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17 pages, 679 KB  
Article
Early Initiation of rhGH Therapy Significantly Improves Height Gain and Reduces the Gap to Target Height in Children Born Small for Gestational Age: A Multicenter Retrospective Study
by Letteria Anna Morabito, Malgorzata Wasniewska, Cecilia Lugarà, Emanuela Pignatone, Domenico Corica, Renato Vaiasuso, Alessandra Cipriani, Giovanni Luppino, Roberto Coco, Giorgia Pepe, Tiziana Abbate, Stefano Stagi and Tommaso Aversa
Children 2026, 13(5), 641; https://doi.org/10.3390/children13050641 (registering DOI) - 3 May 2026
Abstract
Background: Treatment with recombinant human growth hormone (rhGH) is approved for children born small for gestational age (SGA) who fail to show postnatal catch-up growth; however, optimizing its efficacy remains a challenge. Aim: to evaluate the impact of rhGH therapy on growth trajectory [...] Read more.
Background: Treatment with recombinant human growth hormone (rhGH) is approved for children born small for gestational age (SGA) who fail to show postnatal catch-up growth; however, optimizing its efficacy remains a challenge. Aim: to evaluate the impact of rhGH therapy on growth trajectory (GT) and adult height (AH) in SGA children and to identify factors influencing height gain (HG). Methods: A total of 49 SGA children (24 males, 25 females) without postnatal growth recovery and treated with rhGH were enrolled. Clinical and anthropometric data were collected at treatment initiation (T0), after 1 (T1) and 2 years (T2) of therapy, at pubertal onset (P0), during the first (P1) and second year (P2) of puberty, and at attainment of AH. Parameters included age, bone age, H, weight, BMI (all expressed as SDS), HG, and the difference between H and target height (Δ H-TH). Results: a significant increase in HG at all evaluated stages was observed (p < 0.05). The H–TH difference progressively decreased from T0, particularly until the first two years of puberty. Nevertheless, mean AH was −1.75 ± 0.63 SDS, and it was found to fall within the TH range in 86% of cases. Univariate and multivariate regression analysis revealed that age and H at T0 were independent predictors of HG. Conclusions: rhGH treatment has a positive impact on GT in children born SGA. Pubertal growth has a limited contribution in influencing AH of these patients. H and timing of treatment initiation significantly influence HG in SGA children. Early selection of patients for rhGH therapy could further improve their GT. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
14 pages, 357 KB  
Article
Can the Use of Telehealth Guidance Services Reduce Depressive Symptoms Among Family Caregivers of Older Adults with Cognitive Impairment? A Moderated-Mediation Model
by Li Li, Hao Zhou, Xiaorong Gao, Keke Chen and Qiaoqiao Wang
Healthcare 2026, 14(9), 1234; https://doi.org/10.3390/healthcare14091234 (registering DOI) - 3 May 2026
Abstract
Background: Family caregivers of older adults with cognitive impairment commonly encounter heavy care burdens and elevated mental health risks, particularly depressive symptoms. This study aimed to explore the association between telehealth guidance service use and depressive symptoms among family caregivers of older adults [...] Read more.
Background: Family caregivers of older adults with cognitive impairment commonly encounter heavy care burdens and elevated mental health risks, particularly depressive symptoms. This study aimed to explore the association between telehealth guidance service use and depressive symptoms among family caregivers of older adults with cognitive impairment, and to further examine the mediating role of caregiving competence and the moderating role of psychological resilience. Methods: A cross-sectional survey of 491 family caregivers of older adults with cognitive impairment was conducted from August to October 2023. Descriptive statistics, correlation analysis, linear regression analysis, and moderated-mediating-effect analysis were employed. Results: Among the participants, only 17.31% reported using telehealth guidance services. Mean scores for caregiving competence, psychological resilience, and depressive symptoms were 3.04 ± 0.48, 27.11 ± 7.54, and 9.69 ± 1.46, respectively. Telehealth service use was positively associated with caregiving competence, and both telehealth service use and caregiving competence were negatively associated with depressive symptoms. The interaction between psychological resilience and caregiving competence was also significantly negatively associated with depressive symptoms (p < 0.01). Conclusions: Telehealth guidance service use is directly and indirectly negatively associated with depressive symptoms via caregiving competence. Psychological resilience moderates the relationship between caregiving competence and depressive symptoms. These findings contribute to a better understanding of factors linked to mental health among family caregivers of older adults with cognitive impairment. Full article
21 pages, 1585 KB  
Review
Cardiovascular Vulnerability, Including Heart Failure Risk, in Breast Cancer Surgery: The Role of Operative Technique, Frailty, and Postoperative Complications
by Andrei Marginean, Madalin Margan, Dragos-Mihai Gavrilescu, Diana-Maria Mateescu, Ioana Cotet, Cristina Tudoran, Dan Alexandru Surducan and Camelia-Oana Muresan
Medicina 2026, 62(5), 877; https://doi.org/10.3390/medicina62050877 (registering DOI) - 3 May 2026
Abstract
Background and Objectives: Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global [...] Read more.
Background and Objectives: Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global perioperative complication rates and composite medical endpoints, with heart failure events only rarely captured as dedicated outcomes, and operative technique, cardiovascular comorbidity, and frailty are often treated as separate domains rather than components of an integrated risk framework. Materials and Methods: We conducted a systematized narrative review with a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science from inception to 31 January 2026, including original studies of adult patients undergoing breast-conserving surgery, mastectomy, and/or reconstruction that reported early postoperative outcomes in relation to comorbidities, cardiovascular risk, or frailty. Eligibility assessment, data extraction, and qualitative synthesis followed key PRISMA 2020 principles, and findings were organized into three prespecified domains: surgical complexity, cardiovascular vulnerability (including patients with heart failure where reported), and frailty. Results: Nineteen studies (retrospective cohorts, registry-based analyses, and large database studies, primarily ACS NSQIP) met inclusion criteria, encompassing diverse breast surgery populations, including elderly, metastatic, and reconstructive cohorts. Across datasets, escalation from breast-conserving surgery to mastectomy and then to increasingly complex reconstruction was associated with a stepwise increase in perioperative complications, reoperations, bleeding, and, in selected series, catastrophic events. Preexisting cardiovascular disease and systemic vascular pathology significantly amplified postoperative morbidity even in procedures considered low or intermediate cardiac risk, with signals that patients with underlying heart failure carry particularly heightened vulnerability, although HF-specific events were infrequently reported as separate endpoints. Frailty, mainly assessed using modified frailty indices, consistently emerged as a strong, age-independent predictor of 30-day complications, mortality, and readmissions across surgical types, including both breast-conserving and reconstructive procedures. Conclusions: Early postoperative outcomes after breast cancer surgery are associated with the interaction between surgical complexity, cardiovascular comorbidity (with limited HF-specific reporting), and frailty rather than by operative technique alone. In this context, our synthesis primarily reflects overall cardiovascular vulnerability in comorbid and frail patients, with heart failure risk inferred indirectly from the available data. These findings support a patient-centered, risk-adapted surgical strategy in which the extent and timing of surgery and reconstruction are tailored to each patient’s cardiovascular profile and frailty status, with preferential use of breast-conserving or less complex procedures in vulnerable individuals. Integrating standardized frailty assessment and cardio-oncologic evaluation into preoperative workflows, and prospectively validating this tri-axial framework in dedicated cohorts, may improve perioperative risk stratification and reduce the burden of postoperative medical complications in an aging breast cancer population. Full article
(This article belongs to the Special Issue Updates on Prevention of Acute Heart Failure)
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19 pages, 967 KB  
Review
The Contribution of Ultrasound and Doppler Studies on Impaired Intrauterine Conditions and the Development of Future Disease
by Yossi Geron, Yinon Gilboa, Asaf Romano and Jacob Bar
Medicina 2026, 62(5), 875; https://doi.org/10.3390/medicina62050875 (registering DOI) - 3 May 2026
Abstract
The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the [...] Read more.
The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the fact that it is based only on human epidemiological data and animal studies, and also that it is difficult to isolate the effect of the intrauterine environment from postnatal conditions, familial and genetic background. In the last 20 years, the introduction of ultrasound and Doppler techniques in the assessment of fetal and maternal vascularity added a major contribution to the evaluation of the intrauterine environment. Studies based on ultrasound and Doppler assist in differentiating between prematurity and fetal growth restriction (FGR), mainly in those with placental insufficiency, and postnatal morbidity and even mortality. In addition, the Pedersen hypothesis regarding fetuses with overgrowth, mainly with diabetic mothers, states that they are also prone to postnatal morbidity. However, most of the studies on the issue do not emphasize the effects of the intrauterine environment on fetal organs, such as the brain, heart, liver, kidneys and pancreas in FGR and fetal overgrowth, that may impose a different prognosis in later life. This narrative review aims to summarize current evidence from animal and human studies regarding the impact of intrauterine undernutrition and overnutrition on fetal organ development, and to evaluate how ultrasound and Doppler findings may contribute to understanding the link between the intrauterine environment and postnatal morbidity. Full article
16 pages, 291 KB  
Article
Hybrid Cardiac Rehabilitation as an Optimal Strategy for Post-MI Recovery: A 14-Week Prospective Study on Clinical and Functional Outcomes
by Liviu Ionuț Șerbănoiu, Stefan Sebastian Busnatu, Dragos Trache, Gabriel Olteanu, Elena Serbanoiu, Abdul Basit, Narcisa Busnatu, Mihaela Mandu, Gelu Onose, Francesco Perone, Florin Mitu, Cătălina Liliana Andrei and Crina Julieta Sinescu
Healthcare 2026, 14(9), 1231; https://doi.org/10.3390/healthcare14091231 (registering DOI) - 3 May 2026
Abstract
Background: Hybrid cardiac rehabilitation (CR) combining supervised and home-based phases with wearable monitoring may improve access and outcomes after myocardial infarction (MI). Objective: To assess the impact of a 14-week hybrid CR program on functional class, exercise capacity, hemodynamics, body composition, and [...] Read more.
Background: Hybrid cardiac rehabilitation (CR) combining supervised and home-based phases with wearable monitoring may improve access and outcomes after myocardial infarction (MI). Objective: To assess the impact of a 14-week hybrid CR program on functional class, exercise capacity, hemodynamics, body composition, and physical activity in post-MI patients with NYHA class II symptoms. Methods: Sixty-six adults post-MI underwent 2 weeks of in-hospital initiation followed by 12 weeks of home-based rehabilitation via a smartwatch–smartphone platform. Within-subject changes from baseline to week 14 were analyzed using appropriate paired statistical tests. Results: NYHA class improved significantly, with 39% of participants downgrading their class (p < 0.001). Body weight decreased by 1.27 ± 2.51 kg (p < 0.001). Systolic and diastolic blood pressures declined (both p ≤ 0.002). Maximal METS rose markedly (25.7% increase; p < 0.001), and watts/kg improved (p < 0.001). Resting heart rate decreased (p = 0.002); peak exercise heart rate change was non-significant. Fat mass declined and skeletal muscle mass increased (mean gain 0.98 kg; p < 0.001). Daily step count increased from 5550 ± 2026 to 7267 ± 2500 steps (p < 0.001). Total body water also increased (p < 0.001). Conclusions: The hybrid CR program produced significant improvements in functional class, exercise capacity, blood pressure, body composition, and physical activity in post-MI NYHA II patients, supporting its effectiveness as a remotely enabled secondary prevention strategy. However, the results are based on hypotheses and randomized controlled trials must confirm the benefits especially with a control group. Nonetheless, it is a feasible and potentially effective alternative to conventional programs in resource-limited settings. Full article
13 pages, 866 KB  
Article
Comparison of Sevoflurane and Desflurane on Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplantation: A Propensity Score-Matched Analysis
by Hyeun-Joon Bae, Sa-Jin Kang, Kyoung-Sun Kim, Hye-Mee Kwon, In-Gu Jun, Jun-Gol Song and Gyu-Sam Hwang
Medicina 2026, 62(5), 876; https://doi.org/10.3390/medicina62050876 (registering DOI) - 3 May 2026
Abstract
Background and Objectives: While liver transplantation (LT) is a definitive treatment for hepatocellular carcinoma (HCC), tumor recurrence remains a major clinical concern. Although volatile anesthetics influence oncological outcomes, direct comparison between sevoflurane and desflurane remains scarce. This study aimed to investigate the [...] Read more.
Background and Objectives: While liver transplantation (LT) is a definitive treatment for hepatocellular carcinoma (HCC), tumor recurrence remains a major clinical concern. Although volatile anesthetics influence oncological outcomes, direct comparison between sevoflurane and desflurane remains scarce. This study aimed to investigate the impact of the recipient’s volatile anesthetic choice (sevoflurane vs. desflurane) on HCC recurrence following living donor liver transplantation (LDLT). Materials and Methods: This retrospective cohort study included adult patients who underwent LDLT for HCC. Patients were then divided into sevoflurane and desflurane groups, and propensity score matching (PSM) was used to balance baseline variables. The primary outcome was HCC recurrence, and the secondary outcomes were overall survival (OS) and postoperative C-reactive protein (CRP) levels as a marker for the postoperative systemic inflammatory response. Results: After PSM, 373 matched pairs (n = 746) were analyzed. HCC recurrence was significantly higher in the sevoflurane group compared to the desflurane group (19.6% vs. 13.1%, p = 0.023). Kaplan–Meier analysis also demonstrated that cumulative recurrence of HCC was significantly higher in recipients who received sevoflurane anesthesia than in those who received desflurane (log-rank p = 0.0018). In multivariate Cox proportional hazards regression analysis, the use of sevoflurane for anesthesia maintenance was an independent risk factor forHCC recurrence (Hazard Ratio, 1.66; 95% Confidence Interval, 1.15–2.39; p = 0.007). Regarding OS, no significant difference was observed between the two groups (log-rank p = 0.1123). Postoperative CRP levels were significantly higher in the sevoflurane group compared to the desflurane group, suggesting a more intense systemic inflammatory response associated with sevoflurane maintenance. Conclusions: For HCC patients undergoing LDLT, anesthesia maintenance with desflurane is associated with a reduced risk of tumor recurrence compared to sevoflurane, without a significant impact on overall survival. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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11 pages, 228 KB  
Article
Determinants of Quality of Life in Saudi Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study in Jeddah
by Amani A. Alrasheedi and Buthaina M. Aljehany
Healthcare 2026, 14(9), 1228; https://doi.org/10.3390/healthcare14091228 (registering DOI) - 3 May 2026
Abstract
Objective: This study aimed to assess quality of life (QoL) and its determinants among Saudi adults diagnosed with type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study was conducted among 200 (45% male and 55% female) Saudi adults with T2DM aged 30–65 years. [...] Read more.
Objective: This study aimed to assess quality of life (QoL) and its determinants among Saudi adults diagnosed with type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study was conducted among 200 (45% male and 55% female) Saudi adults with T2DM aged 30–65 years. Data were collected using the Audit of Diabetes–Dependent Quality of Life (ADDQoL) and the Personal Diabetes Questionnaire (PDQ). Anthropometric and clinical measures included weight, height, body mass index (BMI), blood pressure, and glycated hemoglobin (HbA1c). Results: Most participants (73.5%) were ≤50 years of age, and the majority were obese (56.0%) or overweight (28.0%). Nearly half (54.5%) had HbA1c levels ≥ 8.0%, while (50.5%) were hypertensive. Overall, 96% of participants reported a poor to extremely poor QoL. Female sex (p = 0.003), higher BMI (p = 0.034), diet type (p = 0.039), and satisfaction with glucose control (p < 0.001) were significantly associated with the QoL. Conclusions: T2DM substantially impairs the QoL of affected Saudi adults. Psychosocial and lifestyle-related factors, particularly obesity, gender, dietary practices, and perceived glucose control, are more influential than traditional clinical markers. Culturally tailored interventions targeting these determinants may improve patient outcomes. Full article
(This article belongs to the Special Issue Health Promotion and Quality of Life in People with Diabetes)
22 pages, 1827 KB  
Article
Effect of Osteoblast-Derived Extracellular Vesicles on Osteosarcoma Cells’ Transcriptional Profile: Role of Shuttled miRNAs
by Luca Giacchi, Argia Ucci, Veronica Zelli, Chiara Compagnoni, Elisa Pucci, Alessandra Tessitore, Marco Ponzetti and Nadia Rucci
Biomedicines 2026, 14(5), 1039; https://doi.org/10.3390/biomedicines14051039 (registering DOI) - 3 May 2026
Abstract
Background/Objectives: Osteosarcoma is the most common primary malignant bone tumour, affecting children and young adults. Recent evidence suggests that extracellular vesicles (EVs), small membrane-bound nanoparticles released by all cell types, play a key role in intercellular communication within the tumour microenvironment. Therefore, [...] Read more.
Background/Objectives: Osteosarcoma is the most common primary malignant bone tumour, affecting children and young adults. Recent evidence suggests that extracellular vesicles (EVs), small membrane-bound nanoparticles released by all cell types, play a key role in intercellular communication within the tumour microenvironment. Therefore, we aimed to investigate the effects of osteoblast-derived EVs (OB-EVs) on osteosarcoma cell behaviour and to characterise the transcriptional and miRNA-mediated mechanisms underlying these effects. Methods: Phenotypic assays were performed to assess metabolic activity, proliferation, apoptosis, and invasion ability of human osteosarcoma cell lines after treatment with OB-EVs. Illumina-based RNAseq was conducted on RNA isolated from OB-EVs-treated cells, and qRT-PCR was assessed using commercially available TaqMan miRNA cards on RNA isolated from OB-EVs. Results: In U2OS cells, OB-EVs reduced metabolic activity (1.30-fold decrease, p = 0.0137) and proliferation (1.70-fold decrease, p = 0.017) while increasing apoptosis (1.15-fold increase, p = 0.014). In MG63, OB-EVs increased proliferation (4.9-fold increase, p = 0.020) without affecting tumour cell aggressiveness, while normal osteoblast behaviour was not affected by OB-EVs. MNNG/HOS cells treated with OB-EVs for 48 h showed substantial transcriptomic changes, with 296 differentially expressed genes (97 up- and 199 down-regulated in OB-EVs treated cells versus untreated cells), indicating a direct impact of OB-EVs on gene expression. Intriguingly, Gene Set Enrichment Analysis (GSEA) showed trends consistent with modulation of signalling pathways, including Wnt/β-catenin and NOTCH. Conversely, miRNA profiling of OB-EVs identified 13 highly expressed miRNA. Integration of transcriptomic and miRNA target prediction data highlighted convergent pathway-level signals, suggesting that OB-EVs may modulate tumour-associated regulatory networks. Conclusions: Taken together, these findings indicate that OB-EVs modulate osteosarcoma cell phenotype, with miRNA shuttling representing a potentially relevant contributing mechanism. The integrative analysis suggests that pathways associated with proliferation and cellular homeostasis, including Wnt/β-catenin signalling, may be involved, although further functional validation is required to confirm these mechanisms. Full article
(This article belongs to the Special Issue MicroRNA and Its Role in Human Health, 2nd Edition)
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37 pages, 6160 KB  
Article
Environmental Implications and Risk Assessment of Pesticide Residues in Soils and Water in One of the Most Important Agricultural Regions in Niger
by Djamilou Gabèye, Martin Wiehle and Abdourahamane Tankari Dan Badjo
Agronomy 2026, 16(9), 930; https://doi.org/10.3390/agronomy16090930 (registering DOI) - 3 May 2026
Abstract
In sub-Saharan Africa, intensive pesticide use in irrigated agriculture is threatening the quality of soil, water bodies and ecosystem services, yet integrated risk assessments remain limited. This study evaluated the environmental implications and risks of pesticide residues in soils (0–20 cm; n = [...] Read more.
In sub-Saharan Africa, intensive pesticide use in irrigated agriculture is threatening the quality of soil, water bodies and ecosystem services, yet integrated risk assessments remain limited. This study evaluated the environmental implications and risks of pesticide residues in soils (0–20 cm; n = 15) and irrigation water (n = 15) from off-season irrigation area of the Goulbi Maradi Valley, Niger. Twelve commonly used pesticides in Djiratawa, Maradi 3 and Tibiri, were quantified by High-Performance Liquid Chromatography with Variable Wavelength Detector (HPLC-VWD), revealing Tibiri as a contamination hotspot, where the total pesticide residues in soil and irrigation water reached 6.4 and 19.7 times the respective European Union soil and drinking water benchmarks, dominated by Cypermethrin, Emamectin benzoate and Chlorpyrifos ethyl in soils, and Emamectin benzoate and Dichlorvos in water. Multivariate analysis showed that soil particle size, particularly higher clay content, controlled the retention of strongly sorbing compounds, while pH and salinity governed the occurrence of more soluble residues in irrigation water. While non-carcinogenic risks for Adults and Children via soil and water exposure were acceptable (Hazard Quotient and Hazard Index < 1), ecological risks were unacceptable, with Folsomia candida and Daphnia magna the most affected organisms, driven by Emamectin benzoate (Toxicity Exposure Ratio < 2). Priority actions include phasing out Dichlorvos and Paraquat dichloride, tightening controls on Emamectin benzoate and expanding food-chain monitoring, particularly in vegetables and fish, to support multi-trophic risk assessment and safer irrigation management. Full article
(This article belongs to the Section Pest and Disease Management)
10 pages, 702 KB  
Article
The Relationship Between Foot Posture, Dorsiflexion Range of Motion and Lower Extremity Biomechanics During a Drop-Landing Task
by Kendra S. Graham and Joshua T. Weinhandl
Biomechanics 2026, 6(2), 43; https://doi.org/10.3390/biomechanics6020043 (registering DOI) - 3 May 2026
Abstract
Background/Objectives: While restricted dorsiflexion range of motion (DF-ROM) is linked to deleterious sagittal and frontal plane knee and hip kinematics during landing, the literature is conflicted as to whether excessive foot pronation is linked to knee injury. The purpose of this study [...] Read more.
Background/Objectives: While restricted dorsiflexion range of motion (DF-ROM) is linked to deleterious sagittal and frontal plane knee and hip kinematics during landing, the literature is conflicted as to whether excessive foot pronation is linked to knee injury. The purpose of this study was to examine the relationship between static foot posture, DF-ROM, and lower extremity biomechanics during a drop-landing task. Methods: Fifteen physically active adults (age: 22.6 ± 2.4 years, height: 1.69 ± 0.08 m, mass: 66.40 ± 9.95 kg) volunteered to participate in this study. Static foot posture was measured by the six criteria of the Foot Posture Index (FPI-6) and DF-ROM was measured using the weight-bearing lunge test (WB-LT). Sagittal and frontal plane kinematics and kinetics of the hip, knee, and ankle were captured using a 3D motion capture system and force plate during a drop-landing task. Results: FPI-6 scores (4.67 ± 2.94) correlated with knee abduction angle at initial contact (1.08 ± 3.30°, r = −0.59, p = 0.02), ankle sagittal plane excursion (39.11 ± 7.67°, r = −0.63, p = 0.01) and knee adduction moment (0.58 ± 0.51 N/kg, r = 0.60, p = 0.017). DF-ROM correlated with knee adduction moment (r = −0.59, p = 0.02). The combination of FPI-6 and DF-ROM accounted for 56% of the variance in knee adduction moment (r = 0.746, p = 0.008). No significant relationships were identified for hip variables (p > 0.05). Conclusions: Participants with a more pronated static foot posture displayed less knee adduction angle at initial contact and decreased ankle sagittal plane excursion. Those with less DF-ROM and a pronated static foot posture exhibited increased maximum knee adduction moment. Foot and ankle structure influence lower extremity biomechanics. Full article
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42 pages, 2506 KB  
Review
Neurodegenerative Diseases in Children: A Comprehensive Review
by Constantin Ailioaie, Laura Marinela Ailioaie, Cristinel Ionel Stan, Anca Sava and Dragos Andrei Chiran
Int. J. Mol. Sci. 2026, 27(9), 4096; https://doi.org/10.3390/ijms27094096 (registering DOI) - 3 May 2026
Abstract
Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular [...] Read more.
Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular pathways, including lysosomal degradation, mitochondrial oxidative phosphorylation, peroxisomal lipid metabolism, and myelin maintenance. This comprehensive review synthesizes current knowledge regarding the epidemiology, molecular classification, pathophysiology, and emerging therapeutic strategies of major pediatric neurodegenerative disorders. Epidemiological data indicate a “rare-but-many” landscape, where individually uncommon diseases collectively impose a measurable population burden. Mechanistically, disease progression reflects converging processes such as toxic substrate accumulation, impaired autophagy–lysosome flux, mitochondrial bioenergetic failure, oxidative stress, neuroinflammation, and glial dysfunction. Representative groups discussed include lysosomal storage disorders, leukodystrophies, mitochondrial encephalopathies, peroxisomal disorders, and other monogenic neurodegenerative syndromes. Advances in next-generation sequencing, metabolic profiling, and neuroimaging have substantially improved diagnostic accuracy and enabled earlier detection, including through newborn screening programs. Therapeutic paradigms are shifting from primarily supportive care toward mechanism-based interventions, including enzyme replacement therapy, hematopoietic stem cell transplantation, substrate reduction strategies, and gene therapy approaches. Early molecular diagnosis is increasingly recognized as critical for optimizing outcomes, particularly in disorders amenable to presymptomatic intervention. Continued integration of genomic medicine, standardized epidemiologic surveillance, and translational research will be essential to refine disease classification, improve prognostication, and expand access to targeted therapies. Collectively, pediatric neurodegenerative diseases exemplify the intersection of developmental neurobiology and inherited metabolic dysfunction, underscoring the need for multidisciplinary, precision-based clinical strategies. Full article
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14 pages, 1420 KB  
Systematic Review
Comparative Efficacy of rTMS and Psychosurgery in Severe OCD: A Systematic Review and Meta-Analysis of Responder Rates
by Andrés Vega-Rosas, Naomi G. Santos-Jacinto, Sergio Martinez-del Angel and Andrea Granados-Juárez
Psychiatry Int. 2026, 7(3), 96; https://doi.org/10.3390/psychiatryint7030096 (registering DOI) - 3 May 2026
Abstract
Background: Severe, treatment-resistant Obsessive–Compulsive Disorder (OCD) remains a major clinical challenge. When conventional pharmacological and psychotherapeutic strategies fail, neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) and psychosurgical approaches are increasingly considered. Although both modalities target nodes within the cortico-striato-thalamo-cortical (CSTC) circuit, [...] Read more.
Background: Severe, treatment-resistant Obsessive–Compulsive Disorder (OCD) remains a major clinical challenge. When conventional pharmacological and psychotherapeutic strategies fail, neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) and psychosurgical approaches are increasingly considered. Although both modalities target nodes within the cortico-striato-thalamo-cortical (CSTC) circuit, their relative effectiveness has not been examined within a unified analytical framework. Objective: We aimed to compare responder rates between rTMS and psychosurgical interventions in adults with treatment-resistant OCD through a systematic review and meta-analysis. Methods: A PRISMA-guided search of PubMed and Scopus (2015–2025) identified clinical studies reporting treatment response. Pooled responder rates were estimated separately for each modality using random-effects models. Between-study heterogeneity and publication bias were systematically assessed. Results: Fourteen studies met inclusion criteria, including 10 rTMS studies (416 participants) and four lesion-based psychosurgical studies (142 participants). Both modalities demonstrated clinically meaningful responder rates. Pooled analyses suggested higher responder proportions in psychosurgical cohorts (RR = 3.06, 95% CI 1.43–6.54); however, this finding was accompanied by substantial heterogeneity (I2 = 63%) and signals of publication bias. Follow-up duration differed markedly between modalities (mean 2.4 months for rTMS vs. 33.0 months for psychosurgery), reflecting fundamentally different study designs and outcome assessment timepoints. Conclusions: Differences in pooled responder rates should be interpreted as exploratory rather than as evidence of comparative efficacy. The lack of a shared comparator, differences in patient selection, and large discrepancies in follow-up limit direct comparisons between modalities. These findings support a stepped-care framework for neuromodulation in treatment-resistant OCD and highlight the need for methodologically harmonized studies to better define the role of each intervention across distinct clinical profiles of treatment resistance. Full article
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23 pages, 870 KB  
Article
Admission Biomarkers as Predictors of Mortality in Comatose Patients in the Intensive Care Unit: A Retrospective Pilot Study
by Pompiliu Mircea Bogdan, Roxana Elena Bogdan-Goroftei, Alina Plesea-Condratovici, Adina Oana Armencia, Letitia Doina Duceac, Camer Salim, Cristian Gutu, Manuela Arbune, Lavinia-Alexandra Moroianu, Constantin Marinel Vlase, Monica Mihaela Scutariu and Alina Mihaela Calin
Diagnostics 2026, 16(9), 1388; https://doi.org/10.3390/diagnostics16091388 (registering DOI) - 3 May 2026
Abstract
Background: Intensive care units (ICUs) provide management of critically ill patients requiring continuous monitoring and complex therapeutic interventions. The aim of this study was to analyze the clinical and biological characteristics associated with mortality in patients admitted to the intensive care unit. [...] Read more.
Background: Intensive care units (ICUs) provide management of critically ill patients requiring continuous monitoring and complex therapeutic interventions. The aim of this study was to analyze the clinical and biological characteristics associated with mortality in patients admitted to the intensive care unit. Methods: This retrospective observational study included 108 adult patients admitted to the Anesthesia and Intensive Care Unit of the “Sf. Apostol Andrei” Emergency County Clinical Hospital in Galați, who were in a coma at the time of admission. Demographic data, comorbidities, clinical parameters and biological biomarkers determined at admission were analyzed. Statistical analysis was performed using the SPSS program and included non-parametric tests (Mann–Whitney U), Spearman correlation analysis, multivariate logistic regression and ROC curve analysis to evaluate the predictive performance of biomarkers. Results: Hypertension (60.2%) and diabetes mellitus (35.2%) were the most common comorbidities. Comparative analysis revealed significant differences between deceased and surviving patients for several biological parameters, including leukocytes, C-reactive protein, LDH, D-dimers, INR and APTT. In multivariate analysis, LDH (OR = 0.998; p < 0.001) and APTT (OR = 0.951; p = 0.033) remained independently associated with mortality. ROC analysis revealed good discrimination capacity for LDH (AUC ≈ 0.805) and moderate performance for APTT. Conclusions: Determination of LDH and APTT at the time of admission to the ICU may provide useful information for assessing the prognosis of critically ill patients and for early stratification of mortality risk. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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18 pages, 2964 KB  
Review
New Directions in Migraine Pathophysiology: The Glymphatic System and PACAP
by Dan Iulian Cuciureanu, Cătălina Elena Bistriceanu, Georgiana-Anca Vulpoi, Victor Constantinescu, Diana Laura Blajuta, Ana-Maria Nădejde, Florina Antochi and Adina-Maria Roceanu
Life 2026, 16(5), 767; https://doi.org/10.3390/life16050767 (registering DOI) - 3 May 2026
Abstract
Migraine severely impacts the quality of life of young adults. During the past few years, many studies have been done regarding the pathophysiology of this condition. There has been intense debate regarding CGRP, but research is still underway about the glymphatic system and [...] Read more.
Migraine severely impacts the quality of life of young adults. During the past few years, many studies have been done regarding the pathophysiology of this condition. There has been intense debate regarding CGRP, but research is still underway about the glymphatic system and PACAP. This review provides an overview of the current literature in this area of migraine pathophysiology. The inflammatory mediators and neuropeptides that activate trigeminovascular pathways can be accumulated during migraine attacks as a result of a failure of glymphatic clearance. Neuroinflammation, CGRP, CSD, and sleep have all been linked to the glymphatic system and migraine. In this article, we also discuss the latest hypotheses regarding the PACAP pathway in the neurophysiology of migraine. Additionally, recent research suggests that glymphatic dysfunction could enhance PACAP-mediated signaling. This article will explore possible correlations between these mechanisms and migraine pathophysiology. Full article
(This article belongs to the Section Physiology and Pathology)
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21 pages, 1613 KB  
Article
Ultrasound-Assisted Enzymatic Hydrolysates from Common Bean and Pumpkin Seed Proteins: Antioxidant and Anti-Inflammatory Properties
by Erick Huerta-Rodriguez, Omar Sanchez-Jimenez, Cristina Chuck-Hernández, Margarita L. Martinez-Fierro, Idalia Garza-Veloz, Diana L. Cárdenas-Chávez, Cesar A. Ponce-Ponce de Leon and Maria del Refugio Rocha-Pizaña
Antioxidants 2026, 15(5), 578; https://doi.org/10.3390/antiox15050578 (registering DOI) - 3 May 2026
Abstract
Chronic low-grade inflammation, a key driver of diabetes and fatty liver disease, is present in obesity, which affects 2.1 billion adults as of 2021. Plant-derived bioactive peptides have emerged as promising alternatives to treat inflammation in these pathological processes. This study evaluated the [...] Read more.
Chronic low-grade inflammation, a key driver of diabetes and fatty liver disease, is present in obesity, which affects 2.1 billion adults as of 2021. Plant-derived bioactive peptides have emerged as promising alternatives to treat inflammation in these pathological processes. This study evaluated the effect of pre- and post-ultrasound-assisted enzymatic hydrolysis on bioactive peptide production and antioxidant activity from common bean (Phaseolus vulgaris L.) and pumpkin (Cucurbita argyoesperma) seed proteins. Pre-treated hydrolysates were fractionated by molecular weight (<3 kDa and 3–10 kDa) and evaluated for their anti-inflammatory properties by measuring nitric oxide and reactive oxygen species in three treatment schemes (pre-, co-, and post-treatment) in an obesity/inflammatory macrophage model. Ultrasound pre-treatment achieved a higher degree of hydrolysis (peptide production) compared to post-treatment, with corresponding increases in antioxidant activity as measured by the ABTS and ORAC assays. All hydrolysate fractions demonstrated dose-dependent inhibition of pro-inflammatory markers. Fractions administered as a co-treatment showed the strongest anti-inflammatory effect, reducing Nos-2 and Cox-2 mRNA expression, as well as secreted levels of pro-inflammatory cytokines (TNF-α, IL-6, MCP-1). These findings indicate that ultrasound treatment, mainly as pre-treatment, represents an effective strategy for producing bioactive peptide hydrolysates with anti-inflammatory properties in vitro that warrant deeper investigation. Full article
(This article belongs to the Section ROS, RNS and RSS)
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