Life

16 pages, 548 KB

Open AccessArticle

Optimising Return to Work for Cardiovascular Patients: An Interdisciplinary Approach in Occupational Medicine and Cardiology

by Donatella Sansone, Antonella Cherubini, Fabiano Barbiero, Marina Bollini, Marcella Mauro, Andrea Di Lenarda, Francesca Rui, Luca Cegolon and Francesca Larese Filon

Life 2026, 16(1), 19; https://doi.org/10.3390/life16010019 (registering DOI) - 22 Dec 2025

Abstract

Background: This study explored facilitators and barriers to return to work (RTW) after acute cardiovascular events or elective cardiac surgery, integrating clinical, functional, and occupational factors. Methods: A prospective cohort study was conducted at the Occupational Medicine and Cardiac Rehabilitation Units of the [...] Read more.

Background: This study explored facilitators and barriers to return to work (RTW) after acute cardiovascular events or elective cardiac surgery, integrating clinical, functional, and occupational factors. Methods: A prospective cohort study was conducted at the Occupational Medicine and Cardiac Rehabilitation Units of the Maggiore Hospital in Trieste, Italy. Employed adults (18–67 years) admitted for acute coronary syndrome, valve replacement, or thoracic aortic surgery between January 2024 and July 2025 were enrolled. Sociodemographic, clinical, and occupational data were collected alongside functional and psychosocial assessments, including the Work Ability Index (WAI) and EQ-5D-5L. Predictors of RTW were analyzed with Cox regression models. Results: Among 103 patients (mean age 56.8 years; 92.2% male), 77.7% returned to work after a mean of 58.9 days. Independent predictors of earlier RTW were self-employment (HR 5.08, 95% CI 2.52–10.27), occupational responsibility (HR 2.12, 95% CI 1.01–4.45), and percutaneous coronary intervention (HR 2.72, 95% CI 1.47–5.06). Higher job-related physical demands, arrhythmias, and cardiac rehabilitation participation were associated with delayed RTW. Mean WAI (37.2 ± 5.1) and EQ-5D index (0.92 ± 0.09; EQ-VAS 77.4 ± 12.9) indicated preserved function and quality of life. Conclusions: RTW after cardiovascular events is multifactorial. Integrating occupational medicine into cardiac rehabilitation is key to ensuring safe, sustainable reintegration. Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment—4th Edition)

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18 pages, 12006 KB

Open AccessArticle

Cells Co-Producing Insulin and Glucagon in Congenital Hyperinsulinism

by Yuliya Krivova, Alexandra Proshchina, Dmitry Otlyga, Diliara Gubaeva, Maria Melikyan and Sergey Saveliev

Life 2026, 16(1), 18; https://doi.org/10.3390/life16010018 (registering DOI) - 22 Dec 2025

Abstract

Alterations of pancreatic islet cell phenotypes are well established in diabetic conditions and considered to be one of the possible causes of insulin deficiency. However, there is limited information about alterations of islet cell phenotypes in opposite metabolic conditions such as hypoglycemia in [...] Read more.

Alterations of pancreatic islet cell phenotypes are well established in diabetic conditions and considered to be one of the possible causes of insulin deficiency. However, there is limited information about alterations of islet cell phenotypes in opposite metabolic conditions such as hypoglycemia in infants with congenital hyperinsulinism (CHI). Surgical biopsies of the pancreas from six infants with diffuse CHI and five infants with focal CHI were examined using double immunofluorescence with antibodies against insulin, glucagon and the key transcriptional factor responsible for β-cell differentiation and maturation—PDX1. The phenotypes of cells within the pancreatic islets in diffuse CHI and within the focus in focal CHI were compared to those in unaltered pancreatic islets located outside the focus. In diffuse CHI, the proportion of bi-hormonal insulin+/glucagon+ cells was increased. Additionally, an increase in the proportion of insulin+ cells lacking PDX1 was observed in diffuse CHI and within the focus. It can be assumed that alterations of the phenotype of β-cells may occur under hypoglycemic conditions, but the role of islet cell plasticity in infants with CHI remains to be established. Full article

(This article belongs to the Section Physiology and Pathology)

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38 pages, 1245 KB

Open AccessReview

Rising Demand for Winter Crops Under Climate Change: Breeding for Winter Hardiness in Autumn-Sown Legumes

by Katalin Magyar-Tábori, Sripada M. Udupa, Alexandra Hanász, Csaba Juhász and Nóra Mendler-Drienyovszki

Life 2026, 16(1), 17; https://doi.org/10.3390/life16010017 (registering DOI) - 22 Dec 2025

Abstract

Climate change in the Pannonian region is accelerating a shift toward autumn sowing of cool-season grain legumes (pea, faba bean, lentil, chickpea, lupine) to achieve higher yields, greater biomass production, enhanced nitrogen fixation, improved soil cover, and superior resource use efficiency compared with [...] Read more.

Climate change in the Pannonian region is accelerating a shift toward autumn sowing of cool-season grain legumes (pea, faba bean, lentil, chickpea, lupine) to achieve higher yields, greater biomass production, enhanced nitrogen fixation, improved soil cover, and superior resource use efficiency compared with spring sowing. However, successful overwintering depends on the availability of robust winter-hardy cultivars. This review synthesizes recent breeding advances, integrating traditional approaches—such as germplasm screening, hybridization, and field-based selection—with genomics-assisted strategies, including genome-wide association studies (GWAS), quantitative trait locus (QTL) mapping, marker-assisted selection (MAS), and CRISPR/Cas-mediated editing of CBF transcription factors. Key physiological mechanisms—LT₅₀ determination, cold acclimation, osmoprotectant accumulation (sugars, proline), and membrane stability—are assessed using field survival rates, electrolyte leakage assays, and chlorophyll fluorescence measurements. Despite challenges posed by genotype × environment interactions, variable winter severity, and polygenic trait control, the release of cultivars worldwide (e.g., ‘NS-Mraz’, ‘Lavinia F’, ‘Ghab series’, ‘Pinklevi’, and ‘Rézi’) and ongoing breeding programs demonstrate substantial progress. Future breeding efforts will increasingly rely on genomic selection (GS), high-throughput phenomics, pangenomics, and G×E modeling to accelerate the development of climate-resilient legume cultivars, ensuring stable and sustainable production under increasingly unpredictable winter conditions. Full article

(This article belongs to the Special Issue Effects of Environmental Factors on Challenges of Plant Breeding: 2nd Edition)

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17 pages, 1079 KB

Open AccessReview

Diabetes Mellitus and Atrial Fibrillation: Mechanistic Insights and Therapeutic Impacts of Glucose-Lowering Drugs

by Mihai Grigore, Andreea-Maria Grigore, Martin-Graur Ruxandra-Elena, Verde Ioana, Gabriela Uscoiu, Camelia Nicolae, Ana-Maria Balahura and Adriana-Mihaela Ilieșiu

Life 2026, 16(1), 16; https://doi.org/10.3390/life16010016 - 22 Dec 2025

Abstract

Background/Objectives: Diabetes mellitus (DM) represents a major global public health challenge and is consistently associated with an increased risk of atrial fibrillation (AF). Despite extensive epidemiological evidence linking the two conditions, the underlying mechanisms and the influence of glucose-lowering therapies on AF susceptibility [...] Read more.

Background/Objectives: Diabetes mellitus (DM) represents a major global public health challenge and is consistently associated with an increased risk of atrial fibrillation (AF). Despite extensive epidemiological evidence linking the two conditions, the underlying mechanisms and the influence of glucose-lowering therapies on AF susceptibility remain incompletely defined. This review aims to summarize the current knowledge on the pathophysiological pathways linking DM and AF and to assess the impact of commonly used antidiabetic therapies on arrhythmic risk. We conducted a narrative review of epidemiological studies, mechanistic research, and cardiovascular outcome trials that evaluate the association between DM and AF. We included data addressing structural, electrical, autonomic, metabolic, and inflammatory mechanisms of AF in diabetes, as well as clinical evidence regarding the impact of metformin, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium–glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on AF incidence or recurrence. Results: DM promotes AF development through multiple complementary mechanisms, including atrial fibrosis, electrical conduction abnormalities, autonomic dysfunction, inflammation, glycemic fluctuations, oxidative stress, and expansion of epicardial adipose tissue. These changes create a vulnerable atrial substrate that facilitates both initiation and maintenance of AF. Evidence from recent trials indicates that the arrhythmic effects of glucose-lowering therapies are heterogeneous. Metformin and SGLT-2 inhibitors appear to offer favorable or neutral effects on AF risk. GLP-1 receptor agonists provide substantial cardiovascular benefits, although their specific impact on AF remains under investigation. Insulin therapy has been linked to a higher AF risk, whereas DPP-4 inhibitors show an overall neutral effect with inconsistent findings across studies. Conclusions: AF in patients with DM results from complex interactions between metabolic disturbances, structural remodeling, and inflammatory activation. Although several antidiabetic drugs appear to have potential antiarrhythmic effects, further dedicated research is needed to clarify their role in AF prevention and management. Full article

(This article belongs to the Section Pharmaceutical Science)

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15 pages, 1846 KB

Open AccessArticle

Positive Selection in Aggression-Linked Genes and Their Protein Interaction Networks

by Asma Awadi, Zelalem Gebremariam Tolesa and Hichem Ben Slimen

Life 2026, 16(1), 15; https://doi.org/10.3390/life16010015 (registering DOI) - 22 Dec 2025

Abstract

Aggressive behavior is a complex and multifactorial trait influenced by several genes and shaped by societal and cultural constraints. To trace adaptation signals and identify potential new genes related to aggressive behavior, we explored variations in nine genes previously linked to aggressive behavior, [...] Read more.

Aggressive behavior is a complex and multifactorial trait influenced by several genes and shaped by societal and cultural constraints. To trace adaptation signals and identify potential new genes related to aggressive behavior, we explored variations in nine genes previously linked to aggressive behavior, as well as their 74 interacting genes retrieved from the STRING database. We identified 15 SNPs under positive selection in four genes (SEC24B, NCOA2, CTNNA1, and ALDH3A2), with selection consistently confirmed by both iHS and xp-EHH analyses. Among these, 15 SNPs showed high pairwise F_ST values and pronounced allele frequency differences between populations, suggesting their potential role in the local adaptation of the studied populations. The functional importance of these SNPs was confirmed by ten acting as eQTLs and five located in transcription factor binding sequences. The observed selection signatures may reflect adaptation in diverse biological processes, including protein trafficking and signal transduction, cell proliferation and differentiation, endocrine regulation, and lipid and aldehyde detoxification. Although these processes are not directly linked to aggression, they may have downstream effects on neurodevelopmental and hormonal regulation that could indirectly influence behavioral phenotypes. Experimental validation is required to confirm these signals and to clarify their functional and biological significance. Full article

(This article belongs to the Section Evolutionary Biology)

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12 pages, 3027 KB

Open AccessCase Report

New Insights into Molecular Mechanisms and Radiomics in Non-Contrast CT for Aortic Dissection: A Case Report and Literature Review

by Jian-Cheng Tian, Jia-Hao Zhou, Jui-Yuan Chung, Po-Chen Lin, Giou-Teng Yiang, Ya-Chih Yang and Meng-Yu Wu

Life 2026, 16(1), 14; https://doi.org/10.3390/life16010014 - 22 Dec 2025

Abstract

Background: Computed tomography (CT) angiography is widely regarded as the gold standard for diagnosing acute aortic dissection. However, in patients with contraindications to iodinated contrast media, such as those with renal insufficiency or hemodynamic instability, non-contrast CT may offer a viable alternative for [...] Read more.

Background: Computed tomography (CT) angiography is widely regarded as the gold standard for diagnosing acute aortic dissection. However, in patients with contraindications to iodinated contrast media, such as those with renal insufficiency or hemodynamic instability, non-contrast CT may offer a viable alternative for initial evaluation. Understanding the molecular mechanisms underlying aortic dissection, including extracellular matrix degradation, smooth muscle cell apoptosis, and inflammatory pathways, is crucial for developing novel diagnostic and therapeutic approaches. This report describes a single case of acute Stanford type A aortic dissection initially detected on non-contrast CT. Case Presentation: We describe a 74-year-old man who presented to the emergency department with fever and suspected infection, but without chest pain. An incidental finding on non-contrast CT revealed ascending aortic dilatation, pericardial effusion, and a suspected intimal flap. Subsequent CT angiography confirmed a Stanford type A aortic dissection. Conclusions: This case highlights the potential value of non-contrast CT in the early detection of aortic dissection, particularly when CT angiography cannot be performed. Recent advances in artificial intelligence (AI) and radiomic analysis have shown promise in augmenting the diagnostic capabilities of non-contrast CT by identifying subtle imaging features that may correlate with underlying molecular pathology and elude human observers. Emerging evidence suggests that radiomic features may reflect molecular alterations in the aortic wall, including metalloproteinase activity, collagen degradation, and inflammatory cell infiltration. Incorporating AI-assisted interpretation alongside insights into molecular mechanisms could facilitate earlier diagnosis, improve risk stratification, and guide personalized treatment strategies in critically ill patients. Although non-contrast CT has limited sensitivity for aortic dissection, it may still reveal crucial findings in selected cases and should be considered when contrast-enhanced imaging is not feasible. Ongoing progress in AI, radiomics, and molecular biomarker research may further expand the clinical applications of non-contrast CT in emergency cardiovascular care and bridge the gap between imaging phenotypes and molecular endotypes. These findings are hypothesis-generating and require validation in larger cohorts before clinical generalization. Full article

(This article belongs to the Special Issue Current and Future Perspectives of Artificial Intelligence in Medicine)

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15 pages, 3093 KB

Open AccessReview

Acute Exercise-Induced Epinephrine Elevation Promotes Post-Learning Memory Consolidation: A Narrative Review of Mechanisms and Implementation Strategies

by Yiwan Zhang, Xuewan Lin, Gen Li and Songtao Wang

Life 2026, 16(1), 13; https://doi.org/10.3390/life16010013 - 22 Dec 2025

Abstract

Memory function is susceptible to decline with age, stress, and neurological diseases, highlighting the importance of exploring effective and sustainable strategies to enhance memory consolidation. Epinephrine plays a key role in memory consolidation; acute, moderate elevations enhance memory, while chronic high levels are [...] Read more.

Memory function is susceptible to decline with age, stress, and neurological diseases, highlighting the importance of exploring effective and sustainable strategies to enhance memory consolidation. Epinephrine plays a key role in memory consolidation; acute, moderate elevations enhance memory, while chronic high levels are inhibitory. Given the limitations of pharmacological interventions, this study aims to investigate exercise as a non-pharmacological means to promote post-learning memory consolidation by inducing acute epinephrine release, focusing on its mechanisms and optimized implementation strategies. This narrative review systematically reviews evidence from neurophysiology, molecular biology, and behavioral experiments and finds that exercise can safely and controllably activate the sympathetic–adrenal system, leading to a rapid rise in epinephrine. The release kinetics align highly with the critical time window for memory consolidation. Moderate-intensity aerobic exercise implemented within 30 min post-learning can significantly improve memory retention. The mechanisms involve not only epinephrine enhancing synaptic plasticity and LTP by activating hippocampal β-adrenergic receptors, but also synergistic effects across multiple systems, such as promoting osteocalcin signaling, upregulating BDNF expression, inducing neurogenesis, and optimizing cerebral metabolism and blood flow. Evidence suggests that exercise, as a non-pharmacological intervention, significantly enhances post-learning memory consolidation through the precise modulation of epinephrine release and multi-system synergy, offering both high efficacy and safety. Future research should focus on developing precise exercise prescriptions based on individual characteristics and leveraging wearable devices and digital technologies to improve intervention adherence and applicability, promoting its widespread use in educational and clinical settings. Full article

(This article belongs to the Section Physiology and Pathology)

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Graphical abstract

11 pages, 247 KB

Open AccessArticle

Factors Associated with Referral to Low Vision for Patients with Advanced Glaucoma

by Julia Ernst, Janice Huang, Jakob Tsosie and David J. Ramsey

Life 2026, 16(1), 12; https://doi.org/10.3390/life16010012 - 22 Dec 2025

Abstract

Glaucoma is one of the most common causes of irreversible visual impairment world wide. Providing low vision rehabilitation (LVR) services is a primary mode of support for patients with permanent vision loss. This retrospective, cross-sectional study evaluated the rate at which patients with [...] Read more.

Glaucoma is one of the most common causes of irreversible visual impairment world wide. Providing low vision rehabilitation (LVR) services is a primary mode of support for patients with permanent vision loss. This retrospective, cross-sectional study evaluated the rate at which patients with severe open-angle glaucoma (OAG) were referred for LVR services at an academic medical center. Patient demographics, glaucoma severity, appointment history, performance on visual field (VF) testing, presenting visual acuity (VA), and change in best-corrected visual acuity (BCVA) after low vision refraction were abstracted from the electronic record and summarized by using descriptive statistics. Logistic regression analysis was used to assess the relationship between study variables and the likelihood of referral for LVR evaluation. Out of 522 patients with severe OAG, 88% of whom qualified as having low vision, 14 were referred for an LVR evaluation (2.7%). Referrals were most strongly associated with VA (adjusted odds ratio [aOR], 7.20; 95% confidence interval [CI], 2.11–24.64, p = 0.001) but not glaucoma-associated VF loss (aOR, 0.90; 95% CI, 0.24–3.37, p = 0.876). Thirteen of 14 patients referred for LVR completed visits (93%). More than one-third of those patients improved in their better-seeing eye after a low vision refraction, gaining an average of −0.18 ± 0.24 logMAR (half gaining ≥2-lines of BCVA). Patients with severe OAG are at risk of progressive visual disability from their eye disease. We found, however, that the majority of these patients were not referred to LVR services, despite meeting eligibility criteria and growing evidence demonstrating their potential benefit. Full article

(This article belongs to the Section Medical Research)

11 pages, 482 KB

Open AccessArticle

Efficacy and Safety of Pirfenidone in Patients with Progressive Pulmonary Fibrosis: A Retrospective Single-Center Study

by Ju Hyun Oh, Jin Han Park, Ji Hoon Jang, Minyoung Her, Een Young Cho and Jae Ha Lee

Life 2026, 16(1), 11; https://doi.org/10.3390/life16010011 - 21 Dec 2025

Abstract

Progressive pulmonary fibrosis (PPF) is an emerging subset of fibrotic interstitial lung diseases (ILD), defined by progressive fibrosis despite standard treatment in patients with other than idiopathic pulmonary fibrosis. The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone [...] Read more.

Progressive pulmonary fibrosis (PPF) is an emerging subset of fibrotic interstitial lung diseases (ILD), defined by progressive fibrosis despite standard treatment in patients with other than idiopathic pulmonary fibrosis. The international guidelines recommended the use of nintedanib for PPF, while evidence supporting pirfenidone remains insufficient. In this study, we aimed to evaluate the efficacy and safety of pirfenidone in treating PPF. In this retrospective single-center study, we analyzed clinical data from patients with PPF who were treated with pirfenidone. Lung function data from six months before and after pirfenidone treatment were collected to assess changes over time. Missing values were imputed using a general linear mixed model (GLMM) for longitudinal data analysis. Of 33 subjects, the median age was 65.0 years, and 51.5% were female. Rheumatoid arthritis-related ILD was the most common subtype (45.5%). The median daily dose of pirfenidone was 600 mg, with a median treatment duration of 7.3 months. GLMM analysis showed a significant forced vital capacity (FVC) improvement, from −114 mL in the 6 months before treatment to +47.3 mL in the 6 months after treatment (p = 0.001). All adverse events related to pirfenidone were mild. In conclusion, the use of pirfenidone in PPF can potentially reduce the rate of FVC decline in real clinical practice. Full article

(This article belongs to the Special Issue Advances in Pulmonology: Transforming Diagnosis and Treatment of Lung Diseases)

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32 pages, 1326 KB

Open AccessReview

Cell Surface Markers of Mesenchymal Stem Cells: Current Knowledge and Advances in Characterization Technologies

by Angelo Santoro, Manuela Grimaldi, Carmen Marino, Enza Napolitano, Michela Buonocore and Anna Maria D’Ursi

Life 2026, 16(1), 10; https://doi.org/10.3390/life16010010 - 21 Dec 2025

Abstract

Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine due to their high differentiation potential and therapeutic versatility. MSCs are multipotent cells capable of differentiating into adipocytes, chondroblasts, osteoblasts, and, under specific conditions, neural, myocyte, and epidermal lineages. This cell type contributes to [...] Read more.

Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine due to their high differentiation potential and therapeutic versatility. MSCs are multipotent cells capable of differentiating into adipocytes, chondroblasts, osteoblasts, and, under specific conditions, neural, myocyte, and epidermal lineages. This cell type contributes to tissue repair, immunomodulation, and regenerative therapies for cardiac, orthopedic, and hematological disorders. Accurate identification and characterization of these stem cells are essential for both research and clinical applications. MSCs are typically defined by plastic adherence, expression of surface markers CD105, CD73, and CD90, low or absent expression of hematopoietic markers (CD45, CD34), and in vitro differentiation potential. Understanding the expression patterns and functional relevance of these surface markers is critical for improving isolation strategies, enhancing therapeutic efficacy, and minimizing adverse effects. This review provides a comprehensive overview of the principal surface markers of MSCs, highlighting their significance in stem cell biology and clinical translation. Full article

(This article belongs to the Special Issue Unlocking New Biochemical Pathways: A Bridge for Drug Development in Human and Animal Diseases)

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14 pages, 9960 KB

Open AccessArticle

Biomechanical Investigation of Head Injuries Caused by Baseball Bat Strikes with Different Bat Sizes and Velocities: A Finite Element Simulation Study

by Han Zhang, Jin Yang, Luyi Guo, Jiani Sun, Shangxiao Li and Weiya Hao

Life 2026, 16(1), 9; https://doi.org/10.3390/life16010009 (registering DOI) - 20 Dec 2025

Abstract

Objective: Traumatic brain injury (TBI) represents a significant clinical problem, with the biomechanical mechanisms of striking from different blunt instruments remaining unclear. This study aims to quantitatively evaluate TBI severity under blunt strikes and to assess the effects of strike velocity and blunt [...] Read more.

Objective: Traumatic brain injury (TBI) represents a significant clinical problem, with the biomechanical mechanisms of striking from different blunt instruments remaining unclear. This study aims to quantitatively evaluate TBI severity under blunt strikes and to assess the effects of strike velocity and blunt instrument size on biomechanical responses to provide a finite element approach for investigating injury mechanisms and informing clinical diagnosis. Methods: A head finite element model incorporating an outer cortical-cancellous-inner cortical bone structure was developed and verified against a previous cadaveric impact study. Strike velocities and blunt instrument parameters, obtained from experiments in which a long bat (LB) and a short bat (SB) were used to strike a dummy head, were applied as the loading conditions in the finite element simulation. Kinetic energy (KE), internal energy (IE), impact force, von Mises stress on skull, intracranial pressure (ICP), and Head_3ms acceleration were analyzed as indicators of injury severity. Results: Simulated force and ICP responses agreed with cadaveric experimental data within a 9.8% error. With increasing strike velocity (10–30 m/s), KE, IE, impact force, ICP, and Head_3ms all rose, while von Mises stress evolved from localized to dispersed distribution. Head_3ms reached an injury threshold of 80 g at a strike velocity of 10 m/s, and ICP peaks for LB and SB exceeded the brain injury threshold (235 kPa, ≈1760 mmHg) at 12 m/s and 14 m/s, respectively. At the same velocity, LB generated higher KE, IE, impact force, ICP and Head_3ms than SB. At 30 m/s, LB generated 390 J KE and 29.0 kN peak force, which were 50.0% and 11.1% higher than those of SB (260 J, 26.1 kN). Conclusion: This study reveals that increasing strike velocity and employing a larger blunt instrument elevate biomechanical responses, resulting in von Mises stress transitioning from localized concentration to multipolar dispersion. Specifically, when striking the head with the LB at velocities exceeding 12 m/s or with the SB exceeding 14 m/s, the impacts indicate a severely life-threatening level. These findings deepen our understanding of the mechanisms of blunt TBI. The constructed and validated finite element model can be repeatedly used for computer simulations of TBI under various blunt striking conditions, providing a scientific basis for clinical diagnosis and surgical planning. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI))

10 pages, 3197 KB

Open AccessArticle

Osteomyelitis in Deep Sternal Wound Infections: Revisited—A Single-Center Observational Study

by Stephan Raab, Tina Schaller, Evaldas Girdauskas and Sebastian Reindl

Life 2026, 16(1), 8; https://doi.org/10.3390/life16010008 (registering DOI) - 20 Dec 2025

Abstract

Objective: Sternum osteomyelitis and deep sternal wound infection (DSWI) are often used to describe the same clinical condition interchangeably. The aim of our current study is to investigate the prevalence of osteomyelitis in cardiac surgery patients with DSWI and its consequences in [...] Read more.

Objective: Sternum osteomyelitis and deep sternal wound infection (DSWI) are often used to describe the same clinical condition interchangeably. The aim of our current study is to investigate the prevalence of osteomyelitis in cardiac surgery patients with DSWI and its consequences in therapy and osteosynthetic reconstruction. Patients and Methods: This is a retrospective single-center observational study. All consecutive patients with DSWI after cardiac surgery between 01/2014 and 12/2019 were included. In all patients, the sternal wound was reopened, sternal closure material was removed, and negative pressure therapy was initiated. Wound swabs were taken for microbiological examination, and a bone biopsy was examined for the presence of osteomyelitis. In the presence of osteomyelitis, long-term antibiotics were administered. Results: A total of 130 patients were identified in whom DSWI occurred after sternotomy. In 102 patients (77%), osteomyelitis could be detected histopathologically. The frequency of transverse sternal fractures was lower (p < 0.05) in the osteomyelitis subgroup (63%) as compared to the non-osteomyelitis subgroup (93%). Pathogens were detected in all patients with osteomyelitis, but less frequently (p < 0.05) in the group with no osteomyelitis (64%). If osteomyelitis was treated with long-term antibiotics, there was no difference in the complication rate (reinfection) after sternal restabilization between the two groups. Conclusions: DSWI and osteomyelitis should not be used interchangeably. If osteomyelitis can be detected histopathologically, long-term antibiotic treatment should be consistently conducted. As DSWI, with or without osteomyelitis, has been suggested to be associated with inadequate or failed sternal osteosynthesis, a key strategy to reduce its risk is to ensure safe and reliable primary sternal fixation. Full article

(This article belongs to the Special Issue Reconstruction of Bone Defects)

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21 pages, 321 KB

Open AccessReview

Catching the Storm Before It Breaks: Advancing Early Diagnosis and Intervention in Bipolar Disorder

by Marianna Mazza, Luca Chisari, Francesco Maria Lisci, Caterina Brisi, Giovanni Camardese, Domenico De Berardis, Luigi Janiri, Gabriele Sani and Giuseppe Marano

Life 2026, 16(1), 7; https://doi.org/10.3390/life16010007 (registering DOI) - 20 Dec 2025

Abstract

In recent years, growing attention has been directed toward the early diagnosis and intervention of bipolar disorder (BD), driven by the recognition that timely clinical action may significantly alter the trajectory of the illness. Early identification of individuals at risk, as well as [...] Read more.

In recent years, growing attention has been directed toward the early diagnosis and intervention of bipolar disorder (BD), driven by the recognition that timely clinical action may significantly alter the trajectory of the illness. Early identification of individuals at risk, as well as intervention during prodromal or subthreshold phases, offers the potential to delay onset, reduce episode severity, improve long-term outcomes, and possibly prevent the full manifestation of the disorder. This narrative review aims to provide a comprehensive overview of the current literature on the early stages of BD, including clinical high-risk states, neurobiological and cognitive markers, and psychosocial indicators. It also explores the latest research findings and their implications for clinical practice, highlighting the importance of integrated approaches that combine biomarker discovery, risk stratification models, and youth-focused mental health services. Finally, the review discusses the ethical and practical challenges of early intervention and underscores the need for further longitudinal studies and personalized preventive strategies. Full article

(This article belongs to the Special Issue Pharmacology, Diagnosis and Treatments of Psychiatric Diseases)

30 pages, 16196 KB

Open AccessArticle

In Silico Optimization of Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2

by Issouf Fofana, Brice Dali, Mawa Koné, Katarina Sujova, Eugene Megnassan, Stanislav Miertus and Vladimir Frecer

Life 2026, 16(1), 6; https://doi.org/10.3390/life16010006 - 19 Dec 2025

Abstract

In this study, new improved inhibitors of the viral enzyme 3-chymotrypsin-like protease (3CL^pro) were designed using structure-based drug design techniques in an effort to discover more effective treatment of coronavirus disease 2019 (COVID-19). Three-dimensional models of 3CL^pro–inhibitor complexes were [...] Read more.

In this study, new improved inhibitors of the viral enzyme 3-chymotrypsin-like protease (3CL^pro) were designed using structure-based drug design techniques in an effort to discover more effective treatment of coronavirus disease 2019 (COVID-19). Three-dimensional models of 3CL^pro–inhibitor complexes were prepared by in situ modification of the crystal structure of the submicromolar covalent inhibitor IPCL6 for a set of 25 known inhibitors with published inhibitory potencies (

{I C}_{50}^{e x p}

). The QSAR model was prepared with a reasonable correlation between the calculated free energies of formation of the 3CL^pro-IPCL complex (∆∆G_com) and the experimentally determined activities

{I C}_{50}^{e x p}

, which explained approximately 92% of the variation in the 3CL^pro inhibition data. A similar agreement was achieved for the QSAR pharmacophore model (PH4) built on the basis of the active conformations of the IPCL inhibitors bound at the active site of the 3CL^pro. The virtual combinatorial library of more than 567,000 IPCL analogues was screened in silico using the PH4 model and resulted in the identification of 39 promising analogues. The best inhibitors designed in this study show high predicted affinity for the 3CL^pro protease, as well as favourable predicted ADME properties. For the best new virtual inhibitor candidate IPCL 80-27-74-4, the inhibitory concentration

{I C}_{50}^{p r e}

was predicted equal to 0.8 nM, which represents a significant improvement in the inhibitory potency of known IPCLs. Ultimately, molecular dynamics simulations of the 12 newly designed top-scoring IPCL inhibitors demonstrated that the 3CL^pro–inhibitor complexes exhibited good structural stability, confirming the potential for further development of the designed IPCL analogues. Full article

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

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12 pages, 1365 KB

Open AccessArticle

Impact of Transanal Drainage Tube Placement on Anastomosis Leakage Incidence After Rectal Cancer Surgery

by Maria-Manuela Răvaș, Marian Marincaș, Eugen Brătucu, Vrgiliu Prunoiu, Laurentiu Simion, Laura-Maria Manea and Mircea-Nicolae Brătucu

Life 2026, 16(1), 5; https://doi.org/10.3390/life16010005 - 19 Dec 2025

Abstract

Background: Anastomotic leakage (AL) following rectal cancer surgery is a significant cause of mortality and morbidity. Although transanal drainage tubes are expected to reduce the rate of AL, their preventive effect remains controversial. Aim: To evaluate whether transanal drainage tube (TAD) [...] Read more.

Background: Anastomotic leakage (AL) following rectal cancer surgery is a significant cause of mortality and morbidity. Although transanal drainage tubes are expected to reduce the rate of AL, their preventive effect remains controversial. Aim: To evaluate whether transanal drainage tube (TAD) provides protection against AL in patients without other protective methods after low anterior resection (LAR). Methods: A retrospective cohort study was performed in patients undergoing LAR for rectal cancer between 2018 and 2023. Based on postoperative management, patients were divided into four distinct groups as follows: in TAD group, after colorectal anastomosis, a 32F silicone tube was inserted through the anus by more than 5 cm above the anastomosis. The tube was secured around the anus with a skin suture and a drainage bag was attached. The tube was removed after 3–5 days after surgery. In the non-TAD group, no transanal drainage tube and no diverting stomas, respectively, were used after the anastomosis. In the ileostomy and colostomy group a stoma was often performed as a primary measure in preventing anastomotic leakage. Clinical characteristics and postoperative complications were compared among the groups. Complications were categorized as general (eventration, seroma) or septic (fistula, abscess) and further classified as early (<7 days after surgery) or tardive (between 7 and 30 days after surgery). Statistical significance was defined as a p-value < 0.05. Results: A total of 171 patients were included: 47 (27.5%) in the TAD group, 54 (32.2%) in the non-TAD group, 25 (14.6%) in colostomy group, and 45 (26.3%) in ileostomy group. Overall, eight patients (4.7%) developed anastomotic leakage (AL). In the non-TAD group, 3 patients experienced AL (all early); in the ileostomy group, 2 patients (1 early, 1 tardive); and in the colostomy group, 2 patients (both tardive). The TAD group had one patient with AL as a tardive complication. The incidence of early general complications was significant lower in TAD group compared with the non-TAD group (OR 0.23, 95% CI [0.06–0.85]; p = 0.004), while there was no significant difference in early septic complications between TAD and ileostomy group (p = 0.71). The incidence of tardive general complications was significantly more frequent in the ileostomy group (OR 0.10, 95% CI [0.02–0.44]; p = 0.0008) compared with TAD group. Overall, total complications were significantly lower in TAD group compared to non-TAD (OR 0.15, 95% CI [0.05–0.44]; p < 0.001), ileostomy (OR 0.20, 95% CI [0.07–0.56]; p = 0.003), and colostomy ((OR 0.46 CI [0.21–0.99]; p = 0.049) groups. Furthermore, the TAD group showed a reduction rate of AL compared to the ileostomy, colostomy, and non-TAD groups (2.12% vs. 4.4%, 8%, and 5.5%) but the incidence of AL was almost similar (p = 0.65). Conclusions: The elective use of TAD is a simple and effective protective method for the prevention of overall postoperative complications, also helping to reduce the rate of AL in patients. Nevertheless, there is limited information in the literature regarding the optimal size and material of TAD, despite these factors playing an important role in the viability and effectiveness of the method. Full article

(This article belongs to the Section Medical Research)

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19 pages, 1129 KB

Open AccessArticle

Higher Prevalence of Sarcopenia in Knee Osteoarthritis and Its Association with Femoral Intercondylar Cartilage Thickness and Functional Outcomes

by Guan-Bo Chen, Chien-Hui Li, Ya-Chun Hu, Yi-Ju Tsai, Ya-Hui Chen and Sheng-Hui Tuan

Life 2026, 16(1), 4; https://doi.org/10.3390/life16010004 - 19 Dec 2025

Abstract

Knee osteoarthritis (KOA) and sarcopenia are prevalent age-related disorders that share common pathophysiological mechanisms such as aging, chronic inflammation, and physical inactivity. Their coexistence may aggravate functional decline and disability. This cross-sectional study aimed to compare the prevalence of sarcopenia between individuals with [...] Read more.

Knee osteoarthritis (KOA) and sarcopenia are prevalent age-related disorders that share common pathophysiological mechanisms such as aging, chronic inflammation, and physical inactivity. Their coexistence may aggravate functional decline and disability. This cross-sectional study aimed to compare the prevalence of sarcopenia between individuals with KOA and matched controls and to explore the relationship between femoral intercondylar cartilage (FIC) thickness and muscle-related parameters. A total of 228 participants (114 KOA, 114 controls) matched by age, sex, and body mass index were enrolled. Assessments included appendicular skeletal muscle mass index (ASMMI), handgrip strength, walking speed, and physical activity. In KOA patients, ultrasound measurements of FIC and quadriceps thickness and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were additionally obtained. Sarcopenia prevalence was higher in the KOA group than in controls (41.2% vs. 26.3%, p = 0.017). Greater FIC thickness was associated with higher ASMMI, stronger handgrip strength, faster walking speed, and lower WOMAC pain and total scores. These findings indicate that FIC thickness may serve as a potential structural biomarker linking cartilage integrity with muscle function in KOA. Full article

(This article belongs to the Section Medical Research)

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11 pages, 14078 KB

Open AccessCase Report

Combined Pharmacological and Pneumatic Displacement Therapy for Sub-Macular Haemorrhage Secondary to Age-Related Macular Degeneration: A Case Series and Review of the Literature

by Agnieszka Kudasiewicz-Kardaszewska, Małgorzata Anna Ozimek, Tomasz Urbański, Kinga Jamontt, Aleksander Tkaczenko, Karolina Bonińska and Sławomir Cisiecki

Life 2026, 16(1), 3; https://doi.org/10.3390/life16010003 - 19 Dec 2025

Abstract

Purpose: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September [...] Read more.

Purpose: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September 2025. All patients received intravitreal alteplase (100 µg) and C₃F₈ gas, followed by aflibercept (2 mg or 8 mg) within a treat-and-extend regimen. BCVA- and OCT-based anatomical changes were recorded at baseline, 7–14 days, 1 month, 3 months, and 6 months. BCVA changes were analysed using repeated-measures testing. Results: Mean BCVA improved from 0.99 ± 0.21 logMAR at baseline to 0.89 ± 0.20 at 7–14 days, 0.80 ± 0.20 at 1 month, 0.60 ± 0.18 at 3 months, and 0.53 ± 0.20 at 6 months (p < 0.05 for overall change). Eight eyes (80 percent) showed restoration of foveal contour, while two developed foveal atrophy. No major adverse events occurred. Conclusion: Combined intravitreal alteplase and C₃F₈, followed by aflibercept, may provide favourable short-term visual and anatomical improvement in SMH secondary to nAMD. Early intervention appears beneficial, but larger controlled studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 3rd Edition)

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15 pages, 1150 KB

Open AccessArticle

Cardiometabolic Candidate Endotypes in Psoriatic Disease: Integration of Clinical, Metabolic, and Immunogenetic Data Across Psoriasis and Psoriatic Arthritis

by Rubén Queiro, Paula Alvarez, Ignacio Braña, Marta Loredo, Estefanía Pardo, Stefanie Burger, Norma Callejas, Sara Alonso and Mercedes Alperi

Life 2026, 16(1), 2; https://doi.org/10.3390/life16010002 - 19 Dec 2025

Abstract

Background/objectives: Psoriatic disease (PsD) encompasses psoriasis (PsO) and psoriatic arthritis (PsA) and is associated with heterogeneous cardiometabolic risk. Integrating immunogenetic markers such as HLA-Cw6 into data-driven analyses may refine phenotyping and uncover clinically meaningful endotypes. We aimed to identify cardiometabolic phenotypes across PsD, [...] Read more.

Background/objectives: Psoriatic disease (PsD) encompasses psoriasis (PsO) and psoriatic arthritis (PsA) and is associated with heterogeneous cardiometabolic risk. Integrating immunogenetic markers such as HLA-Cw6 into data-driven analyses may refine phenotyping and uncover clinically meaningful endotypes. We aimed to identify cardiometabolic phenotypes across PsD, integrating HLA-Cw6 and exploring disease-specific heterogeneity and predictors of high-risk profiles. Methods: In a cross-sectional study of 572 PsD patients (401 PsO, 171 PsA), eight demographic and clinical variables, including HLA-Cw6, were entered into k-means clustering (k = 4). Cardiometabolic risk factors were profiled post hoc. Cluster validity was assessed by Gaussian Mixture Models and principal component analysis (PCA). Stratified analyses (k = 3) were conducted separately for PsO and PsA. Predictors of the high-risk phenotype were examined using bootstrap-resampled logistic regression. Results: Four cardiometabolic phenotypes were identified, ranging from younger patients with active PsO and low cardiometabolic burden to a small, high-risk subgroup (~6%) combining older age, universal cardiovascular disease, and a clustering of hypertension, diabetes, and dyslipidemia. Disease-stratified analyses showed that high-risk phenotypes were present in both PsO and PsA. In stratified analyses, HLA-Cw6 showed opposite associations—enriched in high-risk PsO (OR 2.0, 95% CI 1.3–3.1) but depleted in high-risk PsA (OR 0.24, 95% CI 0.11–0.52). Conclusions: Incorporating HLA-Cw6 into clustering identified reproducible cardiometabolic phenotypes with distinct genetic signatures. The inverse HLA-Cw6 risk patterns in PsO and PsA suggest disease-specific patterns that may have differing cardiometabolic implications, which should be tested in longitudinal studies. Full article

(This article belongs to the Section Physiology and Pathology)

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14 pages, 990 KB

Open AccessArticle

Temporal Expression of NLRP3 Inflammasome Components in Patients with Acute Coronary Syndrome

by Paraskevi Papanikolaou, Andreas Aggelopoulos, Alexios S. Antonopoulos, Panagiotis Theofilis, Maria Gazouli, Konstantinos Tsioufis and Dimitris Tousoulis

Life 2026, 16(1), 1; https://doi.org/10.3390/life16010001 - 19 Dec 2025

Abstract

Background: Inflammation is a central driver of atherothrombosis, yet the temporal behavior of key inflammasome mediators following acute coronary syndrome (ACS) is not well characterized. The NLRP3 inflammasome, a major regulator of interleukin (IL)-1β activation, has been implicated in plaque destabilization and recurrent [...] Read more.

Background: Inflammation is a central driver of atherothrombosis, yet the temporal behavior of key inflammasome mediators following acute coronary syndrome (ACS) is not well characterized. The NLRP3 inflammasome, a major regulator of interleukin (IL)-1β activation, has been implicated in plaque destabilization and recurrent cardiovascular risk. This study aims to investigate the temporal expression of NLRP3 inflammasome components in peripheral blood mononuclear cells (PBMCs) of patients with ACS. Methods: In this prospective observational study, PBMCs were collected from 73 patients with ACS during the early in-hospital phase and at 8–12 weeks follow-up. Gene expression of NLRP3, caspase-1, and IL-1β was quantified by qRT-PCR, and fold-change was calculated using the 2^−ΔΔCT method. Associations with clinical and biochemical variables were evaluated using multivariable linear regression. Results: Expression of all measured inflammasome-related genes increased significantly at follow-up compared with baseline: caspase-1 (≈2-fold, p = 0.003), NLRP3 (>10-fold, p < 0.001), and IL-1β (≈4-fold, p < 0.001). Subgroup analyses showed that the post-ACS upregulation of NLRP3, caspase-1, and IL-1β was consistent across STEMI and NSTEMI presentations and was not significantly modified by diabetes status. Caspase-1 fold-change correlated positively with IL-1β, LDL-cholesterol, peak troponin I, and high sensitivity C reactive protein, whereas NLRP3 showed minimal correlations with clinical variables. In multivariable analysis, caspase-1 upregulation was independently associated with STEMI presentation and low-density lipoprotein-cholesterol, and IL-1β with type 2 diabetes. Conclusions: Patients with ACS exhibit significant and persistent upregulation of NLRP3 inflammasome components weeks after the acute event, indicating sustained immune cell priming during recovery. These findings highlight a potential molecular substrate for residual inflammatory risk and support further exploration of inflammasome-targeted therapies in the post-ACS period. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: From Basic Research to Clinical Application—3rd Edition)

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