. Overall, the results indicate that HA–Starch-based materials containing acidifying compounds exhibit strong in vitro antimicrobial activity against chronic-wound isolates, supporting their potential for further evaluation in wound care applications. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
11 pages, 322 KB  
Article
Gothelf’s Haplotype of COMT in Parkinson’s Disease: A Case–Control Study
by Zdenko Červenák, Ján Somorčík, Žaneta Zajacová, Andrea Gažová, Igor Straka, Zuzana André, Michal Minár and Ján Kyselovič
Biomedicines 2026, 14(2), 262; https://doi.org/10.3390/biomedicines14020262 - 23 Jan 2026
Abstract
Background: Catechol-O-methyltransferase (COMT) catalyzes catecholamine O-methylation and contributes to dopamine turnover, potentially influencing levodopa requirements in Parkinson’s disease (PD). We evaluated whether the Gothelf COMT haplotype—and its constituent variants rs2075507, rs4680 (Val158Met), and rs165599—differ in frequency between PD cases and controls. We then [...] Read more.
Background: Catechol-O-methyltransferase (COMT) catalyzes catecholamine O-methylation and contributes to dopamine turnover, potentially influencing levodopa requirements in Parkinson’s disease (PD). We evaluated whether the Gothelf COMT haplotype—and its constituent variants rs2075507, rs4680 (Val158Met), and rs165599—differ in frequency between PD cases and controls. We then tested associations between these variants and clinical phenotypes, with a prespecified focus on levodopa equivalent daily dose (LEDD). Finally, we examined whether haplotype structure and allele-specific context (e.g., background-dependent effects) help explain observed genotype–phenotype relationships in the PD cohort. Aim: Analysis of the rs2075507, rs4680 and rs165599 at individual and haplotype level between control and diseased groups. Furthermore, analysis of association of individual SNPs or haplotype level with clinical outcomes. Subjects and methods: Fifty-five individuals with Parkinson’s disease (PD) and fifty-three neurologically healthy controls were enrolled at a single center. Genomic DNA was isolated from peripheral blood, and three COMT variants—rs2075507 (promoter), rs4680/Val158Met (coding), and rs165599 (3′UTR)—were genotyped by Sanger sequencing. Allele, genotype, and tri-marker haplotype frequencies were estimated, and case–control differences were evaluated. Within the PD cohort, associations with clinical outcomes—primarily levodopa equivalent daily dose (LEDD)—were analyzed using multivariable linear models. Statistical tests were two-sided, with multiplicity control as specified in the corresponding tables. Results: The rs2075507 polymorphism showed a robust additive association with LEDD; each A allele predicted higher dose (LEDD ≈ +1331 mg/day, p = 0.001) after adjusting for age and sex. The tri-haplotype test did not show significant association with LEDD. Nevertheless, rs2075507 SNP strongly marked downstream backgrounds: in AA carriers, rs4680–rs165599 haplotypes were enriched for Val (G) and rs165599-G; in GG carriers, for rs165599-A with mixed Val/Met; and GA was A-loaded at both loci. Exact tests confirmed that AA and GG differed in rs4680–rs165599 composition, whereas GA vs. GG was not significant. Conclusions: The promoter variation at rs2075507 may represent the genetic contributor to levodopa dose requirements when modeled with SNP–SNP interactions, with its effect is modified mostly by rs165599 polymorphism. Tri-haplotypes do not independently predict LEDD. The rs4680 (coding) and rs165599 (3′UTR) context appears to fine-tune rather than determine dosing needs, mainly via interaction with rs2075507 SNP. Full article
(This article belongs to the Special Issue Advances in Parkinson’s Disease Research)
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