Life

21 pages, 717 KB

Open AccessReview

The Genetic Landscape of Diabetes Mellitus: Lessons from Monogenic and Polygenic Forms

by Davide Nilo, Roberto Nilo, Marta Chiara Sircana, Ferdinando Carlo Sasso, Carlo Acierno, Leonilde Bonfrate and Alfredo Caturano

Life 2026, 16(3), 399; https://doi.org/10.3390/life16030399 (registering DOI) - 1 Mar 2026

Abstract

Diabetes mellitus is increasingly recognized as a biologically heterogeneous disorder that extends beyond traditional phenotype-based classifications. Advances in human genetics have revealed that monogenic and polygenic forms of diabetes are not discrete entities, but rather represent points along a continuum of genetic architectures [...] Read more.

Diabetes mellitus is increasingly recognized as a biologically heterogeneous disorder that extends beyond traditional phenotype-based classifications. Advances in human genetics have revealed that monogenic and polygenic forms of diabetes are not discrete entities, but rather represent points along a continuum of genetic architectures that converge on shared molecular pathways governing pancreatic β-cell identity, function, and survival. Rare monogenic forms, including maturity-onset diabetes of the young and neonatal diabetes, arise from highly penetrant single-gene defects that directly impair transcriptional regulation, glucose sensing, insulin biosynthesis, or stimulus–secretion coupling. Although individually uncommon, these disorders provide high-resolution models of β-cell dysfunction and have demonstrated the clinical value of genotype-guided diagnosis and therapy. At the opposite end of the spectrum, type 1 and type 2 diabetes result from complex interactions between multiple genetic variants and environmental factors, with genome-wide association studies highlighting a central role for genetically determined β-cell vulnerability alongside immune-mediated and metabolic stress pathways. Importantly, intermediate phenotypes such as latent autoimmune diabetes in adults further illustrate the overlap between autoimmune and metabolic mechanisms, challenging rigid diagnostic boundaries. This review synthesizes current evidence on the genetic architecture of diabetes across monogenic and polygenic forms, emphasizing convergent molecular mechanisms and their translational implications. By integrating insights from rare genetic disorders with findings from large-scale population studies, we propose a continuum-based framework that supports a shift from phenotype-driven labels toward a mechanistic, biology-informed approach to diabetes classification, risk stratification, and personalized care. Full article

(This article belongs to the Section Genetics and Genomics)

► Show Figures

Figure 1

21 pages, 3749 KB

Open AccessArticle

The Morphometry of Male Genitalia as a Reliable Tool for Identifying Forest Pests Dendrolimus sibiricus, D. pini (Lepidoptera: Lasiocampidae), and Their Hybrids in Eurasia

by Maria A. Ryazanova, Alexander A. Ageev, Sergey Yu. Sinev, Alexey Yu. Matov, Stanislav Gomboc, Margarita G. Kovalenko, Evgeny N. Akulov, Denis A. Demidko, Dmitrii L. Musolin and Natalia I. Kirichenko

Life 2026, 16(3), 398; https://doi.org/10.3390/life16030398 (registering DOI) - 1 Mar 2026

Abstract

The Siberian moth, Dendrolimus sibiricus Tschetverikov, is one of the most destructive conifer pests in Northern Asia, causing severe ecological and economic losses. In Russia, its range overlaps with that of the closely related pine-tree lappet Dendrolimus pini (L.), and this raises the [...] Read more.

The Siberian moth, Dendrolimus sibiricus Tschetverikov, is one of the most destructive conifer pests in Northern Asia, causing severe ecological and economic losses. In Russia, its range overlaps with that of the closely related pine-tree lappet Dendrolimus pini (L.), and this raises the potential for hybridization and complicates accurate identification, particularly in the context of the potential westward expansion of D. sibiricus. Here, we present the first comprehensive morphometric analysis of male genitalia aimed at distinguishing these two major forest pests and their hybrids. The study was based on D. sibiricus and D. pini specimens collected during the last 130 years (1894–2024) across Europe and Asia, including their hybrids reared indoors by crossing D. pini females with D. sibiricus males in 1956 and preserved in the collection of the Zoological Institute of the Russian Academy of Sciences (St. Petersburg, Russia). Overall, 70 permanent genitalia slides were prepared (33 D. sibiricus, 33 D. pini, and 4 hybrids), and the following genital structures were measured: valva and harpe length, aedeagus width and length, and cornuti length. Dendrolimus sibiricus had significantly larger genital structures compared to D. pini: 74% longer harpe, 32% longer valva, and a 28% wider and longer aedeagus. In contrast, in D. sibiricus cornuti were 21% shorter than in D. pini. Hybrids displayed intermediate values for valva, harpe, and aedeagus lengths, and for these parameters, they significantly differed from both parental species. The following diagnostic indices were suggested to distinguish between the two species and their hybrids: Harpe Length/Valva Length Index (HL/VL) and Cornuti Length/Aedeagus Length Index (CL/AL). Decision-tree analysis identified HL/VL as the strongest predictor for separating the parental species and the Combined Genital Proportion Index (CGPI), which integrates harpe, valva, aedeagus, and cornuti lengths, as the strongest predictor for identifying hybrids. The morphometric criteria developed here have practical applications for monitoring programs and quarantine diagnostics, particularly in sympatric zones and regions at risk of D. sibiricus expansion. Full article

(This article belongs to the Section Animal Science)

► Show Figures

Figure 1

17 pages, 1515 KB

Open AccessReview

The Role of Transcranial Magnetic Stimulation for the Treatment of Alzheimer’s Disease: A Narrative Review

by Vasileios Papaliagkas, Kallirhoe Kalinderi, Maria Moschou, Marianthi Arnaoutoglou, Effrosyni Koutsouraki and Vasileios K. Kimiskidis

Life 2026, 16(3), 397; https://doi.org/10.3390/life16030397 (registering DOI) - 28 Feb 2026

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease that accounts for 60–80% of all dementia cases and affects millions of people worldwide. At present, standard drug therapies provide only limited symptomatic relief. Therefore, the exploration of novel therapeutic approaches is crucial for [...] Read more.

Alzheimer’s disease (AD) is the most common neurodegenerative disease that accounts for 60–80% of all dementia cases and affects millions of people worldwide. At present, standard drug therapies provide only limited symptomatic relief. Therefore, the exploration of novel therapeutic approaches is crucial for improving patient outcomes. Transcranial magnetic stimulation (TMS) has emerged as a promising non-invasive neuromodulation technique that may provide benefit in AD management. This review discusses the pathophysiological mechanisms by which TMS operates, evaluates its clinical efficacy in AD patients, assesses its safety profile, and suggests future directions for research. Full article

(This article belongs to the Section Physiology and Pathology)

19 pages, 1208 KB

Open AccessArticle

The Effects of Clinical Applications of Robot-Assisted Therapy Methods: End-Effector, Fixed Exoskeleton, and Wearable Exoskeleton on Functional Activities in Stroke Patients

by Jung-Ho Lee

Life 2026, 16(3), 396; https://doi.org/10.3390/life16030396 (registering DOI) - 28 Feb 2026

Abstract

Background and Objectives: This study was conducted to investigate the effects of robot-assisted gait rehabilitation approaches using commonly used end-effector, fixed exoskeleton, and wearable exoskeleton on gait and balance abilities in patients with early post-stroke (≤3 months). Materials and Methods: Sixty [...] Read more.

Background and Objectives: This study was conducted to investigate the effects of robot-assisted gait rehabilitation approaches using commonly used end-effector, fixed exoskeleton, and wearable exoskeleton on gait and balance abilities in patients with early post-stroke (≤3 months). Materials and Methods: Sixty patients admitted to a rehabilitation center with confirmed stroke by a medicine specialist were assigned to three groups such as the end-effector group (EG 1), the fixed exoskeleton group (EG 2), and the wearable exoskeleton group (EG 3). The primary endpoint was pre-specified as the change in timed up-and-go gait test (TUG) from baseline to week 6, and all other outcomes were treated as secondary. The functional gait category (FAC), 10-m walk test (10MWT), six-minute walk test (6MWT), timed up-and-go gait test (TUG), dynamic gait index (DGI), and Berg Balance Scale (BBS) were measured at four time points (baseline, 2 weeks, 4 weeks, and 6 weeks). Results: A significant main effect of time was observed for all outcome variables, but neither the main effect of group nor the interaction between group and time was significant for any outcome variable. Within-group analyses revealed that FAC, 6MWT, DGI, and BBS increased over time in all groups, whereas 10MWT and TUG decreased. Conclusions: All three robot-assisted gait rehabilitation approaches in patients with early post-stroke were associated with significant improvements in gait and balance abilities over 6 weeks. However, statistically significant differential trajectories were not detected across robot types in this sample. Full article

(This article belongs to the Special Issue Neurorehabilitation: Technology-Driven Recovery and Functional Rewiring)

► Show Figures

Figure 1

14 pages, 346 KB

Open AccessArticle

Early Postoperative Physical Frailty Reflects Functional Vulnerability and Predicts Prolonged Hospitalization After Major Cardiovascular Surgery

by Seoyon Yang, Younji Kim, Suk-Won Song, Ha Lee, Myeong Su Kim and You Gyoung Yi

Life 2026, 16(3), 395; https://doi.org/10.3390/life16030395 (registering DOI) - 28 Feb 2026

Abstract

Background: Although frailty has emerged as an important determinant of outcomes following cardiovascular surgery, the clinical significance of early postoperative physical frailty assessed during the acute recovery phase has not been investigated. Methods: We conducted a single-center retrospective observational study including patients who [...] Read more.

Background: Although frailty has emerged as an important determinant of outcomes following cardiovascular surgery, the clinical significance of early postoperative physical frailty assessed during the acute recovery phase has not been investigated. Methods: We conducted a single-center retrospective observational study including patients who underwent cardiac or aortic surgery and completed a standardized physical function assessment within 10 days postoperatively. Physical frailty was defined using four objective indicators: Medical Research Council (MRC) sum score, gait speed, Timed Up and Go test, and five-times sit-to-stand test. Frailty was defined as the presence of ≥3 abnormal physical frailty indicators. Clinical outcomes included hospital length of stay (LOS) and postoperative medical complications. Negative binomial regression was used to evaluate factors associated with hospital LOS. Results: Among 441 patients included in the analysis, 308 (69.8%) were classified as frail. Frail patients were older and demonstrated significantly impaired physical performance across all frailty indicators (all p < 0.001). Frailty was associated with longer ICU stay and hospital LOS (both p < 0.001). In multivariable negative binomial regression, postoperative frailty was independently associated with prolonged hospital LOS (incidence rate ratio [IRR] 1.38, 95% CI 1.26–1.51; p < 0.001), after adjustment for age and timing of frailty assessment. Additional adjustment for surgical approach and surgical target did not improve model fit. Postoperative frailty was not significantly associated with the overall incidence of medical complications. Conclusions: Early postoperative physical frailty, assessed during the acute recovery phase, is independently associated with prolonged hospitalization after cardiac and aortic surgery. These findings suggest that early functional vulnerability captures clinically meaningful risk beyond surgical characteristics and may serve as a valuable target for postoperative risk stratification and rehabilitation planning. Full article

(This article belongs to the Special Issue Physical Rehabilitation for Musculoskeletal Disorders: 2nd Edition)

► Show Figures

Figure 1

15 pages, 878 KB

Open AccessCase Report

Delayed Ischemic Hepatocellular Injury Following Cemented Total Hip Arthroplasty: A Case Report Within the Spectrum of Bone Cement Implantation Syndrome

by Bogdan Ștefan Boloș, Ruxandra-Cristina Marin, Răzvan Ene, Simona Bianca Vlad and Oana Andreia Coman

Life 2026, 16(3), 394; https://doi.org/10.3390/life16030394 (registering DOI) - 28 Feb 2026

Abstract

Bone cement implantation syndrome (BCIS) is classically associated with acute intraoperative cardiopulmonary disturbances during cemented arthroplasty. However, accumulating clinical observations suggest that its systemic manifestations may extend beyond the immediate peri-cementation period. Hepatic involvement remains rarely reported and is poorly characterized, particularly in [...] Read more.

Bone cement implantation syndrome (BCIS) is classically associated with acute intraoperative cardiopulmonary disturbances during cemented arthroplasty. However, accumulating clinical observations suggest that its systemic manifestations may extend beyond the immediate peri-cementation period. Hepatic involvement remains rarely reported and is poorly characterized, particularly in frail elderly patients with limited physiological reserve. We report the case of an 82-year-old woman who developed severe but reversible ischemic acute liver failure with concomitant acute kidney injury following cemented total hip arthroplasty. A brief peri-cementation episode of hypotension and mild hypoxemia was followed, within the early postoperative period, by abrupt elevation of aminotransferases (AST 4980 IU/L; ALT 3120 IU/L), coagulopathy (INR ≥ 1.5), transient neurological alteration compatible with early hepatic encephalopathy, severe acute kidney injury, and new-onset atrial fibrillation. An extensive diagnostic evaluation excluded viral, autoimmune, toxic, biliary, vascular, infectious, and structural causes of liver injury. The clinical and biochemical profile was consistent with ischemic hepatocellular injury occurring in the context of systemic hypoperfusion. Management consisted of supportive intensive care focused on hemodynamic stabilization, respiratory support, rhythm control, metabolic management, and close laboratory monitoring, resulting in complete hepatic, renal, and neurological recovery. This case describes a rare presentation of ischemic acute liver failure with multiorgan involvement following cemented total hip arthroplasty. The temporal association with transient peri-cementation hypotension and hypoxemia suggests a possible delayed systemic manifestation within the spectrum of BCIS, even in the absence of overt intraoperative collapse. Although causality cannot be established, the clinical course underscores the importance of careful postoperative evaluation in vulnerable patients who experience perioperative hemodynamic disturbances. Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

39 pages, 3346 KB

Open AccessReview

Targeting the Sleep–Glymphatic–Vascular Continuum in Cerebral Small Vessel Disease: A Nutritional Perspective on Neuroprotective Potential of Tocotrienols (T3)

by Dena Farysah Mazli, Zaw Myo Hein, Che Mohd Nasril Che Mohd Nassir, Ain Hafizah Alias, Sint Sint Win, Mohammad Farris Iman Leong Abdullah, Muhammad Zulfadli Mehat, Hafizah Abdul Hamid and Gehan El-Akabawy

Life 2026, 16(3), 393; https://doi.org/10.3390/life16030393 (registering DOI) - 28 Feb 2026

Abstract

Cerebral small vessel disease (CSVD) is a leading cause of stroke, cognitive impairment, and vascular dementia, yet disease-modifying therapeutic strategies remain limited. Emerging evidence suggests that sleep fragmentation (SF), a common and often under-recognized feature of aging and cardiometabolic disorders, plays a pivotal [...] Read more.

Cerebral small vessel disease (CSVD) is a leading cause of stroke, cognitive impairment, and vascular dementia, yet disease-modifying therapeutic strategies remain limited. Emerging evidence suggests that sleep fragmentation (SF), a common and often under-recognized feature of aging and cardiometabolic disorders, plays a pivotal role in CSVD pathogenesis by disrupting the glymphatic system, the brain’s primary waste clearance pathway. Sleep-dependent glymphatic function facilitates the removal of neurotoxic metabolites and maintains neurovascular homeostasis. In contrast, SF impairs cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange, promotes perivascular space enlargement, endothelial dysfunction, blood–brain barrier (BBB) breakdown, and chronic neuroinflammation, hallmarks of CSVD. This review synthesizes current mechanistic, preclinical, and clinical evidence linking SF to glymphatic dysfunction and small vessel pathology, framing these interactions as a sleep–glymphatic–vascular continuum underlying CSVD progression and cognitive decline. We further explore the emerging therapeutic potential of tocotrienols (T3), vitamin E isoforms with potent antioxidant, anti-inflammatory, and vasculoprotective properties, as modulators of neurovascular integrity within this continuum. Although direct evidence linking T3 to glymphatic regulation remains limited, converging data support their capacity to preserve endothelial function, attenuate oxidative stress, and stabilize astrocytic and BBB dynamics, mechanisms highly relevant to glymphatic and microvascular health. By integrating sleep biology, glymphatic neuroscience, and nutritional vascular protection, this review highlights hypothesis-generating preventive and therapeutic avenues for CSVD and delineates key knowledge gaps, including the need for longitudinal human studies, standardized glymphatic imaging, objective sleep phenotyping, and interventional trials to establish causal and translational relevance. Full article

(This article belongs to the Special Issue Brain Health for All Ages: Leave No One Behind)

► Show Figures

Figure 1

10 pages, 1108 KB

Open AccessArticle

HPLC Purification of TRPM8 and Experimental Confirmation of Its Cholesterol Affinity on Synthetic Lipid Raft-like Models

by Clotilde Beatrice Angelucci, Annalaura Sabatucci, Alexandrine Kurtz, Davide Laurenti, Beatrice Dufrusine, Enrico Dainese and Antonio Francioso

Life 2026, 16(3), 392; https://doi.org/10.3390/life16030392 (registering DOI) - 28 Feb 2026

Abstract

This study presents the successful expression, purification, and functional characterization of the human TRPM8 ion channel, a key player in temperature sensing and pain modulation. Using a modified bacterial expression protocol and DDM-based solubilization, TRPM8 was purified via HPLC-SEC and analyzed for its [...] Read more.

This study presents the successful expression, purification, and functional characterization of the human TRPM8 ion channel, a key player in temperature sensing and pain modulation. Using a modified bacterial expression protocol and DDM-based solubilization, TRPM8 was purified via HPLC-SEC and analyzed for its membrane-binding properties. FRET-based assays with synthetic lipid rafts revealed a strong and selective affinity of TRPM8 for cholesterol-containing membranes, suggesting cholesterol’s role in modulating TRPM8 localization and activity. These findings provide quantitative in vitro evidence of TRPM8–cholesterol interactions and establish a robust model system for future structural and functional studies of membrane-associated proteins. Full article

(This article belongs to the Special Issue Channel Proteins and Transporters in Human Health and Disease)

► Show Figures

Figure 1

11 pages, 398 KB

Open AccessProtocol

Treatment with Kinase Inhibitors Plus Myo-Inositol as Re-Differentiating Agents in Iodine-Refractory Thyroid Cancers

by Carlotta Giani, Michele Russo, Paola Lapi, Maria Antonietta Profilo, Raffaella Forleo, Barbara Mazzi, Arianna Ghirri, Lisa Caresia, Alfredo Campennì, Cosimo Durante, Andrea Corsello, Riccardo Morganti, Vittorio Unfer, Rosa Maria Paragliola and Daniele Barbaro

Life 2026, 16(3), 391; https://doi.org/10.3390/life16030391 (registering DOI) - 28 Feb 2026

Abstract

Background and aim: Recent preclinical studies have confirmed that inhibiting the MAP kinase pathway can induce the re-differentiation of radioiodine (RAI)-refractory (RAIR) follicular cell thyroid cancers (TCs). The aim of this trial is to investigate whether the combination of kinase inhibitors (KIs) with [...] Read more.

Background and aim: Recent preclinical studies have confirmed that inhibiting the MAP kinase pathway can induce the re-differentiation of radioiodine (RAI)-refractory (RAIR) follicular cell thyroid cancers (TCs). The aim of this trial is to investigate whether the combination of kinase inhibitors (KIs) with myo-inositol (MI) can induce or potentiate the re-uptake of RAI in cancer cells. Overview and methods: This is an open label, non-pharmacological, multicenter, randomized pilot study. Patients will be divided into two groups: (1) a control group in which patients are treated with KIs (subgroup a: trametinib plus dabrafenib; subgroup b: lenvatinib); (2) a group in which patients (divided into the two subgroups) are treated with the same KIs in addition to MI. After 30 days of MI treatment, all patients, treated with levothyroxine (L-T4) at a semi-suppressive dosage as per clinical practice, will be stimulated with recombinant human TSH (rhTSH) (days 31 and 32). On day 35, the patients will be subjected to whole-body scintigraphy, with hybrid imaging where possible (SPECT/CT), after the administration of diagnostic activity (185–222 MBq of 123-I in accordance with the SNMMI/EANM guidelines. Blood samples will be collected before starting MI therapy (day 0); after 30 days of MI therapy; and then on days 31, 32, 33, 34, and 35 after MI therapy. Quality of life (QoL) will be assessed at the beginning of the MI treatment and at the end of its administration. The primary endpoint is the restoration of 123-I uptake in RAIR-TC patients already on KI therapy alone and on KI therapy plus MI. The restoration of 123-I uptake in target lesions will be evaluated. Conclusions: MI may have a synergistic effect at the cellular level, and the possible increase in the re-differentiation of RAIR-TC in patients treated with KIs plus MI may have great clinical relevance. The re-uptake of RAI will be evaluated as the primary endpoint, and Tg values and QoL will be evaluated as the secondary endpoints. The main limitation of this study is that we do not investigate any clinical effects. We will have to postpone the clinical analysis to a later date after the administration of RAI for therapeutic purposes. Full article

(This article belongs to the Special Issue Research and Management of Endocrine Tumors)

► Show Figures

Figure 1

15 pages, 2413 KB

Open AccessArticle

Frontal-to-Parietal Theta Interactions Mediate Tactile Decision-Making

by Pritom Mukherjee, Sydney Apraku and Mukesh Dhamala

Life 2026, 16(3), 390; https://doi.org/10.3390/life16030390 (registering DOI) - 28 Feb 2026

Abstract

Decision-making relies on coordinated neural dynamics that integrate sensory evidence with top-down control. In this EEG study, we examined sensor (scalp)-level theta and alpha-band oscillations, as well as fronto-parietal network connectivity, during a tactile spatial discrimination task. Blindfolded participants judged the lateral offset [...] Read more.

Decision-making relies on coordinated neural dynamics that integrate sensory evidence with top-down control. In this EEG study, we examined sensor (scalp)-level theta and alpha-band oscillations, as well as fronto-parietal network connectivity, during a tactile spatial discrimination task. Blindfolded participants judged the lateral offset of the central dot in a three-dot array delivered to the right index finger while an EEG was recorded. Time–frequency analyses revealed that both theta and alpha power were greater for correct than incorrect decision trials during pre-stimulus and post-stimulus intervals, suggesting enhanced preparatory and mnemonic engagement during accurate decisions. Directional connectivity assessed using block (multivariate) Granger causality demonstrated significantly stronger frontal-to-parietal influence in the theta band during both pre- and post-stimulus periods for correct decisions, supporting the role of long-range theta communication for top-down control in guiding tactile judgment. These findings highlight theta-band fronto-parietal communication as a key mechanism supporting successful tactile decision-making. Full article

(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)

► Show Figures

Figure 1

12 pages, 471 KB

Open AccessArticle

Impact of CPAP Therapy Adherence on Time to First Recurrence of Paroxysmal Atrial Fibrillation in Patients with Severe Obstructive Sleep Apnea

by Petar Kalaydzhiev, Radostina Ilieva, Natalia Spasova, Slavi Yakov, Dimitar Markov, Neli Georgieva, Elena Kinova and Assen Goudev

Life 2026, 16(3), 389; https://doi.org/10.3390/life16030389 (registering DOI) - 28 Feb 2026

Abstract

Background: Obstructive sleep apnea (OSA) is a major modifiable risk factor for atrial fibrillation (AF), promoting arrhythmogenesis through intermittent hypoxia, autonomic activation, and atrial remodeling. Although continuous positive airway pressure (CPAP) effectively treats OSA, real-world evidence linking objectively measured CPAP exposure to [...] Read more.

Background: Obstructive sleep apnea (OSA) is a major modifiable risk factor for atrial fibrillation (AF), promoting arrhythmogenesis through intermittent hypoxia, autonomic activation, and atrial remodeling. Although continuous positive airway pressure (CPAP) effectively treats OSA, real-world evidence linking objectively measured CPAP exposure to clinically relevant AF recurrence remains limited. Aims: We aimed to evaluate the association between CPAP adherence and risk of recurrent paroxysmal AF, and to compare time to first recurrence between patients with mean nightly CPAP use ≥4 h/night versus <4 h/night. Materials and Methods: In this prospective observational cohort (2017–2024), consecutive hospitalized and outpatient adults with severe obstructive sleep apnea (OSA; apnea–hypopnea index > 30 events/h) and documented paroxysmal atrial fibrillation (AF) were enrolled. Persistent and long-standing persistent AF were excluded to ensure a homogeneous population with respect to atrial substrate. OSA was assessed using home sleep apnea testing (ResMed ApneaLink), and all patients initiated continuous positive airway pressure (CPAP) therapy (ResMed AirSense 10). Objective adherence data were obtained via the ResMed AirView telemonitoring platform. Exclusion criteria included permanent AF, prior pulmonary vein isolation, central sleep apnea, left ventricular ejection fraction < 50%, end-stage chronic kidney disease (eGFR < 15 mL/min/1.73 m² or dialysis), or inability to initiate or maintain CPAP therapy. Patients were followed for 12 months. The primary endpoint was time to first documented recurrence of paroxysmal AF (≥30 s on 12-lead electrocardiography or 24-h Holter monitoring). Progression to permanent AF, defined after unsuccessful rhythm control attempts and subsequent transition to a rate control strategy, was assessed as a secondary endpoint. Time-to-event analyses used Kaplan–Meier estimates with log-rank testing, and Cox proportional hazards regression adjusted for age, body mass index, apnea–hypopnea index, heart failure, left atrial volume index, and antiarrhythmic drug therapy. Results: The final analysis included 91 patients (mean age 62.15 ± 8.29 years; 68.13% men). Mean nightly CPAP use was ≥4 h/night in 49 patients and <4 h/night in 42 patients. During follow-up, paroxysmal AF recurrence occurred in 12/49 (24.5%) patients in the ≥4 h/night group and 16/42 (38.1%) in the <4 h/night group. Mean arrhythmia-free survival at 12 months was numerically higher in the ≥4 h/night group (11.25 vs. 10.51 months), without a statistically significant difference in Kaplan–Meier curves (log-rank p = 0.11). In multivariable Cox regression, binary adherence (≥4 h/night) was not independently associated with recurrence (HR 0.52, p = 0.13), whereas mean nightly CPAP use analyzed as a continuous variable remained independently associated with delayed recurrence (per 1-h increase: HR 0.66, 95% CI 0.48–0.91, p = 0.01). Progression to permanent AF occurred in 4/49 (10.0%) versus 9/42 (17.6%) patients, respectively (p = 0.29). Conclusions: In this real-world cohort of patients with severe OSA and paroxysmal AF, higher objectively measured CPAP exposure was independently associated with delayed AF recurrence when analyzed as a continuous variable, suggesting a graded association between objectively measured CPAP exposure and AF recurrence. Larger studies with extended follow-up and continuous rhythm monitoring are warranted to confirm long-term rhythm benefits and effects on AF progression. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

► Show Figures

Figure 1

9 pages, 2338 KB

Open AccessCase Report

Allergic Reaction to Titanium Alloy Osteosynthesis Implants: A Case Report of Three Patients

by Hsuan Chou, Yen-Yu Lin, Yu-Ching Huang, Ping-Chun Yeh and Shu-Hao Chang

Life 2026, 16(3), 388; https://doi.org/10.3390/life16030388 (registering DOI) - 28 Feb 2026

Abstract

Background: Titanium is commonly used for fracture fixation and is considered inert, but hypersensitivity reactions to titanium alloy still occur and are difficult to diagnose due to a lack of a universally accepted standard in post-orthopedic surgical patients, and other common diagnoses need [...] Read more.

Background: Titanium is commonly used for fracture fixation and is considered inert, but hypersensitivity reactions to titanium alloy still occur and are difficult to diagnose due to a lack of a universally accepted standard in post-orthopedic surgical patients, and other common diagnoses need to be differentiated. Case Presentation: This case report describes three patients with manifestations of allergic reactions to titanium-alloy implants after Open Reduction and Internal Fixation (ORIF) with Ti-6Al-4V plates. Three patients mainly presented with persistent localized dermatitis. During follow-up, radiographs confirmed bone unions, and there were no signs of purulent drainage, abscess formation, or systemic infection. Taken together, these findings reduce the possibility of fracture-related infection (FRI) and other etiologies. Conservative treatment was ineffective, and the patch test and histopathology in two patients respectively supported hypersensitivity reactions. After the implants were surgically removed, there were significant improvements in symptoms. Conclusion: Three cases of suspected titanium-alloy hypersensitivity were diagnosed by exclusion based on clinical history, laboratory results, and additional testing. The findings showed the importance of clinical history and the identification of signs and symptoms of allergic reactions, emphasizing the need for a standardized diagnostic process. Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

19 pages, 1241 KB

Open AccessArticle

The Effect of Intravenous Thrombolysis and Mechanical Thrombectomy on Change in the Concentrations of Interleukin-18 and Degradation Products of the Endothelial Glycocalyx in Patients with Acute Ischemic Stroke

by Anja Babić, Božena Ćurko-Cofek, Vlatka Sotošek, David Bonifačić, Melani Mamić, Vita Komen, Slavica Kovačić, Vladimira Vuletić and Lara Batičić

Life 2026, 16(3), 387; https://doi.org/10.3390/life16030387 (registering DOI) - 28 Feb 2026

Abstract

Stroke is characterized by a sudden onset of neurological deficit attributed to a focal brain injury. The main treatments for patients with an acute ischemic stroke are intravenous thrombolysis and mechanical thrombectomy. Recanalization therapies have significantly improved patient outcomes; however, their effectiveness depends [...] Read more.

Stroke is characterized by a sudden onset of neurological deficit attributed to a focal brain injury. The main treatments for patients with an acute ischemic stroke are intravenous thrombolysis and mechanical thrombectomy. Recanalization therapies have significantly improved patient outcomes; however, their effectiveness depends on a range of pathophysiological factors. This prospective observational study included 60 patients with acute ischemic stroke. The control group consisted of 20 healthy blood donors. Patients were divided into three groups based on whether they received intravenous thrombolysis, mechanical thrombectomy, or combination therapy. We investigated differences between recanalization therapies in patients with ischemic stroke with respect to peripheral blood concentrations of the proinflammatory cytokine interleukin (IL)-18 and endothelial glycocalyx degradation products: syndecan-1, heparan sulphate, and hyaluronic acid, measured by enzyme-linked immunosorbent assay. The blood samples were collected before, 24, and 48 h after recanalization therapy. The concentration of IL-18, syndecan-1, and heparan sulphate increased statistically significantly in patients treated with mechanical thrombectomy. The concentration of hyaluronic acid increased statistically significantly in patients treated with intravenous thrombolysis. The findings primarily reflect between-group differences. Our findings indicate that IL-18 has a significant role in the early inflammatory response. IL-18 and EG degradation products represent potential biomarkers for identifying high-risk patients. Their measurement could help improve the treatment, recovery, and outcomes in patients with acute ischemic stroke. The aforementioned observations underscore their potential value as biomarkers for future research. Full article

(This article belongs to the Special Issue The 15th Anniversary of Life: Endothelial Glycocalyx—a Determinant of Endothelial Function and Vascular Reactivity)

► Show Figures

Figure 1

17 pages, 298 KB

Open AccessArticle

Weekly Fluctuations in Internal Load and Neuromuscular Performance Across a 10-Week Training Period in Elite Female Boxers

by Ahmet Serhat Aydın, Tolga Altuğ, Coşkun Yılmaz, Adela Badau and Mehmet Söyler

Life 2026, 16(3), 386; https://doi.org/10.3390/life16030386 (registering DOI) - 28 Feb 2026

Abstract

This study examined weekly internal load and neuromuscular performance in elite junior female boxers over 10 weeks. Internal load was quantified using session rating of perceived exertion (sRPE), from which weekly monotony and strain were derived. Neuromuscular performance was assessed weekly using wall-sit [...] Read more.

This study examined weekly internal load and neuromuscular performance in elite junior female boxers over 10 weeks. Internal load was quantified using session rating of perceived exertion (sRPE), from which weekly monotony and strain were derived. Neuromuscular performance was assessed weekly using wall-sit endurance and a repetitive jump test. Twenty elite junior female boxers (Mean ± SD: 18.9 ± 1.2) were monitored during regular training without experimental manipulation. Weekly sRPE-derived training load, monotony, and strain showed statistically significant week-to-week fluctuations (p < 0.001). Neuromuscular performance improved in week 2, declined during weeks 3–5, and partially recovered in week 6. The findings demonstrated consistent temporal alignment between internal-load indices and week-to-week neuromuscular performance changes within an observational monitoring framework. Inter-individual variability was observed across athletes. Overall, sRPE-derived indices reflected training stress patterns and were aligned with neuromuscular performance changes in elite female boxers, supporting their use for contextual monitoring of weekly training responses. These findings support the practical integration of internal-load and performance monitoring in elite female combat-sport settings. Future research incorporating boxing-specific external-load metrics, physiological markers, and longer monitoring periods may further refine individualized load-management strategies. Full article

(This article belongs to the Special Issue Advances and Applications of Sport Physiology: 2nd Edition)

15 pages, 612 KB

Open AccessArticle

Inactivation of BAP1 and the Hippo Pathway Characterizes the Genomic Alterations of Peritoneal Mesothelioma

by Maya Samuels, Madi Williams, Angela Hasan, Susan Rafie, Grace S. Saglimbeni, Beau Hsia, Sunil Nair, Sweety Aeilias and Abubakar Tauseef

Life 2026, 16(3), 385; https://doi.org/10.3390/life16030385 (registering DOI) - 28 Feb 2026

Abstract

Background/Objectives: Peritoneal mesothelioma is a rare malignancy characterized by limited therapeutic options and a poor prognosis. Genomic characterization can enhance the understanding of the molecular mechanisms that lead to this disease and can contribute to improved survival outcomes through therapeutic targets. Methods: Analysis [...] Read more.

Background/Objectives: Peritoneal mesothelioma is a rare malignancy characterized by limited therapeutic options and a poor prognosis. Genomic characterization can enhance the understanding of the molecular mechanisms that lead to this disease and can contribute to improved survival outcomes through therapeutic targets. Methods: Analysis was performed using a dataset from the AACR GENIE database (v17.0-public) comprising 204 samples from 192 patients. Data were analyzed to identify patterns in genomic alterations and clinical demographics. Within the GENIE cohort, histologic subtype information was incomplete and inconsistently reported across contributing institutions. Hence, histological subtype genomic analysis was not viable. Results: The most common somatic mutation was found in the BAP1 gene (25.98%). Other common mutations were found in the NF2 (15.19%), TP53 (9.3%) and SETD2 (8.3%) genes. Several pathways were found as potential treatment targets including the chromatin remodeling, Hippo, and p53 signaling pathways. Given the size of our dataset, we were unable to draw significant conclusions about certain demographics. Conclusions: This study presents data that can help draw conclusions on common mutations, mutual exclusivity patterns, and demographics at risk for peritoneal mesothelioma. Genomic analysis of peritoneal mesothelioma may inform possible intervention targets for therapeutic treatment. Full article

(This article belongs to the Special Issue Cancer Genomics and Transcriptomics: Uncovering New Frontiers in Tumor Biology)

► Show Figures

Figure 1

14 pages, 3047 KB

Open AccessArticle

Analysis of Pediatric Secondary Glaucoma Patients Treated with Micropulse Transscleral Cyclophotocoagulation (MP-TSCPC)

by Bogumiła Wójcik-Niklewska, Karolina Pańczyk, Karina Dzięcioł, Nikola Oleksyk, Zofia Oliwa, Mariola Dorecka, Dorota Wyględowska-Promieńska and Adrian Smędowski

Life 2026, 16(3), 384; https://doi.org/10.3390/life16030384 - 27 Feb 2026

Abstract

Background: Secondary glaucoma in children results from congenital or acquired ocular abnormalities, systemic diseases, or syndromes. These conditions impair aqueous humor outflow despite an open iridocorneal angle, causing elevated intraocular pressure (IOP). Micropulse transscleral cyclophotocoagulation (MP-TSCPC) reduces aqueous humor production by targeting the [...] Read more.

Background: Secondary glaucoma in children results from congenital or acquired ocular abnormalities, systemic diseases, or syndromes. These conditions impair aqueous humor outflow despite an open iridocorneal angle, causing elevated intraocular pressure (IOP). Micropulse transscleral cyclophotocoagulation (MP-TSCPC) reduces aqueous humor production by targeting the ciliary body and restores the aqueous humor’s circulation balance. The aim of the study was to evaluate the safety and efficacy of MP-TSCPC in pediatric secondary glaucoma. Methods: This retrospective study included 59 children who underwent MP-TSCPC procedures. The mean age was 7.2 years (range 4 months–17 years). Data on IOP, prior glaucoma treatments, medication use, and adverse events were analyzed. The mean follow-up was 10.4 months. Results: The mean preoperative IOP was 34.0 mmHg, which significantly decreased to 25.8 mmHg after MP-TSCPC, representing a mean reduction of 20.8% (p < 0.0001). Satisfactory IOP lowering was achieved in 69.6% of procedures. Eyes without prior glaucoma surgery showed a numerically greater IOP reduction (22%) compared to previously treated eyes (19%), though the difference was not statistically significant (p = 0.628). Among repeated MP-TSCPC treatments, 57.1% were successful, with a mean IOP reduction of 7.3%. The mean number of glaucoma medications decreased significantly from 2.42 to 2.02 (p = 0.0002). A sustained reduction in medication use was observed in 33.3% of cases. Conclusions: MP-TSCPC effectively lowers IOP in pediatric secondary glaucoma and has a favorable safety profile. The option for repeated treatments and reduced medication needs supports its use as a less invasive alternative to conventional surgery. Full article

(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Ophthalmic Diseases)

20 pages, 1207 KB

Open AccessFeature PaperArticle

Integrated Urinary and Tissue Proteomic Signatures Reveal Core and Progression Biomarkers in MRI-Visible and MRI-Non-Visible Prostate Cancer

by Ana Blanca, Ana C. Morillo, Antonio Lopez-Beltran, Guillermo Lendinez Cano, Rafael A. Medina, Laura Chamorro Castillo, Daniel López Ruiz, Eduardo Chicano-Galvez, Juan Pablo Campos Hernández and Enrique Gómez-Gómez

Life 2026, 16(3), 383; https://doi.org/10.3390/life16030383 - 27 Feb 2026

Abstract

Background: Prostate cancer (PCa) shows a marked biological heterogeneity that is closely associated with tumor aggressiveness. A substantial proportion of clinically significant tumors remain undetected by multiparametric magnetic resonance imaging (mpMRI). Elucidating the molecular basis of MRI visibility and identifying non-invasive biomarkers could [...] Read more.

Background: Prostate cancer (PCa) shows a marked biological heterogeneity that is closely associated with tumor aggressiveness. A substantial proportion of clinically significant tumors remain undetected by multiparametric magnetic resonance imaging (mpMRI). Elucidating the molecular basis of MRI visibility and identifying non-invasive biomarkers could improve the risk stratification and clinical management of patients. Accordingly, this study aimed to assess tissue and urine proteomic signatures associated with PCa aggressiveness and mpMRI visibility. Methods: In this exploratory study, we performed an integrated proteomic analysis of prostate tissue and preoperative urine samples from 24 patients stratified into four groups: benign prostatic hyperplasia (BPH), indolent PCa (Gleason 6), clinically significant PCa with MRI-visible lesions, and clinically significant PCa with MRI-non-visible lesions. Data-independent acquisition mass spectrometry (DIA workflows) was used to identify differentially expressed proteins associated with malignancy, tumor aggressiveness, and MRI visibility. Results: Pairwise proteomic analyses revealed significant molecular differences between BPH and all PCa groups, identifying 694 non-redundant proteins differentially expressed in tissue and 482 in preoperative urine, showing molecular features associated with both disease presence and progression. Comparative tissue and urine analyses identified 82 proteins, reflecting shared biological pathways in metabolism, cytoskeletal organization, immune processes, and extracellular matrix remodeling. Finally, a direct comparison of MRI-visible and MRI-non-visible clinically significant PCa identified a panel of differentially expressed proteins, including LCN2/NGAL, S100A9, and AOC1/DAO, that showed differential urinary abundance and prognostic relevance in the TCGA-PRAD cohort. Conclusion: Our results suggest that proteomic alterations in PCa are associated with disease progression and aggressiveness and capture biologically relevant differences between tissue and urinary proteomes. These differences are also observed between MRI-visible and MRI-non-visible clinically significant prostate cancers, supporting the potential of urinary proteomics as a non-invasive complement to imaging-based diagnostics. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prognosis of Prostate Cancer)

13 pages, 283 KB

Open AccessArticle

Effects of Different Levels of Carrot Juice Supplementation in Drinking Water on Performance, Egg Quality, Blood Parameters, and Gut Health of Babcock White Laying Hens

by Umit Ozcinar, Muhammet Emre Orman, Cangir Uyarlar, Eyup Eren Gultepe, Oğuz Kağan Türedi, Aamir Iqbal, İbrahim Sadi Çetingül, Beytullah Kenar and Ismail Bayram

Life 2026, 16(3), 382; https://doi.org/10.3390/life16030382 - 27 Feb 2026

Abstract

In this study, the effects of carrot juice on performance, egg quality, blood parameters, and intestinal flora in laying hens were examined. One hundred twenty-eight Babcock white laying hens were divided into four random groups, each with four replicates of eight hens. Fresh [...] Read more.

In this study, the effects of carrot juice on performance, egg quality, blood parameters, and intestinal flora in laying hens were examined. One hundred twenty-eight Babcock white laying hens were divided into four random groups, each with four replicates of eight hens. Fresh carrot juice was introduced to the drinking water of the hens at concentrations of 0% (control), 1%, 2.5%, and 5% for a duration of four weeks. Weekly feed intake, egg weight, feed conversion ratio, and daily egg production were monitored, while yolk color, albumen and yolk indices, shell thickness, and Haugh units were measured in weeks two and four. Blood samples were analyzed for biochemical and physiological parameters, and fecal samples were analyzed for microbial parameters at the end of the study. Carrot juice improved egg production, egg weight, and egg mass, without affecting daily feed intake, feed conversion ratio, or water consumption, while enhancing yolk color but reducing eggshell thickness. Blood analyses showed higher levels of total oxidant status, vitamin E, immunoglobulin G, alkaline phosphatase, lymphocyte count, and mean corpuscular hemoglobin concentration. Moreover, fecal Enterococcus counts were positively affected by the treatment. The findings indicate that carrot juice supplementation could positively affect performance, egg quality, some immune-related blood parameters, and gut microbiota in laying hens. Among the levels evaluated, adding 2.5% carrot juice to drinking water was found to provide the most balanced response. Full article

(This article belongs to the Special Issue Gut Health and Nutritional Strategies in Animals)

34 pages, 596 KB

Open AccessSystematic Review

Concurrent HIIT and Resistance Training for Musculoskeletal Function: A Systematic Review of Neuromuscular, Morphological, and Performance Adaptations

by YuWei Chang, Hsia-Ling Tai, Cheng-Long Yang and Chun-Hsien Su

Life 2026, 16(3), 381; https://doi.org/10.3390/life16030381 - 27 Feb 2026

Abstract

This systematic review focuses on the effect of concurrent high-intensity interval training (HIIT) and resistance training on musculoskeletal function in adult individuals. Four electronic databases (PubMed, Web of Science Core Collection, Scopus, and PsycINFO) were searched for controlled trials in older or middle-aged [...] Read more.

This systematic review focuses on the effect of concurrent high-intensity interval training (HIIT) and resistance training on musculoskeletal function in adult individuals. Four electronic databases (PubMed, Web of Science Core Collection, Scopus, and PsycINFO) were searched for controlled trials in older or middle-aged adults, in recreationally exercising adults, and in athletic or tactical populations, which completed parallel HIIT and resistance training and described musculoskeletal responses to the intervention up to 30 November 2025. A total of 18 trials fulfilled the eligibility criterion and were synthesized narratively across the domains of maximal strength, explosive performance, neuromuscular activity, muscle morphology and architecture, tendon-related outcomes, and adherence and safety. Most 8- to 12-week interventions maintained two to three weekly resistance sessions and were designed in time-effective HIIT formats, increasing or preserving maximal strength in older subjects as well as younger ones that were trained. Explosive performance metrics, including both jump and sprint tasks, were usually preserved or even improved by the maintenance of the power-oriented component in resistance-based exercise sessions. The limited electromyography data indicated improved neuromuscular activation during submaximal tasks, particularly in older subjects, whereas some studies reported subtle increases or maintenance of muscle size and selective architectural patterns during application of progressive loading. Tendon-specific adaptations are difficult to measure, as imaging was seldom available, but functional tasks influenced by the muscle–tendon unit have been studied in multiple studies. Adherence was good, and adverse events were rare in all studies. Overall, the evidence suggests that well-designed concurrent HIIT and resistance training programs can improve or maintain musculoskeletal performance, although the magnitude and expression of these adaptations vary according to population characteristics and intervention design. Importantly, by integrating neuromuscular, morphological, and performance-related outcomes across diverse adult populations, this review provides a musculoskeletal-centered synthesis that extends prior concurrent training reviews beyond cardiorespiratory or interference-focused perspectives. Full article

(This article belongs to the Special Issue Effects of Exercise Training on Muscle Function—2nd Edition)

► Show Figures

Figure 1

Journal Description

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI