Search Results (13,540)

Background/Objectives: Individuals with anorexia nervosa (AN) are known to exhibit both reduced pain sensitivity—when assessed via thresholds and subjective ratings—and diminished facial expressions of emotion. Therefore, investigating the facial response to pain in this population is of particular interest. Method: Seventeen patients with AN and 18 age- and sex-matched healthy controls were assessed using a thermode to induce heat pain. Subjective pain measures included pain threshold, pain tolerance, and pain ratings of supra-threshold stimuli, rated on a numerical rating scale (NRS). Facial responses to the suprathreshold stimuli were analyzed using the Facial Action Coding System (FACS). Eating pathology was assessed using the Eating Attitudes Test (EAT-26), the Eating Disorder Inventory-2 (EDI-2) and the body mass index (BMI), while depression was measured using the Beck Depression Inventory-II (BDI-II). Results: Compared with healthy controls, AN patients showed altogether significantly reduced facial expressions of pain, with particularly pronounced reductions in Action Units AU 6_7 and AU 9_10. In contrast, subjective pain measures showed only marginal differences between groups. Importantly, the reduction in facial expression could not be accounted for by differences in pain thresholds or ratings, nor by levels of eating pathology or depression. Conclusions: Individuals with AN display a markedly reduced facial expression of pain, which was observed for the first time, consistent with similar findings regarding the facial expressions of emotions. As this reduction cannot be explained by subjective pain report, it suggests that the communication of pain is impaired on two levels in AN: both in verbal and in nonverbal signaling. This may hinder the ability of others to recognize and respond to their pain appropriately. Full article

Background: Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are rare hematopoietic disorders that exhibit overlapping pathological and molecular features of both MDS and MPN. This study aimed to investigate the mutational profiles and prognostic implications of MDS/MPN subtypes in Korean patients. Methods: We retrospectively reviewed 53 patients with MDS/MPN who underwent bone marrow examination and next-generation sequencing panel testing. Overall survival was analyzed with 3-year censoring. The cohort included chronic myelomonocytic leukemia (CMML; N = 30); MDS/MPN with neutrophilia (N = 6); MDS/MPN with SF3B1 mutation and thrombocytosis (N = 4); and MDS/MPN, not otherwise specified (MDS/MPN-NOS; N = 13). Results: The most frequently mutated gene was ASXL1 (52.8%), followed by TET2 (39.6%) and U2AF1 (18.9%), in total MDS/MPN. U2AF1 mutations were particularly frequent in myelodysplastic CMML (33.3%) and MDS/MPN-NOS (30.8%). In CMML, ASXL1 and TET2 mutations were associated with a trend toward better prognosis compared with wild-type (HR 0.21, p = 0.052; HR 0.25, p = 0.057, respectively), while U2AF1 mutations were associated with adverse prognosis in univariate analysis with borderline significance (HR 12.20, p = 0.050). Clinical/Molecular CMML-Specific Prognostic Scoring System and Mayo Molecular Model showed stepwise survival patterns across risk groups without statistical significance. In univariate analysis, transfusion dependency was associated with poor prognosis (HR 7.78, p = 0.013). Conclusions: This study provides the first single-institution analysis in Korean patients with MDS/MPN and identified U2AF1 mutations as a potentially significant prognostic factor, enhancing the molecular understanding of MDS/MPN. Full article

RNA-based therapeutics offer transformative potential for treating devastating diseases. However, current RNA delivery technologies face significant hurdles, including inefficient tissue targeting, insufficient selectivity, and severe side effects, leading to the termination of many clinical trials. This review critically assesses the landscape of RNA-derived medicines, examining world-renowned mRNA vaccines (Spikevax, BNT162b2/Comirnaty) and RNA-based therapeutics like Miravirsen (anti-miR-122). It details the composition and clinical trial results of numerous modified short RNA drugs (e.g., siRNAs, miRNA mimetics/inhibitors) targeting various conditions. Prospects for RNA-based medicines are analysed for diseases with substantial societal impact, such as cancer, autoimmune disorders, and infectious diseases, with a focus on evolving delivery methods, including lipid nanoparticles, viral vectors, and exosomes. RNA-mediated macrophage reprogramming emerges as a promising strategy, potentially enhancing both delivery and clinical efficacy. This review highlights that while approved RNA therapies primarily target rare diseases due to delivery limitations, novel approaches in RNA modification, targeted delivery systems, and enhanced understanding of molecular mechanisms are crucial for expanding their application to prevalent diseases and unlocking their full therapeutic potential. Full article

Angiogenesis, the formation of new blood vessels from existing vasculature, is regulated by a balance between pro- and anti-angiogenic factors. In adults, this process typically occurs in response to inflammation, wound healing, and neoplastic growth. Uniquely, the female reproductive system undergoes cyclical and repetitive angiogenesis with folliculogenesis, decidualization, implantation, and embryo development throughout the reproductive cycle. Ovarian angiogenesis involves a coordinated network of signaling pathways and molecular factors. Vascular endothelial growth factor (VEGF) is the primary driver of this process, supported by other regulators such as fibroblast growth factor (FGF) and hypoxia-inducible factor (HIF). Understanding the molecular mechanisms that govern ovarian angiogenesis is essential for developing new diagnostic and therapeutic approaches in reproductive medicine. Vascular dysfunction and impaired angiogenesis are key contributors to various ovarian disorders and infertility, including polycystic ovary syndrome (PCOS). Therefore, in-depth studies of ovarian vascularization are crucial for identifying the pathophysiology of these conditions and guiding the development of effective treatments. Advancing knowledge in this area holds significant potential for innovation in both medicine and biotechnology. Full article

Background/Objectives: Ventriculoperitoneal shunts are the standard treatment for adults diagnosed with several CSF disorders, but often face dysfunction, leading interest in non-invasive methods for diagnosing shunt issues. This study evaluates the potential of non-invasive intracranial pressure waveform monitoring (nICPw) with the brain4care (B4C) system to distinguish overdrainage, underdrainage, and normal shunt function in patients with CSF disorders. Methods: In this single-center, observational study at Hospital das Clínicas, Brazil, adult patients with CSF shunts were enrolled. Patients were categorized as Overdrainage or Underdrainage, based on clinical parameters, with an Asymptomatic group. The B4C system provided nICPw monitoring, and six parameters (including various P2/P1 ratios) were analyzed via MANOVA and ANOVA. Results: Among 30 patients (6 overdrainage, 6 underdrainage, 18 asymptomatic), five asymptomatic patients were excluded from the main analysis due to incomplete data collection, leaving 25 patients. Overdrainage patients had significantly higher ΔP2/P1 values (0.618 ± 0.210) than asymptomatic ones (0.227 ± 0.171). After excluding outliers, differences were more pronounced (H = 10.89; p < 0.01). Underdrainage patients had intermediate ΔP2/P1 values (0.387 ± 0.179) and consistently higher P2/P1 averages (>1.3). ROC analysis indicated that ΔP2/P1 > 0.3 suggested shunt dysfunction (AUC = 0.731), while the highest P2/P1 offered stronger discrimination (AUC = 0.782). A global average P2/P1 > 1.3 was linked to underdrainage, with the lowest P2/P1 values differentiating overdrainage (0.948 ± 0.321) from underdrainage (1.143 ± 0.156). Conclusions: nICPw monitoring with the B4C system demonstrated potential for detecting shunt dysfunction. Combining parameters, especially ΔP2/P1 and highest P2/P1, improves diagnostic accuracy, offering a non-invasive method that may aid in distinguishing normal from abnormal shunt function. Full article

We experimentally investigate the structural, magnetic, transport, and electronic properties of two d⁵ iridate double perovskite materials La₂BIrO₆ (B = Mg, Zn). Notably, despite similar crystallographic structure, the two compounds show distinctly different magnetic behaviors. The M = Mg compound shows an antiferromagnetic-like linear field-dependent isothermal magnetization below its transition temperature, whereas the M = Zn counterpart displays a clear hysteresis loop followed by a noticeable coercive field, indicative of ferromagnetic components arising from a non-collinear Ir spin arrangement. The local structure studies authenticate perceptible M/Ir antisite disorder in both systems, which complicates the magnetic exchange interaction scenario by introducing Ir-O-Ir superexchange pathways in addition to the nominal Ir-O-B-O-Ir super-superexchange interactions expected for an ideally ordered structure. While spin–orbit coupling (SOC) plays a crucial role in establishing insulating behavior for both these compounds, the rotational and tilting distortions of the IrO₆ (and MO₆) octahedral units further lift the ideal cubic symmetry. Finally, by measuring the Ir-L₃ edge resonant inelastic X-ray scattering (RIXS) spectra for both the compounds, giving evidence of spin–orbit-derived low-energy inter-J-state (intra t_2g) transitions (below ~1 eV), the charge transfer (O 2p → Ir 5d), and the crystal field (Ir t_2g → e_g) excitations, we put forward a qualitative argument for the interplay among effective SOC, non-cubic crystal field, and intersite hopping in these two compounds. Full article

Background: Craniofrontonasal dysplasia (CFND) is an X-linked developmental disorder caused by mutations in the EFNB1 gene located on chromosome Xq13. This gene encodes ephrin-B1, a ligand for Eph receptors, which is involved in cell signaling pathways and the development of the nervous and vascular systems, as well as facial and cranial structures. Paradoxically, the syndrome manifests with greater severity in heterozygous females, whereas hemizygous males typically present with mild or no abnormalities. Methods and Results: We report the case of a late preterm female neonate with dysmorphic features at birth, who subsequently developed necrotizing enterocolitis (NEC) caused by thrombosis of the superior mesenteric artery. Extensive bowel resection led to short bowel syndrome, resulting in cholestatic liver disease, malabsorption, and growth impairment. Array-comparative genomic hybridization (a-CGH) analysis identified a ~791 Kb microduplication at Xq13.1, encompassing the EFNB1 gene, confirming the diagnosis of CFND. She was enrolled in a multidisciplinary follow-up program and, at 2 years of age, presents with marked growth and neurodevelopmental delay. Conclusions: This report describes a rare association between CFND and NEC caused by superior mesenteric artery thrombosis. To the best of our knowledge, no previously reported cases of CFND associated with thrombosis or thrombosis-related conditions, including NEC, have been identified. This is based on a literature review (2004–2025) performed using PubMed and Scopus, and limited to English-language case reports and reviews. Full article

Obesity contributes to the development of metabolic disorders such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) through sustained low-grade inflammation and mitochondrial dysfunction. In obesity, hypertrophied adipose tissue release high levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and elevates circulating free fatty acids. These changes promote systemic insulin resistance and ectopic lipid deposition. Mitochondrial dysfunction, including reduced oxidative phosphorylation, excess reactive oxygen species (ROS) production, and mitochondrial DNA damage, further stimulate inflammatory pathways such as the NLRP3 inflammasome, creating a feedback loop that worsens metabolic stress. Ultimately, this interaction disrupts energy balance, weakens insulin signaling, and accelerates β-cell dysfunction and hepatic steatosis. In both T2DM and MASLD, oxidative stress, defective mitochondrial quality control, and dysregulated immunometabolic responses are consistently observed pathophysiological features. Interventions aimed at reducing inflammation and restoring mitochondrial function—including lifestyle modification, mitochondria-targeted therapies, inflammasome regulation, and enhancement of mitochondrial biogenesis or mitophagy—may retard disease progression. Full article

N-glycanase 1 (NGLY1) is a cytoplasmic glycoenzyme that removes N-linked glycans from misfolded glycoproteins. It plays an important role in the endoplasmic reticulum-associated degradation (ERAD) pathway in mammalian cells. NGLY1 dysfunction in humans causes NGLY1 deficiency as a rare autosomal recessive disorder that is characterized by neurodevelopmental delay, hypotonia, movement disorders, seizures, and multi-system involvement. In this review, we summarize recent advances in understanding the neural functions of NGLY1 and the neuropathological phenotypes associated with its deficiency. We discuss the molecular basis of NGLY1 deficiency in the central nervous system (CNS) and pathophysiological insights from animal and human induced pluripotent stem cell (iPSC)-based models. We also highlight emerging gene therapy approaches aimed at restoring NGLY1 activity and alleviating neurological symptoms. Full article

Background: Trelegy Ellipta is a widely prescribed triple inhaler therapy for chronic obstructive pulmonary disease (COPD). Although its clinical efficacy is well established, evidence on sex-specific differences in adverse event (AE) profiles from real-world pharmacovigilance data remains limited. In addition, some AEs may reflect underlying disease characteristics rather than drug exposure, which complicates interpretation of safety signals. Objective: To explore sex-related differences in AEs associated with Trelegy Ellipta using the FDA Adverse Event Reporting System (FAERS). The study aimed to identify potential safety signals while accounting for alternative explanations, including comorbidity burden and disease-related variation. Methods: We retrospectively analyzed FAERS reports from January 2018 to April 2025, identifying 4555 AEs attributed to Trelegy Ellipta. Events were coded by System Organ Class (SOC) and stratified by patient sex. Frequencies were compared between male (n = 1621) and female (n = 2934) patients using chi-square tests, and associations were expressed as reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results: Male patients more frequently reported hypertension (63.4% vs. 47.0%; p = 0.01), pneumonia (87.8% vs. 76.8%; p < 0.001), anxiety (91.0% vs. 66.9%; p < 0.001), sleep disorders (20.1% vs. 6.8%; p < 0.001), and hyperglycemia (92.7% vs. 52.1%; p < 0.001). Female patients more often reported headache (56.7% vs. 32.6%; p < 0.001), depression (33.1% vs. 9.0%; p < 0.001), and osteoporosis (41.7% vs. 2.4%; p < 0.001). Further variation was observed across neurological, musculoskeletal, and respiratory categories, suggesting a multidimensional pattern of sex differences. Conclusions: This FAERS-based analysis indicates distinct sex-specific safety signals for Trelegy Ellipta, particularly in cardiovascular, neuropsychiatric, and steroid-related domains. These findings are hypothesis-generating and highlight the importance of incorporating sex-disaggregated analyses into future pharmacovigilance and clinical studies. Full article

Both epidemiological and animal model studies have revealed that heat stroke is closely related to the development or exacerbation of dementia disorders. The most common form of dementia is Alzheimer’s disease, which is characterized by the accumulation of amyloid-β protein in the central nervous system. Notably, a whole-genome transcriptome analysis of heat stroke patients has identified the increased expression of amyloid-β precursor protein gene and the activation of amyloid processing pathways. This finding provides a molecular basis for the theory that heat stroke is a risk factor for dementia disorders. Down syndrome—a common chromosomal abnormality—is also a dementia disorder that is characterized by the overexpression of amyloid-β precursor protein gene and the accumulation of amyloid-β protein. Thus, heat stroke may also develop or exacerbate Alzheimer’s disease-like dementia in Down syndrome. For individuals with Down syndrome, heat stroke is therefore not only a life-threatening risk factor but may also be a risk factor for accelerating intellectual decline. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Background/Objectives: Diabetes mellitus is a metabolic disorder, and hyperglycemia results in abnormal brain function. Since glycolysis is the main energy pathway in glial cells, astrocytes possess a more developed glyoxalase (Glo) system than neurons and exhibit better survival. Glycolysis helps to protect glia from (i) dicarbonyl stress and (ii) formation of advanced glycation end products (AGEs). Since aminoguanidine (AG) is an inhibitor of AGE production, the purpose of this study was to determine the role of AG in crucial astrocytic proteins, such as Kir4.1, Glo1, and Glo2, in hyperglycemic conditions. Methods: We cultured astrocytes in normal (5 mM)- and high (25 mM)-glucose conditions. After two weeks, we seeded the cells in six-well plates, with 300,000 cells/well, and then treated them with 9 mM of AG for 24 h. Results: Expression of the glyoxalases Glo1 and Glo2, and of Kir4.1, is decreased in hyperglycemic conditions; however, treatment with AG recovers the expression of the Kir4.1 protein as well as the inward currents of hyperglycemic astrocytes. Conclusion: We demonstrated that regulation of the glyoxalase system via AG or another scavenger of carbonyl and aldehydes containing polyamine groups can contribute to the recovery of astrocyte function in diabetic patients. Full article

Background/Objectives: Sarcoidosis is a granulomatous disorder of unknown etiology that can affect multiple organs, including the oral cavity. This study aimed to compare the clinical and demographic characteristics of sarcoidosis cases with and without bone involvement in the jaw. Methods: A systematic review of the case reports and case series of sarcoidosis in the oral cavity between 1943 to 2024 were analyzed. Variables assessed included age, sex, presenting symptoms, duration of symptoms, diagnosis methodology, treatment approaches, and outcomes. Results: A total of 59 studies reporting 77 patients were included, with a mean age of 43.3 yrs. Female predominance was noted in both, bone-involved (61.5%) and non-bone-involvement cases (72.5%). Patients with bone involvement often presented with localized symptoms such as loose teeth (34.6%), bone loss (69.2%), and nasal obstruction (15.4%), whereas non-bone-involvement cases frequently exhibited soft tissue manifestations, like swelling (38%) and bleeding (14%). Treatment typically involved surgical intervention and steroid therapy in both groups, with favorable outcomes achieved in most cases. Conclusions: This systematic review presents the most extensive analysis of oral sarcoidosis. Oral sarcoidosis presents as two distinct clinical entities based on bone involvement. Soft tissue lesions often serve as an early diagnostic clue for systemic disease, while bony manifestations suggest a later, more destructive complication. Recognizing this dichotomy is crucial for dentists and clinicians to ensure timely diagnosis and appropriate referral, and this underscores the oral cavity’s critical role as an indicator of systemic illness and mandates a multidisciplinary management strategy. Full article

Introduction: Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by complex interactions between environmental factors, immune dysregulation, and potential genetic predispositions. Vitamin D deficiency, known for its immunomodulatory properties, has increasingly been implicated in the pathogenesis of DES; however, the underlying mechanisms remain insufficiently elucidated. Of particular interest is the vitamin D receptor (VDR) gene, whose polymorphisms may influence the bioavailability and biological activity of vitamin D. Objective: The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D₃] levels and selected polymorphisms in the VDR gene (Taq, Fok, Apa, and Bsm) in patients with DES and to analyze their potential clinical and genetic interactions. Methods: This prospective observational study included 60 patients with a confirmed diagnosis of DES. Serum 25(OH)D₃ levels were measured, and genotyping of four VDR single-nucleotide polymorphisms (SNPs) was performed using PCR followed by restriction fragment length polymorphism analysis. Genotype distributions were assessed in relation to vitamin D status using appropriate statistical tests and Hardy–Weinberg equilibrium analysis. Results: Over 85% of patients exhibited insufficient or deficient vitamin D levels. Among the analyzed SNPs, only the ApaI polymorphism (rs7975232) showed a statistically significant association with vitamin D status (p = 0.0384), with the homozygous AA genotype being more prevalent among patients with hypovitaminosis. The remaining polymorphisms (TaqI, FokI, BsmI) did not reach statistical significance; however, potential trends were observed that may warrant further investigation in larger cohorts. Conclusion: The findings suggest a potential role for VDR gene variability in the regulation of systemic vitamin D levels in patients with DES. Identification of specific genotypes may contribute to the development of personalized diagnostic and therapeutic strategies, particularly for patients with treatment-resistant forms of the disease. These results support the integration of genetic biomarkers and nutritional parameters into modern ophthalmologic practice. Full article