Search Results (1,337)

Background and clinical significance: Autoimmune encephalitis (AE) is an inflammatory brain disorder that manifests through a diverse, unspecific range of neuropsychiatric symptoms. When AE occurs alongside a primary neurodegenerative disorder, the shared symptoms can create a mixed clinical profile, making diagnosis more difficult and potentially postponing effective management and treatment. Case presentation: We describe the case of a 58-year-old female with a one-year history of progressive behavioral and personality changes who presented a subacute confusional state, psychomotor retardation alternating with psychomotor agitation, apathy, visual hallucinations, and motor symptoms. Examination revealed Parkinsonian symptoms and frontal lobe signs. Neuroimaging showed frontotemporal atrophy, while cerebrospinal fluid analysis excluded infection but demonstrated elevated phosphorylated tau, supporting an underlying neurodegenerative process. An electroencephalogram revealed asymmetric temporal slowing without overt epileptiform activity. An initial diagnosis of behavioral variant frontotemporal dementia (bvFTD) was established. Due to rapid clinical deterioration and fluctuating cognition, autoimmune testing was expanded to a full antibody panel, which identified elevated serum anti-glutamic acid decarboxylase 65 (anti-GAD65) antibodies (60 UI/mL, reference range 0–5 UI/mL), establishing a possible coexisting diagnosis of anti-GAD65 autoimmune encephalitis. Initial treatment with intravenous immunoglobulin produced minimal improvement; however, therapeutic plasma exchange led to the remission of psychosis and significant improvement in rigidity, bradykinesia, and attention, with modest amelioration in global cognition. Conclusions: This case highlights the diagnostic challenges posed by overlapping AE and bvFTD clinical pictures, especially when neurodegenerative features obscure an underlying autoimmune process. Early, panel-based neural antibody testing—and consideration of AE even in patients already diagnosed with a major neurocognitive disorder—is critical for avoiding delays in immunotherapy. Prompt recognition and treatment of AE may substantially improve clinical outcomes, even in complex cases with suspected overlap. Full article

Leakage flow interferes with the main flow movement and has a close relationship with the rotational stall phenomenon. To study the rotational stall characteristics of mixed-flow pumps under different tip clearances (rim clearances), numerical simulations of the internal flow field of the mixed-flow pump were carried out based on the SST k-ω turbulence model and hexahedral structured meshes, with the tip clearances set to 0.2 mm, 0.5 mm, and 0.8 mm respectively. The external characteristics, internal flow field under stall conditions, impeller surface pressure, and internal vorticity distribution of the mixed-flow pump were compared among the three different tip clearances. The research results show that when the tip clearance is 0.5 mm, the numerical simulation results are in good agreement with the experimental results, indicating the high reliability of the simulation. Under the three different tip clearances, the near-stall and deep-stall operating points on the external characteristic curves are consistent. When the tip clearance is 0.8 mm, the positive slope characteristic of the flow rate–head curve of the mixed-flow pump is the most obvious. From the small flow rate condition to the large flow rate condition, the influence of the tip clearance on the efficiency of the mixed-flow pump gradually increases. Under deep-stall conditions, with increasing tip clearance, the stall vortex at the flow passage outlet causes more intense disturbances to the inlet of the downstream flow passage and induces the formation of new stall vortices at the downstream passage inlet, thereby increasing internal flow losses. The increase in the tip clearance leads to changes in the morphology of the leakage vortex, a decrease in the impeller surface pressure, intensification of flow disorder, and enhancement of the leakage vortex intensity. Moreover, compared with the rated condition, the leakage vortex of the mixed-flow pump under stall conditions is more affected by the tip clearance. Full article

Background: Multi-center resting-state functional magnetic resonance imaging (rs-fMRI) is important for neurodevelopmental disorder diagnosis, but cross-site differences in repetition time (TR) can cause temporal feature misalignment. In addition, blood-oxygen-level-dependent (BOLD) signals are non-stationary, so disease-related information may be distributed across multiple time scales. Existing methods usually do not explicitly model physical sampling intervals or coordinate temporal and spectral information across scales, which may limit cross-site generalization in heterogeneous multi-center settings. Methods: We propose Spec-RWKV, a spectrum-guided linear recurrent framework for multi-site rs-fMRI diagnosis. It includes three components: PrismTimeMix, which models temporal dynamics using decay rates derived from physical half-lives and converts them adaptively across TRs; a TR-adaptive continuous wavelet transform, which aligns spectral representations across sites by adjusting frequency coverage; and spectrum-guided adaptive temporal aggregation, which uses spectral context to weight temporal features. Results: On ABIDE-I and ADHD-200, Spec-RWKV achieved AUCs of 75.86% and 76.31%, respectively. Under leave-one-site-out validation, it achieved the best mean AUC on ABIDE-I and the best mean accuracy and AUC on ADHD-200. Conclusions: Spec-RWKV explicitly models sampling-rate differences and multi-scale spectral structure, with results supporting strong cross-site generalizability. Full article

Empowered by nanotechnology, messenger RNA (mRNA) therapeutics have shown a rapid evolution post COVID-19 from a conceptual platform to a clinically validated modality, and they diversified into oncology, cardiovascular diseases, and rare disorders. As a template for in situ protein production, it offers several advantages over traditional proteins and DNA drugs. The intrinsic stability of mRNA and its sensitivity to innate immune sensing hinder its capacity for immediate cellular entry, necessitating its need for a delivery system to obtain optimal therapeutic potential. This review explores the innovations in nanocarrier engineering, design principles for lipid nanoparticles-mRNA (LNPs) platforms, and their clinical translation across the prominent indications. It also addresses their safety, immunogenicity, and scalability while addressing the key limitations and manufacturing scalability through comparative platform analysis. Although LNPs usually dominate their delivery through encapsulation and manufacturability, their limitations, like repeat dose reactogenicity and liver tropism, require next-generation designs like SORT lipids, stimuli-responsive hybrids for extrahepatic targeting. In oncology, LNP-mRNA drives the neoantigen vaccines, and rare diseases leverage the transient enzyme replacement. While the safety profiles highlight the innate immune tuning through nucleoside mods and lipid biodegradability, chronic administration risks are still persistent. While there are novel scalability options like microfluidic mixing to support the production gaps in organ selectivity and durability, their adoption is hindered. We outline the future directions to perceive mRNA’s full potential as a broader therapeutic class. Full article

Environmental chemicals are rarely considered stressors in the way that psychological or physical stressors are. Yet many endocrine-disrupting chemicals (EDCs) interact with the body’s core stress response system. This review examines how EDCs alter hypothalamic–pituitary–adrenal (HPA) regulation and how biological sex influences those responses. Drawing on human epidemiological data and experimental models, we describe how EDC exposure affects cortisol dynamics, feedback sensitivity, and adrenal signaling, with a particular focus on sex-dependent outcomes. We propose the concept of endocrine noise to describe how low-dose, often mixed EDC exposures introduce persistent interference into hormone signaling without necessarily causing overt endocrine deficiency or excess. In this framework, EDCs act as chronic, low-grade stressors that reset the timing, feedback precision, and rhythmic organization of the HPA axis rather than as isolated reproductive toxicants. We argue that EDCs should be understood as chronic, context-dependent stress modifiers that reshape sex-specific “risk architectures” for affective, metabolic, and immune disorders. Recognizing sex-specific HPA architecture and endocrine noise has immediate implications for study design and regulation, including the need for sex-stratified analyses, circadian-sensitive sampling of cortisol, and risk assessments that consider how the same exposure can push female and male stress systems in divergent directions. Full article

Milk production in dairy herds is determined by both intrinsic and extrinsic factors, with reproductive efficiency serving as a primary determinant. Infectious, nutritional, and management-related challenges can reduce this efficiency. Following parturition, cows are more susceptible to clinical disorders due to a temporary loss of integrity in the cervix, vagina, and vulva, which allows environmental bacteria to ascend and alter the vaginal microbiota. These microbial changes may disrupt endocrine responses related to conception and contribute to repeat breeder cow syndrome (RBCS), which is defined as failure to conceive after three or more inseminations. This study investigated associations among cultivable vaginal bacteria, circulating progesterone and glucose concentrations, and reproductive performance in 30 fourth-parity Holstein cows with a body condition score of 3.5. Cows were classified by reproductive history as repeat breeders (RBCS; n = 14) or controls (CTL; n = 16). Vaginal mucosal samples were collected at insemination and cultured on blood agar and MacConkey media under aerobic and microaerobic conditions. Bacterial identification was conducted using Gram staining and standard biochemical assays. Blood samples were collected at insemination, on day 5 post-insemination, and every two days thereafter to measure progesterone and glucose concentrations. Fertility outcomes were analyzed using PROC GLIMMIX, and hormonal data were analyzed using mixed models with repeated measures. The bacterial genera identified included Bacillus, Escherichia coli, Staphylococcus, Klebsiella, Proteus, Streptococcus, and Actinomyces. Progesterone and glucose concentrations did not differ significantly between groups (p > 0.05). However, the fertility rate (p < 0.05; CTL:87.50% vs. RBCS:57.14%) and number of attempts to conceive (p < 0.001; CTL:2.5 vs. RBCS:6.7) differed statistically between treatments. A higher prevalence of S. hyicus was detected in RBCS cows, and E. coli, S. hyicus, and Proteus spp. were more frequently detected in non-pregnant cows. These findings suggest that the identified cultivable vaginal bacteria are associated with reproductive status in dairy cows. Full article

Background: Parents of children with attention-deficit/hyperactivity disorder (ADHD) and sleep problems can experience challenges and negative health effects. The aim of this study was to explore parents’ own health-related experiences as their child with ADHD and sleep problems underwent a sleep intervention with a weighted blanket. Methods: A convergent mixed methods design was undertaken. Sociodemographic and questionnaire data were collected from 68 parents at baseline and at the 16-week follow-up. Paired-samples t-tests were used to analyze the data. An inductive qualitative content analysis was used to analyze interviews with 21 parents after the follow-up. An integrative analysis was performed and assessed for confirmation, expansion, or disconfirmation. Results: At the follow-up, parents reported improvements in their own health status (EQ-5D-3L—index 0.83 ± 0.15 vs. 0.87 ± 0.13; p = 0.034), in well-being (Outcome Rating Scale—individual 7.08 ± 2.22 vs. 7.55 ± 1.82; p = 0.045), and in family life (the Brief Child and Family Phone Interview—family comfort score 5.62 ± 1.62 vs. 5.14 ± 1.66; p = 0.003). Parents’ health-related experiences were described as: (1) having a sense of well-being, including being well rested, sustaining energy, reaching a state of calm, and finding hope, (2) balancing family life, including reclaiming personal sphere and nurturing relationships, and (3) managing everyday life, including keeping to the daily schedule and dealing with household chores. The integrative analysis resulted in the overarching themes of health through: (1) inner strength (confirmed), (2) recovery (expanded), (3) close relationships (confirmed), and (4) social engagements (expanded). Conclusions: The findings suggest that sleep interventions for children with ADHD and sleep problems may also be associated with positive changes in aspects of parents’ health, well-being, and family life. Full article

Central auditory processing efficiency is considered a predictor of how well children can learn to read, with the Frequency Following Response (FFR) serving as a sensitive biomarker of neural speech encoding ability. However, data regarding the 170 ms [da] stimulus in children who are native speakers of Brazilian Portuguese (BP) remain limited. This study investigated FFR results in 37 typically developing, normal-hearing children aged 8 to 10 years. Participants underwent audiological, behavioral, and academic performance screenings, followed by monaural FFR recording (using a 170 ms [da] stimulus at 80 dBnHL). Linear mixed models (LMM) were used to examine the effects of age, sex, and ear on the latencies of waves V, A, D, E, F, and O. The analysis revealed a medium effect size for waves D, E, and F, regarding the Ear factor, though statistical significance was specifically observed for wave E. For this wave, sex was also associated with a medium effect size, characterized by longer latencies in female participants. While the results for age did not reach broad statistical significance, the presence of medium effect sizes in wave E may suggest ongoing refinement of neural synchrony and asymmetric maturation during this developmental period. This study contributes to the characterization of neural speech encoding in the Brazilian Portuguese-speaking children and may support future investigation involving auditory processing disorders and learning difficulties. Full article

Background/Objectives: Hypertensive disorders of pregnancy (HDPs) affect approximately one in seven hospital deliveries in the United States and increase the risk of pregnancy-associated mortality. Home blood pressure monitoring (HBPM) for patients with HDPs has emerged as a model of care poised to improve ascertainment of blood pressure and triage of care during pregnancy and postpartum periods. However, the strength of evidence supporting HBPM approaches has been variable. This rapid review aimed to understand how HBPM approaches for pregnant and postpartum populations with HDPs have been evaluated in order to strengthen future research. Methods: Search criteria included peer-reviewed literature in English and French published during 2018–2024 that assessed HBPM approaches for pregnant and postpartum populations in high-income countries. A total of 370 records were screened and reviewed to identify 52 eligible articles. Key study characteristics, methodologies, and outcome measures were extracted. Identified outcome measures were mapped by outcome type (implementation, health service, and client) to assess gaps in evaluation of HBPM approaches. Results: A range of study designs were employed to evaluate HBPM approaches: experimental (17%), observational (52%), qualitative (10%), mixed method (10%), and economic (11%) designs. Over a third employed a comparison group, most of which compared HBPM approaches to usual antepartum or postpartum care. Only 11 studies reported on impact outcomes (long-term blood pressure control, adverse maternal and perinatal outcomes). Significant gaps were identified among the implementation outcomes examined. While patient engagement measures were common, assessment of provider adherence and engagement was limited. Hospital admissions and emergency department visits were often employed as proxies to measure HBPM effectiveness, efficiency, and safety. However, no studies adequately reported effectiveness measures for remote patient triage. Conclusions: Our results call for improved HBPM metrics to ensure patients are receiving high-quality care responsive to their clinical condition. Future studies on HBPM approaches should prioritize more transparent reporting on health actor engagement. A composite measure including both patient and provider adherence to monitoring and triage processes will provide stronger evidence on the effectiveness of HBPM for pregnant and postpartum patients and share impactful learning for health systems interested in adopting HBPM approaches. Full article

Neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Lewy Body Disease (LBD), and related dementias, represent a global health challenge, particularly in aging populations. The simultaneous occurrence of neurodegenerative diseases in an aging population suggests a potential link between causative proteins. Such neurodegenerative proteins, including amyloid-β (Aβ), τ-protein (tau), α-synuclein, TAR DNA-binding protein 43 (TDP-43), and Fused in Sarcoma (FUS), share key characteristics of intrinsically disordered proteins (IDPs), which can explain promiscuous physical interactions, cross-seeding, co-occurrence, pathological synergy, and shared upstream and downstream mechanisms. This review synthesizes current evidence on (1) shared biophysical features of neurodegeneration-associated proteins, (2) mechanisms driving mixed neuropathology, (3) therapeutic implications of disorder-driven interactions, and (4) key unresolved questions shaping future research. By framing neurodegeneration as a network of interacting, disorder-driven proteinopathies rather than isolated entities, this perspective highlights the need for integrative, systems-level approaches to better understand disease heterogeneity and to identify novel targets for intervention. Full article

Background: Rome IV criteria promote a symptom-based (“positive”) diagnosis of pediatric disorders of gut–brain interaction (DGBIs). In clinical practice, however, organic gastrointestinal diseases may mimic DGBIs and lead to diagnostic revision after further evaluation. We aimed to quantify the diagnostic stability of an initial Rome IV-oriented functional diagnosis in a tertiary pediatric outpatient setting and to identify symptom phenotypes associated with a higher likelihood of later organic reclassification. Methods: We performed a single-center retrospective cohort study (2014–14 May 2021) based on outpatient chart review. Eligible patients were children and adolescents aged 0–18 years with an initial Rome IV-oriented functional diagnosis. Diagnostic reassessment was based on follow-up data, available laboratory and instrumental investigations, and/or response to exclusion therapies. Final diagnoses after reassessment were categorized as functional only, organic, or mixed. Groups were compared using Pearson’s chi-square test. Results: The cohort included 220 males (50.0%) and 220 females (50.0%), with a mean age of 8.86 ± 4.65 years. After reassessment, 343/440 (77.95%) remained functional, 73/440 (16.59%) were reclassified as organic, and 24/440 (5.45%) were classified as mixed. Final diagnosis differed by GI tract involvement (p = 0.001) and by symptom cluster (p = 0.001). Upper GI/dyspepsia-spectrum presentations showed the highest organic yield (27.03%), followed by lower abdominal pain/IBS-spectrum presentations (19.61%). Diarrhea and vomiting/cyclic vomiting each showed 16.67% organic diagnoses (mixed: 10.0% and 7.14%, respectively), whereas constipation showed the greatest diagnostic stability (98.89% functional; 1.11% organic). Functional confirmation rates were similar before and during the pandemic (77.71% vs. 78.70%; p = 0.756). Monthly case volume was higher in 2020–2021 (6.29 vs. 4.61 cases/month). Conclusions: In this tertiary cohort, about one in six children initially diagnosed with a functional disorder were later found to have an organic disease, and an additional 5% had mixed organic–functional presentations. Diagnostic revision was associated with presenting phenotype, with the highest organic yield observed in dyspepsia/upper GI presentations and the lowest in constipation. These findings support symptom-stratified evaluation and follow-up alongside Rome IV criteria. Full article

Lamellar ichthyosis is a rare congenital disorder of keratinization frequently associated with ocular complications, most commonly cicatricial ectropion and exposure keratopathy. We present a case of severe mixed exposure-related and neurotrophic keratopathy with marked corneal thinning in a 61-year-old man with genetically confirmed lamellar ichthyosis. At presentation, the best-corrected visual acuity (BCVA) in the right eye was limited to hand motion (logMAR 2.3). Slit-lamp examination revealed a large central to inferocentral corneal ulcer measuring approximately 3 × 4 mm with severe stromal thinning in the setting of marked lower eyelid ectropion, incomplete eyelid closure, and chronic ocular surface exposure, while anterior segment optical coherence tomography (AS-OCT) demonstrated a minimal corneal thickness of approximately 165 µm. Microbiological swabs obtained from the conjunctival sac were negative, and no purulent discharge, hypopyon, or anterior chamber inflammatory reaction was present, making active infectious keratitis unlikely. Corneal sensitivity measured with Cochet–Bonnet esthesiometry at presentation, centrally and in all four peripheral quadrants of both eyes, was markedly reduced, more severely in the affected right eye, supporting the presence of a severe neurotrophic component contributing to impaired corneal healing. Intensive conservative therapy including preservative-free lubricants, dexpanthenol gel, autologous serum eye drops, topical insulin, prophylactic antibiotics, and systemic doxycycline was initiated. Serial AS-OCT imaging demonstrated progressive structural recovery, with corneal thickness increasing to 438 µm after one month of treatment and complete corneal epithelialization. The BCVA improved to 0.2 Snellen (0.7 logMAR). This case highlights the diagnostic value of multimodal anterior segment imaging in monitoring severe mixed keratopathy with advanced corneal thinning and demonstrates that intensive conservative therapy may stabilize the ocular surface and prevent corneal perforation in patients with lamellar ichthyosis. Full article

Background/Objectives: Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder characterized by persistent intraoral burning in the absence of detectable mucosal alterations. Diagnosis is challenging due to the lack of specific biomarkers and the need to exclude numerous systemic and local conditions that can mimic oral burning. This literature review aims to summarize current and emerging therapeutic strategies for BMS. Methods: A structured and filtered search of PubMed, Scopus, and Web of Science identified studies evaluating pharmacological, phytotherapeutic, and non-pharmacological interventions. Results: Various antidepressants, anticonvulsants, benzodiazepines, H2 receptor antagonists, and low-dose naltrexone have demonstrated varying degrees of symptom reduction, while alpha lipoic acid (ALA) and phytomedicines such as capsaicin, Hypericum perforatum, Catuama, lycopene, crocin, and melatonin show mixed clinical benefits. Non-pharmacological approaches, including photobiomodulation (PBM), oral cryotherapy, neuromodulation techniques, and cognitive behavioral therapy, also provide meaningful symptom improvement in many patients. Conclusions: Across all modalities, therapeutic responses remain heterogeneous and generally incomplete, underscoring the absence of a universally effective treatment. Current evidence supports an individualized and multidisciplinary approach that integrates pharmacological, psychological, and adjunctive therapies to address the multifactorial nature of BMS. Full article

Impulsivity is a core transdiagnostic construct in adolescent psychiatry, associated with emotional dysregulation, behavioral disorders, and increased vulnerability to mental health problems. Adolescents engaged in performing arts education may experience heightened psychosocial stressors that challenge self-regulatory capacities during a critical neurodevelopmental period. Methods: This mixed-methods study examined psychosocial and family-related factors associated with impulsivity in adolescent students enrolled in drama programs. Two focus groups with 28 upper-grade students (grades 11–12) explored subjective experiences of stress, emotional overload, and family communication. Based on these findings, a 77-item questionnaire was developed and administered to 90 ninth-grade students. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS). Results: An exploratory stepwise multiple linear regression analysis identified perceived school-related stress (β = 0.370, p < 0.001), conflictual parental communication (β = 0.273, p = 0.013), and discomfort during school discussions at home (β = 0.331, p < 0.001) as significant predictors of higher impulsivity scores. Conclusions: The findings highlight the interaction between neurodevelopmental vulnerability and environmental stressors in shaping impulsivity during adolescence. These results are clinically relevant for child and adolescent psychiatry, emphasizing the importance of early psychosocial interventions targeting stress regulation and family communication to prevent the escalation of impulsivity-related psychopathology. Full article

Long-chain polyunsaturated fatty acids (LC-PUFAs) of omega-3 family, particularly docosahexaenoic acid and eicosapentaenoic acid, are essential nutrients that play a critical role in children’s growth and health. This review examines the evidence on the effects of omega-3 supplements and omega-3-enhanced foods on children’s development, as well as on neurological and metabolic disorders. Research consistently highlights the importance of DHA in brain and visual development, especially during early childhood, when rapid neural growth occurs. PubMed, Web of Science, Scopus and the Cochrane Library databases were searched for relevant articles published up to January 2026. Adequate omega-3 intake has been associated with improvements in cognitive performance, attention, and learning outcomes. In children with neurodevelopmental conditions such as attention-deficit/hyperactivity disorder and autism spectrum disorder, omega-3 supplementation shows modest but potential benefits in reducing behavioral symptoms and supporting executive function, although results remain mixed. Additionally, omega-3 fatty acids exhibit anti-inflammatory properties that may positively influence metabolic health, including lipid profiles, insulin sensitivity, and obesity-related risk factors in children. Omega-3-enhanced foods provide an alternative to supplements and may improve adherence and overall dietary quality. However, variability in dosage, study design, and baseline nutritional status limits definitive conclusions. Overall, omega-3 fatty acids appear to support healthy development and may aid in managing certain neurological and metabolic disorders in children. Full article