Search Results (238)

Down syndrome (DS), stemming from the triplication of human chromosome 21, results in intellectual disability, with early mid-life onset of Alzheimer’s disease (AD) pathology. Early interventions to reduce cognitive impairments and neuropathology are lacking. One modality, maternal choline supplementation (MCS), has shown beneficial effects on behavior and gene expression in neurodevelopmental and neurodegenerative disorders, including trisomic mice. Loss of basal forebrain cholinergic neurons (BFCNs) and other DS/AD relevant hallmarks were observed in a well-established trisomic model (Ts65Dn, Ts). MCS attenuates these endophenotypes with beneficial behavioral effects in trisomic offspring. We postulate MCS ameliorates dysregulated cellular mechanisms within vulnerable BFCNs, with attenuation driven by novel gene expression. Here, choline acetyltransferase immunohistochemical labeling identified BFCNs in the medial septal/ventral diagonal band nuclei of the basal forebrain in Ts and normal disomic (2N) offspring at ~11 months of age from dams exposed to MCS or normal choline during the perinatal period. BFCNs (~500 per mouse) were microisolated and processed for RNA-sequencing. Bioinformatic assessment elucidated differentially expressed genes (DEGs) and pathway alterations in the context of genotype (Ts, 2N) and maternal diet (MCS, normal choline). MCS attenuated select dysregulated DEGs and relevant pathways in aged BFCNs. Trisomic MCS-responsive improvements included pathways such as cognitive impairment and nicotinamide adenine dinucleotide signaling, among others, indicative of increased behavioral and bioenergetic fitness. Although MCS does not eliminate the DS/AD phenotype, early choline delivery provides long-lasting benefits to aged trisomic BFCNs, indicating that MCS prolongs neuronal health in the context of DS/AD. Full article

Background/Objectives: Multimodal large language models (LLMs) are increasingly used in radiology. However, their ability to recognize fundamental imaging features, including modality, anatomical region, imaging plane, contrast-enhancement status, and particularly specific magnetic resonance imaging (MRI) sequences, remains underexplored. This study aims to evaluate and compare the performance of three advanced multimodal LLMs (ChatGPT-4o, Claude 4 Opus, and Gemini 2.5 Pro) in classifying brain MRI sequences. Methods: A total of 130 brain MRI images from adult patients without pathological findings were used, representing 13 standard MRI series. Models were tested using zero-shot prompts for identifying modality, anatomical region, imaging plane, contrast-enhancement status, and MRI sequence. Accuracy was calculated, and differences among models were analyzed using Cochran’s Q test and McNemar test with Bonferroni correction. Results: ChatGPT-4o and Gemini 2.5 Pro achieved 100% accuracy in identifying the imaging plane and 98.46% in identifying contrast-enhancement status. MRI sequence classification accuracy was 97.7% for ChatGPT-4o, 93.1% for Gemini 2.5 Pro, and 73.1% for Claude 4 Opus (p < 0.001). The most frequent misclassifications involved fluid-attenuated inversion recovery (FLAIR) sequences, often misclassified as T1-weighted or diffusion-weighted sequences. Claude 4 Opus showed lower accuracy in susceptibility-weighted imaging (SWI) and apparent diffusion coefficient (ADC) sequences. Gemini 2.5 Pro exhibited occasional hallucinations, including irrelevant clinical details such as “hypoglycemia” and “Susac syndrome.” Conclusions: Multimodal LLMs demonstrate high accuracy in basic MRI recognition tasks but vary significantly in specific sequence classification tasks. Hallucinations emphasize caution in clinical use, underlining the need for validation, transparency, and expert oversight. Full article

Background/Objectives: The Lowenstein Communication Scale (LCS) is a tool for the evaluation of communicative performance in patients with disorders of consciousness (DOC). This study investigated the reliability and validity of the LCS. Methods: We evaluated 23 inpatients with unresponsive wakefulness syndrome (UWS) and 18 in a minimally conscious state (MCS), at admission to a Consciousness Rehabilitation Department and one month later. The evaluations included assessments of LCS by two raters, and of the Coma Recovery Scale–Revised (CRS-R) by one rater. Results: Total inter-rater agreement in LCS task scoring was found in 58–100% of the patients. Cohen’s kappa values were >0.6 for most tasks. High correlations were found between the two raters on total scores and most subscales (r = 0.599–1.000, p < 0.001), and the differences between them were small. LCS subscales and total score intraclass correlations (ICC) were high. Internal consistency was acceptable (Cronbach’s α > 0.7) for most LCS subscales and total scores. Moderate to strong correlations were found between LCS and CRS-R scores (r = 0.554–0.949, p < 0.05), and the difference in responsiveness between LCS and CRS-R was non-significant. Conclusions: The findings indicate that the LCS is reliable and valid, making it a valuable clinical and research assessment tool for patients with DOC. Full article

Complex regional pain syndrome (CRPS) is a disabling pain condition, which is distinct from other pain syndromes by the presence of autonomic dysfunction and regional inflammatory changes. Objectives: To explore the impact of pharmacological treatment strategies, specifically scheduled, on-demand dosing regimens versus lack of medical treatment, on pain-related and functional outcomes in rehabilitation for individuals with CRPS. Methods: A total of 32 participants with CRPS were assigned to three treatment groups depending on analgesic treatment during the course of complex rehabilitation. Pre- and post-rehabilitation assessments were conducted using validated measures, including the Numerical Rating Scale (NRS) for pain, the Short-Form McGill Pain Questionnaire (SF-MPQ), PainDETECT, the Disabilities of the Arm, Shoulder, and Hand (DASH), and the Lower Extremity Functional Scale (LEFS). Results: Significant improvements in pain and upper limb function (DASH scores) were observed across all groups (p < 0.05). No statistically significant changes were found in lower limb function (LEFS). Between-group comparisons revealed significant differences in post-treatment pain scores (SFMPQ-B), particularly between groups with a constant treatment regimen and those without treatment. Conclusions: There were no statistically significant changes compared to different treatment regimen groups. The constant treatment group showed slightly better average improvements in pain and disability compared to other groups. Statistically significant improvements in all CRPS patients were observed in pain-related and functional measures. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a multifactorial disorder influenced by both environmental and genetic factors. The aim of this study was to evaluate associations between selected polymorphisms (CYP19, INSR, FTO, MC4R) and the clinical manifestations of PCOS in a Polish female population. Methods: A total of 50 women (25 with PCOS and 25 healthy controls) were included. Genetic variants were identified using Polymerase Chain Reaction (PCR)-based methods. The frequencies of genotypes and alleles were compared between groups. Clinical symptoms such as irregular menstruation, hirsutism, acne, androgenetic alopecia, and overweight were assessed in relation to genotype. Results: No significant differences were found in genotype distributions for CYP19, FTO, INSR, or MC4R between PCOS and control groups. The MC4R polymorphisms showed deviations from Hardy–Weinberg equilibrium, possibly reflecting population-specific effects. Conclusions: Although most analyzed variants were not directly associated with PCOS in this cohort, the observed link between INSR rs1799817 and acne suggests a role in androgen-related symptoms. These findings contribute new insights to the genetic background of PCOS in Polish women and support the need for further studies combining genetic and phenotypic data in diverse populations. Full article

Sepsis, a systemic inflammatory response syndrome triggered by infection, is characterized by acute onset, rapid progression, and high mortality. Ferroptosis, a form of programmed cell death induced by iron-dependent lipid peroxidation, is closely associated with the occurrence and development of various diseases. Microcystin-LR (MC-LR) can exacerbate sepsis by causing multi-organ damage via the ferroptosis pathway. Currently, the relationship between MC-LR, ferroptosis, and sepsis remains unclear. Understanding its pathogenesis and identifying potential therapeutic targets may reduce the mortality of sepsis patients and lead to clinical improvement. This article reviews the relationship among MC-LR, ferroptosis, and sepsis, focusing on the mechanism by which MC-LR exposure induces sepsis from the ferroptosis perspective, providing a theoretical basis for the prevention and treatment of MC-LR-exposure-induced sepsis in the population. Full article

Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes—typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in about 30% of MC patients and it is a manifestation with poor prognosis. Nowadays, types II and III MC are the most common forms, often linked to autoimmune diseases like Sjögren’s syndrome and systemic lupus erythematosus, or to viral infections such as hepatitis B or persisting despite hepatitis C eradication. This review explores renal involvement in MC, offering a comprehensive perspective on current knowledge, including recent advances in pathophysiological understanding, evolving diagnostic strategies, and novel therapeutic approaches. In this context, “perspectives” refers to the growing recognition of the shifting epidemiology of MC—particularly the changing etiological landscape following hepatitis C virus eradication—as well as the integration of emerging clinical and pathological entities such as cryofibrinogenemia and monoclonal gammopathy of renal significance into diagnostic and management frameworks. Furthermore, the review highlights current therapeutic strategies recognized as most effective, emphasizing the importance of a multidisciplinary and multimodal approach that combines etiological treatment, B-cell–targeted therapy (notably rituximab), plasma exchange in selected cases, and comprehensive supportive care for renal and systemic complications. Moreover, the landscape of management could be enriched in future years, since clinical trials are ongoing to explore novel therapies for refractory or relapsing cases of MC with renal involvement. Full article

Differentiating central diabetes insipidus (CDI), nephrogenic diabetes insipidus (NDI), and primary polydipsia (PP) in pediatric patients with polyuria–polydipsia syndrome (PPS) remains a clinical challenge. The water deprivation test (WDT) is the traditional gold standard; however, it is time-consuming, burdensome, and prone to equivocal results. Stimulated copeptin, a surrogate marker of vasopressin, has emerged as a promising diagnostic alternative. We conducted a prospective, observational, cross-sectional study involving 27 pediatric patients (ages 2–17) presenting with PPS. Each patient underwent a WDT with desmopressin and hypertonic saline infusion (3% NaCl) for stimulated copeptin testing. Diagnostic accuracy was assessed using clinical diagnoses as a reference. The WDT showed high accuracy with an area under the curve (AUC) of 0.97, and there was an increased optimal threshold of ≥14% urine osmolality after desmopressin acetate (1-deamino-8-D-arginine vasopressin, DDAVP) administration (sensitivity 88.9%, specificity 100%). Stimulated copeptin at a threshold of <6.5 pmol/L demonstrated 100% sensitivity and specificity (AUC = 1.00) for CDI versus PP. Basal copeptin ≥21.4 pmol/L accurately identified all NDI cases. The agreement between the WDT and copeptin was low (κ = 0.06, McNemar p = 0.021), suggesting that copeptin has greater specificity, particularly for borderline or partial CDI. These results support the use of stimulated copeptin as a first-line diagnostic tool in pediatric PPS, offering improved objectivity, tolerability, and diagnostic clarity compared with the WDT. Basal copeptin also demonstrated excellent performance in rapid noninvasive NDI identification. Full article

Phelan–McDermid syndrome (PMS; #MIM: 606232) is a rare neurodevelopmental disorder primarily caused by the haploinsufficiency of the SHANK3 gene, most often due to deletions encompassing the gene or single nucleotide variants within it. Individuals with PMS display a wide range of clinical abnormalities and considerable genetic heterogeneity. This study aims to investigate genotype–phenotype correlations in a cohort of 213 individuals with PMS and to identify novel candidate genes, beyond SHANK3, that may contribute to the syndrome’s diverse clinical manifestations. Unsupervised clustering based on deletion size and Global Functional Assessment of the Patient (GFAP, previously described and developed by our group), along with additional analytical approaches, were employed to explore genotype–phenotype relationships. Deletion size within the 22q13.3 region emerged as a major determinant of phenotype, with larger deletions associated with more severe global functional impairment. Furthermore, CERK, TBC1D22A, CELSR1, and GRAMD4 were identified as candidate genes within 22q13.3, potentially contributing to core PMS phenotypes, and their putative interactions were explored. Our findings support the central role of SHANK3 in PMS, while also indicating that it does not account for the full phenotypic spectrum. This study underscores the variable impact of distinct genetic alterations in PMS and proposes additional loci implicated in its pathogenesis. These insights may inform future therapeutic strategies, emphasizing the importance of patient stratification and precision medicine. Full article

Certain strains of Influenza A virus (IAV), a primary cause of influenza, can lead to pneumonia. Patients recovering from influenza pneumonia may experience physical discomfort akin to post-acute sequelae of COVID-19 (PASC). Despite extensive clinical research on viral pneumonia during convalescence, animal model studies are scarce, highlighting the need for a reliable model for pharmaceutical research. In this study, BALB/c mice were divided into three groups: NC (control), MC (infected with IAV), and Model (treated with oseltamivir post-infection for five days). A fatigue model was then induced in the Model group through diet restriction and weight-bearing swimming. The results showed the MC group had a 75% survival rate, while the NC and Model groups had 100%. Both the MC and Model groups experienced rapid weight loss followed by gradual recovery, differing significantly from the NC group. From dpi (days post-inoculation) 6 to dpi9, the MC group lost more weight than the NC group. The MC group had the highest pulmonary index, but there was no significant difference in IAV Nucleoprotein (NP) expression across groups. The Model group had higher IL-10 levels than the NC and MC groups, while the MC group had the highest TNF-α expression. Hematoxylin and eosin (H&E) staining revealed pathological changes in the MC and Model groups, with severe damage and pulmonary fibrosis in the MC group. Oxidative stress markers showed the MC group had the highest lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and lowest superoxide dismutase (SOD) activity. Electron microscopy indicated mitochondrial damage in both the MC and Model groups. The Model group had the lowest splenic and thymic indices, with histological findings showing larger splenic nodules in the MC group and poor thymocyte density and atrophy in the Model group. The successful creation of this mouse model of influenza pneumonia convalescence phase fatigue, exhibiting fatigue syndrome with various symptoms, holds significance for PASC and other viral pneumonia convalescence phase animal model research. Full article

Background: Prolonged use of inotropes drugs in the early postoperative period is one of the most common complications occurring in patients undergoing heart valve surgery. Patients requiring prolonged support via inotropes drugs are significantly more likely to experience serious postoperative complications such as acute kidney injury, cardiogenic shock, multiple organ dysfunction syndrome, and death. This study assessed the usefulness of selected perioperative parameters in predicting prolonged postoperative use of inotropic drugs and cardiogenic shock and/or death in a group of patients requiring prolonged supply of inotropes drugs. Methods: This prospective study was conducted on a group of 607 patients undergoing heart valve surgery. The primary endpoint in-hospital follow-up was prolonged postoperative use of inotropes drugs. The secondary composite endpoint was cardiogenic shock requiring mechanical circulatory support (MCS) and/or death from any cause in patients with prolonged postoperative use of inotropes drugs. Results: A total of 210 patients required inotropes drugs for more than 48 h. Age (p = 0.03), preoperative atrial fibrillation (p < 0.001), preoperative NT-proBNP level (p < 0.001), Troponin T measured one day after surgery (TnT II) (p < 0.001), and the need for urgent postoperative rethoracotomy (p < 0.001) remained independent predictors of primary endpoint. Preoperative hemoglobin level (p = 0.001) and TnT II (p < 0.001) were independent predictors of death and cardiogenic shock requiring MCS. Conclusions: Patients with elevated preoperative NT-proBNP values, as well as with increasing postoperative troponin T levels, are at risk of prolonged postoperative use of inotropes drugs, a complication which is associated with a significant risk of developing further adverse consequences, such as cardiogenic shock and death. Full article

Multiple sclerosis (MS) is a chronic autoimmune-mediated neurodegenerative disease that affects young adults. The diagnosis of MS currently based on the McDonald criteria, which based on four core principles: the presence of a symptomatic demyelinating syndrome, an objective neurologic finding, the dissemination in space (DIS), and the dissemination in time (DIT). In addition, the diagnosis of MS relies on the exclusion of any alternative diagnosis. This may implicate the absence of systemic non-neurological symptoms and signs, such as rheumatological, cutaneous, or ophthalmological findings. Nevertheless, the non-neurological symptoms are commonly observed in patients with MS either at the onset of MS, which therefore can delay the diagnosis and the incrementation of a disease-modifying therapy, or during the course of the disease progression. The purpose of our review is to highlight non-neurological symptoms of MS that frequently go undiagnosed or mistakenly linked to other conditions, aiming for the more accurate and earlier diagnosis of MS. Full article

Background/Objectives: Paediatric osteoarticular infections (POAIs) present unique diagnostic and therapeutic challenges. Microbiological culture (MC) is typically time-consuming and lacks sensitivity, especially when patients have received antibiotics. The BIOFIRE^® Joint Infection Panel (BJIP) is a syndromic molecular assay for the direct identification of most pathogens causing POAIs. Methods: We evaluated BJIP in 17 synovial fluids, and then, we retrospectively assessed its utility in 93 off-label specimens (i.e., 25 purulent fluids/biopsies and 68 whole blood samples). All specimens were collected from October 2022 to March 2024 from paediatric patients admitted at the Bambino Gesù Children’s Hospital in Rome. Results: A bacterial pathogen was isolated in only one of 17 synovial fluid cultures, while BJIP identified eight additional microorganisms in MC-negative cases. The most frequently detected pathogen was S. aureus (44.5%, 4/9). BJIP performance in synovial fluids showed an overall positive percentage agreement (PPA) and negative percentage agreement (NPA) of 100% and 88.1%, respectively, compared to MC. All positive results (n/N = 9/17) were considered medically significant, with an increase in NPA to 100%. In purulent fluids/biopsies, BJIP and MC were concordant in 72% of cases (n/N = 18/25), with a per-sample PPA and NPA of 90% and 60%, respectively. For whole blood samples, almost all samples were negative by both methods (i.e., reference blood culture and BJIP), and the molecular test did not enable any further microbiological diagnosis. Conclusions: The BIOFIRE^® Joint Infection Panel rapidly and accurately enabled or excluded a diagnosis of a POAI (~1 vs. 24–96 h for MC), optimising antimicrobial therapy. Full article

Phelan–McDermid syndrome (PMS) is a rare genetic disorder primarily caused by deletions or structural alterations of chromosome 22q13, often involving the SHANK3 gene. However, mutations in other genes, such as CELSR1, or deletions in the interstitial regions of 22q13 contribute to the phenotypic variability of PMS. The syndrome is characterized by developmental delay, cognitive impairment, absent or significant impairment speech, autism spectrum disorder (ASD), and distinctive craniofacial features. Lymphedema, present in 10–25% of cases, typically affects peripheral regions, while facial involvement has not been documented to date. Orofacial manifestations frequently include dolichocephaly, widely spaced eyes, prominent ears, and dysmorphic features, such as a bulbous nose and arched palate. This scoping review analyzed seven studies on orofacial features associated with PMS, highlighting a higher phenotypic variability, with frequent findings of intellectual disability, hypotonia, and craniofacial dysmorphisms. Genomic analyses identified consistent deletions in 22q13.31–q13.33 and complex genomic rearrangements. This review, through the report of the first documented case of hemifacial lymphedema in the literature, analyzes the facial features of patients with PMS and their genetic origins. It also highlights the importance of interdisciplinary collaboration and inclusive genetic testing to better define the phenotypic spectrum of this syndrome. A deeper understanding of the genetic and clinical characteristics of PMS can facilitate early diagnosis and personalized management for these patients. Full article

Background/Objectives: The standard evaluation of children and adolescents suspected of having thyroid disorders consists of anthropometric measurements. Body composition features provide additional information for enhanced therapeutic management. We explored the muscle-to-fat ratio of pediatric patients referred for thyroid disorders and its interaction with thyroid function and metabolic syndrome components. Methods: This retrospective cross-sectional study consisted of 147 pediatric subjects (ages 5–19 years) diagnosed with childhood-onset thyroid disorders treated at a tertiary medical center. Sociodemographic, clinical and laboratory data [thyroid-stimulating hormone (TSH), free T4 (FT4), and lipid profile] were extracted from the electronic medical records. Body composition was measured using bioimpedance analysis (Tanita MC-780 MA and GMON Professional Software). Body mass index (BMI), appendicular muscle mass (ASMM), and muscle-to-fat ratio (MFR) were converted to z-scores. Results: The diagnoses included Hashimoto thyroiditis (30.6%), subclinical hypothyroidism (26.5%), congenital hypothyroidism (21.7%), and Graves’ disease (21%). Based on BMI z-scores, 31.3% of the cohort was overweight or obese. The TSH levels were positively correlated with the BMI z-scores (r = 0.238, p = 0.005) and negatively with the MFR z-scores (r = 0.215, p = 0.012). The ASMM z-scores were negatively associated with the FT4 levels (r = −0.255, p = 0.003). Dyslipidemia was prevalent. TSH was correlated with LDL cholesterol (r = 0.472, p < 0.001) and triglycerides (r = 0.232, p = 0.05). Conclusions: Elevated thyroid-stimulating levels were linked to higher BMI and lower MFR levels. Our findings on the relationship between thyroid function and lipid profile underscore the necessity of optimizing thyroid balance and implementing targeted lifestyle interventions to improve body composition in young patients with thyroid disorders. Full article