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10 pages, 914 KB  
Case Report
Toxic Shock Syndrome in a 45-Year-Old Woman Possibly Associated with Tampon Use: A Case Report of Multiorgan Failure Due to Streptococcus agalactiae
by Tina Zavidić, Ema Dejhalla and David Zahirović
Diseases 2025, 13(11), 376; https://doi.org/10.3390/diseases13110376 (registering DOI) - 16 Nov 2025
Abstract
Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, [...] Read more.
Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, such as multiorgan failure. Case Description: We report the case of a 45-year-old woman who developed TSS associated with tampon use. She presented with fever, chills, hypotension, and leg pain, progressing rapidly to septic shock and multiorgan failure. Blood and urine cultures revealed S. agalactiae group B, while a gynecological examination identified Ureaplasma urealyticum and S. agalactiae. Imaging demonstrated bilateral pneumonic infiltrates and pleural effusion. The patient required intensive care, vasopressor support, and broad-spectrum antibiotic therapy, leading to full clinical recovery. Discussion: Despite advances in tampon design, menstrual TSS remains a significant clinical concern. Early symptoms may be nonspecific, but rapid progression highlights the need for timely recognition and intervention. Although S. agalactiae is an uncommon cause of TSS, it should be considered in relevant clinical scenarios. Prompt empirical antibiotic therapy, followed by targeted treatment based on culture results, along with supportive intensive care, is essential to improve outcomes. Conclusions: Menstrual TSS continues to pose a serious health risk. Physicians should maintain a high index of suspicion in tampon users presenting with fever, rash, and shock. Early diagnosis and rapid initiation of appropriate therapy are crucial to reducing morbidity and mortality. Full article
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16 pages, 1370 KB  
Article
Evaluation of Immune Response Dynamics: Analyzing the Parameters of Complete Blood Count (CBC) in Experimental Borreliosis
by Diana Mihaela Alexandru, Diana Larisa Ancuţa and Cristin Coman
Life 2025, 15(11), 1758; https://doi.org/10.3390/life15111758 (registering DOI) - 16 Nov 2025
Abstract
The spirochete Borrelia is responsible for Lyme disease, a multisystemic infection and growing public health concern. This study aimed to evaluate host response dynamics to Borrelia bavariensis by analyzing hematological parameters as potential immuno-inflammatory markers in a murine model. Forty C3He/HeNCrl mice were [...] Read more.
The spirochete Borrelia is responsible for Lyme disease, a multisystemic infection and growing public health concern. This study aimed to evaluate host response dynamics to Borrelia bavariensis by analyzing hematological parameters as potential immuno-inflammatory markers in a murine model. Forty C3He/HeNCrl mice were inoculated intradermally with B. bavariensis (5 × 105 spirochetes/100 µL/mouse) and monitored for 90 days. Samples were collected at defined intervals for microbiological examination, hematology, and qPCR. Microbiological and qPCR testing revealed infection between days 7–21; results were negative on days 28–42. At later stages (days 60 and 90), Borrelia was only detectable by qPCR, highlighting differences in diagnostic sensitivity. Hematological analysis showed that the neutrophil-to-lymphocyte ratio (NLR) and systemic immuno-inflammatory index (SII) peaked on day 7 (p < 0.0001), followed by gradual normalization until day 35. These markers reflected the intensity of the inflammatory response and defined three distinct phases of host reaction. Overall, results demonstrate the complexity of immune responses in B. bavariensis infection and underscore the value of monitoring hematological indices for understanding host–pathogen interactions. This approach supports the potential use of simple blood markers in diagnostic strategies with translational relevance for clinical practice. Full article
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20 pages, 407 KB  
Article
The Association of Unhealthy Eating Behaviors with Sleep Quality Outcomes Among University Students: A Cross-Sectional Study
by Maha Al-Jawarneh, Shalini Chauhan, Ildikó Csölle and Szimonetta Lohner
Nutrients 2025, 17(22), 3580; https://doi.org/10.3390/nu17223580 (registering DOI) - 15 Nov 2025
Abstract
Background: This study examined the association between specific unhealthy eating behaviors and sleep quality among university students. Understanding how dietary habits affect sleep during significant lifestyle transitions associated with university experience can inform health promotion strategies. Methods: A cross-sectional design was [...] Read more.
Background: This study examined the association between specific unhealthy eating behaviors and sleep quality among university students. Understanding how dietary habits affect sleep during significant lifestyle transitions associated with university experience can inform health promotion strategies. Methods: A cross-sectional design was employed using a self-reported questionnaire to assess eating behaviors, timing of meals, and sleep-related behavior among a sample of international university students. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) tool. Statistical analyses were used to assess the relationship between eating patterns, overall sleep quality, and its components. Results: More than half of the students had poor sleep quality (51.7%). Daytime dysfunction was significantly more common in females than in males (27.9% vs. 8.3%, respectively; p < 0.001). Conversely, poor sleep efficiency was more prevalent among males than females (27.5% vs. 15.8%; p = 0.008). Multivariate logistic regression revealed that, compared to students who did not frequently consume heavy evening meals, those who did were more likely to experience poor sleep quality (OR = 2.73, 95% CI: 1.575–4.731). Similarly, those who frequently substitute snacks for main meals were more likely to experience poor sleep quality than those who did not (OR = 2.68, 95% CI: 1.465–4.895). Finally, students who ate within three hours of bedtime had higher odds of poor sleep quality compared to those who had their last meal more than three hours before bedtime (OR = 2.06, 95% CI: 1.173–3.629). Conclusions: Unhealthy dietary habits, such as consuming heavy evening meals, substituting snacks for main meals, and having a short meal-to-bedtime interval, were significantly associated with poor sleep quality. Interventions promoting healthier dietary patterns and appropriate meal timing could help improve sleep in this population. Full article
(This article belongs to the Section Nutrition and Public Health)
10 pages, 451 KB  
Article
Sleep Stage Monitoring in Congenital Heart Disease (CHD) Using a Digital Health Application Programming Interface (API)
by Charlotte Schöneburg, Isabel Uphoff, Viktoria Ludwig, Renate Oberhoffer-Fritz, Peter Ewert and Jan Müller
J. Clin. Med. 2025, 14(22), 8097; https://doi.org/10.3390/jcm14228097 (registering DOI) - 15 Nov 2025
Abstract
Background: Adults with congenital heart disease (CHD) are living longer but face increasing comorbidities. Sleep is a key health determinant, yet objective data in CHD remain limited. This study compared sleep characteristics of adults with CHD and controls using wearable technology and [...] Read more.
Background: Adults with congenital heart disease (CHD) are living longer but face increasing comorbidities. Sleep is a key health determinant, yet objective data in CHD remain limited. This study compared sleep characteristics of adults with CHD and controls using wearable technology and a Health Application Programming Interface (API). Methods: A total of 175 CHD patients (33.1 ± 10.3 years, 49.2% women) and 52 controls (34.4 ± 12.4 years, 40.4% women) completed seven continuous days of wrist-worn Garmin Vivosmart® 5 during routine follow-up at the TUM Klinikum Deutsches Herzzentrum. Sleep duration, phases, Sleep Scores, and weekday-weekend differences were analyzed, and multivariate models examined clinical and demographic predictors. Results: Total sleep duration and rapid eye movement (REM) sleep did not differ between groups. CHD patients had more deep sleep (83 ± 19 vs. 75 ± 16 min, p = 0.004) but lower Sleep Scores (74 ± 9 vs. 77 ± 9, p = 0.041). Within CHDs, deep sleep was higher on weekends than on weekdays (p = 0.033). Multivariate analyses showed no overall group effect, but age (p = 0.016), sex (p = 0.013), and body mass index (BMI; p < 0.001) significantly predicted sleep outcomes. Regression analyses in CHDs revealed female sex associated with longer REM sleep (p < 0.001), while higher BMI consistently predicted poorer outcomes. Disease severity was linked to lower Sleep Scores. Conclusions: Sleep in CHDs is broadly comparable to controls, but BMI, sex, and disease severity significantly shape outcomes. The additional variability between weekends and weekdays and a higher risk of sleep-disordered breathing, according to the literature, underscores that sleep is an underestimated target for prevention and clinical care in CHD. Full article
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20 pages, 13781 KB  
Article
Longitudinal Microbiome and Metabolome Shifts After Successful Intervention in Impending Stunting in Indonesian Infants
by Conny Tanjung, Ryohei Shibata, Bahrul Fikri, Titis Prawitasari, Andi Alfian Zainuddin, Aidah Juliaty, Dwi Sora Yullyana, Tonny Sundjaya, Hedi Kuswanto, Jessica Clarensia, Naoki Shimojo, Berthold Koletzko, Hiroshi Ohno and Nasrum Massi
Nutrients 2025, 17(22), 3570; https://doi.org/10.3390/nu17223570 - 14 Nov 2025
Abstract
Background/Objectives: Stunting and weight faltering (WF) remain pressing public health challenges in low- and middle-income countries, with long-term consequences for child growth, development, and survival. While the role of gut health in early growth is increasingly recognized, evidence on how the gut [...] Read more.
Background/Objectives: Stunting and weight faltering (WF) remain pressing public health challenges in low- and middle-income countries, with long-term consequences for child growth, development, and survival. While the role of gut health in early growth is increasingly recognized, evidence on how the gut microbiome and metabolome respond to nutritional interventions in WF infants is scarce. This study explored gut microbiome and metabolome changes in Indonesian infants aged 6–12 months who overcame WF following a one-month intervention. Methods: Infants were assigned to either a Nutritional Advice (NA) group or a Nutritional Advice plus Oral Nutritional Supplements (NAONS) group. Stool samples were collected before and after the intervention for microbiome (16S rRNA sequencing) and metabolome (LC-MS) analysis. Results: Significant shifts in gut microbial composition (beta diversity) and species richness (Chao1 index) were observed in both groups, suggesting enhanced microbial diversity and gut resilience. Within-group analysis revealed increases in beneficial genera such as Faecalibacterium and Peptostreptococcus, and a reduction in pro-inflammatory Fusobacterium in the NA group. The NAONS group showed a notable decrease in Proteus, a potentially pathogenic genus. Between-group comparisons indicated higher abundances of Lactococcus and Leuconostoc in the NAONS group, likely reflecting the influence of milk protein-rich supplements on microbial colonization, favoring lactic acid bacteria over SCFA-producing taxa, leading to better gut health. Metabolome analysis revealed significant changes in the NA group, increases in metabolites like Threonine, Tryptophan, and Xylose pointed to improved energy metabolism and gut health, while a decrease in Oxalic Acid suggested better metabolic efficiency. In contrast, the NAONS group, while benefiting from rapid weight gain, displayed a distinct metabolic profile influenced by high milk protein intake. No significant correlations were found between microbiome and metabolome changes, highlighting the complexity of gut-host interactions, suggesting that the interventions led to independent shifts in the aforementioned profiles. Conclusions: Overall, the findings suggest that nutritional interventions may enhance gut health and support recovery from weight faltering, providing insights into strategies that may contribute to restoring healthy growth trajectories and preventing stunting by modulating gut health. Full article
(This article belongs to the Section Pediatric Nutrition)
14 pages, 616 KB  
Article
Oman Vision 2040: A Transformative Blueprint for a Leading Healthcare System with International Standards
by Mohammed Al Ghafari, Badar Al Alawi, Idris Aal Jumaa and Salah Al Awaidy
Healthcare 2025, 13(22), 2911; https://doi.org/10.3390/healthcare13222911 - 14 Nov 2025
Abstract
Background/Objectives: Oman Vision 2040, the national blueprint for socio-economic transformation, aims to elevate the Sultanate to developed nation status, with the “Health” priority committed to building a “Leading Healthcare System with International Standards” via a Health in All Policies (HiAP) approach. This paper [...] Read more.
Background/Objectives: Oman Vision 2040, the national blueprint for socio-economic transformation, aims to elevate the Sultanate to developed nation status, with the “Health” priority committed to building a “Leading Healthcare System with International Standards” via a Health in All Policies (HiAP) approach. This paper critically reviews Oman’s strategic health directions and implementation frameworks under Vision 2040, assessing their alignment with global Sustainable Development Goals (SDGs) and serving as a case model for health system transformation. Methods: This study employs a critical narrative synthesis based on a comprehensive literature search that included academic, official government reports, and international organization sources. The analysis is guided by the World Health Organization’s (WHO) Health Systems Framework, providing a structured interpretation of progress across its six building blocks. Results: Key interventions implemented include integrated governance (e.g., Committee for Managing and Regulating Healthcare), diversified health financing (e.g., public private partnership (PPPs), Health Endowment Foundation), and strategic digital transformation (e.g., Al-Shifa system, AI diagnostics). Performance metrics show progress, with a rise in the Legatum Prosperity Index ranking and an increase in the Community Satisfaction Rate. However, critical challenges persist, including resistance to change during governance restructuring, cybersecurity risks from digital adoption, and system fragmentation that complicates a unified Non-Communicable Disease (NCD) response. Conclusions: Oman’s integrated approach, emphasizing decentralization, quality improvement, and investment in preventive health and human capital, positions it for sustained progress. The transformation offers generalizable insights. Successfully realizing Vision 2040 demands rigorous, evidence-informed policymaking to effectively address equity implications and optimize resource allocation. Full article
(This article belongs to the Special Issue Policy Interventions to Promote Health and Prevent Disease)
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23 pages, 3752 KB  
Article
Exploring the Relationship Between 15 Minute Access and Life Satisfaction
by Hamza Yasin, Inmaculada Mohíno and José Carpio-Pinedo
Land 2025, 14(11), 2259; https://doi.org/10.3390/land14112259 - 14 Nov 2025
Abstract
The 15 min city concept seeks to promote health, well-being, and quality of life by ensuring that essential services are located within a 15 min walking or cycling distance from housing and are accessible through sustainable modes of transportation. This study aims to [...] Read more.
The 15 min city concept seeks to promote health, well-being, and quality of life by ensuring that essential services are located within a 15 min walking or cycling distance from housing and are accessible through sustainable modes of transportation. This study aims to evaluate the compliance of this concept in a developing country context and provide supporting evidence by examining if residing within the 15 min reach to basic services affects perceived health, perceived accessibility, and life satisfaction. To assess pedestrian accessibility in Lahore, Pakistan, we adapted the NEXT proximity index—originally developed as part of the Landscape Metropolis Project in Italy—which scores 15 min access using open data sources. A network analysis was conducted to determine the shortest travel times to various points of interest, including education, transportation, healthcare, shops, restaurants, leisure spaces, places of worship, and financial services. Each hexagonal unit in the study area was assigned an access score proportional to its proximity to these facilities. These access scores were then analyzed using multiple regression models, based on survey data collected from 519 university students regarding their perceived health, perceived accessibility, and life satisfaction. According to the network analysis conducted using WorldPop estimates of Lahore’s population, only up to 30% of the population resides in areas that qualify as a 15 min city for each facility type. Moreover, access to bus stops significantly enhances both perceived accessibility and life satisfaction, while proximity to healthcare services shows the strongest positive association with life satisfaction. Full article
(This article belongs to the Special Issue Healthy and Inclusive Urban Public Spaces)
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21 pages, 698 KB  
Article
Effect of D-β-Hydroxybutyric Acid on Body Fat in Japanese Adults: A Randomized, Double-Blind, Placebo-Controlled Study
by Shohei Katsuya, Yoshikazu Kawata, Jun Kawamura, Tsuyoshi Goto, Tsuyoshi Takara and Jun Tsubota
Obesities 2025, 5(4), 82; https://doi.org/10.3390/obesities5040082 - 14 Nov 2025
Abstract
Ketone metabolism is currently being spotlighted for its health benefits. Strict dietary carbohydrate restriction is required to increase plasma ketone levels, which can be achieved with D-β-hydroxybutyric acid (D-BHB) supplementation as well. Although 2.9 g/day of D-BHB may reduce body fat without dieting [...] Read more.
Ketone metabolism is currently being spotlighted for its health benefits. Strict dietary carbohydrate restriction is required to increase plasma ketone levels, which can be achieved with D-β-hydroxybutyric acid (D-BHB) supplementation as well. Although 2.9 g/day of D-BHB may reduce body fat without dieting or exercise interventions, the lower effective intake limit of exogenous D-BHB remains unknown. In this randomized, double-blind, placebo-controlled study (UMIN000054231), we aimed to assess the safety and fat-reduction effects of a 12-week intake of D-BHB in healthy Japanese adults (low-dose [1.5 g/day, n = 33], normal-dose [2.9 g/day, n = 33], and placebo [n = 34] groups). Blood samples were collected pre- and post-intervention. Participants’ blood chemistry, anthropometric, and body composition parameters were investigated. The low-dose group had a lower visceral fat area and body mass index (BMI) and higher plasma ketone levels than the placebo group. The normal-dose group had a significantly lower visceral fat area than the placebo group. Significant between-group (normal-dose vs. placebo) differences were observed in body weight, BMI, body fat percentage, fat mass, and plasma ketone levels. Participants reported no D-BHB-related adverse effects or discomfort. In conclusion, 1.5 or 2.9 g/day of D-BHB may reduce body fat without dieting or exercise interventions. Full article
(This article belongs to the Special Issue The Impact of Food Compounds on Obesity Mechanisms)
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17 pages, 757 KB  
Article
Associations of Sociodemographic Factors, Lifestyle Habits, and Insomnia Severity with Obesity Indices in Spanish Workers: Sex-Specific Differences
by José Luis Ribes Valles, Pedro Juan Tárraga López, Ángel Arturo López González, Irene Coll Campayo, Carla Busquets-Cortés and José Ignacio Ramírez-Manent
Med. Sci. 2025, 13(4), 271; https://doi.org/10.3390/medsci13040271 - 14 Nov 2025
Abstract
Background: Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in [...] Read more.
Background: Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. Obesity and insomnia are prevalent public health issues with shared behavioral and physiological pathways. However, their interplay remains understudied in occupational cohorts. This study aimed to evaluate the associations of sociodemographic factors, lifestyle habits, and insomnia severity with multiple obesity indices in a large population of Spanish workers. Methods: We conducted a cross-sectional analysis of 84,898 workers (2021–2024). Data were obtained from annual occupational health assessments conducted across multiple Spanish regions between 2020 and 2024. Insomnia severity was assessed using the Insomnia Severity Index (ISI), dietary quality using the 14-item Mediterranean Diet Adherence Screener (MEDAS-14), and physical activity using the International Physical Activity Questionnaire—Short Form (IPAQ-SF). Adiposity was measured using Body Mass Index (BMI), waist-to-height ratio (WtHR), the Clínica Universidad de Navarra–Body Adiposity Estimator (CUN-BAE), and the Metabolic Score for Visceral Fat (METS-VF). Multivariable logistic regression models were used to examine associations adjusted for age, sex, education, and occupational social class. Results: Higher ISI scores were significantly and independently associated with elevated adiposity across all indices, with the strongest association observed for METS-VF (odds ratio = 1.19, 95% CI 1.14–1.25, p < 0.001). Women showed higher mean CUN-BAE and METS-VF values than men (CUN-BAE: 37.4 ± 6.2 vs. 25.6 ± 6.4; p < 0.001; METS-VF: 5.7 ± 0.7 vs. 6.4 ± 0.6; p < 0.001), despite lower BMI (25.3 ± 4.8 vs. 26.8 ± 4.3; p < 0.001). Lower physical activity (OR = 5.70; 95% CI 4.91–6.50), poor adherence to the Mediterranean diet (OR = 3.29; 95% CI 2.88–3.70), smoking (OR = 1.29; 95% CI 1.22–1.36), and lower occupational class (Class III: OR = 1.77; 95% CI 1.56–1.97) were also significantly associated with higher obesity markers. Associations were more pronounced among women and participants with severe insomnia symptoms. Conclusions: Insomnia severity, sociodemographic disadvantage, and unhealthy behaviors (low physical activity, poor diet, smoking) were all independent correlates of general and visceral adiposity. The findings underscore the need for comprehensive workplace health programs that integrate sleep quality assessment, dietary improvement, and physical activity promotion to prevent obesity and its metabolic consequences. Full article
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11 pages, 322 KB  
Article
Psychological and Demographic Predictors of Insomnia Severity: Evidence from a Community Sample in Ecuador
by Daniel Oleas, Paula Alvarado-Zurita, Elías Briones, Elizabeth Terranova, Nadia Soria-Miranda and Jose A. Rodas
Behav. Sci. 2025, 15(11), 1553; https://doi.org/10.3390/bs15111553 - 14 Nov 2025
Abstract
(1) Background: Insomnia is one of the most prevalent sleep disorders worldwide and a growing public health concern, yet the combined contribution of psychological and demographic factors remains understudied in Latin America. This study aimed to examine how perceived stress, generalized anxiety, and [...] Read more.
(1) Background: Insomnia is one of the most prevalent sleep disorders worldwide and a growing public health concern, yet the combined contribution of psychological and demographic factors remains understudied in Latin America. This study aimed to examine how perceived stress, generalized anxiety, and sociodemographic variables predict insomnia severity in Ecuadorian adults. (2) Methods: A community sample of 698 participants (31.7% men; M = 25.6 years, SD = 10.4) completed an online survey during nationwide electricity blackouts in 2024. Measures included the Insomnia Severity Index (ISI), the Perceived Stress Scale (PSS-10), the Generalized Anxiety Disorder Scale (GAD-7), and a demographic questionnaire. Hierarchical linear regressions were conducted to evaluate the relative contribution of predictors. (3) Results: Demographic variables (age, sex, employment status, and socioeconomic level) were not significant predictors of insomnia severity (R2 = 0.007). Perceived stress strongly predicted insomnia (ΔR2 = 0.207, p < 0.001), and generalized anxiety added further explanatory power (ΔR2 = 0.074, p < 0.001), with both factors contributing independently (β ≈ 1.96 and β ≈ 2.67). Interaction effects with socioeconomic status were non-significant. (4) Conclusions: Psychological factors explained nearly one-third of the variance in insomnia severity, underscoring the importance of stress and anxiety as core predictors and supporting the need for integrated psychological interventions to improve sleep health in Ecuador. Full article
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15 pages, 1238 KB  
Article
Comparative Effects of Abdominal Bracing and Valsalva Maneuver on Cerebral and Peripheral Hemodynamics in Healthy Adults: A Randomized Crossover Study
by Ji-Hyeon Yu, Ju-Yeon Jung, Yeong-Bae Lee, Jeong-Min Shim, Young-Don Son, Jiwon Yang and Chang-Ki Kang
Medicina 2025, 61(11), 2031; https://doi.org/10.3390/medicina61112031 - 14 Nov 2025
Abstract
Background and Objectives: Blood flow is critical for tissue oxygenation, and alterations in cerebrovascular and peripheral circulation have important health implications. This study aimed to examine the impact of distinct mechanisms for increasing intra-cavity pressure through the abdominal bracing (AB) and Valsalva [...] Read more.
Background and Objectives: Blood flow is critical for tissue oxygenation, and alterations in cerebrovascular and peripheral circulation have important health implications. This study aimed to examine the impact of distinct mechanisms for increasing intra-cavity pressure through the abdominal bracing (AB) and Valsalva maneuver (VM) on central and peripheral hemodynamics. Materials and Methods: A randomized crossover design was used, and thirty healthy young adults (age 21.9 ± 1.5 years; BMI 20.9 ± 1.8 kg/m2) performed AB and VM in a randomized order. All participants provided written informed consent, and the study protocol was approved by the Clinical Research Information Service (KCT0009742; registered on 30 August 2024). Hemodynamic responses were measured before and after each intervention, including heart rate, blood pressure, pulse wave velocity, carotid artery diameter, pulsatility index, resistive index, peripheral oxygen saturation, and cerebral oxygenation. Repeated-measures analysis of variance and paired t-tests were conducted on the datasets. Results: Both the VM and AB significantly increased heart rate (p < 0.001) and systolic blood pressure (VM: p = 0.015; AB: p < 0.001). Cerebral oxygen saturation decreased significantly (VM: p < 0.05; AB: p < 0.05), whereas oxyhemoglobin increased during both interventions, suggesting higher cerebral oxygen demand. The VM specifically increased the carotid pulsatility index (pre = 1.76 ± 0.28; post2 = 1.87 ± 0.33; p = 0.008), reflecting elevated central vascular resistance. In contrast, AB decreased peripheral oxygen saturation (pre = 98.43 ± 0.71; post1 = 97.49 ± 1.76; p < 0.001) and increased peripheral (heart–finger) pulse wave velocity (Lt: p = 0.026; Rt: p = 0.010), indicating greater stimulation of peripheral circulation. Conclusions: Distinct mechanisms that elevate intra-cavity pressure differentially influence central and peripheral hemodynamics. These findings suggest that intra-cavity pressure can selectively modulate hemodynamic responses, with potential applications in both clinical and exercise settings. Full article
(This article belongs to the Special Issue Physical Therapy: A New Perspective)
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19 pages, 7376 KB  
Article
Toxicological Impacts and Mechanistic Insights of Bisphenol a on Clear Cell Renal Cell Carcinoma Progression: A Network Toxicology, Machine Learning and Molecular Docking Study
by Jie Chen, Biao Ran, Bo Chen, Jingxing Bai, Shibo Jian, Yin Huang, Jiahao Yang, Jinze Li, Zeyu Chen, Qiang Wei, Jianzhong Ai, Liangren Liu and Dehong Cao
Biomedicines 2025, 13(11), 2778; https://doi.org/10.3390/biomedicines13112778 - 13 Nov 2025
Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent urological malignancy, accounting for approximately 1.6% of all cancer-related deaths in 2022. While endocrine-disrupting chemicals (EDCs) have been implicated as risk factors for ccRCC, the toxicological profiles and immune mechanisms underlying Bisphenol A [...] Read more.
Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent urological malignancy, accounting for approximately 1.6% of all cancer-related deaths in 2022. While endocrine-disrupting chemicals (EDCs) have been implicated as risk factors for ccRCC, the toxicological profiles and immune mechanisms underlying Bisphenol A (BPA) exposure in ccRCC progression remain inadequately understood. Materials and Methods: Protein–protein interaction (PPI) analysis and visualization were performed on overlapping genes between ccRCC and BPA exposure. This was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate potential underlying mechanisms. Subsequently, 108 distinct machine learning algorithm combinations were evaluated to identify the optimal predictive model. An integrated CoxBoost and Ridge regression model was constructed to develop a prognostic signature, the performance of which was rigorously validated across two independent external datasets. Finally, molecular docking analyses were employed to investigate interactions between key genes and BPA. Results: A total of 114 overlapping targets associated with both ccRCC and BPA were identified. GO and KEGG analyses revealed enrichment in cancer-related pathways, including pathways in cancer, endocrine resistance, PD-L1 expression and PD-1 checkpoint signaling, T-cell receptor signaling, endocrine function, and immune responses. Machine learning algorithm selection identified the combined CoxBoost-Ridge approach as the optimal predictive model (achieving a training set concordance index (C-index) of 0.77). This model identified eight key genes (CHRM3, GABBR1, CCR4, KCNN4, PRKCE, CYP2C9, HPGD, FASN), which were the top-ranked by coefficient magnitude in the prognostic model. The prognostic signature demonstrated robust predictive performance in two independent external validation cohorts (C-index = 0.74 in cBioPortal; C-index = 0.81 in E-MTAB-1980). Furthermore, molecular docking analyses predicted strong binding affinities between BPA and these key targets (Vina scores all <−6.5 kcal/mol), suggesting a potential mechanism through which BPA may modulate their activity to promote renal carcinogenesis. Collectively, These findings suggested potential molecular mechanisms that may underpin BPA-induced ccRCC progression, generating hypotheses for future experimental validation. Conclusions: These findings enhance our understanding of the molecular mechanisms by which BPA induces ccRCC and highlight potential targets for therapeutic intervention, particularly in endocrine and immune-related pathways. This underscores the need for collaborative efforts to mitigate the impact of environmental toxins like BPA on public health. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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12 pages, 275 KB  
Article
Positive Emotional States in Dairy Cows: Reflections in Milk Quality and Udder Health
by Silvana Popescu, Daniela Elena Babiciu, Eva Andrea Lazar, Anamaria Blaga Petrean and Sorana Daina
Animals 2025, 15(22), 3290; https://doi.org/10.3390/ani15223290 - 13 Nov 2025
Abstract
Integrating positive welfare indicators into dairy science is gaining attention, yet the biological correlates of affective states in commercial herds remain poorly understood. This study explored associations between dairy cows’ emotional states quantified through the Positive Affect Index (PAI) derived from the Qualitative [...] Read more.
Integrating positive welfare indicators into dairy science is gaining attention, yet the biological correlates of affective states in commercial herds remain poorly understood. This study explored associations between dairy cows’ emotional states quantified through the Positive Affect Index (PAI) derived from the Qualitative Behaviour (QBA) Assessment and milk biomarkers, yield, and udder health indicators across 37 commercial farms. Descriptive statistics, housing-adjusted linear regressions, and partial Spearman correlations were used to explore these relationships. Higher PAI values, indicating more positive herd-level emotional states, were significantly associated with lower SCC (22% reduction, p = 0.016) and lower odds of elevated DSCC (OR = 0.69, p = 0.002), reflecting improved udder health. Positive affect was also linked to a higher lactose concentration (p < 0.001) and an increased fat-to-protein ratio (FPR). A tendency for higher milk yield (+1.07 L per milking, p = 0.077) and slightly lower protein content was observed, consistent with a dilution effect. These associations remained robust after sensitivity analyses and were independent of housing type. The results demonstrate that milk composition and udder health biologically reflect positive emotional states, supporting the integration of behavioural assessments and milk biomarkers as a non-invasive framework for advancing welfare-oriented and precision dairy farming. Full article
(This article belongs to the Special Issue Ruminant Welfare Assessment—Second Edition)
21 pages, 1901 KB  
Article
Phase II Clinical Study on Low-Intensity-Noise Tinnitus Suppression (LINTS) for Tinnitus Treatment
by Konstantin Tziridis, Lara Heep, Nathalie Piwonski, Katharina Nguyen, Nikola Kölbl, Achim Schilling and Holger Schulze
Brain Sci. 2025, 15(11), 1222; https://doi.org/10.3390/brainsci15111222 - 13 Nov 2025
Abstract
Background/Objectives: Tinnitus treatment is often based on coping strategies, as, still, no causal treatment is available. Based on our “Erlangen model” of tinnitus development, we treated tinnitus patients with individualized, non-masking low-intensity noise (LIN) to reduce the tinnitus loudness. Methods: A [...] Read more.
Background/Objectives: Tinnitus treatment is often based on coping strategies, as, still, no causal treatment is available. Based on our “Erlangen model” of tinnitus development, we treated tinnitus patients with individualized, non-masking low-intensity noise (LIN) to reduce the tinnitus loudness. Methods: A total of 72 adult patients with a tinnitus severity index below IV (tinnitus health questionnaire, THQ), a hearing loss not exceeding 40 dB up to 6 kHz, and without experience in hearing aid (HA) usage were included in this study. Their audiograms, tinnitus parameters, THQ scores, and optimal LIN were determined individually. Patients were double-blinded, assigned to a treatment-only (TO) or placebo-and-treatment (PT) group. The TO patients received treatment for four weeks while the PT patients initially received a placebo (low-intensity white noise) stimulation for two weeks and, hereinafter, treatment for four weeks. Every two weeks, the measurements listed above were repeated. The long-term effects on THQ were assessed four weeks after the end of treatment. The data were analyzed by parametric and nonparametric statistics. Results: We identified a significant decrease in the THQ score already after two (η2 = 0.14) and four weeks of treatment (η2 = 0.43), that was still present four weeks after the end of treatment (η2 = 0.15) in the TO group. Subjective individual patient reports hint at a possible complete suppression of the percept by LINTS. The PT group profited much less, as the initial placebo treatment seemed to counteract the LIN effects. Conclusions: Individually fitted LIN treatment seems to be able to suppress tinnitus, in some cases completely. The optimal fitting of the LIN is crucial for treatment success. Full article
(This article belongs to the Special Issue New Insights Into the Treatment of Subjective Tinnitus)
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17 pages, 6038 KB  
Article
Impact of Hypoxia on Intestinal Health and Gut Microbiota in Anadara granosa
by Yueyue Li, Guangzhi Cheng, Jiaqi Jin, Yangguang Ji, Xiaolin Zhang, Yongbo Bao and Zhilan Peng
Fishes 2025, 10(11), 584; https://doi.org/10.3390/fishes10110584 - 13 Nov 2025
Abstract
Dissolved oxygen (DO) is a crucial determinant of aquatic organism health. This study demonstrates that hypoxia (at MH, 2.0 mg/L; SH, 0.5 mg/L) disrupts intestinal homeostasis in the blood clam, Anadara granosa. Exposure to hypoxia induced severe histopathological damage, including villus loss, [...] Read more.
Dissolved oxygen (DO) is a crucial determinant of aquatic organism health. This study demonstrates that hypoxia (at MH, 2.0 mg/L; SH, 0.5 mg/L) disrupts intestinal homeostasis in the blood clam, Anadara granosa. Exposure to hypoxia induced severe histopathological damage, including villus loss, inflammatory cell infiltration, and epithelial cell vacuolization. Immune-related gene expression analysis revealed coordinated regulation, with TLR4 and NF-κB significantly up-regulated by 4.5-fold and 5-fold, respectively, in the SH14 group, while HSP70 showed a remarkable 13-fold increase in the MH14 group. In contrast, TAK1 and TRAF6 exhibited substantial downregulation. High-throughput sequencing of the 16S rRNA gene revealed a significant reduction in gut microbiota diversity under hypoxic conditions, as evidenced by notable decreases of approximately 30% in the Chao1 index and 35% in the Shannon index in the SH group compared to the normoxic control (N group). Functional pathway analysis indicated alterations in pathways associated with xenobiotic biodegradation, lipid metabolism, and energy metabolism. These findings highlight a strong association between hypoxia and adverse intestinal health outcomes in A. granosa, underscoring the critical importance of maintaining adequate dissolved oxygen levels to support bivalve health. Future research should aim to develop strategies to mitigate hypoxia-induced stress and further elucidate the molecular mechanisms underlying hypoxia adaptation in bivalves. Full article
(This article belongs to the Section Physiology and Biochemistry)
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