Life

26 pages, 1080 KB

Open AccessReview

Peripartum Depression as a Heart–Brain–Endocrine–Immune Syndrome: Neuroendocrine, Cardiovascular, and Inflammatory Pathways Underlying Maternal Vulnerability

by Giuseppe Marano and Marianna Mazza

Life 2026, 16(2), 236; https://doi.org/10.3390/life16020236 (registering DOI) - 1 Feb 2026

Abstract

Peripartum depression (PPD) represents one of the most prevalent and disabling psychiatric conditions among women, yet its underlying biology remains poorly integrated across medical disciplines. Emerging evidence highlights PPD as a prototypical disorder of the heart–brain axis, where neuroendocrine changes, immune activation, and [...] Read more.

Peripartum depression (PPD) represents one of the most prevalent and disabling psychiatric conditions among women, yet its underlying biology remains poorly integrated across medical disciplines. Emerging evidence highlights PPD as a prototypical disorder of the heart–brain axis, where neuroendocrine changes, immune activation, and cardiovascular dysregulation converge to shape maternal vulnerability. During pregnancy and the postpartum period, abrupt fluctuations in estrogen, progesterone (P4), and placental corticotropin-releasing hormone (CRH) interact with a sensitized hypothalamic–pituitary–adrenal (HPA) axis, altering neural circuits involved in mood regulation, stress reactivity, and maternal behavior. Parallel cardiovascular adaptations, including endothelial dysfunction, altered blood pressure variability, and reduced heart rate variability (HRV), suggest a profound perturbation of autonomic balance with potential long-term implications for maternal cardiovascular health. Neuroinflammation, microglial activation, and systemic cytokine release further mediate the bidirectional communication between the heart and the brain, linking emotional dysregulation with vascular and autonomic instability. Evidence also indicates that conditions such as preeclampsia and peripartum cardiomyopathy share biological pathways with PPD, reinforcing the concept of a unified pathophysiological axis. This review synthesizes current knowledge on the neurobiological, cardiovascular, endocrine, and inflammatory mechanisms connecting PPD to maternal heart–brain health, while discussing emerging biomarkers and therapeutic strategies aimed at restoring integrative physiology. Understanding PPD as a multisystem heart–brain disorder offers a transformative perspective for early detection, risk stratification, and personalized intervention during one of the most biologically vulnerable periods of a woman’s life. Full article

(This article belongs to the Section Reproductive and Developmental Biology)

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10 pages, 422 KB

Open AccessCommunication

α-Glucosidase and Pancreatic Lipase Inhibitory Activity of Chemical Constituents from Adzuki Bean (Vigna angularis)

by Qingfeng Guo, Xia Zhang, Hao Zhang, Mengxue Wang, Haoran Zhou, Meiru Chen, Zhenhua Yin, Juanjuan Zhang, Baocheng Yang, Li Wang and Lin Chen

Life 2026, 16(2), 235; https://doi.org/10.3390/life16020235 (registering DOI) - 1 Feb 2026

Abstract

Originating in East Asia, the adzuki bean (Vigna angularis) is a diploid crop mainly grown in this region that belongs to the Fabaceae family. As a potential functional food resource with both medicinal and nutritional value, it offers various health benefits. [...] Read more.

Originating in East Asia, the adzuki bean (Vigna angularis) is a diploid crop mainly grown in this region that belongs to the Fabaceae family. As a potential functional food resource with both medicinal and nutritional value, it offers various health benefits. However, research on its chemical constituents, particularly key bioactive components such as triterpenoid saponins and flavonoids, remains relatively limited. In this study, a new triterpenoid saponin, adzukisaponin A (1), along with eleven known compounds (2–12), were isolated from adzuki bean (V. angularis). Among them, compounds 3 (yunganoside B1), 6 (3β-acetyl oleanolic acid), and 7 (β-amyrin) are reported from this source for the first time. Saponins 1–3 and flavonoid 8 exhibited significant dual inhibitory activity. Notably, saponins 1–3 inhibited pancreatic lipase (IC₅₀ = 0.11 ± 0.18 to 0.40 ± 0.21 mM) more strongly than the positive control orlistat, while also acting against α-glucosidase (IC₅₀ = 0.14 ± 0.11 to 0.23 ± 0.17 mM). Molecular docking supported their binding to the enzymes’ active sites. This study identifies 1–3 and 8 as dual α-glucosidase/pancreatic lipase inhibitors, underscoring the potential of adzuki bean as a source of bioactive functional food ingredients. Full article

(This article belongs to the Section Pharmaceutical Science)

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18 pages, 3788 KB

Open AccessReview

Neurovascular Issues in Neurofibromatosis Type I: Focus on Intracranial Stenosis

by Marialuisa Zedde and Rosario Pascarella

Life 2026, 16(2), 234; https://doi.org/10.3390/life16020234 (registering DOI) - 1 Feb 2026

Abstract

Background/Objectives: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by various clinical manifestations, including significant neurovascular complications. This review aims to synthesize current knowledge regarding intracranial stenoses and associated vascular abnormalities in patients with NF1, emphasizing the differences between pediatric and adult [...] Read more.

Background/Objectives: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by various clinical manifestations, including significant neurovascular complications. This review aims to synthesize current knowledge regarding intracranial stenoses and associated vascular abnormalities in patients with NF1, emphasizing the differences between pediatric and adult populations. Methods: A narrative review was conducted, analyzing the existing literature on the epidemiology, clinical manifestations, and management of neurovascular issues related to NF1. Data were collected from a range of studies, including retrospective analyses and case series, focusing on the incidence and outcomes of intracranial vascular abnormalities. Results: The study found that intracranial vasculopathy affects between 0.4% and 6.4% of NF1 patients, with children experiencing higher rates of stenotic lesions. However, vascular issues in adults are less understood, with 3.5% of adult patients presenting vascular abnormalities. The review highlights a significant underdiagnosis of these conditions due to the lack of routine use of magnetic resonance angiography (MRA) in standard evaluations. The management of NF1-related vascular conditions, particularly in adults, remains poorly defined, particularly regarding the efficacy of antithrombotic therapies. Conclusions: The management of neurovascular complications in NF1 requires urgent attention, with a need for standardized screening protocols and further research to elucidate the natural history and optimal treatment strategies for these patients. Enhanced diagnostic practices, including routine neuroimaging, are essential to improve outcomes and reduce the risk of significant vascular events. Full article

(This article belongs to the Special Issue Advances in Vascular Medicine: From Endovascular Innovations to Pathophysiological Insights)

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33 pages, 963 KB

Open AccessReview

Transcranial Magnetic Stimulation in Parkinson’s Disease and Parkinsonian Syndromes: A Narrative Expert Review

by Mariagiovanna Cantone, Manuela Pennisi, Rita Bella, Raffaele Ferri, Francesco Fisicaro, Giuseppe Lanza, Maria P. Mogavero, Aurora Palmigiano, Angelica Quercia and Mario Zappia

Life 2026, 16(2), 233; https://doi.org/10.3390/life16020233 (registering DOI) - 1 Feb 2026

Abstract

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool for investigating the neurophysiology of different neurological and neuropsychiatric disorders, including Parkinson’s disease (PD) and other parkinsonian syndromes and movement disorders. Briefly, TMS enables targeted stimulation of specific cortical regions through externally applied [...] Read more.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool for investigating the neurophysiology of different neurological and neuropsychiatric disorders, including Parkinson’s disease (PD) and other parkinsonian syndromes and movement disorders. Briefly, TMS enables targeted stimulation of specific cortical regions through externally applied magnetic pulses, avoiding surgical intervention (as it occurs in deep brain stimulation) and making it a safe, repeatable, and well-tolerated approach. Over the past two decades, extensive research has explored the clinical utility of TMS in PD, with particular emphasis on motor cortex excitability, synaptic plasticity, and functional connectivity, which are central contributors to both motor and non-motor symptoms in PD patients. In addition, repetitive TMS and related stimulation paradigms have been shown to positively modulate cortical plasticity, i.e., the brain’s capacity to reorganize neural circuits, suggesting potential benefits for longer-term non-pharmacological management and rehabilitation protocols. More recently, studies have also investigated the role of TMS in atypical and secondary parkinsonisms, indicating that it may help characterize distinct neurophysiological abnormalities and provide symptomatic improvement in selected patients. This narrative expert review provides a comprehensive summary of TMS applications across the wide spectrum of parkinsonian syndromes, highlighting not only clinical potential, but also methodological limitations and future research directions. Full article

(This article belongs to the Special Issue Advances in Non-Invasive Brain Stimulation)

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12 pages, 1521 KB

Open AccessArticle

Serum and Clinical Factors Associated with Total Knee Arthroplasty in Patients with Knee Osteoarthritis

by Sergiu Andrei Iordache, Adrian Cursaru, Bogdan Serban, Mihnea Ioan-Gabriel Popa, Mihai Aurel Costache, Sergiu Stanciu, Bogdan Stefan Cretu and Florin Catalin Cirstoiu

Life 2026, 16(2), 232; https://doi.org/10.3390/life16020232 (registering DOI) - 1 Feb 2026

Abstract

Knee osteoarthritis (KOA) is one of the most prevalent chronic joint disorders, with its incidence rising over the past decade due to an increase in risk factors, including age, obesity, metabolic conditions, sedentary behavior, and mechanical stress on the knee joints. We conducted [...] Read more.

Knee osteoarthritis (KOA) is one of the most prevalent chronic joint disorders, with its incidence rising over the past decade due to an increase in risk factors, including age, obesity, metabolic conditions, sedentary behavior, and mechanical stress on the knee joints. We conducted a cross-sectional, two-group comparison including 70 knee-pain patients aged ≥ 44 years: 50 patients meeting clinical and radiological criteria for TKA and 20 patients undergoing knee arthroscopy as controls. All patients underwent clinical assessments, WOMAC scoring, radiography, and 3T knee MRI. Serum interleukin-6 (IL-6), cartilage oligomeric matrix protein (COMP), vitamin D3, calcium, and phosphorus were measured at admission. TKA patients were older and had higher WOMAC scores. WOMAC discriminated groups perfectly (AUC = 1.000), but age discriminated well (AUC = 0.911). IL-6 (AUC = 0.819) and COMP (AUC = 0.838) were significant discriminators, with IL-6 threshold ≥ 4.585 pg/mL achieving 66% sensitivity and 85% specificity and COMP cutoff ≥ 11.52 ng/mL achieving 84% sensitivity and 75% specificity. TKA group vitamin D3 levels were considerably lower but had limited discriminatory performance (AUC = 0.683). Although all patients had adequate mineral metabolism, TKA patients had lower serum calcium and higher serum phosphorus levels than controls. Full article

(This article belongs to the Special Issue Osteoarthritis: New Insights into Mechanisms, Diagnosis, Therapy and Management)

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21 pages, 3419 KB

Open AccessReview

Effect of Hypoxic Exercise with Different Oxygen Concentrations on Metabolic Outcomes in Obesity: A Systematic Review and Network Meta-Analysis

by Kai Gao, Shuting Liu, Chengyu Zhou, Diandong Lang and Huaichuan Zhang

Life 2026, 16(2), 231; https://doi.org/10.3390/life16020231 (registering DOI) - 1 Feb 2026

Abstract

Objective: This study aimed to systematically evaluate the effects of hypoxic exercise at different oxygen concentrations on body composition, glucose metabolism, and lipid metabolism in individuals with obesity, and to explore potential optimal oxygen concentration ranges to inform personalized hypoxic exercise prescriptions. Methods: [...] Read more.

Objective: This study aimed to systematically evaluate the effects of hypoxic exercise at different oxygen concentrations on body composition, glucose metabolism, and lipid metabolism in individuals with obesity, and to explore potential optimal oxygen concentration ranges to inform personalized hypoxic exercise prescriptions. Methods: We searched databases including the Cochrane Library, PubMed, Web of Science, Embase, and CNKI for randomized controlled trials and pre-post studies on hypoxic exercise interventions in obese populations published before 30 June 2025. A network meta-analysis was performed using Stata 18.0 software to assess the effects of various oxygen concentrations on BMI, FBG, FINS, HOMA-IR, TG, LDL-C, and HDL-C. Subgroup analyses were conducted to explore sources of heterogeneity. Results: Fourteen studies with a total sample size of 189 participants were included. The meta-analysis revealed that exercise in a moderate hypoxic environment (12–14% FiO₂) significantly reduced BMI, FBG, TG, and LDL-C. Notably, hypoxic exercise did not show a statistically significant effect on HDL-C. In contrast, a higher oxygen concentration (≥15% FiO₂) was more effective for improving FINS and HOMA-IR. Conclusion: Hypoxic exercise can significantly improve the body composition, glucose metabolism and lipid metabolism indicators of obese people. Tailored exercise in specific hypoxic environments provides preliminary evidence for a non-pharmacological intervention strategy in obesity management. Full article

(This article belongs to the Special Issue Explore Innovative Exercise-Based Interventions for Chronic Diseases)

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11 pages, 915 KB

Open AccessArticle

Primary Adrenal Gland Lymphoma: Report of 13 Cases—A Retrospective Multicenter Polish Lymphoma Research Group Analysis

by Magdalena Witkowska, Kacper Kościelny, Agnieszka Giza, Ryszard Swoboda, Joanna Drozd-Sokołowska and Dariusz Wołowiec

Life 2026, 16(2), 230; https://doi.org/10.3390/life16020230 (registering DOI) - 1 Feb 2026

Abstract

Introduction: The existence of primary adrenal gland lymphoma (PAGL) has been debated due to lack of lymphoid tissue in the adrenal glands. PAGL is extremely rare, accounting for less than 1% of all types of lymphomas. The aim of this study was to [...] Read more.

Introduction: The existence of primary adrenal gland lymphoma (PAGL) has been debated due to lack of lymphoid tissue in the adrenal glands. PAGL is extremely rare, accounting for less than 1% of all types of lymphomas. The aim of this study was to analyze patients with PAGL in Polish population. Material and Methods: We retrospectively reviewed 13 adult patients with PAGL diagnosed in Polish Hematological Centers. Results: A total of 13 patients (5 women and 8 men) with PAGL were included into the study. The median age at the diagnosis was 69.1 years (range: 31–85). The most common histological type was diffuse large B-cell lymphoma (DLBCL)-12 patients, the remaining one was diagnosed with Hodgkin lymphoma (HL). In 7 patients (54%), the left adrenal gland was involved; in 3 patients (23.5%), the right adrenal gland was involved; and 3 patients (23.5%) had bilateral lymphoma. Systemic symptoms (B symptoms) were observed in 11 out of 13 patients (85%). Two patients (15%) were treated with chemotherapy alone and the remaining eleven patients (85%) with immune and chemotherapy together (85%). During the follow-up period, 11 patients died, 8 had relapsed or refractory disease (62%), and 3 patients (23%) had relapse in central nervous system (CNS). The median progression-free survival (PFS) was 14.63 months, while the median overall survival (OS) was 20.30 months. Adrenalectomy of the involved adrenal gland was associated with shorter PFS (p = 0.0165), with trend of shorter OS. Achieving complete remission (CR) after front line treatment was associated with significantly longer OS (p = 0.0239) and PFS (p = 0.0152). Conclusions: Adrenal glands are extremely rare as primary locations of extranodal lymphoma. The prognosis of PAGL is generally poor. In this study, we described demographic, clinical, and pathological characteristics as well as factors that may affect survival among these groups. So far, it is the largest polish multicenter experience describing patients with PAGL. Full article

(This article belongs to the Special Issue Recent Advances in Lymphomas)

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14 pages, 602 KB

Open AccessArticle

Comparative Effects of Weighted Vest and Whole-Body Vibration Training on Bone and Muscle Health in Osteopenia

by Jidapa Tantanasest, Apiwan Manimmanakorn, Orathai Tunkamnerdthai, Chiraphorn Khaengkhan, Peeraporn Nithisup, Suphawijak Youdprang, Nuttaset Manimmanakorn and Michael John Hamlin

Life 2026, 16(2), 229; https://doi.org/10.3390/life16020229 (registering DOI) - 1 Feb 2026

Abstract

Background: The growing elderly population faces health problems like osteoporosis, but novel exercises like weighted vests (WV) and whole-body vibration (WBV) may help prevent bone loss. Methods: Thirty-one women aged 60–79 years with osteopenia or osteoporosis (T-score −2.15 ± 0.9) were randomly assigned [...] Read more.

Background: The growing elderly population faces health problems like osteoporosis, but novel exercises like weighted vests (WV) and whole-body vibration (WBV) may help prevent bone loss. Methods: Thirty-one women aged 60–79 years with osteopenia or osteoporosis (T-score −2.15 ± 0.9) were randomly assigned to three groups: a control group performed exercise only; a whole-body vibration group performed the exercise on a 40 Hz, 2 mm vibration platform; and a weighted vest group performed the exercise while wearing a weighted vest. T-score, bone mineral density (BMD), muscle mass, and physical performance were assessed before and after 8 weeks. Results: The WV showed a greater T-score increase than the CT and WBV groups (WV: 0.08 ± 0.03; CT: −0.18 ± 0.04; WBV: −0.11 ± 0.16; p = 0.01, 95%CI). Leg BMD increased in the WV group (1.75 ± 0.13 to 1.79 ± 0.16 g/cm²; p = 0.02). Leg lean mass also increased in the WV (1.28 ± 0.91 kg) compared to WBV (0.17 ± 0.14 kg) and CT (0.06 ± 0.79 kg, p = 0.01, 95%CI). The WV group showed greater physical performance improvements (5TSTS and 6-MWT). The WBV group showed improved total lean mass compared to the CT group (WBV: 0.32 ± 0.17; CT = −1.20 ± 1.86, p = 0.006, 95%CI). Conclusions: WV exercise improved bone density, leg lean mass, and physical performance in older women. WBV exercise increased total lean mass and skeletal muscle index while reducing fat mass. WV exercise provides an additive effect beyond exercise alone or WBV. Full article

(This article belongs to the Special Issue Musculoskeletal Pain and Disorders: Diagnosis, Treatment and Management)

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4 pages, 157 KB

Open AccessEditorial

Cystic Fibrosis: A Disease with a New Face

by Janice Wang and Patricia A. Walker

Life 2026, 16(2), 228; https://doi.org/10.3390/life16020228 - 30 Jan 2026

Abstract

Medical advancements in the field of Cystic Fibrosis (CF), a rare, genetic disorder, have been profound over the last decade, allowing care to evolve in ways previously thought unimaginable by those living with CF and those caring for people with CF [...] Full article

(This article belongs to the Special Issue Cystic Fibrosis: A Disease with a New Face)

10 pages, 9152 KB

Open AccessCommunication

Dissection of Cell Death Induction by Arabidopsis thaliana CC-NBS-LRR Receptor SUT1 and Its Interacting Protein TOPP4 Mutant in Nicotiana benthamiana

by Jianzhong Huang, Xiaoqiu Wu, Kai Chen and Zhiyong Gao

Life 2026, 16(2), 227; https://doi.org/10.3390/life16020227 - 29 Jan 2026

Abstract

Nucleotide-binding and leucine-rich repeat receptors (NLRs) play an important role in plant innate immunity. Previous reports indicate that SUT1 (SUPPRESSOR OF TOPP4 1) is required for the autoimmune response mediated by TYPE ONE PROTEIN PHOSPHATASE 4 (TOPP4) mutation topp4-1 (namely TOPP4^T246M) [...] Read more.

Nucleotide-binding and leucine-rich repeat receptors (NLRs) play an important role in plant innate immunity. Previous reports indicate that SUT1 (SUPPRESSOR OF TOPP4 1) is required for the autoimmune response mediated by TYPE ONE PROTEIN PHOSPHATASE 4 (TOPP4) mutation topp4-1 (namely TOPP4^T246M) in Arabidopsis. We observed that co-expression of SUT1 with TOPP4 mutant versions, instead of wild-type TOPP4, produced robust cell death in N. benthamiana. The YFP-labeled SUT1 was localized on the plasma membrane (PM), and Gly2, Cys4, and Ser6 are crucial amino acid sites for its PM localization and function. Further dissection proclaimed that the function and localization of SUT1 are influenced by mutations in conserved specific residues. These findings may provide a new perspective for elucidating the activation mechanism of SUT1. Full article

(This article belongs to the Section Plant Science)

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19 pages, 3977 KB

Open AccessArticle

Modulation of Forward Propulsion and Foot Dorsiflexion by Spinal and Muscular Stimulation During Human Stepping

by Sergey Ananyev, Ivan Sakun, Vsevolod Lyakhovetskii, Alexander Grishin, Tatiana Moshonkina and Yury Gerasimenko

Life 2026, 16(2), 226; https://doi.org/10.3390/life16020226 - 29 Jan 2026

Abstract

(1) Background: We developed a novel technology that regulates human locomotion using transcutaneous electrical spinal cord stimulation to activate spinal locomotor networks and posterior root stimulation to activate leg flexor and extensor motor pools during swing and stance phases, respectively. This technology effectively [...] Read more.

(1) Background: We developed a novel technology that regulates human locomotion using transcutaneous electrical spinal cord stimulation to activate spinal locomotor networks and posterior root stimulation to activate leg flexor and extensor motor pools during swing and stance phases, respectively. This technology effectively restores walking in post-stroke individuals while forward propulsion in the stance phase and foot dorsiflexion in the swing phase are insufficient. In this study the effectiveness of regulating the stance and swing phases while healthy volunteers walked on a treadmill with transcutaneous electrical stimulation of the posterior roots, leg muscles, and their combined effects has been examined. (2) Methods: We analyzed the kinematic characteristics of stepping movements in healthy participants with spinal stimulation of the posterior roots and flexor/extensor leg muscles. (3) Results: Our findings clearly show that posterior root stimulation at T12 combined with tibialis anterior muscle stimulation during the swing phase effectively regulates foot dorsiflexion, whereas posterior root stimulation at L2 combined with hamstrings and medial gastrocnemius stimulation during the stance phase effectively regulates forward propulsion. (4) Conclusions: Combined stimulation in the stance and swing phases within the same gait cycle resulted in the most coordinated stepping, and effective control of forward propulsion and foot dorsiflexion. Full article

(This article belongs to the Section Physiology and Pathology)

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14 pages, 545 KB

Open AccessSystematic Review

Efficacy and Safety of Biologic and Targeted Synthetic DMARDs in Young-Onset Rheumatoid Arthritis: A Systematic Review

by Mara Russu, Vladia Lăpuște, Diana Elena Cosău, Alexandra Lori Donica, Alexandra-Diana Diaconu, Georgiana Strugariu, Cristina Pomîrleanu and Codrina Ancuța

Life 2026, 16(2), 225; https://doi.org/10.3390/life16020225 - 29 Jan 2026

Abstract

Background: Young-onset rheumatoid arthritis (YORA), defined by disease onset between 16–40 years, raises distinct clinical challenges related to long-term disease burden, fertility, and prolonged exposure to immunomodulatory therapy. Despite its relevance, evidence regarding treatment outcomes in this population remains limited and heterogeneous, [...] Read more.

Background: Young-onset rheumatoid arthritis (YORA), defined by disease onset between 16–40 years, raises distinct clinical challenges related to long-term disease burden, fertility, and prolonged exposure to immunomodulatory therapy. Despite its relevance, evidence regarding treatment outcomes in this population remains limited and heterogeneous, largely due to inconsistent definitions of YORA across studies. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines to synthesize contemporary evidence on the efficacy and safety of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in younger rheumatoid arthritis populations. A structured search of PubMed and Embase was performed to identify studies published between 2020 and 2025 that evaluated advanced therapies in patients with young-onset rheumatoid arthritis or in rheumatoid arthritis cohorts reporting age-stratified outcomes for younger adults. Results: From the screened literature, 16 studies met the predefined inclusion criteria, including 6 studies explicitly defining YORA based on age at disease onset and 10 studies reporting outcomes in younger adult subgroups (<40–45 years). Across studies, younger patients demonstrated higher remission rates, greater reductions in disease activity, and superior treatment persistence compared with older-onset rheumatoid arthritis cohorts. Tumor necrosis factor inhibitors, interleukin-6 receptor antagonists, and Janus kinase inhibitors showed consistent clinical efficacy. Structural outcomes, reported in a limited number of studies, suggested low rates of radiographic progression in younger patients. Safety profiles were generally favorable, with infections and laboratory abnormalities representing the most reported adverse events and no age-specific safety signals being identified. Conclusions: Biologic and targeted therapies provide substantial clinical benefit in YORA and younger adult RA populations, with outcomes being generally superior to those observed in older-onset RA. However, heterogeneity in YORA definitions and limited long-term data highlight the need for prospective, age-at-onset-defined studies and extended pharmacovigilance to better inform lifelong treatment strategies. Full article

(This article belongs to the Special Issue Musculoskeletal Medicine in Rheumatic Diseases)

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9 pages, 4033 KB

Open AccessCase Report

Surviving Adulthood with Rare Combined Congenital Heart Defects: Complete AV Canal Defect, Ebstein’s Anomaly, and Right Ventricular Hypoplasia

by Ana Peruničić, Stefan Veljković, Jovana Lakčević, Mirko Lipovac, Armin Šljivo, Slobodan Tomić, Milovan Bojić, Miloš Babić, Sanja Vučinić and Aleksandra Nikolić

Life 2026, 16(2), 224; https://doi.org/10.3390/life16020224 - 29 Jan 2026

Abstract

Background/Objectives. Ebstein’s anomaly (EA), which accounts for fewer than 1% of congenital heart diseases, and atrioventricular canal defect (AVCD), present in approximately 4–5% of cases, exceptionally coexist, with this combination observed in fewer than 0.5% of patients with AVCD. We aim to report [...] Read more.

Background/Objectives. Ebstein’s anomaly (EA), which accounts for fewer than 1% of congenital heart diseases, and atrioventricular canal defect (AVCD), present in approximately 4–5% of cases, exceptionally coexist, with this combination observed in fewer than 0.5% of patients with AVCD. We aim to report the oldest documented case of a 45-year-old female with the exceptionally rare combination of complete AVCD, EA, and right ventricular hypoplasia and to provide a concise review of these anomalies. Case presentation. Diagnosed in early childhood with a complete AVCD, pulmonary stenosis, and right ventricular (RV) hypoplasia, the patient underwent palliative surgical intervention with a modified Blalock–Taussig shunt at the age of 10 but did not receive subsequent regular follow-up. Over the ensuing 35 years, she remained largely untreated until presentation at 45 years of age with progressive exertional dyspnea, central cyanosis, and palpitations, corresponding to NYHA class III. Comprehensive multimodal imaging, including transthoracic echocardiography and cardiac magnetic resonance, revealed a complete AVCD with moderate-to-severe mitral regurgitation secondary to an anterior mitral leaflet cleft, severe tricuspid regurgitation, RV hypoplasia, and hallmark features of EA. Given the complex cardiac anatomy and the elevated surgical risk, the patient was considered inoperable, and a strategy of conservative management with multidisciplinary follow-up was implemented. Conclusions. This case highlights the exceptional longevity of a patient with the rare coexistence of complete AVCD, EA, and RV hypoplasia, surviving 45 years from diagnosis despite limited early intervention. It underscores the importance of lifelong follow-up in complex congenital heart disease and illustrates the role of multimodal imaging in assessing anatomy and guiding management when surgical options are high-risk or not feasible. Full article

(This article belongs to the Section Medical Research)

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23 pages, 3230 KB

Open AccessSystematic Review

Pre-Eclampsia-Induced Maternal Liver Dysfunction: Systematic Review, Meta-Analysis and Meta-Regression of Observation Studies

by Kay-Lee E. Strauss, Wendy N. Phoswa and Kabelo Mokgalaboni

Life 2026, 16(2), 223; https://doi.org/10.3390/life16020223 - 29 Jan 2026

Abstract

Introduction: Pre-eclampsia (PE) is a pregnancy-related hypertensive condition defined by the onset of hypertension after 20 weeks of gestation that is associated with proteinuria and maternal organ damage or uteroplacental dysfunction. It continues to be a leading cause of maternal and perinatal [...] Read more.

Introduction: Pre-eclampsia (PE) is a pregnancy-related hypertensive condition defined by the onset of hypertension after 20 weeks of gestation that is associated with proteinuria and maternal organ damage or uteroplacental dysfunction. It continues to be a leading cause of maternal and perinatal morbidity and mortality globally. PE is linked to systemic inflammation, endothelial dysfunction, and oxidative stress, which may compromise hepatic function. Aim: This meta-analysis assesses the impact of PE on maternal liver function by evaluating hepatic biomarkers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum bilirubin. Methods: This meta-analysis of observational studies in Epidemiology (MOOSE) involved a search of PubMed and Scopus and manual screening of studies published between 2000 and 2025. Eligible studies included cross-sectional, case–control, and cohort designs. The quality of the studies was evaluated using the Newcastle–Ottawa Scale. Statistical analysis was conducted using the online meta-analysis, Jamovi version 2.6.44, and IBM SPSS Statistics version 30, and effect estimates were reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Forty-five studies, comprising 257,929 women 9420 with PE; 248,509 normotensive, were included. Women with PE had elevated AST, MD = 1.81 (95% CI: 1.51 to 2.10; p < 0.0001) and ALT, SMD = 1.73 (95% CI: 1.38 to 2.07; p < 0.0001); ALP, SMD = 1.43 (95% CI: 0.97 to 1.88; p < 0.0001); and total serum bilirubin (TSB), SMD = 0.62 (95% CI: 0.36 to 0.88; p < 0.0001) in comparison to normotensive controls. In the meta-regression, maternal age and quality were significant moderators, with older age and high-quality studies associated with smaller and larger effect sizes, respectively, for ALP (β = −0.720 and β = 1.444) and TSB (β = −0.304 and β = 0.761). For every 1-unit increase in body mass index, there was a significant 0.406-unit decrease in ALT effect size. Conclusions: PE is significantly associated with elevated maternal hepatic enzyme levels, indicating hepatocellular damage and impaired liver function. These findings emphasise the necessity for routine liver function monitoring in pregnant women with hypertensive disorders. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Preeclampsia)

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32 pages, 5469 KB

Open AccessSystematic Review

Systematic Review and Meta-Analysis of RCTs on Efficacy of Conventional vs. Emerging Treatments for Amblyopia

by Clara Martinez-Perez and Ana Paula Oliveira

Life 2026, 16(2), 222; https://doi.org/10.3390/life16020222 - 28 Jan 2026

Abstract

Amblyopia affects 1–4% of the population and remains a leading cause of unilateral visual impairment, with adherence and residual deficits limiting outcomes of standard therapies. This systematic review and meta-analysis compared the effectiveness of conventional and emerging amblyopia treatments in children, adolescents, and [...] Read more.

Amblyopia affects 1–4% of the population and remains a leading cause of unilateral visual impairment, with adherence and residual deficits limiting outcomes of standard therapies. This systematic review and meta-analysis compared the effectiveness of conventional and emerging amblyopia treatments in children, adolescents, and adults with anisometropic, strabismic, or mixed amblyopia. Following PRISMA guidelines and PROSPERO registration (CRD420251123552), PubMed, Web of Science, and Scopus were searched up to 5 August 2025 for randomized controlled trials. Sixty-six trials (sample sizes 7–404) were included, with thirty-six contributing to the meta-analysis. Primary outcomes were best-corrected visual acuity (logMAR) and stereopsis. Risk of bias was assessed using the Cochrane tool, and certainty of evidence was assessed using GRADE. Atropine penalization and occlusion demonstrated equivalent effects on visual acuity (mean difference 0.04 logMAR; 95% CI −0.04 to 0.12; moderate-certainty evidence). Digital, dichoptic, binocular, and virtual reality therapies showed a statistically significant but small improvement over patching (mean difference 0.02 logMAR; 95% CI 0.00–0.04; low-certainty evidence). Pharmacological adjuvants combined with patching yielded slightly larger gains (mean difference 0.08 logMAR; 95% CI 0.03–0.13; low-to-moderate certainty). No consistent benefit was observed for stereopsis outcomes. Overall, the certainty of evidence ranged from low to moderate, and most pooled effects were below commonly accepted thresholds for clinically meaningful visual acuity improvement (≈0.1 logMAR, one line). Atropine and occlusion remain equivalent first-line treatments, while adjunctive and multimodal approaches may offer limited additional benefit in selected patients when adherence, tolerability, and engagement are prioritized. Full article

(This article belongs to the Special Issue Advances in Binocular Vision Assessment and Management: From Anomalies to Oculomotor Norms)

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18 pages, 1141 KB

Open AccessArticle

Recovery from Post-Traumatic Amnesia During Inpatient Rehabilitation: A Retrospective Cohort Study

by Tay Kai Wen Elvina, Lim Gek Hsiang and Chua Karen

Life 2026, 16(2), 221; https://doi.org/10.3390/life16020221 - 28 Jan 2026

Abstract

Background: Traumatic brain injury (TBI) is a global healthcare problem, and post-traumatic amnesia (PTA) is a known predictor of long-term and societal outcomes. However, factors influencing PTA recovery during the inpatient rehabilitation phase remain underexplored, particularly in Asian populations. Objective: To identify factors [...] Read more.

Background: Traumatic brain injury (TBI) is a global healthcare problem, and post-traumatic amnesia (PTA) is a known predictor of long-term and societal outcomes. However, factors influencing PTA recovery during the inpatient rehabilitation phase remain underexplored, particularly in Asian populations. Objective: To identify factors associated with PTA duration and emergence during inpatient rehabilitation and examine their impact on functional outcomes. Materials and Methods: We conducted a retrospective, single-center cohort study over a 7-year period among patients with acute TBI who were admitted to an inpatient rehabilitation hospital. Outcomes included PTA emergence and duration, discharge Functional Independence Measure (FIM), rehabilitation length of stay, and Glasgow Outcome Scale (GOS) at ≥1 year. Results: A total of 100 patients were analyzed. In an adjusted Cox regression, age ≥ 55 years (Hazard Ratio [HR] 0.47) and non-infective medical complications during rehabilitation (HR 0.31) were associated with reduced likelihood of PTA emergence, while mild admission GCS (13–15; HR 4.80) and epidural hemorrhage (EDH) (HR 2.00) were associated with PTA emergence. PTA non-emergence was associated with approximately a 20-point lower discharge FIM total score (adjusted model, p < 0.001). A PTA duration of ≥90 days was associated with a lower total discharge FIM score by approximately 45 points compared with those with a PTA duration of <28 days (p < 0.001). PTA emergence was associated with better GOS at ≥1 year (odds ratio [OR] 3.92, p = 0.02). Conclusion: Both acute injury characteristics and intra-rehabilitation factors were associated with PTA recovery functional outcomes. PTA emergence, beyond PTA duration, was strongly associated with discharge functional status and long-term global outcome, supporting the clinical value of PTA in prognostication, rehabilitation planning, and goal setting. Full article

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

17 pages, 527 KB

Open AccessReview

United Airway Disease: An Evolving Concept? A Scoping Review of the Modern Literature on Integrated Treatment Approaches

by Victor Alexandru, Alexia Manole, Ligia Salomea Groza and Felicia Manole

Life 2026, 16(2), 220; https://doi.org/10.3390/life16020220 - 28 Jan 2026

Abstract

Background: This scoping review screens modern literature in search of effective treatment approaches that target both upper and lower airway diseases. Methods: After the establishment of a research protocol, 227 potential articles were obtained through a logged search method. These were screened and [...] Read more.

Background: This scoping review screens modern literature in search of effective treatment approaches that target both upper and lower airway diseases. Methods: After the establishment of a research protocol, 227 potential articles were obtained through a logged search method. These were screened and narrowed down to 26 included articles. Data were extracted using a standardized data extraction form and were analyzed thematically and analytically. Results: The main integrated treatment approaches are biological (dupilumab was the most mentioned molecule) and non-biological (allergen immunotherapy, nasal saline irrigation, and endoscopic polypectomy). Data suggest that these approaches are effective in improving upper and lower airway outcomes and showcase a good safety profile. Conclusions: Patients with upper and lower airway diseases should benefit from integrated treatment approaches when possible. Full article

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

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24 pages, 1950 KB

Open AccessReview

Evolution from Composome to RNA Replicase

by Shaojie Deng, Doron Lancet and Roy Yaniv

Life 2026, 16(2), 219; https://doi.org/10.3390/life16020219 - 28 Jan 2026

Abstract

This paper proposes a novel scheme for the origin of RNA replicase based on the replication-first stable complex evolution (SCE) model, also known as the stable complex encoding (SCE) model, and attempts to derive this scheme from the metabolism-first graded autocatalysis replication domain [...] Read more.

This paper proposes a novel scheme for the origin of RNA replicase based on the replication-first stable complex evolution (SCE) model, also known as the stable complex encoding (SCE) model, and attempts to derive this scheme from the metabolism-first graded autocatalysis replication domain (GARD) model, thereby theoretically integrating the two hypotheses of the origin of life: replication-first and metabolism-first. Currently, although the replication-first model has made some progress in the artificial selection of RNA replicase, it has yet to achieve a true breakthrough. Meanwhile, metabolism-first models such as the CAS (Collectively Autocatalytic Set) and its graph version RAF (Reflexively Autocatalytic and Food-generated) models, have conducted in-depth research into the origin of metabolic networks but have failed to address the critical transformation issue from metabolism to RNA replication. This paper argues that these two hypotheses should mutually support each other. By introducing oligonucleotide assemblies and expanding the concept of composomes in the GARD model, this paper attempts to understand the general evolutionary mechanism of enzymes, thereby addressing the long-standing neglect of enzymatic catalysis in metabolism-first theories. This integrated scheme not only provides new theoretical support for the evolution of RNA replicase but also offers important insights into solving the key transition problem from chemical evolution to biological evolution. Full article

(This article belongs to the Special Issue The 15th Anniversary of Life—Alternatives to RNA World)

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17 pages, 571 KB

Open AccessArticle

Comparative Effects of Home-Based and Aquatic Resistance Training on Hand Tremor Severity and Manual Dexterity in Older Adults with Essential Tremor: A Preliminary Randomized Controlled Trial

by Cemal Polat, Tuba Sevil, Zarife Pancar and Luca Russo

Life 2026, 16(2), 218; https://doi.org/10.3390/life16020218 - 28 Jan 2026

Abstract

Essential tremor (ET) negatively affects neuromuscular control and hand function in older adults. Resistance exercise may enhance musculoskeletal and functional capacity, yet its modality-specific effects in ET remain unclear. This study compared the effects of home-based and aquatic resistance training on tremor severity, [...] Read more.

Essential tremor (ET) negatively affects neuromuscular control and hand function in older adults. Resistance exercise may enhance musculoskeletal and functional capacity, yet its modality-specific effects in ET remain unclear. This study compared the effects of home-based and aquatic resistance training on tremor severity, manual dexterity, and handgrip strength in older adults with ET. Twenty-seven participants were randomly assigned using block randomization to a home-based resistance exercise group (HBREG; n = 9), an aquatic resistance exercise group (AREG; n = 9), or a control group (CG; n = 9). Both intervention groups completed an 18-session resistance exercise program, with initial sessions supervised and subsequent sessions performed independently under regular monitoring. Tremor severity (FTMTRS), manual dexterity (Nine-Hole Peg Test), and handgrip strength were assessed pre- and post-intervention. Within-group changes were analyzed using the Wilcoxon signed-rank test and between-group differences using the Kruskal–Wallis test with Bonferroni-adjusted Mann–Whitney U tests (p < 0.05). Both HBREG and AREG demonstrated significant improvements in drawing and pouring tremor tasks, manual dexterity, and handgrip strength compared with the control group, with large effect sizes across outcomes. No significant differences were observed between the two exercise modalities, and no improvement occurred in the highest-difficulty spiral-B task. These findings indicate that both home-based and aquatic resistance training are safe and effective non-pharmacological strategies for reducing tremor severity and enhancing upper-extremity function in older adults with ET. Full article

(This article belongs to the Special Issue Effects of Exercise and Functional Interventions on Musculoskeletal Health)

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