Search Results (2,243)

Background and Clinical Significance: Neuroleptic malignant syndrome (NMS) is a life-threatening condition usually caused by the exposure to antipsychotics. This case report presents a catatonia syndrome that may have developed in the context of a moderate NMS. Case Presentation: An 18-year-old male patient presented with a treatment-resistant catatonia syndrome that debuted 2 weeks prior to the presentation (creatin kinase levels = 4908 U/lL maximum temperature = 38.9°C, white blood count = 13.20 × 10⁹/L, Bush–Francis Catatonia Rating Scale = 30 points). Possible organic causes of catatonia were ruled out, according to the negative results obtained. The patient’s condition improved under benzodiazepine treatment and he was later discharged. After discharge, the catatonia was attributed to a possible NMS with moderate severity. The diagnosis was supported by NMS Diagnosis Criteria Score = 85 points and the presence of Levenson’s triad. Conclusions: This case highlights the concomitant manifestation of both catatonia and NMS in the same patient and the difficulty of establishing a correct diagnosis involving both entities. Full article

Metabolic syndrome is a global health crisis. However, there are no effective therapeutic strategies for metabolic syndrome. Therefore, this study was conducted to find out a novel silkworm-based metabolic syndrome model that bridges microbial ecology and metabolic dysregulation by integrating hemolymph lipids and midgut microbiota. Our results showed that the levels of HDL-C in the hemolymph of the lean silkworm strain were significantly higher than that in the obese silkworm strain. Furthermore, correlation analysis revealed that Lactococcus and Oceanobacillus were positively related to HDL-C levels, while SM1A02 and Pseudonocardia were negatively associated with HDL-C levels. These relationships between the identified bacteria in the midgut and HDL-C, known as the “good” lipid, in the hemolymph could help guide the development of new treatments for obesity and metabolic problems like high cholesterol in humans. Overall, our results not only established a framework for understanding microbiota-driven lipid dysregulation in silkworms but also offered potential probiotic targets and a bacterial biomarker for obesity and metabolic dysfunction intervention in humans. Full article

Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of this study is to characterize the clinical spectrum of anti-Ku-positive patients and evaluate the clinical significance of anti-Ku-borderline results in CTD management. A retrospective cohort study was conducted at Hôpital Erasme, including all patients with anti-Ku-positive or borderline results, over a 10-year period. Clinical and biological data were collected from medical records and analyzed for disease associations, organ involvement, and outcomes. Among 47 anti-Ku-positive patients, systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) were the most common diagnoses. Interstitial lung disease (ILD) occurred in 23.4% and renal involvement in 12.8% of patients. Cytopenia was significantly associated with glomerulonephritis. Organ damage, particularly pulmonary and renal involvement, correlated with increased mortality. In the borderline group (n = 33), SLE and SS remained the predominant diagnoses. During follow-up, three patients died (all with isolated ILD without associated CTD), one required chronic dialysis, and one underwent lung transplantation. ILD was present in 7/22 (31.8%) borderline patients, and renal involvement in 7/32 (21.9%). This study demonstrates significant associations between anti-Ku antibodies and organ damage, with increased mortality risk. The high prevalence of pulmonary and renal involvement in anti-Ku-borderline patients suggests that these results carry substantial clinical significance and should prompt comprehensive CTD evaluation. These findings support treating borderline anti-Ku results with the same clinical vigilance as positive results, given their similar association with severe organ involvement and adverse outcomes. Full article

Insulin resistance is a fundamental pathophysiological mechanism contributing to the development of type 2 diabetes and metabolic syndrome. Recently, attention has focused on mitochondria’s role in glucose and lipid metabolism. Mitochondrial dysfunction is strongly associated with impaired energy metabolism and elevated oxidative stress. We investigated the mitochondrial DNA (mtDNA) copy number in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in insulin-sensitive (IS) and insulin-resistant (IR) individuals. Twenty-seven paired adipose tissue biopsies were obtained during elective abdominal surgery. DNA and RNA were extracted, and mtDNA copy number was quantified using Real-Time PCR. We found that mtDNA content in VAT was approximately two-fold lower than in SAT. Furthermore, in IR individuals, mtDNA copy number was significantly reduced in both SAT and VAT compared to IS subjects. A strong positive correlation was observed between mtDNA content in VAT and body mass index (BMI), and a negative correlation was found with the QUICKI index. Additionally, mtDNA copy number in VAT positively correlated with the expression of several genes involved in insulin signalling, lipid metabolism, and other metabolic pathways. These findings underscore the central role of mitochondrial function in VAT in the context of metabolic disorders and suggest that targeting mitochondrial regulation in this tissue may represent a promising therapeutic approach. Full article

Background: Delirium is a common, underdiagnosed neuropsychiatric syndrome in older adults, associated with high mortality and functional decline. Given its multifactorial nature and overlap with frailty, radiological markers may improve risk stratification in the emergency department (ED). Methods: We conducted a retrospective study on a small sample of 30 patients diagnosed with delirium in the emergency department who had recently undergone brain, thoracic, or abdominal CT scans for unrelated clinical indications. Using post-processing software, we analyzed radiological markers, including coronary artery calcifications (to estimate vascular age), cerebral atrophy (via the Global Cortical Atrophy scale), and cachexia (based on abdominal fat and psoas muscle volumetry). Results: Five domains were identified as significant predictors of 12-month mortality in univariate Cox regression: vascular age, delirium etiology, cerebral atrophy, delirium subtype (hyperactive vs. hypoactive), and cachexia. Based on these domains, we developed an exploratory 10-point delirium score. This score demonstrated acceptable diagnostic accuracy for mortality prediction (sensitivity 0.93, specificity 0.73, positive predictive value 0.77, negative predictive value 0.91) in this limited cohort. Conclusions: While preliminary and based on a small, retrospective sample of 30 patients, this multidimensional approach integrating clinical and radiological data may help improve risk stratification in elderly patients with delirium. Radiological phenotyping, particularly in terms of vascular aging and sarcopenia/cachexia, offers objective insights into patient frailty and could inform more personalized treatment pathways from the ED to safe discharge home, pending further validation. Full article

In Gram-negative bacteria, lipopolysaccharides (LPSs, also known as endotoxin) can induce extensive immune responses that will enable victims to produce severe septic shock syndrome. Because of the high mortality of sepsis in the face of standard treatment, advance detoxification schemes are urgently needed in clinics. Herein, we described a supramolecular detoxification approach via direct host–guest complexation by a giant macrocycle. Cationic pentaphen[3]arene (CPP3) bearing multiple quaternary ammonium groups was screened as a candidate antidote. CPP3 exhibited robust binding affinity toward LPS with an association constant of (4.79 ± 0.29) × 10⁸ M⁻¹. Co-dosing with an equivalent amount of CPP3 has been demonstrated to decrease LPS-induced cytotoxicity on a cellular level through inhibiting ROS generation and proinflammatory cytokine expression. In vivo experiments have further proved that post-treatment by CPP3 could significantly improve the survival rate of LPS-poisoned mice from 0 to 100% over a period of 3 days, and inflammatory abnormalities and tissue damage were also alleviated. Full article

The etiology of schizophrenia remains poorly understood. Although certain risk factors have been identified, effective preventive measures are still lacking. This study investigates potential preventive methods while focusing on the role of vitamin D and its status. The role of malnutrition in schizophrenia risk was first identified in studies on the Dutch Hunger Winter. Vitamin D deficiency was hypothesized as a contributing factor shortly thereafter. This review aims to explore the correlations between vitamin D deficiency at various life stages (maternal, neonatal, adult) and schizophrenia risk, as well as its effects on pharmacokinetics, neurobiology, bone health, and metabolic syndrome. The studies were retrieved from two indexed databases, PubMed and Web of Science, following PRISMA guidelines and included studies published between 2000 and 2024. No correlation was found between maternal vitamin D levels and schizophrenia in offspring while a positive correlation was observed between low neonatal vitamin D levels and schizophrenia in later life. Approximately half of the studies on adults reported mean vitamin D concentrations of below 20 ng/mL which were negatively correlated with gray matter volume and bone health while positively correlated with the prevalence of metabolic syndrome. Additionally, vitamin D levels were also found to correlate with antipsychotic drug concentrations. Full article

Metabolic syndrome (MetS) is defined as a group of metabolic defects that include hypertension, insulin resistance, visceral obesity, fatty liver disease, and atherosclerotic cardiovascular disease (CVD). The first step in controlling the progression of MetS is lifestyle changes, including dietary modification. Regular consumption of fruits, vegetables, whole grains and other plant foods negatively correlates with the risk of developing chronic diseases. Green leafy vegetables (GLVs) are a key element of healthy eating habits and an important source of vitamins C and E, carotenoids—mainly β-carotene and lutein—and minerals. This review discusses and summarizes the current knowledge on the health benefits of consuming GLVs in the prevention and treatment of MetS to provide a compendium for other researchers investigating new natural products. Full article

Background: Polygenic risk scores (PRS) have emerged as promising tools for disease risk stratification. However, their validity across different populations remains unclear, particularly for autoimmune diseases, where environmental factors may play crucial roles. Methods: We calculated the population-level PRS for Sjögren’s syndrome using seven validated genetic variants (PGS001308) and allele frequency data from the 1000 Genomes Project Phase 3 for five European populations (CEU, TSI, FIN, GBR, and IBS). PRS values were correlated with published prevalence estimates from a systematic literature review. Statistical analyses included Pearson’s correlation and sensitivity analyses. Results: PRS values varied across European populations, ranging from 0.317 in the Spanish population to 0.370 in the Northern European population. A non-significant negative trend was observed between population PRS and Sjögren’s syndrome prevalence (r = −0.407, R² = 0.166). Italy showed the lowest genetic risk score (TSI: 0.349) but the highest disease prevalence (58.2 per 100,000), while Northern European populations demonstrated a higher PRS but lower prevalence. Conclusions: No significant correlation was found between genetic risk scores and disease prevalence in this limited sample of five European populations. Larger studies are needed to clarify the relationship between polygenic risk and disease prevalence. Full article

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infections such as dengue virus. Due to overlapping features with severe dengue and sepsis, diagnosis of HLH in dengue-infected patients remains challenging. Methods: We conducted a narrative review and individual patient data meta-analysis of published cases of dengue-associated HLH. Eligible studies were identified through a search of PubMed and Scopus databases up to 5 March 2025. Clinical, laboratory, microbiological, treatment, and outcome data were extracted and analyzed. Results: A total of 133 patients from 71 studies were included. The median patient age was 18 years, and 56.8% were male. Common clinical features included fever (96.9%), cytopenias, organomegaly, and liver dysfunction. ALT elevation, jaundice, and hypofibrinogenemia were associated with mortality. DENV-1 was the most common serotype (57.4%) and was negatively associated with death. Overall, 19.3% of patients died. Multivariate analysis did not identify independent mortality predictors. Conclusions: Dengue-associated HLH predominantly affects young individuals and carries significant mortality. Key indicators of poor prognosis include hepatic dysfunction and the presence of shock or organ failure. Early recognition and prompt immunomodulatory treatment, particularly corticosteroids, may improve outcomes. Full article

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m² (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article

Disorders in glucose metabolism are well-established features of polycystic ovary syndrome (PCOS) and are linked to its clinical severity and phenotypic variability. This study aimed to assess serum concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) and to examine their relationships with glucose and insulin levels, selected sex hormone concentrations, body weight, and exposure to tobacco smoke. Women with PCOS exhibited significantly elevated levels of fasting glucose, insulin, GIP, and GLP-1 compared to controls. Tobacco smoke exposure in women with PCOS was associated with reduced DPP-4 levels, which were approximately two-fold lower in smokers than in non-smokers. A significant negative correlation between DPP-4 and cotinine levels further supported this relationship. Comorbidities such as overweight/obesity or insulin resistance (IR) were also linked to elevated incretin hormone levels. However, no significant age-related trends in incretin levels were identified, despite the known association between age and glucose dysregulation. The notable alterations in incretin hormone profiles in PCOS, along with the consistent patterns of GIP or GLP-1 with metabolic and hormonal parameters, suggest that these hormones may play coordinated regulatory roles in the pathophysiology of PCOS. Full article

Anticytokine autoantibodies (AAbs), particularly anti-interferon-gamma (anti-IFN-γ) AAbs, disrupt cytokine functions, leading to infections, autoimmune-like diseases, and conditions resembling interleukin-12 (IL-12)/IFN-γ pathway defects. Advances in genetic testing have clarified overlaps between autoinflammatory, autoimmune disorders, and primary immunodeficiencies but reveal complex phenotypes and pathways. While these insights deepen our understanding of immune mechanisms, they also complicate diagnosis and treatment, with limited options for IFN-γ deficiencies caused by genetic mutations. The adult-onset immunodeficiency with disseminated lymphadenitis due to nontuberculous mycobacteria (NTM) and other opportunistic infections has been linked to high levels of anti-IFN-γ AAbs. This syndrome, initially identified in HIV-negative Asian patients, frequently affects individuals of Asian descent and may be associated with specific human leukocyte antigen (HLA) alleles. The presence of neutralizing anti-IFN-γ AAbs impairs the IFN-γ-dependent immune response, likely contributing to the persistent NTM infection. This study underscores the potential for late-onset anti-IFN-γ AAb syndrome to manifest with disseminated NTM (dNTM) infections, highlights the importance of timely diagnosis and considers rituximab as a potential therapeutic option. Full article

The global obesity and metabolic syndrome epidemic have accelerated demand for reduced-sugar food, prompting the food industry to adopt functional sugar alcohols as sucrose substitutes. Threitol is a four-carbon sugar alcohol and an isomer of erythritol. However, there is a scarcity of studies reporting on the edible safety of threitol. This study assessed threitol’s toxicological and metabolic properties. Acute oral administration (10 g/kg) caused no mortality or abnormalities in mice. Repeated 28-day exposure revealed no behavioral or histopathological alterations, with negative outcomes in three genotoxicity tests. Metabolic studies in rats demonstrated that the majority of ingested threitol is excreted in the urine within 24 h. Sensory evaluation indicated threitol’s sweetness equivalence to sucrose, exceeding erythritol and allulose. Notably, 16S rRNA sequencing revealed gut microbiota modulation in threitol-fed mice, indicating potential intestinal health benefits. These integrated findings establish threitol’s preclinical safety and support its development as a novel low-calorie sweetener. Full article