Search Results (344)

Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is an inflammatory demyelinating disorder of the central nervous system characterised by heterogeneous clinical and radiological presentations. Accurate interpretation of serum anti–myelin oligodendrocyte glycoprotein (anti-MOG) antibody titres is critical to improve diagnostic precision and prognostic assessment. This single-centre retrospective study evaluated 19 patients diagnosed with MOGAD in 2023, all of whom were seropositive for anti-MOG IgG, as confirmed by live cell-based assays (CBAs) using full-length human MOG and IgG1-specific secondary antibodies. Antibody quantification combined a ratiometric semi-quantitative fluorescence index with classical endpoint dilution titres, enabling classification into low, medium, and high titre groups. Stratification revealed titre-dependent phenotypic heterogeneity: high-titre patients were older at onset and predominantly presented with optic neuritis, often bilateral, and encephalic involvement, whereas low-titre patients more frequently exhibited spinal cord syndromes, cerebellar or brainstem symptoms, and a higher prevalence of cerebrospinal fluid-restricted oligoclonal bands. Semi-quantitative fluorescence ratios correlated consistently with endpoint titres, and exponential decay analysis demonstrated slower signal loss in high-titre sera, confirming assay reliability. No significant association emerged between titre level and monophasic versus relapsing disease course. Anti-MOG antibody titres could serve not only as a diagnostic biomarker but also to capture clinically relevant immunopathological diversity, supporting a titre-stratified approach to diagnosis and early prognostication. Incorporating semi-quantitative metrics alongside clinical and imaging features may refine the diagnostic algorithm and prevent misclassification of atypical presentations. Full article

Background: Phenylketonuria (PKU) is a rare autosomal recessive metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to hyperphenylalaninemia (HPA). Untreated, elevated phenylalanine (Phe) levels cause severe neurocognitive, developmental, and psychiatric complications. Management relies on a Phe-restricted diet, which is challenging to maintain, particularly in adolescents and adults. Sapropterin dihydrochloride, a synthetic form of tetrahydrobiopterin (BH4), can enhance residual PAH activity, lowering blood Phe levels and increasing dietary tolerance in responsive patients. However, real-world alignment with best practices remains underexplored. This study aims to report a tertiary referral center’s experience with sapropterin treatment in PKU and assess adherence to international guidelines. Methods: We retrospectively analyzed 23 PKU patients treated with sapropterin from 2007 to 2025. Patients with baseline Phe levels of 360–2000 µmol/L underwent a 10 mg/kg/day loading test over two weeks. Responsiveness was defined as a ≥30% reduction in blood Phe levels. Phe levels were measured pre- and post-test, and dietary tolerance was evaluated. Adherence to best practices was critically reviewed. Results: All patients showed significant Phe reductions (mean 71.43%, p < 0.0001), exceeding responsiveness thresholds. Most achieved substantial increases in dietary Phe tolerance, with three patients partially responsive (800–1200 mg/day). Responsiveness was unrespectful of the patient’s genotype, for those individuals for whom this was known (8/23 patients). Although effective, the test dose and duration differed from guideline recommendations (20 mg/kg/day). Neuropsychological and QoL assessments were not systematically performed, representing a key limitation. Conclusions: Sapropterin dihydrochloride effectively identified responders and improved dietary flexibility even with lower dosing protocols. Greater adherence to international standards, particularly regarding long-term neuropsychological monitoring, is needed to optimize patient care. Full article

The growing environmental and economic impacts of agri-food waste have intensified interest in digital and circular strategies for more sustainable resource management. This study investigates how digital technologies are being applied to enhance the circular management of agri-food waste. A systematic literature review was conducted following PRISMA guidelines, using Scopus as the primary database. The bibliometric analysis included 373 publications from 2015 to 2025 and was complemented by a thematic review of the 20 most cited articles. Results revealed six major research clusters, ranging from predictive waste analytics and smart traceability systems to circular bioeconomy applications such as anaerobic digestion and pyrolysis. In addition, the study examined structural indicators such as food waste per capita and hunger indices to contextualize geographic disparities in research output. The findings underscore the dual role of digital technologies as both operational tools and mechanisms for reducing systemic inequalities. Overall, the integration of intelligent systems and circular models offers promising pathways to support the Sustainable Development Goals and foster a more inclusive and resilient agri-food sector. Full article

Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies. Full article

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

Over the last decade, the scientific community has increasingly focused on forest-based practices for human well-being (FBPW), a term that includes all forest activities (e.g., forest bathing, forest therapy, social outdoor initiatives) important for improving people’s health and emotional status. This paper aims to develop a quantitative literature review on FBPW based on big data analysis (text mining on Scopus title and abstract) and PRISMA evaluation. The two techniques facilitate investigations across different geographic areas (major areas and geographical regions) and allow a focus on various topics. The results of text mining highlight the prominence of publications on FBPW for the improvement of human health in East Asia (e.g., Japan and South Korea). Furthermore, some specific themes developed by the literature for each geographical area emerge: urban green areas, cities, and parks in Africa; sustainable forest management and planning in the Americas; empirical studies on physiological and psychological effects of FBPW in Asia; and forest management and FBPW in Europe. PRISMA indicates a gap in studies focused on the reciprocal influences of forest variables and well-being responses. An investigation of the main physiological indicators applied in the scientific literature for the theme is also developed. The main strengths and weaknesses of the method are discussed, with suggestions for potential future lines of research. Full article

Gender-specific cardiology has gained increasing recognition in recent years, emphasizing the need for tailored management strategies for women with cardiovascular disease. Among these, cardiomyopathies—dilated, arrhythmogenic, hypertrophic, and restrictive—pose unique challenges throughout a woman’s reproductive life, affecting contraception choices, pregnancy outcomes, and breastfeeding feasibility. Despite significant advances in cardiovascular care, there is still limited guidance on balancing maternal safety and neonatal well-being in this complex setting. This review provides a comprehensive overview of the current evidence on reproductive counseling, pregnancy management, and postpartum considerations in women with cardiomyopathies. We discuss the cardiovascular risks associated with each cardiomyopathy subtype during pregnancy, highlighting risk stratification tools and emerging therapeutic strategies. Additionally, we address the safety and implications of breastfeeding, an often overlooked but increasingly relevant aspect of postpartum care. A multidisciplinary approach involving cardiologists, gynecologists, obstetricians, and anesthesiologists is crucial to optimizing maternal and fetal outcomes. Improved risk assessment, tailored patient counseling, and careful management strategies are essential to ensuring safer reproductive choices for women with cardiomyopathy. From now on, greater attention is expected to be given to bridging existing knowledge gaps, promoting a more personalized and evidence-based approach to managing these patients throughout different stages of reproductive life. Full article

Background and Objectives: Sesamoiditis is a painful and functionally limiting condition that affects the sesamoid bones of the hallux, frequently seen in athletic populations. Despite its clinical relevance, there are no standardised guidelines for its conservative management. This systematic review aims to evaluate the effectiveness of conservative treatments for sesamoiditis by summarising individual-level data from published studies. Materials and Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, ISI/Web of Science, and PEDro (Physiotherapy Evidence Database) up to December 2024 in accordance with PRISMA 2020 guidelines and following a protocol specifically devised for rare or underrepresented medical conditions. Eligible studies included case reports and case series involving patients aged ≥16 years who were conservatively treated for clinically and/or radiologically diagnosed sesamoiditis. Data on patient demographics, diagnosis, type and duration of treatment, pain- (Visual Analogue Scale (VAS) and Numeric Rating Scale (NRS)) and function-related (Foot and Ankle Ability Measure (FAAM) and Foot and Ankle Outcome Score (FAOS)) outcomes, and return to activity were extracted. Study quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Pooled effect sizes were computed where applicable. Results: Out of 2380 initial records, 11 studies comprising 59 patients (29 females) were included. Treatments varied widely, including orthotics, corticosteroid injections, physical therapy, and biologic approaches such as concentrated bone marrow aspirate (CBMA). VAS scores improved in 66% of cases. NRS scores returned to baseline in some patients after initial improvement, revealing recurrence. FAAM and FAOS subscales showed functional improvements, particularly in sports-specific domains. Return to activity varied: in a case series, 45.4% resumed pain-free sports participation, while others remained symptomatic. Conclusions: Conservative treatment options for sesamoiditis showed variable effectiveness with promising outcomes in selected patients. Corticosteroid injections and orthotics appeared beneficial, but high recurrence and limited functional recovery persisted in some cases. Standardised treatment protocols and high-quality prospective studies are needed to improve clinical decision-making and optimise non-surgical management. Full article

A prior history of falls remains the strongest predictor of future falls in individuals with Parkinson’s disease (PD). There are limited biomarkers available to identify falls risk before falls begin to occur. The aim of this review is to investigate if features associated with falls risk may be detected by wearable sensors in patients with PD. A systematic search of the MEDLINE, EMBASE, Cochrane, and Cinahl databases was performed. Key quality criteria include sample size adequacy, data collection procedures, and the clarity of statistical analyses. The data from each included study were extracted into defined data extraction spreadsheets. Results were synthesized in a narrative manner. Twenty-four articles met the inclusion criteria. Of these, twelve measured falls prospectively, while the remaining relied on retrospective history. The definition of a “faller” varied across studies. Most assessments were conducted in a clinical setting (18/24). There was considerable variability in sensor placement and mobility tasks assessed. The most common sensor-derived measures that significantly differentiated “fallers” from “non-fallers” in Parkinson’s disease included gait variability, stride variability, trunk motion, walking speed, and stride length. Full article

Background and Clinical Significance: Traumatic brain injury (TBI) represents a major public health concern due to its profound neurological, psychological, and socioeconomic consequences. Effective management is essential to optimize patient outcomes and reduce healthcare burden. In cases involving extensive bone loss or complex fractures, particularly when decompressive craniectomy (DC) is considered, secondary cranial reconstruction is typically required. However, DC is associated with prolonged hospitalization, multiple surgical interventions, an increased risk of complications, and higher costs. Case Presentation: We present the case of a 59-year-old male involved in a high-energy bicycle accident, sustaining severe craniofacial trauma with multiple midface fractures, a multifragmented left cranial fracture, and a left-sided epidural hematoma with brain compression. Hematoma evacuation and immediate primary reconstruction of the fractured skull using autologous bone were successfully performed, avoiding the need for DC. The patient recovered under intensive care and was transferred to a neurorehabilitation center. Conclusions: Primary reconstruction of large skull fractures using autologous bone should remain the goal, whenever possible, in order to avoid additional costs, risks, and complications. Full article

Androgens are emerging as important regulators of connective tissue remodeling, but current knowledge about their role in human fascia is still limited. This study examined the expression of the androgen receptor (AR) in human deep fascia and investigated the effects of dihydrotestosterone (DHT) on collagen production by fascial fibroblasts. Fascia lata and thoracolumbar fascia samples were collected from four adult donors (two male and two female). AR expression was assessed by immunohistochemistry and immunocytochemistry. Fascial fibroblasts were treated in vitro for 24 h with DHT at concentrations reflecting physiological levels: 0.4 ng/mL (female), 4 ng/mL (male average), and 10 ng/mL (high male dose). Collagen content was quantified using Picrosirius Red staining, and collagen I and III were evaluated using immunocytochemistry and image analysis, and were compared to an untreated control group. AR was detected in all samples. Low-dose DHT (0.4 ng/mL) significantly increased collagen I (4.80 ± 1.75%) and decreased collagen III (3.32 ± 0.46%) compared to controls (2.09 ± 0.91% and 10.46 ± 0.53%, respectively; p < 0.05). Higher DHT doses induced smaller or no significant changes in collagen subtype expression (e.g., 10 ng/mL: 2.03 ± 0.81% for collagen I, 8.49 ± 1.85% for collagen III). The results demonstrated that human fascia is hormonally responsive via AR, with DHT modulating matrix composition in a dose-dependent manner. The distinct effects at male and female levels may help explain gender differences in fascial stiffness and pain. Full article

Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved disease control. The STARR trial (NCT05455736) is a prospective, multicenter study evaluating the efficacy and safety of SSRT in patients with macroscopic prostate bed recurrence. This interim analysis reports early findings from the initial patient cohort. Materials and Methods: Patients with BR (PSA > 0.2 ng/mL) post-prostatectomy and PET-confirmed macroscopic recurrence (PSMA or Choline PET, confirmed by MRI) were eligible. Treatment involved CyberKnife^®-based SSRT delivering 35 Gy in five fractions to the visible lesion. Androgen deprivation therapy (ADT) was not permitted. Complete biochemical response (CBR) was defined as PSA < 0.2 ng/mL, and biochemical response (BR) as a ≥50% PSA reduction. Additional outcomes included biochemical, radiological, and ADT-free survival (bPFS, rPFS, aPFS). Results: As of analysis, 51 patients were enrolled, with a median follow-up of 16 months (95% CI: 16–22). CBR and BR were achieved in 45.1% and 80.4% of patients, respectively. Events affecting bPFS, rPFS, and aPFS occurred in 12, 5, and 6 patients, with median values not yet reached. Toxicity was minimal, with two cases each of acute grade 2 GI and GU events, and one late grade 2 GI event. No grade ≥ 3 toxicities were reported. Conclusion: Early data support SSRT as a safe and a promising option for macroscopic local recurrence, with encouraging response rates and minimal toxicity. Full article

Objectives: Fosfomycin is an old antibiotic that has recently gained attention owing to its preserved activity against multidrug-resistant (MDR) bacteria. Data on its use in real life are limited. Thus, we evaluated the efficacy and safety of fosfomycin disodium in the context of our hospital clinical practice. Methods: Single-center, retrospective, observational study on 56 patients who received fosfomycin disodium from September 2016 to July 2023, focusing on clinical and microbiological outcomes and adverse events. Results: Included in this study were 56 patients. Fosfomycin disodium was administered for a median duration of 10 days [5–13.5] and was always used in combination with other antibiotics, more frequently with meropenem (16 cases, 28.6%) and colistin (11 cases, 19.6%). It was mostly used for treating pneumonia (41%), followed by bloodstream infections (19.6%), urinary tract infections (16.1%), bone infections (16.1%), and surgical site infections (7.1%). The most common isolated pathogen was Pseudomonas aeruginosa (17%), and polymicrobial infections were detected in 18 patients (32%). Among the isolated bacteria, 36 (44.4%) were MDR. The complete resolution, defined as the disappearance of symptoms, eradication of the causative microorganism, and decrease in CRP levels, was achieved in 39% of cases. During treatment, we observed electrolyte imbalances, in particular a decrease in serum potassium (0.6 mEq/L [0.3–1.1]), calcium (0.7 mEq/L [0.3–1.1]) and magnesium levels (0.3 mg/dL [0.20–0.48]), and an increase in serum sodium levels (4 mEq/dL [2–7]). Changes in potassium and sodium levels were more pronounced in patients with prior kidney dysfunction and heart failure, respectively, and in patients receiving fosfomycin diluted with saline compared with 5% glucose solution (p = 0.04). Conclusions: Fosfomycin is effective in treating complicated infections in comorbid patients when combined with other antimicrobials. During treatment, major electrolyte imbalances occur that require careful monitoring and correction, especially in patients with prior kidney disease. Full article

Background/Objectives: Child abuse is a pervasive global issue with significant implications for the physical, emotional, and psychological well-being of victims. This review highlights the clinical, molecular, and therapeutic dimensions of child abuse, emphasizing its long-term impact and the need for interdisciplinary approaches. Early exposure to abuse activates the hypothalamic-pituitary-adrenal (HPA) axis, leading to chronic cortisol release and subsequent neuroplastic changes in brain regions such as the hippocampus, amygdala, and prefrontal cortex. These molecular alterations, including epigenetic modifications and inflammatory responses, contribute to the heightened risk of psychiatric disorders and chronic illnesses in survivors. Clinically, child abuse presents with diverse manifestations ranging from physical injuries to psychological and developmental disorders, making timely diagnosis challenging. Methods: A multidisciplinary approach involving thorough clinical evaluation, detailed histories, and collaboration with child protection services is essential for accurate diagnosis and effective intervention. Results: Recent advances in molecular biology have identified biomarkers, such as stress-related hormones and epigenetic changes, which provide novel insights into the physiological impact of abuse and potential targets for therapeutic intervention. Current treatment strategies prioritize the child’s safety, psychological well-being, and prevention of further abuse. Trauma-focused cognitive behavioral therapy and family-centered interventions are pivotal in promoting recovery and resilience. Conclusions: Emerging research focuses on integrating molecular findings with clinical practice, utilizing digital health tools, and leveraging big data to develop predictive models and personalized treatments. Interdisciplinary collaboration remains crucial to translating research into policy and practice, ultimately aiming to mitigate the impact of child abuse and improve outcomes for survivors. Full article