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Volume 16
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Life, Volume 16, Issue 4 (April 2026) – 169 articles

Cover Story (view full-size image): Hypertension and chronic kidney disease (CKD) are closely linked and are major global health concerns. Hypertension increases the risk of cardiovascular disease, the leading cause of death in CKD. Damage to the endothelial glycocalyx (eGC), which protects the endothelium, regulates permeability, and maintains homeostasis, plays a key role in both conditions. Its damage (“shedding”) is an early sign of dysfunction, driven by oxidative stress and inflammation. In hypertension, eGC loss, often worsened by a high-salt diet, can reduce nitric oxide availability and increase arterial stiffness. In CKD, toxins, inflammation, and pressure further damage the eGC, leading to albuminuria and increased cardiovascular risk. eGC shedding markers like SDC-1 and HA may indicate early disease progression. View this paper
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20 pages, 3983 KB  
Review
Beyond the Beam: Multimodal Imaging and Surveillance of Post-Radiotherapy Changes in the Breast
by Silvia Gigli, Giacomo Bonito, Emanuele David, Corrado Spatola, Brandon M. Ascenzi, Roberta Valerieva Ninkova, Sandrine Riccardi, Lucia Malzone, Paolo Ricci and Lucia Manganaro
Life 2026, 16(4), 701; https://doi.org/10.3390/life16040701 - 21 Apr 2026
Viewed by 790
Abstract
Breast-conserving therapy, consisting of lumpectomy followed by adjuvant radiotherapy, is the standard of care for early-stage breast cancer, providing oncologic outcomes equivalent to mastectomy while preserving breast anatomy and quality of life. Radiotherapy remains a cornerstone of treatment across disease stages, significantly reducing [...] Read more.
Breast-conserving therapy, consisting of lumpectomy followed by adjuvant radiotherapy, is the standard of care for early-stage breast cancer, providing oncologic outcomes equivalent to mastectomy while preserving breast anatomy and quality of life. Radiotherapy remains a cornerstone of treatment across disease stages, significantly reducing local recurrence rates and improving long-term survival. Advances in radiotherapy techniques—including conventional fractionation, hypofractionation, tumor-bed boost delivery, and regional nodal irradiation—have optimized oncologic efficacy while inducing a broad spectrum of time-dependent morphological changes in breast tissue. Accurate imaging surveillance is therefore essential to distinguish expected post-radiotherapy changes from tumor recurrence and to avoid unnecessary diagnostic or therapeutic interventions. This review provides a comprehensive overview of contemporary breast radiotherapy protocols, their impact on post-treatment imaging appearances, and current recommendations for imaging surveillance. Characteristic findings across mammography, ultrasound, magnetic resonance imaging, and nuclear medicine modalities are discussed, with emphasis on their temporal evolution from acute inflammatory changes to chronic fibrosis, fat necrosis, and architectural distortion. Recognition of these imaging patterns, together with integration of radiotherapy-related parameters into image interpretation, is crucial for accurate diagnosis, early detection of recurrence, and informed clinical management of breast cancer survivors. Full article
(This article belongs to the Special Issue Advances in Imaging for Female Patients: Breast and Gynecological Diagnostics)
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22 pages, 1043 KB  
Systematic Review
Update on Repetitive Transcranial Magnetic Stimulation in Post-Stroke Cognitive Rehabilitation: A Systematic Review of Randomized Clinical Trials
by Davide N. Tringali, Rosario Ferlito, Rita Bella, Mariagiovanna Cantone, Rita Chiaramonte, Raffaele Ferri, Francesco Fisicaro, Michele Iacona, Maria P. Mogavero, Manuela Pennisi, Michele Vecchio and Giuseppe Lanza
Life 2026, 16(4), 700; https://doi.org/10.3390/life16040700 - 21 Apr 2026
Viewed by 754
Abstract
Background: We synthesized evidence from randomized clinical trials (RCTs) published between 2019 and 2025 on repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI) and compared different stimulation parameters, cortical targets, and combinations with rehabilitation interventions. Methods: A systematic review according to [...] Read more.
Background: We synthesized evidence from randomized clinical trials (RCTs) published between 2019 and 2025 on repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI) and compared different stimulation parameters, cortical targets, and combinations with rehabilitation interventions. Methods: A systematic review according to PRISMA guidelines examined the RCTs applying rTMS in adults with PSCI compared with control or sham groups. The primary outcome was improvement in cognitive function and functional outcomes measured with standardized scales. Results: Fifteen studies, involving a total of 732 patients, were included. The most frequently investigated were high-frequency (≥10 Hz) stimulation protocols of the left dorsolateral prefrontal cortex, with treatment cycles ranging from 2 to 6 weeks. Overall, rTMS was generally safe and well tolerated, with rare and mild adverse events. Several studies reported improvements in cognitive performance following rTMS, although effects were variable across trials and need caution in light of heterogeneity in stimulation protocols, sample sizes, outcome measures, and methodological quality. In most cases, rTMS or intermittent theta burst stimulation combined with structured cognitive training yielded greater cognitive and functional gains than stimulation or rehabilitation alone. This suggests a positive interaction between rTMS and cognitive training, although current evidence does not yet allow definitive conclusions. Conclusions: rTMS appears to be a promising strategy for post-stroke cognitive rehabilitation, particularly for attention and executive functioning. However, heterogeneity in stimulation protocols and outcome measures, along with limited sample sizes and short follow-up, reduces the certainty and comparability of current evidence. The widespread reliance on global screening tools may further underestimate domain-specific effects. Future multicentre trials with standardized protocols and more sensitive cognitive assessments are needed to clarify efficacy and guide further clinical application of rTMS in PSCI. Full article
(This article belongs to the Special Issue Neurological Disorders: Pathophysiological Mechanisms, Translational Breakthroughs, and Therapeutic Horizons)
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19 pages, 1042 KB  
Systematic Review
Sleep Disorders and Cognitive Function in Multiple Sclerosis: A Systematic Review of Polysomnographic Studies and Implications for Neurorehabilitation Strategies
by Laura-Elena Cucu, Laura-Cristina Baciu, Cristina Grosu, Emilian Bogdan Ignat, Carmen Marinela Cumpăt, Mihai Roca, Costin Chirica, Gabriela Popescu and Maria-Magdalena Leon
Life 2026, 16(4), 699; https://doi.org/10.3390/life16040699 - 21 Apr 2026
Viewed by 515
Abstract
Cognitive rehabilitation represents a cornerstone of disease management in multiple sclerosis (MS), targeting the progressive cognitive decline that affects a significant proportion of patients. Despite growing evidence supporting its clinical utility, rehabilitation outcomes remain variable, and identifying modifiable factors that limit its efficacy [...] Read more.
Cognitive rehabilitation represents a cornerstone of disease management in multiple sclerosis (MS), targeting the progressive cognitive decline that affects a significant proportion of patients. Despite growing evidence supporting its clinical utility, rehabilitation outcomes remain variable, and identifying modifiable factors that limit its efficacy has become a research priority. Sleep disorders are common in MS and have been increasingly linked to cognitive impairment, yet evidence based on objective polysomnographic assessment remains limited, and the specific parameters that influence cognitive function are poorly understood. This review synthesizes evidence from polysomnographic studies examining how sleep disturbances influence cognitive performance in MS patients. Following a systematic search of PubMed, EMBASE, and the Cochrane Library, 488 patients were included. Sleep fragmentation, reduced sleep efficiency, and oxygen desaturation indices were associated with impairments in attention, information processing speed, and verbal memory, with nocturnal hypoxia emerging as a potentially important mechanism of cognitive impairment. These findings suggest that identifying and treating sleep disorders may be essential for optimizing cognitive rehabilitation outcomes in MS. Further longitudinal studies are needed to determine whether addressing sleep pathology can enhance rehabilitation efficacy and preserve cognitive function over time. Full article
(This article belongs to the Special Issue Neurological Diseases: Prevention, Diagnostics, Treatment and Rehabilitation—2nd Edition)
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13 pages, 582 KB  
Systematic Review
Preclinical Evidence for Antidepressant-like Effects of Histamine H3 Receptor Modulation: A Systematic Review and Meta-Analysis
by Ilaria Pullano, Anna Maria Iazzolino, Stefania Landi, Annarita Vignapiano, Francesco Monaco and Luca Steardo, Jr.
Life 2026, 16(4), 698; https://doi.org/10.3390/life16040698 - 21 Apr 2026
Viewed by 539
Abstract
Background: Histamine H3 receptor-targeting compounds modulate histaminergic tone and downstream monoaminergic/arousal circuits and have been proposed to exert potential antidepressant-like effects in preclinical models. Methods: We conducted a systematic review and meta-analysis of rodent studies evaluating H3-related interventions on depression-like behavior. We screened [...] Read more.
Background: Histamine H3 receptor-targeting compounds modulate histaminergic tone and downstream monoaminergic/arousal circuits and have been proposed to exert potential antidepressant-like effects in preclinical models. Methods: We conducted a systematic review and meta-analysis of rodent studies evaluating H3-related interventions on depression-like behavior. We screened 60 records, assessed 12 studies qualitatively (four CORE, eight sensitivity), and included nine studies in random-effects meta-analyses (REML). Primary outcomes were the forced swim test (FST) and tail suspension test (TST); effect sizes were summarized as Hedges’ g (positive values indicate reduced immobility). Results: In the primary ALL analysis, H3-related interventions improved FST outcomes (g = 1.40, 95% CI 0.83–1.97; k = 7) and were also associated with improved TST outcomes, albeit with substantial heterogeneity (g = 2.27, 95% CI 0.80–3.73; k = 5). CORE-only analyses were directionally consistent but less precise (FST: g = 1.11, 95% CI −0.06–2.27; k = 3; TST: g = 2.95, 95% CI 0.87–5.02; k = 2). Sucrose preference was reported in one study and indicated improvement (g = 1.61, 95% CI 0.29–2.92). Conclusions: H3-related interventions show an antidepressant-like signal in rodent FST and TST, with greater heterogeneity for TST, highlighting the need for more standardized and adequately powered preclinical studies. Full article
(This article belongs to the Section Pharmaceutical Science)
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15 pages, 269 KB  
Article
The Role of Central Sensitization and Emotional Comorbidities in Temporomandibular Involvement Among Patients with Psoriatic Arthritis
by José Antonio Blanco, Antonio Márquez, Esther Toledano, Rubén Queiro, Javier Martín-Vallejo, María José Fernández-Gómez, Carolina Chacón, Roberto Díaz-Peña, Daniel Martín, Cristina Hidalgo, María Dolores Sánchez, Moisés León González and Carlos Montilla
Life 2026, 16(4), 697; https://doi.org/10.3390/life16040697 - 21 Apr 2026
Viewed by 581
Abstract
Background: Temporomandibular disorders (TMDs) are frequently underdiagnosed in patients with psoriatic arthritis (PsA), and the mechanisms underlying their development remain poorly understood. While inflammatory processes may contribute, central pain sensitization and psychological factors could play a significant role in TMD pathogenesis. Objective: The [...] Read more.
Background: Temporomandibular disorders (TMDs) are frequently underdiagnosed in patients with psoriatic arthritis (PsA), and the mechanisms underlying their development remain poorly understood. While inflammatory processes may contribute, central pain sensitization and psychological factors could play a significant role in TMD pathogenesis. Objective: The objectives of this study were to evaluate clinical characteristics, disease activity, psychiatric comorbidities, and pain processing mechanisms in PsA patients with and without TMD and to identify factors independently associated with temporomandibular involvement. Methods: This cross-sectional observational study included 190 consecutive PsA patients (CASPAR criteria) from a single tertiary center. Patients with fibromyalgia were excluded. TMD was assessed by maxillofacial specialists. Disease activity (cDAPSA), functional status (HAQ-DI), disease impact (PsAID-12), central sensitization (Central Sensitization Inventory, CSI), kinesiophobia (Tampa Scale for Kinesiophobia, TSK-11), pressure pain threshold (algometry), and emotional comorbidities (Hospital Anxiety and Depression Scale, HADS) were evaluated. An exploratory binary logistic regression identified a factor independently associated with TMD. Results: Twenty-five patients (13.1%) had confirmed TMD, with a significant female predominance (76% vs. 39%; p = 0.001). Only 24% of patients exhibited structural damage on orthopantomography. TMD patients showed higher CSI scores (52 vs. 32; p < 0.001), greater kinesiophobia (TSK-11: 30 vs. 23; p = 0.002), lower pressure pain thresholds (2.1 vs 2.7 kg/cm2; p = 0.03), and higher anxiety (HADS-A: 9 vs. 5; p = 0.001) and depression scores (HADS-D: 6.5 vs. 3; p = 0.001). TMD patients also exhibited worse functional status (HAQ-DI: 0.7 vs. 0.3; p = 0.001) and greater disease impact (PsAID-12: 4.8 vs. 2.9; p = 0.001). In multivariate analysis, central sensitization (OR: 1.1; 95%CI: 1.04–1.18; p = 0.001) and anxiety (OR: 1.2; 95%CI: 1.02–1.61; p = 0.02) were independently associated with TMD (Nagelkerke R2 = 0.48). Conclusion: TMD in PsA is associated with central sensitization and anxiety rather than mechanisms secondary to bone damage. These findings support a multidimensional approach incorporating screening for central sensitization and psychiatric comorbidities in PsA patients with temporomandibular symptoms. Full article
(This article belongs to the Special Issue New Advances in the Treatment and Assessment of Temporomandibular Joint Disorders)
18 pages, 1356 KB  
Review
Neutrophil Heterogeneity: Molecules to Cellular Behavior
by Jonghee Lee and Jingu Lee
Life 2026, 16(4), 696; https://doi.org/10.3390/life16040696 - 21 Apr 2026
Viewed by 828
Abstract
Neutrophils constitute the largest fraction of total circulating leukocytes in humans and mediate early innate immune responses. Although they are often considered a uniform population of short-lived immune cells, emerging evidence from single-cell RNA sequencing and high-dimensional flow cytometry has revealed that neutrophils [...] Read more.
Neutrophils constitute the largest fraction of total circulating leukocytes in humans and mediate early innate immune responses. Although they are often considered a uniform population of short-lived immune cells, emerging evidence from single-cell RNA sequencing and high-dimensional flow cytometry has revealed that neutrophils are functionally and phenotypically heterogeneous in both healthy and pathological conditions. However, a critical gap is how molecularly defined neutrophil states translate into distinct spatiotemporal behaviors in vivo. This review summarizes our current understanding of the molecular signatures underlying neutrophil heterogeneity and explores the functional in vivo behaviors in various diseases, including cancer, sepsis, and ischemic stroke. We also discuss the potential of intravital imaging to bridge the gap between static molecular profiling and dynamic cellular behavior, offering a comprehensive view of the functional heterogeneity of neutrophils. Full article
(This article belongs to the Section Physiology and Pathology)
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15 pages, 371 KB  
Article
Effect of Lateralization, Age, and Sex on Frequency Following Response in Children: Neural Speech Encoding to a 170 ms [da] Stimulus
by Caroline Donadon, Milaine Dominici Sanfins, Aline Buratti Sanches, Gabriele Libano de Souza Cardoso, Ayla Gabrielle Paschoalon de Mello, Piotr Henryk Skarzynski and Maria Francisca Colella-Santos
Life 2026, 16(4), 695; https://doi.org/10.3390/life16040695 - 21 Apr 2026
Viewed by 453
Abstract
Central auditory processing efficiency is considered a predictor of how well children can learn to read, with the Frequency Following Response (FFR) serving as a sensitive biomarker of neural speech encoding ability. However, data regarding the 170 ms [da] stimulus in children who [...] Read more.
Central auditory processing efficiency is considered a predictor of how well children can learn to read, with the Frequency Following Response (FFR) serving as a sensitive biomarker of neural speech encoding ability. However, data regarding the 170 ms [da] stimulus in children who are native speakers of Brazilian Portuguese (BP) remain limited. This study investigated FFR results in 37 typically developing, normal-hearing children aged 8 to 10 years. Participants underwent audiological, behavioral, and academic performance screenings, followed by monaural FFR recording (using a 170 ms [da] stimulus at 80 dBnHL). Linear mixed models (LMM) were used to examine the effects of age, sex, and ear on the latencies of waves V, A, D, E, F, and O. The analysis revealed a medium effect size for waves D, E, and F, regarding the Ear factor, though statistical significance was specifically observed for wave E. For this wave, sex was also associated with a medium effect size, characterized by longer latencies in female participants. While the results for age did not reach broad statistical significance, the presence of medium effect sizes in wave E may suggest ongoing refinement of neural synchrony and asymmetric maturation during this developmental period. This study contributes to the characterization of neural speech encoding in the Brazilian Portuguese-speaking children and may support future investigation involving auditory processing disorders and learning difficulties. Full article
(This article belongs to the Section Physiology and Pathology)
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13 pages, 440 KB  
Article
Postoperative Pain and Functional Limitations After Corneal Cross-Linking for Keratoconus: A Patient-Reported Outcome Study
by Ruta Jaruseviciene, Gintare Kirkickaite and Saulius Galgauskas
Life 2026, 16(4), 694; https://doi.org/10.3390/life16040694 - 21 Apr 2026
Viewed by 467
Abstract
Background: Keratoconus is a progressive corneal condition that leads to visual impairment and is primarily managed with corneal cross-linking (CXL), a procedure designed to halt its progression. However, while the clinical outcomes of CXL are well-documented, its impact on patient well-being, including postoperative [...] Read more.
Background: Keratoconus is a progressive corneal condition that leads to visual impairment and is primarily managed with corneal cross-linking (CXL), a procedure designed to halt its progression. However, while the clinical outcomes of CXL are well-documented, its impact on patient well-being, including postoperative pain and recovery, remains underexplored. This study aimed to evaluate postoperative pain, functional limitations, visual recovery, and patient-reported outcomes following corneal cross-linking (CXL) for keratoconus. Methods: A structured survey was conducted among 31 patients who underwent CXL for keratoconus. The survey assessed postoperative pain using a Numeric Rating Scale (NRS) and collected information on visual recovery, functional limitations, and the socioeconomic effects of the procedure. Clinical data, including best-corrected visual acuity (BCVA) and keratometry, were also recorded before and after CXL to evaluate the procedure’s efficacy. Results: The study found that postoperative pain was moderate, with a mean pain score of 6.06 ± 1.82, typically lasting 1–3 days. Nearly 54.8% of patients reported significant disruption to daily activities, including missing work or studies, and 77.4% experienced some degree of functional limitation. A statistically significant correlation was observed between postoperative pain intensity and quality-of-life impairment (Spearman’s ρ = 0.503, p = 0.004). Despite these challenges, 93.5% of participants reported improvement in vision, with most recovering within a week. Objective clinical data supported the effectiveness of the procedure. Conclusions: Corneal cross-linking is associated with favorable clinical outcomes; however, the early postoperative period is characterized by moderate pain and functional limitations, highlighting the importance of patient-centered care. Full article
(This article belongs to the Special Issue Ocular Diseases: Mechanisms, Diagnostics, and Emerging Therapeutic Strategies)
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6 pages, 1773 KB  
Case Report
Nevus Lipomatosus Superficialis with Mixed Morphologic Features: Gross, Sonographic, and Histopathologic Correlation
by Michelle T. Nguyen, Leo P. Wu and Grant M. Pham
Life 2026, 16(4), 693; https://doi.org/10.3390/life16040693 - 21 Apr 2026
Viewed by 464
Abstract
Nevus lipomatosus superficialis (NLS) is an uncommon benign hamartoma characterized by ectopic adipocytes within the dermis and may present with features that overlap clinically with other soft, pedunculated, or cerebriform lesions. We report a rare presentation with mixed morphologic traits that created diagnostic [...] Read more.
Nevus lipomatosus superficialis (NLS) is an uncommon benign hamartoma characterized by ectopic adipocytes within the dermis and may present with features that overlap clinically with other soft, pedunculated, or cerebriform lesions. We report a rare presentation with mixed morphologic traits that created diagnostic uncertainty on gross examination. The lesion demonstrated atypical surface contour and texture, prompting multimodal evaluation to clarify the differential diagnosis and support safe outpatient management. Point-of-care ultrasound (POCUS) was used to evaluate lesion architecture and vascularity. Findings provided real-time, noninvasive support for benign morphology and informed procedural planning. Subsequent histopathologic analysis established the diagnosis by demonstrating dermal adipose deposition consistent with NLS. This case underscores the value of integrating gross examination with sonographic assessment and histopathology when cutaneous lesions have overlapping clinical features. In addition, it contributes to the limited literature describing ultrasound findings in NLS. Incorporating POCUS into the assessment of atypical cutaneous growths may improve diagnostic confidence, reduce unnecessary escalation of care, and support efficient, safe treatment in outpatient settings. Full article
(This article belongs to the Special Issue New Horizons of Adipose Tissue Disorders: From Hormonal Issues to Loose Connective Disease: 2nd Edition)
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13 pages, 254 KB  
Study Protocol
Effects of Positive Airway Pressure Therapy on Cognitive Function in Patients with Obstructive Sleep Apnea: A Prospective Observational Study Protocol
by Branislav Kollár, Stela Biathová, Katarína Klobučníková, Peter Turčáni, Žofia Rádiková, Ingrid Žitňanová, Ľubica Argalášová and Pavel Šiarnik
Life 2026, 16(4), 692; https://doi.org/10.3390/life16040692 - 21 Apr 2026
Viewed by 681
Abstract
Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is increasingly recognized as a contributor to cognitive decline and a potential risk factor for neurodegeneration. Previous studies have also identified various associated comorbidities such as vascular dysfunction, metabolic alterations, and [...] Read more.
Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is increasingly recognized as a contributor to cognitive decline and a potential risk factor for neurodegeneration. Previous studies have also identified various associated comorbidities such as vascular dysfunction, metabolic alterations, and neuroinflammatory changes. Positive airway pressure (PAP) therapy has been associated with cognitive improvement in some studies, but its long-term effects on cognitive function remain uncertain. This study employs a prospective, observational, longitudinal cohort design to examine longitudinal associations between disease severity, PAP therapy and cognition. Additionally, we aim to examine the relationships between cognitive dysfunction, brain structure and associated OSA-related risk factors. A total of 100 eligible participants with mild to severe OSA will be recruited. All participants will undergo comprehensive assessments at baseline and after 12 months, including neurological, pulmonary, and ear, nose and throat clinical examinations, polysomnography, neuropsychological testing, brain magnetic resonance imaging with volumetry, anthropometric measurements, blood and saliva sampling for the assessment of the selected laboratory parameters, gut microbiome analysis, and evaluation of endothelial function and baroreflex sensitivity. This study may improve understanding of how PAP therapy and OSA-related pathophysiological processes influence cognitive outcomes. Full article
(This article belongs to the Section Medical Research)
10 pages, 540 KB  
Article
Association Between Time to First Mobilization and Recovery of Oral Intake Function in Patients with Pneumonia: A Two-Center Retrospective Cohort Study
by Shinichi Watanabe, Takaaki Sakurai, Takahiro Kanaya, Takumi Iwasaki, Hyosuke Oshima, Tetsuya Furukawa, Tomohiro Yoshikawa, Seichi Nakahashi and Yasunari Morita
Life 2026, 16(4), 691; https://doi.org/10.3390/life16040691 - 20 Apr 2026
Viewed by 661
Abstract
Delayed recovery of oral intake is common in hospitalized patients with pneumonia, particularly among older adults with reduced physical activity. Despite the recent emphasis on early mobilization, the relationship between the timing of first mobilization and recovery of oral intake function remains unclear. [...] Read more.
Delayed recovery of oral intake is common in hospitalized patients with pneumonia, particularly among older adults with reduced physical activity. Despite the recent emphasis on early mobilization, the relationship between the timing of first mobilization and recovery of oral intake function remains unclear. Thus, this retrospective cohort study investigated the association between time to first mobilization and recovery of oral intake in patients hospitalized with pneumonia. We analyzed 431 admitted patients with pneumonia, including aspiration pneumonia and coronavirus disease 2019 pneumonia, at two institutions. The Functional Oral Intake Scale ≥ 4 (partial oral intake recovery) was designated as the primary outcome. The main exposure was the number of days from admission to first mobilization. Multivariable Cox proportional hazards models were used after appropriate adjustments. The median time to first mobilization was 4 days (IQR: 2–14 days). Longer time to first mobilization was significantly associated with delayed recovery of oral intake (HR: 0.96, 95% CI: 0.94–0.98, p < 0.001). Thus, early mobilization may promote the recovery of oral intake in patients with pneumonia. These findings suggest that avoiding excessive delays in mobilization may support the recovery of oral intake and swallowing function in hospitalized patients with pneumonia. Full article
(This article belongs to the Special Issue Intensive Care Medicine: Current Concepts and Future Perspectives)
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17 pages, 1452 KB  
Article
Preliminary Characterization of Skin Microbiota and Mycobiota in Atopic Dermatitis by Metagenomic and Culture-Based Analyses
by Federica Carraturo, Michela Salamone, Martina Annunziata, Eugenia Veronica Di Brizzi, Caterina Mariarosaria Giorgio, Arianna Petrillo, Ludovica Fedi, Angela Maione, Marco Guida and Emilia Galdiero
Life 2026, 16(4), 690; https://doi.org/10.3390/life16040690 - 20 Apr 2026
Viewed by 675
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by several factors, including immune system imbalance, impairment of the epidermal barrier, and alterations in the composition of the gut and skin bacterial and fungal microbiota. This study combines metagenomic sequencing and culture-based [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by several factors, including immune system imbalance, impairment of the epidermal barrier, and alterations in the composition of the gut and skin bacterial and fungal microbiota. This study combines metagenomic sequencing and culture-based methods to explore the impact of probiotic supplementation on the cutaneous microbiota and mycobiota of AD patients. Twenty-five adults diagnosed with AD were enrolled, and skin swabs were analyzed to characterize microbial diversity and load. Culturomic analyses identified 42 bacterial and 6 fungal species, confirming Staphylococcus aureus and Candida parapsilosis as predominant taxa. High-throughput sequencing revealed Staphylococcus spp. and Malassezia spp. as dominant genera, with notable interindividual variability. While probiotic use did not significantly influence bacterial diversity, it was associated with higher richness and evenness in fungal communities, as shown by alpha and beta diversity metrics. Malassezia restricta was more prevalent among probiotic users, whereas Candida parapsilosis and Rhodotorula mucilaginosa were enriched in non-users. These findings indicate an association between probiotic use and differences in the composition and diversity of the skin mycobiota compared with the bacterial microbiota, suggesting that fungal communities may be more responsive to probiotic-associated factors. Integrating metagenomic and culturomic approaches offers valuable insights into the complex interactions among host factors, microbial communities, and probiotic use in AD, paving the way for targeted microbiome-based therapeutic strategies. Full article
(This article belongs to the Special Issue Microbiome Dynamics: Advancing Therapeutic Development in Health and Disease)
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2 pages, 132 KB  
Correction
Correction: Yuan et al. White Matter Integrity of the Corpus Callosum Mediates the Association Between Aging and Skin Condition. Life 2025, 15, 1664
by Daihaoyi Yuan, Keisuke Kokubun, Kiyotaka Nemoto and Yoshinori Yamakawa
Life 2026, 16(4), 689; https://doi.org/10.3390/life16040689 - 20 Apr 2026
Viewed by 268
Abstract
In the original publication [...] Full article
(This article belongs to the Section Physiology and Pathology)
14 pages, 2474 KB  
Article
Joint-Specific and Cross-Joint Strength Profiles in Relation to Maximal Soccer Kicking Speed
by İbrahim Orkun Akcan, Sultan Şenyurt, Tolga Altuğ, Betül Ateş, Şeyma Tuba Acar, Büşra Yücelsoy, Gizem Kızılörs, Christopher B. Taber, Hamza Küçük, Ahmet Serhat Aydın, Mehmet Söyler and Cengiz Ölmez
Life 2026, 16(4), 688; https://doi.org/10.3390/life16040688 - 18 Apr 2026
Viewed by 683
Abstract
The purpose of this study was to examine associations between lower-limb mechanical strength, phase-oriented composite strength indices, generalized neuromuscular activation, and maximal soccer ball kicking speed in trained athletes. Twenty-five male soccer players (age: 20.64 ± 2.50 years; height: 179.28 ± 4.27 cm; [...] Read more.
The purpose of this study was to examine associations between lower-limb mechanical strength, phase-oriented composite strength indices, generalized neuromuscular activation, and maximal soccer ball kicking speed in trained athletes. Twenty-five male soccer players (age: 20.64 ± 2.50 years; height: 179.28 ± 4.27 cm; body mass: 75.80 ± 9.41 kg) participated in this cross-sectional study. Isometric ankle and knee joint torques were assessed using an isokinetic dynamometer, and joint-specific and phase-oriented cross-joint composite indices were computed to represent integrated strength capacity across the kinetic chain. Neuromuscular activation was evaluated via surface electromyography during a standardized squat jump task. Ball-kicking speed was measured using Doppler radar during maximal instep kicks. Associations were analyzed using Pearson correlation coefficients (p ≤ 0.05) with false discovery rate correction for multiple comparisons. In unadjusted analyses, moderate positive correlations were observed for several ankle torque variables and composite ankle strength indices, while swing-phase composite measures demonstrated moderate correlations (r = 0.43–0.55). Knee strength indices and sEMG variables showed no significant relationships. However, none of the variables remained statistically significant after FDR correction, suggesting limited independent explanatory value of isolated isometric strength and non-task-specific neuromuscular activation assessed during a standardized squat jump for maximal kicking performance. Full article
(This article belongs to the Section Physiology and Pathology)
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18 pages, 902 KB  
Article
Optimizing Surgical Choice in Mild and Moderate OSA: Anterior Palatoplasty vs. Radiofrequency Uvulopalatoplasty
by Ionut Tanase, Mircea-Sorin Ciolofan, Codrut-Caius Sarafoleanu, Mihaela Cristina Neagu, Florentina-Carmen Badea and Carmen Aurelia Mogoantă
Life 2026, 16(4), 687; https://doi.org/10.3390/life16040687 - 18 Apr 2026
Viewed by 585
Abstract
Background: Surgical palatal techniques are established alternatives to continuous positive airway pressure (CPAP) in selective patients with obstructive sleep apnea (OSA) with retropalatal airway collapse. Anterior palatoplasty (AP) stiffens and advances the soft palate, whereas radiofrequency-assisted uvulopalatoplasty (RF-UPP) uses thermal ablation to reduce [...] Read more.
Background: Surgical palatal techniques are established alternatives to continuous positive airway pressure (CPAP) in selective patients with obstructive sleep apnea (OSA) with retropalatal airway collapse. Anterior palatoplasty (AP) stiffens and advances the soft palate, whereas radiofrequency-assisted uvulopalatoplasty (RF-UPP) uses thermal ablation to reduce palatal tissue. This study aimed to compare the 6-month efficacy and morbidity of AP vs. RF-UPP in treating mild-to-moderate OSA. Materials and Methods: We conducted a single-center retrospective cohort study (March 2023–March 2025) of 86 adults (mean age ~42 years; 69.8% male) with mild-moderate OSA (apnea–hypopnea index [AHI] 5–30) due to palatal obstruction; 43 patients underwent AP and 43 patients underwent RF-UPP. Polysomnographic AHI, Epworth sleepiness scale (ESS), snoring severity (0–10 visual analog scale, VAS) and sleep-related quality of life (functional outcomes of sleep questionnaire, FOSQ) were analyzed at baseline and 6 months postoperatively. Postoperative pain (0–10 VAS), recovery time, and bleeding events were also assessed. Results: Baseline characteristics were similar between groups (AHI ~22 vs. 21 events/h; ESS ~11 vs. 10; snoring VAS ~8.4 vs. 8.2 in AP vs. RF-UPP, all p > 0.1). At 6 months, the AP group achieved a greater mean AHI reduction than the RF-UPP group (−13.5 ± 7.5 vs. −8.0 ± 7.2, p < 0.001), with post-treatment AHI averaging 8.5 ± 6.0 vs. 13.2 ± 6.5 events/h (AP vs. RF-UPP). AP yielded a higher surgical success rate (34/43 (79.1%) vs. 23/43 (53.5%), p = 0.012), meeting the criteria of ≥50% AHI reduction to <15; p = 0.01. Subjective outcomes improved in both groups, but AP showed greater mean reductions in ESS (−5.5 vs. −3.1 points, p = 0.001) and snoring VAS (−5.7 vs. −3.1, p = 0.002). The improvements in ESS, snoring VAS, and FOSQ scores were observed in both groups, with significantly greater gains after AP. Postoperative pain and time to resumption of normal diet were higher in the AP group. No major complications occurred in either group. Conclusions: Anterior palatoplasty demonstrated superior efficacy to RF-UPP in mild-moderate OSA at the expense of increased postoperative pain and a longer recovery period. AP may offer a greater therapeutic benefit in appropriately selected patients with palatal obstruction. Full article
(This article belongs to the Section Medical Research)
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14 pages, 250 KB  
Article
Asthma and Obstructive Sleep Apnea Overlap Syndrome Identifies a Phenotype of Sleep Instability and Increased Psychological Burden
by Antonio Fabozzi, Izolde Bouloukaki, Violeta Moniaki, Eleni Mavroudi, Matteo Bonini, Paolo Palange and Sophia E. Schiza
Life 2026, 16(4), 686; https://doi.org/10.3390/life16040686 - 18 Apr 2026
Viewed by 612
Abstract
Background: The alternative Overlap Syndrome (aOVS), the coexistence of bronchial asthma and Obstructive Sleep Apnea (OSA), represents a distinct clinical phenotype associated with worse clinical outcomes, but little is yet known about its characteristics. We aimed to investigate differences in sleep stability and [...] Read more.
Background: The alternative Overlap Syndrome (aOVS), the coexistence of bronchial asthma and Obstructive Sleep Apnea (OSA), represents a distinct clinical phenotype associated with worse clinical outcomes, but little is yet known about its characteristics. We aimed to investigate differences in sleep stability and clinical burden between OSA and aOVS patients matched for age, gender, BMI and Apnea-Hypopnea Index (AHI). Methods: 45 aOVS and 45 OSA patients were compared using demographic, clinical and polysomnographic data. Results: Patients with aOVS exhibited significantly higher odds ratio product (ORP) values for total sleep time (ORPmed: 0.8 ± 0.2 vs. 0.5 ± 0.1, p < 0.001) and Non-Rapid Eye Movement (ORPnr: 0.7 ± 0.3 vs. 0.4 ± 0.1, p < 0.001) sleep compared with OSA patients. Furthermore, patients with aOVS showed a significantly higher risk of developing clinically significant anxiety and fatigue, showing a significantly higher General Anxiety Disorder-7 (GAD-7: 8.7 ± 5.6 vs. 5.7 ± 4.7, p = 0.02) and significantly higher prevalence of fatigue (71% vs. 41%, p = 0.01). These associations remained significant after multivariable adjustment and were independent of OSA severity (AHI). Conclusions: Our findings support the concept that aOVS is characterised by significantly more unstable sleep and a greater psychological burden, even after matching with OSA patients for age, gender, BMI and AHI. Our study also highlights the need to integrate traditional sleep measures with more recent ones, such as ORP, in order to better capture the multidimensional burden of aOVS. Full article
(This article belongs to the Special Issue Chronic Respiratory Comorbidities in Sleep-Disordered Breathing: A Holistic Approach)
22 pages, 2232 KB  
Article
Effects of Fibrolytic Enzymes Alone or with Live Yeast on Rumen Microbiota and Fermentation During Grazing-to-Indoor Transition in Dairy Cows
by Ignas Šilinskas, Ilma Tapio, Ingrida Monkevičienė, Kristina Musayeva, Hanna Huuki, Rūta Šilinskienė, Dovile Klupsaite, Elena Bartkiene, Aldona Baltušnikienė, Renata Japertienė, Vaidas Oberauskas and Rasa Želvytė
Life 2026, 16(4), 685; https://doi.org/10.3390/life16040685 - 18 Apr 2026
Viewed by 371
Abstract
Rumen microbial fermentation plays a central role in nutrient utilization and milk production in dairy cows. This study evaluated the effects of supplementation with exogenous fibrolytic enzymes, alone or in combination with live yeast on rumen microbiota, fermentation characteristics, nitrogen-related metabolites, and production [...] Read more.
Rumen microbial fermentation plays a central role in nutrient utilization and milk production in dairy cows. This study evaluated the effects of supplementation with exogenous fibrolytic enzymes, alone or in combination with live yeast on rumen microbiota, fermentation characteristics, nitrogen-related metabolites, and production performance during the transition from outdoor grazing to indoor housing. Thirty Lithuanian Red dairy cows were assigned to control (CTR), enzyme (E), or enzyme plus yeast (YE) treatments across outdoor (OD) and transit (T) periods, while nine cows (three per group) were selected for rumen and microbiota analysis. Rumen bacterial communities were characterized using 16S rRNA gene sequencing, and functional parameters were evaluated using linear mixed-effects models. Supplementation resulted in selective changes in several bacterial genera, including Blautia spp., WPS-2, Ruminococcus spp., Erysipelotrichaceae UCG-009, Sharpea spp., uncultured Bacteroidales, and Prevotellaceae UCG-003, and was associated with alterations in fermentation patterns, particularly propionate concentration, and in nitrogen metabolism, including putrescine dynamics. The transition period significantly influenced microbial diversity and total bacterial abundance across treatments. Cows in the YE group maintained higher milk yield during the transition period. Overall, dietary supplementation modulated specific rumen metabolic responses and contributed to production stability without causing large-scale changes in overall microbial structure. Full article
(This article belongs to the Special Issue Innovations in Dairy Cattle Health and Nutrition Management)
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11 pages, 933 KB  
Case Report
“Polyradiculoneuritis” as an Atypical Clinical Presentation of Creutzfeldt–Jakob Disease: A Case Report and Review of Literature
by Elisa Colaizzo, Anna Ladogana, Dorina Tiple, Luana Vaianella, Giuseppe Bufano, Fabio Moda, Daniela Merlo, Eloise Longo and Alessia Perna
Life 2026, 16(4), 684; https://doi.org/10.3390/life16040684 - 17 Apr 2026
Viewed by 580
Abstract
(1) Background: Creutzfeldt–Jakob disease (CJD) is a progressive neurodegenerative disorder, characterized by cognitive decline, and motor and psychiatric symptoms; it primarily affects the central nervous system; however, peripheral nervous system involvement has rarely been described, particularly as an atypical presentation. (2) Methods: A [...] Read more.
(1) Background: Creutzfeldt–Jakob disease (CJD) is a progressive neurodegenerative disorder, characterized by cognitive decline, and motor and psychiatric symptoms; it primarily affects the central nervous system; however, peripheral nervous system involvement has rarely been described, particularly as an atypical presentation. (2) Methods: A 78-year-old Caucasian man, a retired farmer with no family history of neurological disease, presented with diarrhea followed by progressive lower limb weakness, which eventually evolved into encephalopathy and generalized areflexia. An initial diagnosis of inflammatory neuropathy was considered; the diagnostic assessment included blood and cerebrospinal fluid testing, a CT whole body scan, brain MRI, neuropsychological testing, electroencephalography, a nerve conduction study and electromyography. (3) Results: Neurophysiological studies demonstrated an acute asymmetrical sensorimotor, predominantly axonal polyneuropathy, initially suggestive of an axonal form of inflammatory polyradiculoneuritis. This pattern was confirmed on follow-up neurophysiological assessment performed three weeks later. Unexpectedly, the diagnostic course ultimately led to a diagnosis of sporadic Creutzfeldt–Jakob disease, confirmed by post-mortem neuropathological examination. Based on these findings, we conducted a literature review to summarize the current evidence on CJD-related neuropathy. (4) Conclusions: Our case emphasizes the importance of maintaining clinical suspicion for CJD even in patients presenting with progressive lower limb weakness and suggests that peripheral neuropathy may be concomitant or even precede the CNS manifestations. Careful consideration is required to avoid misdiagnosis of inflammatory neuropathy in the context of neurodegenerative diseases such as CJD. Full article
(This article belongs to the Special Issue Neurological Diseases: Prevention, Diagnostics, Treatment and Rehabilitation—2nd Edition)
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13 pages, 7366 KB  
Article
Dynamics of Postmortem Gene Expression in Normal and Neoplastic Murine Liver
by Evgeny E. Buyko, Ekaterina A. Perina, Danil S. Sobakin, Matvey M. Tsyganov, Dmitry V. Vasilchenko, Sergey V. Vtorushin, Alexander A. Ufandeev, Elena B. Diksas, Olga A. Kaidash, Ekaterina S. Hmelevskaya, Ekaterina V. Parochkina, Igor A. Popov, Vladimir V. Ivanov, Stanislav I. Pekov and Elena V. Udut
Life 2026, 16(4), 683; https://doi.org/10.3390/life16040683 - 16 Apr 2026
Viewed by 703
Abstract
The use of postmortem (autopsy) material in fundamental and applied biomedical research significantly facilitates the collection of biomaterial for statistically robust sample cohorts. However, natural adaptive processes to developing cellular stress in the early postmortem period, caused by oxygen and nutrient deprivation, trigger [...] Read more.
The use of postmortem (autopsy) material in fundamental and applied biomedical research significantly facilitates the collection of biomaterial for statistically robust sample cohorts. However, natural adaptive processes to developing cellular stress in the early postmortem period, caused by oxygen and nutrient deprivation, trigger the activation of numerous genes promoting cell survival under stress. Many of these activated pathways are also crucial for tumor cell survival in vivo, as evidenced by various transcriptomic studies. This study aimed to investigate the potential influence of postmortem interval (PMI) duration on gene expression in normal and tumor tissues. Using a model of chemically induced hepatocellular carcinoma in mouse liver, we comparatively analyzed the dynamics of transcript levels for several genes (BRCA1, BRCA2, CHEK1, CHEK2, ATM, CDK12) in paired samples of normal and tumor tissue over a 24-h PMI using RT-qPCR. In normal tissue, gene expression increased significantly, while tumor tissue demonstrated relative transcriptional stability, with no substantial changes in the studied transcript levels. A critical finding was the observed convergence of expression profiles: initial differences between the tissues were completely eliminated by 24 h PMI. This pattern developed despite formally adequate RNA quality (RQN) and the absence of clear signs of progressive autolysis in histology, indicating the insufficiency of standard quality criteria for detecting postmortem changes. These findings collectively underscore the critical importance of minimizing and controlling PMI during the biobanking of oncological samples for reliable transcriptomic research. Full article
(This article belongs to the Special Issue Cancer Genomics and Transcriptomics: Uncovering New Frontiers in Tumor Biology)
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18 pages, 1578 KB  
Review
Beyond Blood Pressure: Arterial Stiffness as a Hemodynamic and Neuroadrenergic Axis Linking Hypertension, Cardiac Remodeling, and Heart Failure
by Pasquale Ambrosino, Cesare Cuspidi, Claudio Candia, Christian Basile, Mauro Maniscalco and Guido Grassi
Life 2026, 16(4), 682; https://doi.org/10.3390/life16040682 - 16 Apr 2026
Viewed by 779
Abstract
Arterial stiffness has traditionally been interpreted as a marker of vascular ageing and cumulative blood pressure exposure. Increasing evidence, however, indicates that it should be viewed as an active determinant of cardiovascular loading conditions rather than a passive epiphenomenon. By accelerating pulse wave [...] Read more.
Arterial stiffness has traditionally been interpreted as a marker of vascular ageing and cumulative blood pressure exposure. Increasing evidence, however, indicates that it should be viewed as an active determinant of cardiovascular loading conditions rather than a passive epiphenomenon. By accelerating pulse wave velocity and altering the timing of wave reflection, large artery stiffening increases central systolic pressure, augments late systolic load, and facilitates the transmission of pulsatile energy to the microcirculation. These hemodynamic alterations shape ventricular remodeling, influence ventricular–vascular coupling, and contribute to organ vulnerability even when brachial blood pressure appears adequately controlled. In this review, population-based observations and mechanistic human studies are integrated to position arterial stiffness as a stage-dependent dimension of cardiovascular disease. Community data illustrate its association with different blood pressure phenotypes and early cardiac structural changes, whereas evidence from advanced heart failure settings helps contextualize arterial stiffness within states of marked autonomic activation. Taken together, this perspective suggests that arterial stiffness is not merely a marker of cumulative damage, but a mediator that contributes to disease progression across clinical stages and, in practical terms, a phenotyping dimension along the trajectory from hypertension to heart failure. Full article
(This article belongs to the Special Issue Microvascular and Macrovascular Response in Healthy and Critically Ill)
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17 pages, 892 KB  
Article
Artificial Intelligence for Biomedical Diagnostics: Diagnostic Accuracy and Reliability of Multimodal Large Language Models in Electrocardiogram Interpretation
by Henrik Stelling, Armin Kraus, Gerrit Grieb, David Breidung and Ibrahim Güler
Life 2026, 16(4), 681; https://doi.org/10.3390/life16040681 - 16 Apr 2026
Viewed by 858
Abstract
The electrocardiogram (ECG) is a central tool in cardiovascular diagnostics, yet interpretation requires expertise and remains subject to variability. Multimodal large language models (MLLMs) have shown emerging capabilities in medical image analysis, but their performance in ECG interpretation remains insufficiently characterized. This study [...] Read more.
The electrocardiogram (ECG) is a central tool in cardiovascular diagnostics, yet interpretation requires expertise and remains subject to variability. Multimodal large language models (MLLMs) have shown emerging capabilities in medical image analysis, but their performance in ECG interpretation remains insufficiently characterized. This study evaluated the diagnostic accuracy and inter-run reliability of five MLLMs across ECG interpretation tasks. Thirteen standard 12-lead ECGs were presented to five models (ChatGPT-5.3, Gemini 3.1 Pro, Claude Opus 4.6, Grok 4.1, and ERNIE 5.0) across five independent runs per case, yielding 2275 task-level assessments. Six categorical interpretation tasks (rhythm, electrical axis, PR/P-wave morphology, QRS duration, ST/T-wave morphology, and QTc interval) were compared with expert-consensus ground truth, while heart rate estimation was evaluated using mean absolute error (MAE). Overall categorical accuracy ranged from 52.3% to 64.9%. QRS duration classification achieved the highest accuracy (66.2–90.8%), whereas ST/T-wave assessment showed the lowest performance (20.0–41.5%). Heart rate MAE ranged from 14.8 to 46.7 bpm. A dissociation between diagnostic accuracy and inter-run reliability was observed across models. These findings indicate that current MLLMs do not achieve clinically reliable ECG interpretation performance and highlight the importance of assessing diagnostic accuracy and inter-run reliability when evaluating artificial intelligence systems in biomedical diagnostics. Full article
(This article belongs to the Special Issue Artificial Intelligence and Machine Learning for Biomedical Diagnostics and Prognostics)
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15 pages, 1002 KB  
Article
Adjunctive Use of VGH4 for Moderate-to-Severe Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Trial
by Ying-Ju Liao, Ta-Peng Wu, Chou-Cheng Lai, Yen-Ying Kung, Cheng-Hung Tsai, Yun-Ting Chang, Chih-Chiang Chen, Ching-Mao Chang, Shinn-Jang Hwang and Fang-Pey Chen
Life 2026, 16(4), 680; https://doi.org/10.3390/life16040680 - 16 Apr 2026
Viewed by 807
Abstract
Moderate-to-severe atopic dermatitis (AD) requires safe, long-term management strategies to complement conventional pharmacotherapy. This study evaluated the efficacy and safety of VGH4, a standardized multi-herb traditional Chinese medicine (TCM) formula, as an adjunct to standard care. In a randomized, double-blind, placebo-controlled crossover pilot [...] Read more.
Moderate-to-severe atopic dermatitis (AD) requires safe, long-term management strategies to complement conventional pharmacotherapy. This study evaluated the efficacy and safety of VGH4, a standardized multi-herb traditional Chinese medicine (TCM) formula, as an adjunct to standard care. In a randomized, double-blind, placebo-controlled crossover pilot trial, 19 patients with moderate-to-severe AD (SCOring Atopic Dermatitis Index (SCORAD) ≥ 25) received VGH4 or placebo for 6 weeks, separated by a 2-week washout. Primary outcomes assessed disease severity (SCORAD), while secondary outcomes included quality of life (DLQI/CDLQI) and safety. Eighteen patients completed the study. VGH4 yielded a median within-patient SCORAD reduction 10.2 points greater than placebo (p = 0.054). The primary endpoint did not reach statistical significance at the α = 0.05 level (p = 0.054); nevertheless, the observed magnitude of improvement exceeded the established minimal clinically important differences (MCIDs). The subjective SCORAD component showed a significant between-treatment difference favoring VGH4 (p = 0.015), and a statistically significant improvement in quality of life was also observed in adult patients (p = 0.023). In conclusion, VGH4 was generally well tolerated in this short-term pilot trial, with no serious adverse events, and showed preliminary signals of possible benefits in patient-reported outcomes as an adjunct therapy. These exploratory findings warrant confirmation in larger, adequately powered trials. Full article
(This article belongs to the Collection Clinical Trials)
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15 pages, 556 KB  
Hypothesis
Revisiting Colon Cancer Progression: A Containment-Based Conceptual Framework
by Roxana Loriana Negrut, Adrian Cote and Adrian Marius Maghiar
Life 2026, 16(4), 679; https://doi.org/10.3390/life16040679 - 16 Apr 2026
Viewed by 506
Abstract
Patterns of colon cancer recurrence demonstrate a high degree of anatomical reproducibility, consistently aligning with mesofascial planes and compartmentalized vascular and lymphatic territories, as evidenced by pathological, surgical and imaging studies. These frameworks describe recognized routes of spread but do not provide an [...] Read more.
Patterns of colon cancer recurrence demonstrate a high degree of anatomical reproducibility, consistently aligning with mesofascial planes and compartmentalized vascular and lymphatic territories, as evidenced by pathological, surgical and imaging studies. These frameworks describe recognized routes of spread but do not provide an integrated anatomical explanation for understanding why tumor progression often aligns with mesofascial planes, embryological boundaries and cavity-specific niches, nor for why preservation of structural integrity during surgery is associated with improved oncological outcomes. This work proposes a spatial containment model of colon cancer progression, in which tumor dissemination reflects sequential breaches of anatomically defined barrier systems. The Colon Cancer Containment System is proposed as a three-tier framework in which tumor progression reflects sequential breaches of containment at the tissue (microcontainment), mesenteric (mesocontainment) and peritoneal or systemic (macrocontainment) levels. At each stage, anatomical structures function as barrier systems that constrain tumor spread and shape directionality of progression. Disruption of these barriers, whether tumor-driven or iatrogenic, is associated with relatively consistent patterns of local, regional, and distant recurrence. Within this approach, established prognostic features such as tumor–node–metastasis (TNM) stage, extramural vascular invasion, perineural invasion and margin status may also be interpreted as markers of containment integrity, in addition to their established roles as indicators of tumor aggressiveness. Surgical plane preservation is reframed as a biologically meaningful act of containment maintenance. By organizing validated observations within an anatomically patterned architecture, the containment framework provides a coherent model for interpreting reproducible recurrence patterns and clarifies the biological significance of surgical integrity. This perspective complements existing oncological paradigms, supports anatomically informed risk stratification and generates testable hypotheses for future clinical and translational research. Full article
(This article belongs to the Section Medical Research)
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13 pages, 592 KB  
Article
Agreement Between Non-Cycloplegic Photorefraction and Retinoscopy in Pediatric Refraction
by Ana Roque, Amélia Fernandes Nunes, Henrique Nascimento, NIAOO Group and Clara Martinez-Perez
Life 2026, 16(4), 678; https://doi.org/10.3390/life16040678 - 16 Apr 2026
Viewed by 448
Abstract
Accurate assessment of refractive error in children is essential for clinical decision-making, yet agreement between non-cycloplegic techniques remains uncertain, particularly due to differences in accommodative demand. This study evaluated the agreement between static retinoscopy and handheld photorefraction for measuring spherical power, cylindrical power, [...] Read more.
Accurate assessment of refractive error in children is essential for clinical decision-making, yet agreement between non-cycloplegic techniques remains uncertain, particularly due to differences in accommodative demand. This study evaluated the agreement between static retinoscopy and handheld photorefraction for measuring spherical power, cylindrical power, and spherical equivalent in children aged 4–16 years and assessed whether agreement varied by refractive status. In this cross-sectional observational study, 193 children underwent objective refraction during a single visit using non-cycloplegic static retinoscopy (distance fixation) and handheld infrared photorefraction (~1 m fixation). Inter-method differences were analyzed using Bland–Altman plots, intraclass correlation coefficients (ICCs), mean absolute error (MAE), and non-parametric tests. Photorefraction showed a statistically significant myopic shift compared with retinoscopy for spherical power (−0.16 D), cylindrical power (−0.24 D), and spherical equivalent (−0.28 D). Agreement was moderate in statistical terms for spherical equivalent (ICC = 0.73) and spherical power (0.71), and lower for cylindrical power (0.46); however, wide limits of agreement indicate clinically relevant variability. MAE for spherical equivalent was 0.80 D overall, with 45.1% of measurements within ±0.50 D, and varied by refractive status, being lowest in emmetropic eyes and higher in hyperopic and myopic eyes. These findings indicate that, under non-cycloplegic conditions, photorefraction shows modest mean differences but substantial individual variability, likely influenced by differences in accommodative demand between techniques. While suitable for pediatric vision screening, photorefraction should not be considered interchangeable with retinoscopy for individual refractive assessment. Full article
(This article belongs to the Special Issue Vision Science and Optometry: 2nd Edition)
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7 pages, 3963 KB  
Case Report
Distal Ureteral Stricture Secondary to Urolithiasis: Stepwise Endourological and Surgical Management with Ureteral Reimplantation and Drug-Coated Balloon Dilation (Optilume)
by Patricia Rodriguez-Parras, Ana Morales-Martinez, Alberto Zambudio-Munuera, Miguel Arrabal-Martin and Miguel Angel Arrabal-Polo
Life 2026, 16(4), 677; https://doi.org/10.3390/life16040677 - 15 Apr 2026
Viewed by 480
Abstract
Introduction: Acquired ureteral stricture is an uncommon but clinically relevant complication, mainly associated with long-standing urolithiasis, chronic inflammatory processes, and repeated endourological procedures. Case presentation: We present the case of a 48-year-old woman with left distal ureteral stricture secondary to urolithiasis and repeated [...] Read more.
Introduction: Acquired ureteral stricture is an uncommon but clinically relevant complication, mainly associated with long-standing urolithiasis, chronic inflammatory processes, and repeated endourological procedures. Case presentation: We present the case of a 48-year-old woman with left distal ureteral stricture secondary to urolithiasis and repeated endourological procedures, with a complicated clinical course and progressive renal functional impairment. Despite stepwise management including balloon dilations, endoscopic incision, prolonged urinary diversion, and ultimately ureteral reimplantation with a psoas hitch, the patient developed restenosis of the ureteral neomeatus. Due to persistent obstruction, endoscopic dilation with a paclitaxel-coated balloon (Optilume®) was performed. Subsequent imaging demonstrated partial improvement in ureteral drainage and relative functional improvement of the left kidney. Conclusion: This case highlights the potential complementary role of drug-coated balloons in complex and refractory benign ureteral strictures, although the currently available evidence remains limited. Full article
(This article belongs to the Section Medical Research)
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12 pages, 525 KB  
Article
An Exploratory Study of Matrix Metalloproteinase Protein Changes in Unexplained Infertility
by Zainab Alhalwachi, Thozhukat Sathyapalan, Stephen L. Atkin and Alexandra E. Butler
Life 2026, 16(4), 676; https://doi.org/10.3390/life16040676 - 15 Apr 2026
Viewed by 591
Abstract
Background: Matrix metalloproteinases (MMPs) have been found to be associated with reproductive complications, including female infertility. This study was conducted to explore the link between MMPs in non-obese women with unexplained infertility (UI) in comparison to women with male factor infertility (MFI) [...] Read more.
Background: Matrix metalloproteinases (MMPs) have been found to be associated with reproductive complications, including female infertility. This study was conducted to explore the link between MMPs in non-obese women with unexplained infertility (UI) in comparison to women with male factor infertility (MFI) as controls. Methods: This pilot exploratory study was carried out on 25 women, 11 with UI and 14 with MFI, undergoing IVF. Blood was drawn on day 21 of the luteal phase. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 12 matrix metalloproteinase proteins. Welch’s t-test and a permutation test were used to compare group means, and Pearson’s correlations to examine relationships with matrix metalloproteinases. Results: No significant differences were seen for baseline demographics and hormonal parameters between the groups, and parameters of the response following IVF did not differ. In the UI group, MMP-3 levels were lower (p = 0.045), while MMP-1 and MMP-17 levels were higher (p = 0.007 and p = 0.010, respectively) compared to the MFI group. In MFI alone, MMP-1 positively correlated with vitamin D3 (p < 0.05). Conclusions: This exploratory study suggests altered circulating MMP-1, MMP-3, and MMP-17 profiles in women with unexplained infertility. These findings require confirmation in larger cohorts and in studies examining endometrial tissue expression and MMP functional activity. Full article
(This article belongs to the Section Physiology and Pathology)
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15 pages, 30995 KB  
Article
Features of Cross-Seeding of Wild-Type Alpha-Synuclein and Its Mutant Form A53T Potentially Useful for the Development of Test Systems
by Kseniya Barinova, Sofiya Kudryavtseva, Lidia Kurochkina, Sergei Golyshev, Nataliya Kolotyeva, Sergei Illarioshkin, Michail Piradov and Vladimir Muronetz
Life 2026, 16(4), 675; https://doi.org/10.3390/life16040675 - 15 Apr 2026
Viewed by 497
Abstract
Since the features of cross-seeding of alpha-synuclein forms may affect the sensitivity and specificity of the test systems, we developed a modified approach to obtain alpha-synuclein amyloid seeds with particle sizes from 20 to 50 nm prepared from either the wild-type protein (α-synWT) [...] Read more.
Since the features of cross-seeding of alpha-synuclein forms may affect the sensitivity and specificity of the test systems, we developed a modified approach to obtain alpha-synuclein amyloid seeds with particle sizes from 20 to 50 nm prepared from either the wild-type protein (α-synWT) or its more fibrillation-prone form A53T (α-synA53T). These seeds had optimal properties for subsequent initiation of fibrillation. Our data showed that the elevated efficiency of alpha-synuclein A53T monomer transformation was hardly affected by the type of used seeds, whereas the addition of the seeds obtained from the alpha-synuclein mutant form to wild-type protein monomers had a significantly smaller effect than α-synWT seeds. Transmission electron microscopy data revealed that in the presence of α-synWT seeds the wild-type alpha-synuclein formed long and wide fibrils, while the addition of α-synA53T seeds led to the formation of long, but thin fibrils. Since the lag period of α-synA53T monomer fibrillation was significantly reduced compared to the wild-type protein, the replacing of α-synWT with α-synA53T in current assay systems designed to detect aberrant forms of α-synuclein in biological fluid samples (e.g., RT-QuIC) could substantially cut the time of analysis. In the future, a set of alpha-synuclein mutant forms could be used for the differential diagnosis of synucleinopathies caused by the different mutations of this protein. Full article
(This article belongs to the Section Medical Research)
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38 pages, 1831 KB  
Review
Rejection-Focused Precision Medicine in Kidney Transplantation: Biology, Biomarkers, and Artificial Intelligence
by Luis Ramalhete, Rúben Araújo, Miguel Bigotte Vieira, Emanuel Vigia, Cecília R. C. Calado and Anibal Ferreira
Life 2026, 16(4), 674; https://doi.org/10.3390/life16040674 - 15 Apr 2026
Viewed by 1004
Abstract
Chronic kidney disease is rising worldwide, and kidney transplantation remains the preferred modality of kidney replacement therapy. However, long-term graft survival continues to be limited by chronic alloimmune injury, particularly antibody-mediated rejection (ABMR) and its chronic active form. This narrative review synthesizes contemporary [...] Read more.
Chronic kidney disease is rising worldwide, and kidney transplantation remains the preferred modality of kidney replacement therapy. However, long-term graft survival continues to be limited by chronic alloimmune injury, particularly antibody-mediated rejection (ABMR) and its chronic active form. This narrative review synthesizes contemporary evidence on the immunopathogenesis, epidemiology, diagnosis, and management of kidney allograft rejection, with a deliberate focus on studies from the last five years and on United States and European cohorts. We summarize current concepts of T cell–mediated rejection (TCMR), ABMR, mixed and donor-specific antibody (DSA)–negative phenotypes, and the evolution of the Banff classification, highlighting how chronic active ABMR has emerged as a leading cause of death-censored graft loss. We then critically appraise the conventional diagnostic triad of creatinine/eGFR, DSA, and biopsy and review emerging tools, including donor-derived cell-free DNA, urinary chemokines such as CXCL9 and CXCL10, additional blood- and urine-based biomarkers, and biopsy transcriptomics. We also examine how artificial intelligence and machine learning may support digital pathology, multimodal risk prediction, and data integration, while recognizing the current challenges of biological interpretability, external validation, and clinical implementation. Finally, we propose a rejection-focused precision-medicine framework and outline key research gaps, including multicenter validation, trial-ready endpoints, and governance for AI-enabled pathways. Overall, the field is moving from isolated diagnostic signals toward integrated, biologically informed, and clinically actionable approaches to rejection detection and risk stratification. Full article
(This article belongs to the Special Issue Multimodal AI for Genomic-Clinicopathologic Integration: From Preventive Screening to Precision Diagnosis)
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9 pages, 204 KB  
Article
Oral Manifestations of Varicella and Their Contribution to Clinical Assessment in Hospitalized and Outpatient Patients
by Velina Stoeva, Veselina Kondeva and Rumyana Stoyanova
Life 2026, 16(4), 673; https://doi.org/10.3390/life16040673 - 15 Apr 2026
Viewed by 527
Abstract
Background: Oral lesions, particularly enanthema, may accompany chickenpox and represent an important but often underrecognized component of the clinical presentation. Their timely identification is especially relevant in dental practice, as oral manifestations may be more frequent in patients with a more severe clinical [...] Read more.
Background: Oral lesions, particularly enanthema, may accompany chickenpox and represent an important but often underrecognized component of the clinical presentation. Their timely identification is especially relevant in dental practice, as oral manifestations may be more frequent in patients with a more severe clinical course. This study aimed to describe characteristic oral cavity changes in hospitalized and outpatient patients with chickenpox, to identify patterns in the occurrence of oral findings in relation to disease severity, and to support clinical assessment in practice. Methods: A retrospective review of medical records was conducted for patients diagnosed with chickenpox in Bulgaria between December 2023 and May 2025. Data from hospitalized patients and outpatient cases were analyzed and compared to evaluate the distribution of oral manifestations and their association with clinical severity. Results: A total of 144 patients were included, of whom 32.6% required hospitalization. Oral enanthema was more frequently observed among hospitalized patients (48.8%). In univariate analyses, oral enanthema and tongue changes were associated with hospitalization. Multivariable logistic regression identified age and body temperature as independent factors associated with hospitalization, while oral manifestations did not retain independent predictive significance. Conclusion: Oral enanthema was more frequently observed among hospitalized patients and was associated with a more severe clinical presentation in univariate analyses. Although oral findings should not be interpreted as independent predictors of disease severity, their recognition may support clinical assessment, dental treatment planning, and appropriate infection control measures. Full article
(This article belongs to the Section Medical Research)
18 pages, 1522 KB  
Article
Edge Effect and the Influence of Biotic and Abiotic Factors on Calliphoridae and Mesembrinellidae (Insecta: Diptera) in Três Picos State Park, Brazil
by Wellington Thadeu de Alcantara Azevedo, Mariana dos Passos Nunes, Valmíria Moura Leôncio de Albuquerque, Cláudia Soares Santos Lessa, Jeronimo Alencar and Valéria Magalhães Aguiar
Life 2026, 16(4), 672; https://doi.org/10.3390/life16040672 - 15 Apr 2026
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Abstract
The Atlantic Forest is a highly diverse biome that is under constant pressure due to human action, resulting in habitat fragmentation and intensifying edge effects, affecting biodiversity. The aim was to study the edge effect and influence of biotic and abiotic parameters on [...] Read more.
The Atlantic Forest is a highly diverse biome that is under constant pressure due to human action, resulting in habitat fragmentation and intensifying edge effects, affecting biodiversity. The aim was to study the edge effect and influence of biotic and abiotic parameters on Calliphoridae and Mesembrinellidae communities in Três Picos State Park. Two traps baited using beef liver were placed at each site (n = 5) across 1000 m from the edge toward the interior of the forest, with vegetal characterization at each point. Collections occurred between June 2021 and May 2023, encompassing each season twice. The dipterans were identified taxonomically using a stereoscope microscope with the aid of taxonomic keys, totaling 5476 specimens. Dipteran abundance and species composition were primarily influenced by seasonal variation, while the distance from the forest edge or vegetation structure showed no effect. Abundance peaked during warmer periods, and temperature showed a positive effect on overall dipteran abundance. No species showed a strong association with specific seasons or distance along the edge–interior gradient. These results indicate that, in a relatively continuous and well-preserved forest remnant, edge effects do not lead to significant species loss, and climatic seasonality shapes patterns of dominance and abundance. Our findings highlight the ecological stability of the studied conservation unit and support the use of Calliphoridae and Mesembrinellidae as effective bioindicators. Understanding how dipteran assemblages respond to seasonal and edge-related gradients contributes to the development of cost-effective biomonitoring tools for tropical forest conservation. Full article
(This article belongs to the Section Biodiversity, Ecology and Evolution)
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