Search Results (798)

Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic diabetes forms that are frequently misclassified as type 1 or type 2 diabetes due to overlapping phenotypic features. The true prevalence of MODY is likely substantially underestimated. As DNA-based diagnostics become increasingly accessible, an expanding number of novel genetic variants are being identified. Objectives: The aim of this study was to characterize the clinical and genetic features of patients carrying rare variants in the BLK, KLF11, PAX4, PDX1, and CEL genes, with attention to population-specific aspects, family history, and treatment outcomes. Methods: Targeted next-generation sequencing (NGS) using a custom-designed panel covering 27 genes implicated in MODY, neonatal diabetes, and related hereditary syndromes was performed on the Illumina NovaSeq 6000 platform (Illumina). Results: We identified 21 variants in five genes associated with rare MODY subtypes among 24 unrelated patients. MODY9 was diagnosed in two unrelated patients of Russian ethnicity harboring an identical heterozygous missense mutation in exon 5 of the PAX4 gene (HG38, chr7:127615049G>A, c.191C>T, p.Thr64Ile), which has not been previously described in patients with diabetes. MODY11 was diagnosed in a patient carrying the c.773-1G>A variant in the BLK gene. A patient with a de novo c.40_41dupGC (p.Val15Glnfs*41) variant in the KLF11 gene was clinically diagnosed with type 1 diabetes. Conclusion: Our findings expand the current understanding of rare MODY subtypes and contribute to the growing body of evidence on the spectrum and frequency of potentially pathogenic variants in BLK, CEL, KLF11, PDX1, and PAX4 genes across ethnically diverse populations worldwide. Full article

The study of faults in seismic gap areas is essential for assessing the potential for future seismic activity and developing strategies to mitigate its impact. In this research, we employed a combination of geomorphological analysis, aerophotogrammetry, high-resolution topography, and soil analysis to estimate the age of tectonically exposed fault surfaces in a seismic gap area. Our focus was on the Piano delle Rose Fault in the northern Calabria region, (southern Italy), which is a significant regional tectonic structure associated with seismic hazards. We conducted a field survey to carry out structural and pedological observations and collect soil samples from the fault surface. These samples were analyzed to estimate the fault’s age based on their features and degree of pedogenic development. Additionally, we used high-resolution topography and aerophotogrammetry to create a detailed 3D model of the fault surface, allowing us to identify features such as fault scarps and offsets. Our results indicate recent activity on the fault surface, suggesting that the Piano delle Rose Fault may pose a significant seismic hazard. Soil analysis suggests that the onset of the fault surface is relatively young, estimated in an interval time from 450,000 to ~ 300,000 years old. Considering these age constraints, the long-term slip rates are estimated to range between ~0.12 mm/yr and ~0.33 mm/yr, which are values comparable with those of many other well-known active faults of the Apennines extensional belt. Analyses of key fault exposures document cumulative displacements up to 21 m. These values yield long-term slip rates ranging from ~0.2 mm/yr (100,000 years) to ~1.0 mm/yr (~20,000 years LGM), indicating persistent Late Quaternary activity. A second exposure records ~0.6 m of displacement in very young soils, confirming surface faulting during recent times and suggesting that the fault is potentially capable of generating ground-rupturing earthquakes. High-resolution topography and aerophotogrammetry analyses show evidence of ongoing tectonic deformation, indicating that the area is susceptible to future seismic activity and corresponding risk. Our study highlights the importance of integrating multiple techniques for examining fault surfaces in seismic gap areas. By combining geomorphological analysis, aerophotogrammetry, high-resolution topography, and soil analysis, we gain a comprehensive understanding of the structure and behavior of faults. This approach can help assess the potential for future seismic activity and develop strategies for mitigating its impact. Full article

There are close relationships between vertical positions in space and auditory experiences of fundamental frequency (F0), which even very young children seem to use. Like adults, they associate higher or rising F0 values with upper positions in space and vice versa for lower or falling F0 values. Here, we tested whether caregivers’ speech capitalizes on these associations to guide the attention of very young children (18 to 24 months). Together with their child, caregivers saw four different objects (in the corners of a computer screen). Caregivers produced standardized sentences (e.g., “Look at the hat.”). We observed a significantly increased maximum F0 (but no differences in mean or minimum F0) at the onset of the utterance when the to be named object appeared at an upper position compared to the same object at a lower position. Furthermore, exploratory analyses of F0 dynamics of caregivers’ utterances indicated that the higher F0 maximum was part of a more prominent F0 increase for objects appearing at an upper compared to a lower position. Adults without a child present and less experience in interacting with children did not show systematic pitch modulation when addressing an imagined child in the same study set-up. Thus, caregivers appear to systematically modulate F0 dynamics to provide an effective language environment when they are interacting with their child. Full article

Unaccustomed eccentric exercise is well established to induce exercise-induced muscle damage (EIMD), characterized by transient strength loss, delayed onset muscle soreness (DOMS), reduced range of motion, and proprioceptive disturbances. While limb dominance has been proposed as a potential modulator of susceptibility to EIMD, evidence remains inconclusive. This exploratory study aimed to compare alterations in muscle damage indices between dominant and non-dominant knee extensors 48 h after eccentric isokinetic exercise. Eighteen physically active young women (23 ± 2 years) completed two eccentric exercise sessions (5 × 15 maximal contractions at 60°/s), one per limb, with sessions separated by 24–30 days. For all participants, testing was conducted during the early follicular phase. Muscle strength (isometric and eccentric peak torque), DOMS (palpation and pain pressure threshold), range of motion, fatigue index, and position sense were assessed pre- and 48 h post-exercise. Significant reductions in isometric and eccentric peak torque, increased DOMS, impaired position sense, and altered fatigue index were observed 48 h post-exercise in the exercised limb (p < 0.001), with no differences between dominant and non-dominant limbs across all indices. These findings demonstrate that limb dominance does not influence the magnitude of EIMD in knee extensors of young women. Practical implications include equal consideration of both limbs in eccentric training, rehabilitation, and injury prevention programs. Full article

Background/Objectives: Adolescent Idiopathic Scoliosis persisting into adulthood (AAIS) presents progressive stiffening and degenerative changes that are not fully captured by existing classifications. This heterogeneity complicates clinical decision-making and surgical planning. The aim of this study was to propose a novel, treatment-oriented classification system for AAIS. Methods: A retrospective review was performed on patients with AAIS who underwent surgical correction between 2018 and 2022. Pre- and postoperative radiographs, CT scans, and MRI were analyzed to define curve characteristics and evaluate surgical outcomes. Subgroups were identified according to age and deformity features, and corresponding surgical strategies were outlined. Results: AAIS was stratified into Young Adult Idiopathic Scoliosis (YAdIS, 19–30 years) and Adult Idiopathic Scoliosis (AdIS, >30 years). YAdIS was divided into mild, flexible curves (YAdIS 1) and severe/stiff curves (YAdIS 2). AdIS was classified into three categories: AdIS 1 (isolated coronal deformity), AdIS 2 (combined coronal and sagittal deformity), and AdIS 3 (revision cases). Within AdIS 1, additional refinement by age (30–45, 45–60, >60 years) reflected increasing stiffness and degenerative changes. Tailored surgical strategies included selective fusions, posterior releases, high-density constructs, three-column osteotomies, and combined anterior–posterior approaches, depending on curve type and age group. Conclusions: This classification provides a comprehensive, treatment-oriented framework to support surgical decision-making in AAIS, enabling optimized planning and improved outcomes for adult patients with scoliosis of adolescent onset. Full article

Duck viral hepatitis, caused by Duck Hepatitis A Virus Type 3 (DHAV-3), remains a major threat to young ducklings. Although DHAV-3 has circulated in China since the 1999s, the complete genomic architecture, exact virulence parameters, and evolutionary distance between early Yunnan isolates and current field strains have remained undefined. This study investigated six DHAV-3 strains isolated in Yunnan Province, China, between 2004 and 2006, to elucidate their genetic and biological characteristics. Full-genome sequencing and phylogenetic analysis revealed >99.5% nucleotide and >99.6% amino acid identity among the strains, suggesting a common ancestral origin. In vivo challenge assays showed rapid onset of clinical signs and >90% mortality in ducklings within 36 h post-inoculation. Embryonic deaths began at 24 h post-infection and peaked by 90 h. Viral replication was efficient in DEF, DEK, Vero, and BHK-21 cells, but absent in chicken fibroblasts (DF-1). Comparative genomic analysis between the YN/LR/2005 strain and recent field isolates (2022–2024) revealed substantial nucleotide divergence in structural regions, with 32 unique amino acid substitutions—all five located in the immunodominant VP1 region that may influence viral antigenicity and host interaction—alongside changes in N-glycosylation sites and alterations in protein secondary structure. Histopathological examination confirmed characteristic hepatic lesions. These findings demonstrate that while DHAV-3 has undergone genetic evolution, it retains high virulence, underscoring the need for ongoing molecular surveillance and supporting future vaccine and diagnostic development. Full article

Alzheimer’s disease (AD) is the most prevalent form of dementia, particularly in those aged 65 and older. Dementia can also occur under age 45, known as young-onset dementia (YOD), although this is rarer. Marchiafava–Bignami disease (MBD) is a rare disorder characterized by demyelination and necrosis of the corpus callosum, primarily affecting individuals with chronic alcohol use. We present the case of a 49-year-old woman admitted for psychiatric and neurological evaluation due to a multidomain cognitive disorder with a sudden onset approximately four years prior, which progressed rapidly, resulting in complete dependence on others for daily activities. Her medical history included moderate depression, chronic alcohol consumption, and professional exhaustion. Psychological assessments revealed severe neurocognitive impairment. MRI scans highlighted significant bilateral parietal atrophy, hippocampal atrophy, and demyelinating lesions in the corpus callosum, consistent with MBD. Despite initial inconsistencies in biomarkers, later tests showed elevated tau protein, phosphorylated tau, and amyloid-beta, supporting an AD diagnosis. Clinical presentation, combined with neuroimaging findings and chronic alcohol consumption history, led to a diagnosis of AD with young onset and chronic MBD. This case illustrates the complexities involved in diagnosing overlapping neurodegenerative disorders. The coexistence of MBD and AD complicates the treatment plan, requiring a multifaceted approach addressing both neurodegenerative and nutritional aspects. Full article

Background: Cervical artery dissection (CAD) is a leading cause of acute ischemic stroke among young and middle-aged patients. Currently, the growing availability of high-resolution magnetic resonance imaging (MRI), particularly fat-saturated T1-weighted black-blood SPACE sequences, allows the non-invasive, rapid, and reliable diagnosis of multiple arterial dissections. Methods: We reported our experience from two tertiary stroke centers of patients diagnosed with spontaneous multiple cervical artery dissections, detected with high-resolution MRI, during a three-year period (2022–2025). Results: Among 95 consecutive patients with CAD, 11 patients (mean age: 48 ± 9 years, 6 (55%) females) were diagnosed with multiple symptomatic or asymptomatic CADs, whereas in 84 patients (mean age: 49 ± 11 years, 32 (38%) females) a single CAD was detected. In all patients, high-resolution MRI and MR-angiography were performed, whereas digital subtraction angiography (DSA) with simultaneous evaluation of renal arteries was conducted in nine patients. A history of trauma or chiropractic manipulations, intense physical exercise prior to symptom onset, recent influenza-like illness, and recent childbirth in a young female patient were reported as predisposing risk factors. Cervicocranial pain, cerebral infarctions leading to focal neurological signs, and Horner’s syndrome were among the most commonly documented symptoms. Characteristic findings in the high-resolution 3D T1 SPACE sequence were detected in all patients. Fibromuscular dysplasia and Eagle syndrome were detected in four patients and one patient, respectively. Eight patients were treated with antiplatelets, whereas three patients received anticoagulation with low-molecular-weight heparin. There was only one case of stroke recurrence during a mean follow-up period of 9 ± 4 months. Conclusions: This case series highlights the utility of specific high-resolution MRI sequences as a very promising method for detecting multiple CADs in young patients. The systematic use of these sequences could enhance the sensitivity of detecting multiple cervical CADs, affecting also the thorough investigation for underlying connective tissue vasculopathies, stratifying the risk for first-ever or recurrent ischemic stroke, and influencing acute reperfusion and secondary prevention therapeutic strategies. Full article

This study investigated the associations among age, physical activity level, knee muscle function, and neuromuscular junction (NMJ) biomarkers in a cohort of 80 middle-aged and young men residing in the Republic of Korea. Despite comparable levels of physical activity between the groups, the middle-aged participants exhibited significantly higher body fat percentage, elevated levels of the neurodegeneration marker neurofilament light chain (NfL), and a marked decline in lower-extremity muscle function compared to their younger counterparts. Advancing age was negatively associated with knee extensor peak torque, body weight–normalized torque (BW/PT), and the rate of torque development at 0.18 s (RTD@0.18s). In contrast, higher physical activity levels were positively correlated with certain indicators of muscle function and were associated with lower circulating concentrations of the NMJ degeneration marker, C-terminal agrin fragment (CAF). These findings suggest that neuromuscular decline and muscle function deterioration may begin as early as middle age. The results underscore the importance of implementing tailored exercise regimens and lifestyle interventions to preserve neuromuscular health and prevent early-onset muscle loss. Full article

Background: Systemic lupus erythematosus (SLE) is reported to be the most common rheumatological disorder associated with catatonia. To date, reports on catatonia manifestations in SLE patients are uncommon in published literature, which has often favored a fragmented vision. We performed a narrative review with the aim of identifying all published reports of catatonia in SLE patients to ascertain—in a comprehensive view—its clinical characteristics and to provide useful insights for daily clinical practice. Methods: Comprehensive literature searches were carried out on 10 March 2025 (subsequently repeated ahead of draft on 6 June) in all main bibliographic databases: MEDLINE and EMBASE (OVID interface); PsycINFO (ProQuest); and PubMed, to capture within-text references. All searches combined controlled (MESH, Entree, and APA Headings) and free-text elements for both areas under observation: systemic lupus erythematosus (SLE) AND catatonia, with primary focus on case reports and series. Sets of findings were reviewed separately by the authors, and the full text of selected items was sourced. Further useful references were retrieved through citation lists. Results: 39 cases of patients with SLE and catatonia were identified (35 females and 4 males), with a mean age of 22.64 years (range 11–46). Only three patients were over the age of 40; a total of 10 had catatonia at the same time of SLE onset and 5 within a month of SLE diagnosis. Antiphospholipid and anti-ribosomal P protein antibodies were rarely identified. Almost all the patients improved following treatment with lorazepam and/or electroconvulsive therapy. Only one case of malignant catatonia was reported. Finally, a large number of patients were Asian or Afro-American, at least in the reports where ethnicity was specified. Conclusions: Catatonia can occur in patients with SLE, and it may be its first clinical manifestation, especially in young patients. Its prognosis is mostly favorable. Full article

Background: The use of benzodiazepines among university students has been scarcely investigated. This situation raises particular concerns in medical students, due to their exposure to stressful situations and, especially, their familiarity with psychotropic drugs. Material and methods: A descriptive cross-sectional observational study was conducted using an anonymous online survey disseminated among universities in the Community of Madrid during April 2024. Results: 25.07% of students stated they had used benzodiazepines at least once, especially from the third academic year onwards. The prevalence was higher among medical students (32.34%). Use was mainly occasional, although 20.21% reported daily use. Among the reasons for use, managing academic stress reached 45.74%. Up to 15.96% of respondents reported a feeling of dependence, and 32.26% noticed concentration difficulties as a side effect of benzodiazepine use. Conclusions: Benzodiazepine use is a relevant phenomenon among university students, with particular incidence in medical degrees. Its onset usually coincides with advanced stages of the degree, which underscores the need for preventive interventions tailored to the academic environment and for the rational use of psychotropic drugs in young populations. Full article

Background: Although adolescents are at a lower risk of developing scaphoid non-union than adults, this complication is not uncommon in younger patients. The current gold standard for surgical treatment is non-vascularized bone grafting from the iliac crest or distal radius, and it is often considered the first-line option. However, non-union can persist in 10–20% of cases, and failure rates can reach up to 50% when the proximal pole is necrotic. Methods: We evaluated a modified vascularized bone graft surgical technique in selected adolescent patients, with the goal of avoiding growth-related complications. Our experience is based on three cases of scaphoid non-union treated surgically between June 2019 and June 2022. Results and Conclusions: The modified surgical technique has shown promising results in the selected cases and carries no risk of donor site morbidity. It enables preservation of severely compromised scaphoid bones, prevents early-onset wrist osteoarthritis, and facilitates the return to sports activities for young patients. Full article

Maturity-Onset Diabetes of the Young Type 5 (MODY5) is caused by heterozygous pathogenic variants in the HNF1B gene, encoding the transcription factor hepatocyte nuclear factor-1β. HNF1B haploinsufficiency typically leads to young-onset non-immune diabetes and highly variable renal involvement, whose more frequent features are bilateral kidney cysts and renal hypodysplasia. Kidney cysts or echogenic kidneys can be identified by ultrasonography in the prenatal period, but the renal involvement can also start in childhood or later. Notably, a recurrent microdeletion syndrome at 17q12 (deleting HNF1B plus ~15 neighboring genes) accounts for ~40–50% of cases. The 17q12 deletion is a contiguous gene syndrome and affected individuals present with a complex phenotype, including neurodevelopmental disorders, liver and pancreas abnormalities, and other congenital defects. When counseling the patient and the parents, the clinician must consider multiple factors, including the molecular defect and the age of onset of the symptoms, with particular attention to prenatal diagnosis. A multidisciplinary approach and an early diagnosis are essential for the management of these conditions. Full article

Background: Young-onset colorectal cancer (YO-CRC) has emerged as a distinct clinical entity, often presenting at advanced stages. Despite the increasing incidence, the molecular and clinical underpinnings of YO-CRC remain underexplored. This study aims to characterize the clinical and molecular features of YO-CRC and to evaluate their impact on OS. Methods: We reviewed 110 patients diagnosed with YO-CRC at our institution who underwent next-generation sequencing. Demographic, clinical, and molecular data, including age, gender, race, tumor location, cancer stage, and mutation status (KRAS, NRAS, BRAF, POLE, ERBB-2/HER2, microsatellite status), were collected by reviewing electronic medical records. For OS analysis, we focused on patients diagnosed with de novo stage IV. Cox proportional hazards regression and Kaplan–Meier survival analysis were utilized to assess the association of these factors with OS, with statistical significance determined by a p-value threshold of <0.05. Results: Among 110 patients, n = 44 (40%) presented with local disease (stage 1–3), while n = 66 (60%) presented with de novo metastatic disease at the time of diagnosis. The median age at diagnosis was 44.5 years. The cohort consisted of 64% males and 36% females, with 84% of patients identified as White. Most tumors were left-sided (77%), including the distal colon/sigmoid (44%) and rectum (33%). KRAS and BRAF mutations were present in 36% and 5.5%, respectively. ERBB-2/HER2 amplification and microsatellite instability were observed in 4.5% and 6.4%, respectively. Tumor mutation burden (TMB) was <10 in 57% of patients, with 14% having TMB > 20. CNV analysis revealed that 14% of patients had copy gains, 12% had concurrent gains/losses, and 31% had copy losses. Among 66 patients with de novo metastatic disease, 44% had died by the time of analysis, with a median overall survival (OS) of 43.6 months (95% CI, 28.7—not reached). KRAS mutations were found to be significantly associated with worse survival outcomes. Cox regression analysis reveals the prognostic significance of KRAS status, with a hazard ratio (HR) of 3.52 (95% CI: 1.59–7.76, p = 0.002), indicating a significantly higher risk of death for KRAS-mutant YO-CRC patients. Conclusions: Patients with YO-CRC are more likely to present with de novo metastatic disease and left-sided tumors with distinct molecular characteristics. KRAS mutations are a key prognostic factor in YO-CRC, highlighting the need for therapeutic interventions to improve outcomes in this high-risk group. Full article

Maturity-onset diabetes of the young type 10 (MODY10) is a monogenic diabetes subtype caused by heterozygous mutations in the insulin gene (INS), leading to defective proinsulin processing, endoplasmic reticulum (ER) stress, and β-cell dysfunction. Current management relies on sulfonylureas or insulin therapy, but these fail to address the underlying genetic defect. Recent research has elucidated the molecular mechanisms of MODY10, including ER stress induced by proinsulin misfolding, activation of the unfolded protein response (UPR), and β-cell apoptosis. Emerging therapies such as Adeno-Associated Virus (AAV)-mediated gene delivery to induce the glucose-responsive hepatic insulin expression, plasmid-based single-chain insulin analogs, and cell-based therapies show promise in preclinical studies. However, critical challenges remain, including immune responses to AAV vectors, incomplete correction of dominant-negative mutant effects, and the need for long-term safety data. This review summarizes current knowledge on MODY10 genetics, pathophysiology, and therapeutic innovations, while identifying key gaps for future research to enable precision medicine approaches. Full article