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24 pages, 3149 KiB  
Article
Evaluation of Aggregate Oral Fluid Sampling for Early Detection of African Swine Fever Virus Infection
by Bonto Faburay, Kathleen O’Hara, Marta Remmenga, Theophilus Odoom, Sherry Johnson, William Tasiame, Matilda Ayim-Akonor, Benita Anderson, Kingsley Kwabena Amoako, Diane Holder, Wu Ping, Michelle Zajac, Vivian O’Donnell, Lizhe Xu, Robin Holland, Corrie Brown, Randall Levings and Suelee Robbe-Austerman
Viruses 2025, 17(8), 1089; https://doi.org/10.3390/v17081089 - 6 Aug 2025
Abstract
African swine fever (ASF) needs to be controlled, and prevention of the spread of African swine fever virus (ASFV) is dependent on enhanced surveillance and early disease detection. Commercial swine operations, especially in North America, Europe, and Asia, are characterized by comparatively large [...] Read more.
African swine fever (ASF) needs to be controlled, and prevention of the spread of African swine fever virus (ASFV) is dependent on enhanced surveillance and early disease detection. Commercial swine operations, especially in North America, Europe, and Asia, are characterized by comparatively large numbers of pigs, and sampling individual pigs, which represents the main strategy for current ASF surveillance, can be both costly and labor intensive. A study performed in Ghana was designed to estimate the diagnostic sensitivity of pen-based aggregate oral fluid testing for ASFV in infected pigs in a pen of 30 animals and to evaluate its utility as a tool to support surveillance of ASF in the US. This study was performed in three phases: (i) virus (Ghana ASFV24) amplification in a target host species to generate the challenge inoculum; (ii) titration of the inoculum (10% spleen homogenate) in target host species to determine the minimum dose inducing acute ASF in pigs with survival up to 5–6 days post-inoculation (dpi); and (iii) the main study, involving 186 pigs, consisting of 6 replicates of 30 pigs per pen and one seeder pig inoculated with wildtype ASFV (highly virulent genotype II) per pen. Daily sampling of aggregate oral fluids, uncoagulated blood, oropharyngeal swabs, fecal and water nipple swabs, and recording of rectal temperatures and clinical observations was carried out. The seeder pigs were each inoculated intramuscularly with 0.5 mL of the 10% spleen homogenate, which induced the desired clinical course of ASF in the pigs, with survival of up to 6 dpi. ASFV DNA was detected in the seeder pigs as early as 1 dpi and 2 dpi in the blood and oropharyngeal swabs, respectively. Transmission of ASFV from the seeder pigs to the contact pig population was detected via positive amplification of ASFV DNA in aggregate oral fluid samples at 3 days post-contact (dpc) in 4 out of 6 pens, and in all 6 pens, at 4 dpc. Testing of oropharyngeal swabs and blood samples from individual pigs revealed a variable number of ASFV-positive pigs between 3 and 5 dpc, with detection of 100% positivity between 6 and 18 dpc, the study endpoint. These findings demonstrate the potential utility of aggregate oral fluid sampling for sensitive and early detection of ASFV incursion into naïve swine herds. It also demonstrates that testing of environmental samples from the premises could further enhance overall ASF early detection and surveillance strategies. Full article
(This article belongs to the Collection African Swine Fever Virus (ASFV))
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20 pages, 2316 KiB  
Article
Detection of Dental Anomalies in Digital Panoramic Images Using YOLO: A Next Generation Approach Based on Single Stage Detection Models
by Uğur Şevik and Onur Mutlu
Diagnostics 2025, 15(15), 1961; https://doi.org/10.3390/diagnostics15151961 - 5 Aug 2025
Abstract
Background/Objectives: The diagnosis of pediatric dental conditions from panoramic radiographs is uniquely challenging due to the dynamic nature of the mixed dentition phase, which can lead to subjective and inconsistent interpretations. This study aims to develop and rigorously validate an advanced deep [...] Read more.
Background/Objectives: The diagnosis of pediatric dental conditions from panoramic radiographs is uniquely challenging due to the dynamic nature of the mixed dentition phase, which can lead to subjective and inconsistent interpretations. This study aims to develop and rigorously validate an advanced deep learning model to enhance diagnostic accuracy and efficiency in pediatric dentistry, providing an objective tool to support clinical decision-making. Methods: An initial comparative study of four state-of-the-art YOLO variants (YOLOv8, v9, v10, and v11) was conducted to identify the optimal architecture for detecting four common findings: Dental Caries, Deciduous Tooth, Root Canal Treatment, and Pulpotomy. A stringent two-tiered validation strategy was employed: a primary public dataset (n = 644 images) was used for training and model selection, while a completely independent external dataset (n = 150 images) was used for final testing. All annotations were validated by a dual-expert team comprising a board-certified pediatric dentist and an experienced oral and maxillofacial radiologist. Results: Based on its leading performance on the internal validation set, YOLOv11x was selected as the optimal model, achieving a mean Average Precision (mAP50) of 0.91. When evaluated on the independent external test set, the model demonstrated robust generalization, achieving an overall F1-Score of 0.81 and a mAP50 of 0.82. It yielded clinically valuable recall rates for therapeutic interventions (Root Canal Treatment: 88%; Pulpotomy: 86%) and other conditions (Deciduous Tooth: 84%; Dental Caries: 79%). Conclusions: Validated through a rigorous dual-dataset and dual-expert process, the YOLOv11x model demonstrates its potential as an accurate and reliable tool for automated detection in pediatric panoramic radiographs. This work suggests that such AI-driven systems can serve as valuable assistive tools for clinicians by supporting diagnostic workflows and contributing to the consistent detection of common dental findings in pediatric patients. Full article
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37 pages, 5366 KiB  
Article
Oral Microbiota Composition and Its Association with Gastrointestinal and Developmental Abnormalities in Children with Autism Spectrum Disorder
by Zuzanna Lewandowska-Pietruszka, Magdalena Figlerowicz and Katarzyna Mazur-Melewska
Microorganisms 2025, 13(8), 1822; https://doi.org/10.3390/microorganisms13081822 - 4 Aug 2025
Abstract
Autism Spectrum Disorder (ASD) is frequently accompanied by gastrointestinal disturbances, dietary selectivity, and altered stress responses, with growing evidence pointing to gut–brain axis involvement. While intestinal microbiota has been extensively studied, the role of the oral microbiota remains underexplored. This study investigates the [...] Read more.
Autism Spectrum Disorder (ASD) is frequently accompanied by gastrointestinal disturbances, dietary selectivity, and altered stress responses, with growing evidence pointing to gut–brain axis involvement. While intestinal microbiota has been extensively studied, the role of the oral microbiota remains underexplored. This study investigates the associations between oral microbiota composition and behavioral, gastrointestinal, dietary, and neuroendocrine parameters in children with ASD. A total of 45 children aged 2–18 years comprised the study group. Data collection included oral swabs for 16S rRNA gene sequencing, salivary cortisol sampling, dietary records, and standardized behavioral assessments using the Vineland Adaptive Behavior Scale. A total of 363 microbial species across 11 phyla were identified. Significant correlations were observed between specific bacterial taxa and functional gastrointestinal disorders (FGIDs), dietary patterns, salivary cortisol rhythms, and functioning. Children with FGIDs, food selectivity, or macronutrient imbalances exhibited enriched pro-inflammatory taxa (e.g., Selenomonas, Megasphaera), whereas those with typical cortisol secretion or higher adaptive functioning showed greater microbial diversity and abundance of health-associated genera (e.g., Bifidobacterium dentium). These findings suggest that oral microbiota profiles may reflect systemic physiological and neurobehavioral traits in children with ASD. Further longitudinal studies are needed to clarify causal relationships and support the development of microbiota-targeted interventions. Full article
(This article belongs to the Special Issue Focus on Pediatric Infectious Diseases)
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13 pages, 248 KiB  
Article
The Prevalence and Impact of Dentinal Hypersensitivity on Adults’ Quality of Life in Saudi Arabia
by Haya Alayadi, Omar Alsadon, Maram Ali Alwadi, Alaa A. Alkhateeb, Deema Alroweilly, Zainab Alassmi and Wedad Alshehri
Dent. J. 2025, 13(8), 353; https://doi.org/10.3390/dj13080353 - 4 Aug 2025
Abstract
Background: Dentinal hypersensitivity (DH) significantly impacts oral health-related quality of life. While global prevalence estimates range from 10–15%, region-specific data from Saudi Arabia remain limited. This study also aligns with Saudi Vision 2030’s mental health initiatives, as DH-associated anxiety impacts overall well-being. This [...] Read more.
Background: Dentinal hypersensitivity (DH) significantly impacts oral health-related quality of life. While global prevalence estimates range from 10–15%, region-specific data from Saudi Arabia remain limited. This study also aligns with Saudi Vision 2030’s mental health initiatives, as DH-associated anxiety impacts overall well-being. This study assessed DH prevalence and quality of life impact among Saudi adults. Methods: A cross-sectional online survey was conducted among 748 Saudi adults aged ≥ 18 years between April and May. Data were collected using a validated Arabic Dentinal Hypersensitivity Experience Questionnaire (DHEQ) alongside socio-demographic variables. Participants reporting DH symptoms within 12 months were included in impact analyses. Descriptive statistics and one-way ANOVA examined associations between DHEQ scores and participant characteristics. Results: Self-reported DH prevalence was 54.3% (n = 406), substantially exceeding global estimates. Among affected individuals, mean DHEQ score was 0.56 ± 0.19, indicating moderate-to-substantial quality-of-life impact. Functional limitations were most affected, particularly enjoyment of eating and drinking (0.72 ± 0.21). Significant associations were identified between higher DHEQ scores and age extremes (<18 and >35 years; p < 0.001), higher income levels (p = 0.032), fewer teeth (p = 0.040), and dental pain presence (p = 0.009). Sex, residence, education, and employment showed no significant associations. Conclusions: More than half of Saudi adults reported DH symptoms, representing a significant public health concern with substantial quality of life implications. Prevalence substantially exceeds global estimates, highlighting the need for targeted interventions. Age, income, tooth count, and pain presence emerged as key factors. These findings support developing population-specific prevention strategies, particularly targeting younger and older adults with tooth loss. Full article
(This article belongs to the Special Issue Dentinal Hypersensitivity)
16 pages, 1991 KiB  
Article
Antihypertensive Effects of Lotus Seed (Nelumbo nucifera Gaertn.) Extract via eNOS Upregulation and Oxidative Stress Reduction in L-NAME-Induced Hypertensive Rats
by Anjaree Inchan, Tippaporn Bualeong, Worasak Kaewkong, Nitra Nuengchamnong, Phapada Apaikawee, Pakaporn Sa-Nguanpong, Wiriyaporn Sumsakul, Natthawut Charoenphon, Usana Chatturong, Watcharakorn Deetud and Krongkarn Chootip
Pharmaceuticals 2025, 18(8), 1156; https://doi.org/10.3390/ph18081156 - 4 Aug 2025
Abstract
Background/Objectives: Nelumbo nucifera Gaertn. (lotus) seeds have traditionally been used to treat hypertension, though their mechanisms remain unclear. This study investigated the antihypertensive effects of lotus seed extract (LSE) and its mechanisms in rats with Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. [...] Read more.
Background/Objectives: Nelumbo nucifera Gaertn. (lotus) seeds have traditionally been used to treat hypertension, though their mechanisms remain unclear. This study investigated the antihypertensive effects of lotus seed extract (LSE) and its mechanisms in rats with Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Methods: Male Sprague Dawley rats received L-NAME (40 mg/kg/day) in drinking water and were treated orally with LSE (5, 10, or 100 mg/kg/day), captopril (5 mg/kg/day), or a combination of LSE and captopril (2.5 mg/kg/day each) for 5 weeks. Hemodynamic parameters and histological changes in the left ventricle and aorta were assessed. Mechanistic studies included measurements of plasma nitric oxide (NO) metabolites, malondialdehyde (MDA), superoxide dismutase (SOD) activity, angiotensin II (Ang II), angiotensin-converting enzyme (ACE) activity, and protein expression via western blot. Results: L-NAME elevated systolic blood pressure and induced cardiovascular remodeling, oxidative stress, and renin-angiotensin system activation. LSE treatment reduced blood pressure, improved antioxidant status, increased NO bioavailability, and downregulated gp91phox and AT1R expression. The combination of low-dose LSE and captopril produced stronger effects than LSE alone, with efficacy comparable to captopril. Conclusions: These findings suggest that LSE exerts antihypertensive effects via antioxidant activity and inhibition of the renin-angiotensin system, supporting its potential as an adjunct therapy for hypertension. Full article
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13 pages, 3914 KiB  
Article
Biomechanical Analysis of Different Pacifiers and Their Effects on the Upper Jaw and Tongue
by Luca Levrini, Luigi Paracchini, Luigia Ricci, Maria Sparaco, Stefano Saran and Giulia Mulè
Appl. Sci. 2025, 15(15), 8624; https://doi.org/10.3390/app15158624 (registering DOI) - 4 Aug 2025
Viewed by 8
Abstract
Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study [...] Read more.
Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study aimed to simulate and predict the behavior of six different types of pacifiers and their functional interaction with the tongue and palate, with the goal of understanding their potential effects on orofacial growth and development. Materials and Methods: Biomechanical analysis using Finite Element Analysis (FEA) mathematical models was employed to evaluate the behavior of six different commercial pacifiers in contact with the palate and tongue. Three-dimensional solid models of the palate and tongue were based on the mathematical framework from a 2007 publication. This allowed for a detailed investigation into how various pacifier designs interact with soft and hard oral tissues, particularly the implications on dental and skeletal development. Results: The findings of this study demonstrate that pacifiers exhibit different interactions with the oral cavity depending on their geometry. Anatomical–functional pacifiers, for instance, tend to exert lateral compressions near the palatine vault, which can influence the hard palate and contribute to changes in craniofacial growth. In contrast, other pacifiers apply compressive forces primarily in the anterior region of the palate, particularly in the premaxilla area. Furthermore, the deformation of the tongue varied significantly across different pacifier types: while some pacifiers caused the tongue to flatten, others allowed it to adapt more favorably by assuming a concave shape. These variations highlight the importance of selecting a pacifier that aligns with the natural development of both soft and hard oral tissues. Conclusions: The results of this study underscore the crucial role of pacifier geometry in shaping both the palate and the tongue. These findings suggest that pacifiers have a significant influence not only on facial bone growth but also on the stimulation of oral functions such as suction and feeding. The geometry of the pacifier affects the soft tissues (tongue and muscles) and hard tissues (palate and jaw) differently, which emphasizes the need for careful selection of pacifiers during infancy. Choosing the right pacifier is essential to avoid potential negative effects on craniofacial development and to ensure that the benefits of proper oral function are maintained. Therefore, healthcare professionals and parents should consider these biomechanical factors when introducing pacifiers to newborns. Full article
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16 pages, 1047 KiB  
Article
Measuring Adult Heritage Language Lexical Proficiency for Studies on Facilitative Processing of Gender
by Zuzanna Fuchs, Emma Kealey, Esra Eldem-Tunç, Leo Mermelstein, Linh Pham, Anna Runova, Yue Chen, Metehan Oğuz, Seoyoon Hong, Catherine Pan and JK Subramony
Languages 2025, 10(8), 189; https://doi.org/10.3390/languages10080189 - 4 Aug 2025
Viewed by 15
Abstract
The present study analyzes individual differences in the facilitative processing of grammatical gender by heritage speakers of Spanish, asking whether these differences correlate with lexical proficiency. Results from an eye-tracking study in the Visual World Paradigm replicate prior findings that, as a group, [...] Read more.
The present study analyzes individual differences in the facilitative processing of grammatical gender by heritage speakers of Spanish, asking whether these differences correlate with lexical proficiency. Results from an eye-tracking study in the Visual World Paradigm replicate prior findings that, as a group, heritage speakers of Spanish show facilitative processing of gender. Importantly, in a follow-up within-group analysis, we test whether three measures of lexical proficiency—oral picture-naming, verbal fluency, and LexTALE—predict individual performance. We find that lexical proficiency, as measured by LexTALE, predicts overall word recognition; however, we observe no effects of the other measures and no evidence that lexical proficiency modulates the strength of the facilitative effect. Our results highlight the importance of carefully selecting tools for proficiency assessment in experimental studies involving heritage speakers, underscoring that the absence of evidence for an effect of proficiency based on a single measure should not be taken as evidence of absence. Full article
(This article belongs to the Special Issue Language Processing in Spanish Heritage Speakers)
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14 pages, 1169 KiB  
Article
Putting DOAC Doubts to Bed(Side): Preliminary Evidence of Comparable Functional Outcomes in Anticoagulated and Non-Anticoagulated Stroke Patients Using Point-of-Care ClotPro® Testing
by Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák, Eszter Johanna Jozifek and László Szapáry
J. Clin. Med. 2025, 14(15), 5476; https://doi.org/10.3390/jcm14155476 - 4 Aug 2025
Viewed by 14
Abstract
Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at [...] Read more.
Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article
(This article belongs to the Section Clinical Neurology)
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16 pages, 424 KiB  
Article
Evaluation of Clinical and Quality of Life Effects of Oral Semaglutide Use in Type 2 Diabetes from a Public Health View: A Prospective Study in Italy
by Paola Pantanetti, Vanessa Ronconi, Stefano Mancin, Cristina De Carolis, Sara Alberti, Orietta Pazzi, Sandra Di Marco, Grazia Michetti, Silvia Coacci, Veronica Mignini, Franco Gregorio, Giulia Baldoni, Sara Toderi, Sara Morales Palomares, Fabio Petrelli, Gabriele Caggianelli, Mauro Parozzi and Giovanni Cangelosi
Diabetology 2025, 6(8), 80; https://doi.org/10.3390/diabetology6080080 - 4 Aug 2025
Viewed by 23
Abstract
Background and Aim: Type 2 diabetes (T2D) continues to pose a significant public health challenge worldwide. Among therapeutic options, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven effective in optimizing glycemic control and improving cardiometabolic profiles. Semaglutide, now available in an oral formulation, [...] Read more.
Background and Aim: Type 2 diabetes (T2D) continues to pose a significant public health challenge worldwide. Among therapeutic options, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven effective in optimizing glycemic control and improving cardiometabolic profiles. Semaglutide, now available in an oral formulation, represents a modern strategy to improve patient adherence while supporting glucose and weight regulation. This study primarily investigated the effects of oral semaglutide on key metabolic indicators and secondary endpoints included cardiovascular risk markers (blood pressure and lipid profile) and patient-reported quality of life (QoL). Study Design and Methods: A longitudinal, prospective observational study was conducted involving patients with T2D across two Italian healthcare facilities. Participants were assessed at baseline (T0) and at three subsequent intervals—6 months (T1), 12 months (T2), and 18 months (T3)—following the initiation of oral semaglutide use. Key Findings: Out of 116 participants enrolled, 97 had complete and analyzable data. Across the 18-month follow-up, significant improvements were observed in glycemic parameters, with a notable reduction in HbA1c levels (T0 vs. T3, p = 0.0028; p ≤ 0.05, statistically significant). Self-reported outcomes showed enhanced quality of life, especially in treatment satisfaction and perceived flexibility (T0 vs. T3, p < 0.001). Conclusions: Daily administration of 14 mg oral semaglutide in individuals with T2D resulted in substantial benefits in glycemic regulation, weight reduction, cardiovascular risk management, and overall patient satisfaction. These findings reinforce its potential role as a sustainable and effective option in long-term diabetes care from both a clinical and public health perspective. Full article
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20 pages, 4007 KiB  
Article
Sublethal and Lethal Effects of Low-Dose Prothioconazole Alone and in Combination with Low-Dose Lambda-Cyhalothrin on Carabid Beetles in a Field-Realistic Scenario
by Enno Merivee, Anne Mürk, Karin Nurme, Mati Koppel, Angela Ploomi and Marika Mänd
Pollutants 2025, 5(3), 24; https://doi.org/10.3390/pollutants5030024 - 4 Aug 2025
Viewed by 84
Abstract
Environmental risk assessment (ERA) for pesticide approval in the context of predatory insects remains inadequate as it often overlooks the influence of agricultural practices. An increasing number of studies have shown that prolonged and synergistic pesticide exposure can elevate insect mortality. However, such [...] Read more.
Environmental risk assessment (ERA) for pesticide approval in the context of predatory insects remains inadequate as it often overlooks the influence of agricultural practices. An increasing number of studies have shown that prolonged and synergistic pesticide exposure can elevate insect mortality. However, such effects remain largely unstudied in non-target predatory carabid beetles. The carabid beetle Platynus assimilis was subjected to repeated oral and continuous contact exposure to low doses of prothioconazole (20 g ha−1), lambda-cyhalothrin (0.4 g ha−1), or their combination over a 64-day period. The food consumption rate, body mass, locomotor activity, and mortality were monitored throughout the experiment. All pesticide-treated groups showed significantly increased final mortality, with median lethal times (LT50) of 51.6 days for prothioconazole, 60.3 days for lambda-cyhalothrin, and 12.2 days for their combination. A significant synergistic effect on mortality was observed in the combined treatment group, with the highest synergistic ratio detected 20 days after the first exposure. Pesticide-treated beetles exhibited significant abnormalities in locomotor activity and body mass compared to the untreated group. These findings demonstrate that both time-cumulative mortality and potential synergistic interactions, reflecting field-realistic conditions, must be considered in ERA. Failure to do so may lead to an underestimation of pesticide toxicity to predatory carabids. Full article
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12 pages, 2639 KiB  
Article
Interspecies Interactions of Single- and Mixed-Species Biofilms of Candida albicans and Aggregatibacter actinomycetemcomitans
by Adèle Huc, Andreia S. Azevedo, José Carlos Andrade and Célia Fortuna Rodrigues
Biomedicines 2025, 13(8), 1890; https://doi.org/10.3390/biomedicines13081890 - 3 Aug 2025
Viewed by 288
Abstract
Polymicrobial biofilms involving fungal and bacterial species are increasingly recognized as contributors to persistent infections, particularly in the oral cavity. Candida albicans and Aggregatibacter actinomycetemcomitans are two commensals that can turn into opportunistic pathogens and are able to form robust biofilms. Objectives: [...] Read more.
Polymicrobial biofilms involving fungal and bacterial species are increasingly recognized as contributors to persistent infections, particularly in the oral cavity. Candida albicans and Aggregatibacter actinomycetemcomitans are two commensals that can turn into opportunistic pathogens and are able to form robust biofilms. Objectives: This study aimed to assess the interaction dynamics between these two microorganisms and to evaluate their susceptibility to fluconazole and azithromycin in single- and mixed-species forms. Methods: Biofilm biomass was quantified using crystal violet assays, while biofilm cell viability was assessed through CFU enumeration (biofilm viability assay). To assess the resistance properties of single versus mixed-species coincubations, we applied the antimicrobial susceptibility test (AST) to each drug, and analysed spatial organization with confocal laser scanning microscopy, using PNA-FISH. Results: The results indicated that both species can coexist without significant mutual inhibition. However, a non-reciprocal synergism was also observed, whereby mixed-species biofilm conditions promoted the growth of A. actinomycetemcomitans, while C. albicans growth remained stable. As expected, antimicrobial tolerance was elevated in mixed cultures, likely due to enhanced extracellular matrix production and potential quorum-sensing interactions, contributing to increased resistance against azithromycin and fluconazole. Conclusions: This study provides novel insights into previously rarely explored interactions between C. albicans and A. actinomycetemcomitans. These findings underscore the importance of investigating interspecies interactions within polymicrobial biofilms, as understanding their mechanisms, such as quorum-sensing molecules and metabolic cooperation, can contribute to improved diagnostics and more effective targeted therapeutic strategies against polymicrobial infections. Full article
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17 pages, 2487 KiB  
Article
Personalized Language Training and Bi-Hemispheric tDCS Improve Language Connectivity in Chronic Aphasia: A fMRI Case Study
by Sandra Carvalho, Augusto J. Mendes, José Miguel Soares, Adriana Sampaio and Jorge Leite
J. Pers. Med. 2025, 15(8), 352; https://doi.org/10.3390/jpm15080352 - 3 Aug 2025
Viewed by 169
Abstract
Background: Transcranial direct current stimulation (tDCS) has emerged as a promising neuromodulatory tool for language rehabilitation in chronic aphasia. However, the effects of bi-hemispheric, multisite stimulation remain largely unexplored, especially in people with chronic and treatment-resistant language impairments. The goal of this [...] Read more.
Background: Transcranial direct current stimulation (tDCS) has emerged as a promising neuromodulatory tool for language rehabilitation in chronic aphasia. However, the effects of bi-hemispheric, multisite stimulation remain largely unexplored, especially in people with chronic and treatment-resistant language impairments. The goal of this study is to look at the effects on behavior and brain activity of an individualized language training program that combines bi-hemispheric multisite anodal tDCS with personalized language training for Albert, a patient with long-standing, treatment-resistant non-fluent aphasia. Methods: Albert, a right-handed retired physician, had transcortical motor aphasia (TCMA) subsequent to a left-hemispheric ischemic stroke occurring more than six years before the operation. Even after years of traditional treatment, his expressive and receptive language deficits remained severe and persistent despite multiple rounds of traditional therapy. He had 15 sessions of bi-hemispheric multisite anodal tDCS aimed at bilateral dorsal language streams, administered simultaneously with language training customized to address his particular phonological and syntactic deficiencies. Psycholinguistic evaluations were performed at baseline, immediately following the intervention, and at 1, 2, 3, and 6 months post-intervention. Resting-state fMRI was conducted at baseline and following the intervention to evaluate alterations in functional connectivity (FC). Results: We noted statistically significant enhancements in auditory sentence comprehension and oral reading, particularly at the 1- and 3-month follow-ups. Neuroimaging showed decreased functional connectivity (FC) in the left inferior frontal and precentral regions (dorsal stream) and in maladaptive right superior temporal regions, alongside increased FC in left superior temporal areas (ventral stream). This pattern suggests that language networks may be reorganizing in a more efficient way. There was no significant improvement in phonological processing, which may indicate reduced connectivity in the left inferior frontal areas. Conclusions: This case underscores the potential of combining individualized, network-targeted language training with bi-hemispheric multisite tDCS to enhance recovery in chronic, treatment-resistant aphasia. The convergence of behavioral gains and neuroplasticity highlights the importance of precision neuromodulation approaches. However, findings are preliminary and warrant further validation through controlled studies to establish broader efficacy and sustainability of outcomes. Full article
(This article belongs to the Special Issue Personalized Medicine in Neuroscience: Molecular to Systems Approach)
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16 pages, 2901 KiB  
Article
Unveiling the Genetic Landscape of Canine Papillomavirus in the Brazilian Amazon
by Jeneffer Caroline de Macêdo Sousa, André de Medeiros Costa Lins, Fernanda dos Anjos Souza, Higor Ortiz Manoel, Cleyton Silva de Araújo, Lorena Yanet Cáceres Tomaya, Paulo Henrique Gilio Gasparotto, Vyctoria Malayhka de Abreu Góes Pereira, Acácio Duarte Pacheco, Fernando Rosado Spilki, Mariana Soares da Silva, Felipe Masiero Salvarani, Cláudio Wageck Canal, Flavio Roberto Chaves da Silva and Cíntia Daudt
Microorganisms 2025, 13(8), 1811; https://doi.org/10.3390/microorganisms13081811 - 2 Aug 2025
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Abstract
Papillomaviruses (PVs) are double-stranded DNA viruses known to induce a variety of epithelial lesions in dogs, ranging from benign hyperplasia to malignancies. In regions of rich biodiversity such as the Western Amazon, data on the circulation and genetic composition of canine papillomaviruses (CPVs) [...] Read more.
Papillomaviruses (PVs) are double-stranded DNA viruses known to induce a variety of epithelial lesions in dogs, ranging from benign hyperplasia to malignancies. In regions of rich biodiversity such as the Western Amazon, data on the circulation and genetic composition of canine papillomaviruses (CPVs) remain scarce. This study investigated CPV types present in oral and cutaneous papillomatous lesions in domiciled dogs from Acre and Rondônia States, Brazil. Sixty-one dogs with macroscopically consistent lesions were clinically evaluated, and tissue samples were collected for histopathological examination and PCR targeting the L1 gene. Among these, 37% were histologically diagnosed as squamous papillomas or fibropapillomas, and 49.2% (30/61) tested positive for papillomavirus DNA. Sequencing of the L1 gene revealed that most positive samples belonged to CPV1 (Lambdapapillomavirus 2), while one case was identified as CPV8 (Chipapillomavirus 3). Complete genomes of three CPV1 strains were obtained via high-throughput sequencing and showed high identity with CPV1 strains from other Brazilian regions. Phylogenetic analysis confirmed close genetic relationships among isolates across distinct geographic areas. These findings demonstrate the circulation of genetically conserved CPVs in the Amazon and reinforce the value of molecular and histopathological approaches for the accurate diagnosis and surveillance of viral diseases in domestic dogs, especially in ecologically complex regions. Full article
(This article belongs to the Topic Advances in Infectious and Parasitic Diseases of Animals)
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16 pages, 703 KiB  
Article
Retinoic Acid Profiles in Proliferative Verrucous Versus Homogeneous Leukoplakia: A Preliminary Nested Case–Control Study
by Cintia M. Chamorro-Petronacci, Alba Pérez-Jardón, Susana B. Bravo, Pilar Gándara-Vila, Andrés Blanco-Carrión, Yajaira Vanessa Avila-Granizo, Alejandro I. Lorenzo-Pouso, Sara A. Prieto-Barros and Mario Pérez-Sayáns
Biomedicines 2025, 13(8), 1881; https://doi.org/10.3390/biomedicines13081881 - 2 Aug 2025
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Abstract
Background: Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) remain challenging entities due to the absence of reliable prognostic biomarkers. All-trans retinoic acid (atRA), a pivotal modulator of epithelial differentiation and mucosal integrity, has been proposed as a candidate biomarker. This study [...] Read more.
Background: Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) remain challenging entities due to the absence of reliable prognostic biomarkers. All-trans retinoic acid (atRA), a pivotal modulator of epithelial differentiation and mucosal integrity, has been proposed as a candidate biomarker. This study sought to quantify plasma RA levels in patients with OL and PVL compared to healthy controls, assessing their potential clinical utility. Methods: A cohort of 40 participants was recruited, comprising 10 patients with OL, 10 with PVL, and 20 healthy controls. This nested case–control study was derived from previously characterized institutional databases of oral potentially malignant disorders. Plasma samples were analyzed for atRA concentration using high-precision mass spectrometry. Statistical comparisons were conducted to evaluate differences between groups and associations with clinical outcomes. Results: Patients with homogeneous OL exhibited significantly reduced plasma atRA concentrations (mean 2.17 ± 0.39 pg/mL) relative to both PVL patients (2.64 ± 0.56 pg/mL) and healthy controls (2.66 ± 0.92 pg/mL), with p-values of 0.009 and 0.039, respectively. No statistically significant difference was found between PVL patients and controls. Furthermore, atRA levels demonstrated no correlation with clinicopathological variables or malignant progression within the PVL cohort. Conclusions: These preliminary findings indicate that diminished plasma atRA levels may serve as a prognostic marker for homogeneous oral leukoplakia, whilst its role in PVL appears limited. However, effect estimates were imprecise, and additional studies are warranted. Full article
(This article belongs to the Special Issue Cellular and Pathogenesis Mechanisms in Oral Cancer)
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15 pages, 2024 KiB  
Article
Oxy210 Inhibits Hepatic Expression of Senescence-Associated, Pro-Fibrotic, and Pro-Inflammatory Genes in Mice During Development of MASH and in Hepatocytes In Vitro
by Feng Wang, Simon T. Hui, Frank Stappenbeck, Dorota Kaminska, Aldons J. Lusis and Farhad Parhami
Cells 2025, 14(15), 1191; https://doi.org/10.3390/cells14151191 - 2 Aug 2025
Viewed by 252
Abstract
Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, [...] Read more.
Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article
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