Background Extrapyramidal disorders, including Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy, are commonly associated with balance disabilities and an increased risk of falls. Therefore, continuous balance training is important for maintaining quality of life. Recently, rehabilitation using virtual reality (VR) has been introduced; however, most studies have focused on non-immersive VR. In addition, there have been no reports of immersive VR (IVR) training being applied to patients with extrapyramidal disorders. Therefore, we developed a safe, task-oriented standing balance training protocol using IVR combined with a body weight support (BWS) system. The purpose of this study was to evaluate the safety, feasibility, and potential efficacy of IVR training using a BWS system for standing balance and walking speed in patients with extrapyramidal disorders. Methods This pilot case series study (a before-after trial) enrolled seven patients with extrapyramidal disorders. All participants were admitted to our rehabilitation ward to receive long-term inpatient rehabilitation. After admission, physical assessments were performed, and participants then underwent 20 minutes of IVR training for standing balance and walking speed combined with conventional physical therapy. This combined protocol was continued for 10 consecutive days (a total of 10 sessions). IVR training was designed to facilitate center-of-gravity shifts and stepping movements in a standing position by requiring participants to reach and touch virtual targets. Visual and auditory feedback were provided, and performance was quantified as a VR score based on the duration of successful target contact. Task difficulty was adjusted according to each participant's ability. A BWS system was used to ensure safety during training. Berg Balance Scale (BBS), Functional Reaching Test (FRT), and maximum walking speed during the 10-m walking test were assessed as primary outcomes before the first IVR training session and after completing all sessions. Significant differences in the outcomes were determined using the paired Student's t-test, with a significance level of <0.05. The effect size (ES) was calculated using Cohen's d. Results Among the study participants, five participants completed the 10-day protocol of IVR training, although two participants were discharged before training completion for non-study-related reasons. The total score of the Simulator Sickness Questionnaire was 5.9 ± 5.2, and no serious adverse events were observed during IVR training. No cases of falls were reported. VAS scores for satisfaction, enjoyment, and immersion were high (75.9 ± 19.6, 83.4 ± 17.0, and 81.3 ± 20.4, respectively). The 10-day IVR training promoted significant improvements in the BBS and FRT (p < 0.01). Although no significant improvement was found in maximum walking speed (p = 0.058), a moderate ES was observed (d = 0.69). Conclusions Our proposed IVR training using a BWS system could safely and feasibly improve standing balance and may contribute to improvements in walking speed among patients with extrapyramidal disorders. Further studies with larger sample sizes are needed to confirm the efficacy of this training.
"It Would have been Better if I had Never been Born" - Suicidality in Early Childhood Depressive Disorders and its Association with Externalizing Symptoms Empirical evidence on suicidality in early childhood (< 9 years) and on the role of comorbid externalizing symptoms in depressive disorders remains limited. We aimed to examine how externalizing symptoms, as assessed by multiple informants, are associated with suicidality in young children with depression. In a clinical help-seeking sample of 61 children (3-8 years) with depressive disorders, suicidality was assessed using a clinical interview (Preschool Age Psychiatric Assessment, PAPA) with the primary caregiver. Externalizing symptoms were assessed via child report (Berkeley Puppet Interview), parent report (Child Behavior Checklist 4-18), and (kindergarten) teacher report (Teacher Report Form 5-18). Criteria for suicidality (PAPA) were met by 39.3 % of the children. Suicidal ideation was reported for 21.3 %, suicide attempts for 3.3 %, and no child exhibited a suicide plan. In multiple regression analyses controlling for sociodemographic variables and child and parental depressive symptoms, higher levels of externalizing symptoms reported by the child and the mother were significantly associated with suicidality. The findings indicate that suicidality is a frequent phenomenon in early childhood depression and is associated with comorbid externalizing symptoms. To clarify the meaning of suicidal statements in early childhood, an individual case-based approach is required, as illustrated by a case study. Zusammenfassung Empirische Erkenntnisse zu Suizidalitat im fruhen Kindesalter (unter 9 Jahren) sowie zur Rolle komorbider externalisierender Symptome bei depressiven Storungen sind bislang begrenzt. Ziel dieser Studie war es zu untersuchen, inwieweit externalisierende Symptome - eingeschatzt durch mehrere Informanten - mit Suizidalitat bei fruhkindlichen depressiven Storungen assoziiert sind. Untersucht wurde eine klinische Inanspruchnahmepopulation von 61 Kindern im Alter von 3 bis 8 Jahren mit depressiven Storungen. Suizidalitat wurde mittels klinischen Interviews (Preschool Age Psychiatric Assessment, PAPA) basierend auf dem Bericht der Hauptbezugsperson erfasst. Externalisierende Symptome wurden anhand von Berichten durch Kinder (Berkeley Puppet Interview), Mutter und Vater (Child Behavior Checklist 4-18) und Lehrer-/Erzieher:innen (Teacher Report Form 5-18) erhoben. Die Kriterien fur Suizidalitat (PAPA) erfullten 39,3 % der Kinder. Suizidale Gedanken wurden bei 21,3 % berichtet, Suizidversuche bei 3,3 %; kein Kind wies einen Suizidplan auf. In multiplen Regressionsanalysen unter Kontrolle soziodemografischer Variablen sowie kindlicher und elterlicher depressiver Symptome waren hohere externalisierende Symptome laut Kind- und Mutterbericht signifikant mit Suizidalitat assoziiert. Die Befunde zeigen, dass Suizidalitat bei Depressionen im fruhen Kindesalter haufig vorkommt und mit komorbiden externalisierenden Symptomen verbunden ist. Zur Klarung der Bedeutung suizidaler Auserungen in der fruhen Kindheit ist eine einzelfallbezogene Betrachtung erforderlich, wie ein Fallbeispiel illustriert.
Digital Psychotherapy for Depression in Children and Adolescents: Evidence-Based Efficacy, Conditions and Recommendations for Clinical Practice Depressive disorders in childhood and adolescence are among the most common mental disorders, often follow a recurrent course, and are associated with substantial individual, social, and economic consequences. Against the background of limited treatment success and multiple barriers to help-seeking, digital psychotherapeutic interventions are increasingly being discussed as a potentially low-threshold and scalable addition to routine care. Based on 13 meta-analyses, this article provides a narrative overview of the effectiveness of digital interventions for depressive symptoms and disorders in children and adolescents and situates these findings within relevant ethical, legal, and clinical practice frameworks. Overall, the evidence suggests predominantly small to moderate effects, particularly for cognitive behavioral therapy-based and guided self-management interventions. However, the interpretability of these findings is limited by the heterogeneity of interventions, predominantly subclinical samples, methodological shortcomings, and the limited evidence on adverse effects. For AIbased and especially large language model (LLM)-based applications, the evidence remains very limited, while ethical and legal requirements are particularly demanding. In Germany, no reimbursable digital health applications are currently available for minors with depressive disorders. Digital interventions may meaningfully complement care, but their use requires careful evaluation of effectiveness, safety, data protection, and clinical suitability. Zusammenfassung Depressive Störungen im Kindes- und Jugendalter zählen zu den häufigsten psychischen Erkrankungen, verlaufen häufig rezidivierend und sind mit erheblichen individuellen, sozialen und ökonomischen Folgen verbunden. Vor dem Hintergrund begrenzter Behandlungserfolge und vielfältiger Barrieren der Inanspruchnahme gewinnen digitale psychotherapeutische Anwendungen als potenziell niedrigschwellige und skalierbare Ergänzung der Versorgung an Bedeutung. Der vorliegende Beitrag gibt anhand von 13 Metaanalysen einen narrativen Überblick über die Wirksamkeit digitaler Anwendungen bei depressiven Symptomen und Störungen im Kindes- und Jugendalter und ordnet diese im Hinblick auf ethische, rechtliche und klinisch-praktische Rahmenbedingungen ein. Insgesamt zeigen sich überwiegend kleine bis mittlere Effekte, insbesondere für kognitiv-verhaltenstherapeutisch fundierte und begleitete Selbstmanagementinterventionen. Die Aussagekraft der Befunde wird jedoch durch die Heterogenität der Interventionen, überwiegend subklinische Stichproben, methodische Limitationen sowie die geringe Datenlage zu unerwünschten Wirkungen eingeschränkt. Für KI- und insbesondere Large Language Model (LLM)-basierte Anwendungen ist die Evidenz bislang sehr begrenzt, während zugleich erhöhte ethische und rechtliche Anforderungen bestehen. In Deutschland stehen derzeit keine erstattungsfähigen digitalen Gesundheitsanwendungen (DiGA) für Minderjährige mit depressiven Störungen zur Verfügung. Digitale Anwendungen können die Versorgung sinnvoll ergänzen, ihr Einsatz erfordert jedoch eine sorgfältige Prüfung von Wirksamkeit, Sicherheit, Datenschutz und klinischer Eignung.
Methods to improve sleep classification of wearable data often emphasize model choice. However, without widely used benchmark datasets, it is difficult to determine factors driving performance gains (model architecture, dataset selection, or evaluation decisions). This study examines how dataset characteristics influence sleep classification performance beyond model choice. We collected SleepAccel-Clinical, a dataset of Apple Watch acceleration and polysomnography from 28 individuals with sleep apnea. Neural network models were trained on this dataset alongside SleepAccel (31 healthy individuals) and DREAMT (100 individuals with suspected sleep disorders) to evaluate how training and testing set choices impact performance. All models were compared against an Easy To Classify (ETC) wake model, which estimates wake probability by smoothing and scaling activity in a brief time window. The ETC model's average area under the receiver operating characteristic curve (AUROC) on each dataset was used to quantify intrinsic ease of classification. The ETC model accounted for substantial amount of the models' performance across the architectures, datasets, and training conditions, with significant correlations (p≪ .01) between ETC performance and all other scenarios. Including individuals with obstructive sleep apnea (OSA) in the training data improved performance when testing on datasets in which sleep disorders were suspected. Sleep classification performance depends heavily on training and testing dataset characteristics, not solely on model choice. The presence of ETC wake epochs can markedly inflate performance metrics. Researchers should benchmark models on widely available datasets and quantify intrinsic class separability when introducing new datasets. This article is part of the Consumer Sleep Technology Special Collection.
Breast milk insufficiency is a significant public health concern, as it directly affects infant nutrition and immunity. Inadequate milk production remains a major barrier to effective breastfeeding, and it is reported in approximately 60 -90% of mothers in low- and middle-income countries. Emotional stress, anxiety, lack of sleep, and maternal illness are various psychological and physiological factors that influence breast milk production. Galactagogues are used to induce, maintain, and increase breast milk production. Commonly used galactagogues include domperidone, metoclopramide, chlorpromazine, and sulpiride. These medications are associated with side effects such as xerostomia, gastrointestinal disorders, cardiac arrhythmia, lethargy, sedation, and hypertension. In Ayurvedic classical texts, several drugs possessing sthanya janana properties are described. Bhavaprakasha Nighantu and Priya Nighantu mention Śālūkaṃ as sthanya pradam. In an article titled "Report on folklore medicinal plants used for female healthcare in Assam", a tablet prepared from the rhizome of Nelumbium speciosum Willd. is reported to be used to increase lactation and to manage painful menstruation. Twenty- four female Wistar albino rats were divided into four groups, with six rats in each group. Two trial drug groups received śālūkaṃ chūrṇa (finely powdered dried plant material) at single and double doses, while the control group received standard feed, and the standard group received domperidone from the 5th to the 14th day of lactation. All treatments were administered orally in distilled water using an oral gavage needle at 1:30 PM daily. The chūrṇa of śālūkaṃ is administered by mixing 1.08g/kg of in 10ml distilled water in Single dose group, 2.16g/kg in 20ml distilled water and 1g/kg of Domperidone in 10ml distilled water in standard group. Milk yield was estimated by separating the mothers from the pups for four hours, followed by 60 minutes of suckling, with pre- and post-suckling body weights measured using an electronic balance. The results suggest that the trial drug double-dose group demonstrated better galactagogue activity than the standard drug domperidone group in parameters serum prolactin and cortisol levels and trial drug single dose group demonstrated better galactagogue activity than the standard drug domperidone group in parameters serum prolactin and milk yield of 10 days. The findings suggests that the double dose group demonstrates stronger galactagogue potential.
Premature ejaculation (PE) is one of the most common male sexual disorders and is influenced by both psychological and biological factors. Despite available treatments, including psychosexual therapy and pharmacological interventions, no definitive cure exists. In addition, various interventional approaches have been investigated for lifelong PE, such as glandular filler injections, partial dorsal nerve neurectomy, and frenulectomy. This pilot study evaluated the effect of glandular frenulectomy in 25 married men with lifelong PE who had not responded to conventional treatments for at least six months. Participants underwent glandular frenulectomy and were assessed before surgery and three months postoperatively using Intravaginal Ejaculatory Latency Time (IELT) and the Arabic Index of Premature Ejaculation (AIPE) scores. No statistically significant improvement was observed in IELT or AIPE scores after surgery. The mean IELT and AIPE scores before and three months postoperatively yielded P-values of 0.058 and 0.090, respectively. In this pilot study, glandular frenulectomy did not result in significant short-term improvement in men with lifelong PE unresponsive to conventional therapy. Larger studies with longer follow-up are needed to further evaluate its therapeutic role.
We present SNIPSNP (crisprtools.org/snipsnp), a comprehensive bioinformatics pipeline for designing experiments for CRISPR-induced homology-directed repair (HDR). The tool addresses the critical challenge of Cas9 re-cleavage by simplifying the selection of "blocking" silent variants that are effective at inhibiting RNP binding upon donor-templated editing. SNIPSNP handles complex edits, including indels, and uses multi-objective optimization to balance editing efficiency with biological safety. From user-defined wild-type and desired HDR alleles, the pipeline identifies candidate guides, annotating them with integrated efficiency scores and genome-wide off-target assessments. Uniquely, SNIPSNP evaluates guide binding against the post-edit genome to determine whether the therapeutic variant alone disrupts repeated Cas9 recognition. When necessary, it introduces synonymous blocking variants, prioritizing PAM and seed regions to minimize re-cleavage probability and editing of the wild-type (WT) allele when editing heterozygous variants. All candidate modifications undergo safety profiling and prioritization of known benign variants from dbSNP. We experimentally validated SNIPSNP and benchmarked it on pathogenic inborn error of immunity variants in primary patient T-cells. Across loci, SNIPSNP-designed templates outperform standard "correction-only" strategies, demonstrating enhanced precision editing, and reduced re-cleavage, establishing SNIPSNP as a robust platform for genome editing and disease modeling.
Alzheimer's disease (AD) and periodontitis are prevalent chronic conditions that disproportionately affect aging populations and pose substantial public health challenges worldwide. Increasing evidence suggests a potential association between these two diseases, with chronic oral infection and systemic inflammation emerging as key linking mechanisms. Periodontitis is characterized by a dysbiotic oral microbiome and persistent inflammatory responses that can lead to the dissemination of periodontal pathogens and their virulence factors into the systemic circulation. Notably, some studies have reported the detection of pathogens such as Porphyromonas gingivalis and their toxic products in the brains of individuals with AD, implicating a possible role in neuroinflammation and neurodegeneration. However, it should be clarified that detection does not establish causation. This narrative review aims to synthesize the existing evidence from animal studies exploring the link between periodontitis and AD and its related mechanisms, including neuroinflammation, amyloid and tau pathology, blood-brain barrier dysfunction, and systemic interactions. The electronic search in PubMed yielded 585 results. We focused on the past 10 years, thus removing 114 results. A total of 471 studies remained. Of the 471 articles reviewed, 239 studies were excluded based on their titles, abstracts, publication types, and topics because of inappropriate study designs (i.e., designs other than cross-sectional or animal studies). A total of 232 studies were further investigated. In this review, the analysis focused exclusively on animal studies, and the full texts were assessed against predefined eligibility criteria focusing on study design, animal model, periodontal exposure, and AD-related outcomes. Studies that met all inclusion criteria were included, whereas articles with inappropriate study designs or irrelevant outcomes were excluded. After full-text screening, 101 studies remained. Preclinical (animal) evidence supported plausible mechanistic links between periodontitis and AD. Furthermore, oral pathogens appear to mediate this ongoing neuroinflammation.
Non-resolving pneumonia in elderly patients with chronic obstructive pulmonary disease (COPD) and a smoking history poses a significant diagnostic challenge, particularly in tuberculosis-endemic regions where infectious causes are often prioritized. We report a 68-year-old male patient with COPD, type 2 diabetes mellitus, and hypertension who presented with progressive dyspnea, evening low-grade fever, anorexia, and significant weight loss over three months. Initial treatment for presumed infective exacerbation of COPD failed despite antibiotics. Extensive workup for tuberculosis, multiple myeloma, and sarcoidosis was negative. Notably, prominent parathyroid hormone (PTH)-independent hypercalcemia was detected early and persisted, serving as the pivotal diagnostic clue. Contrast-enhanced CT (CECT) chest revealed a left lower lobe mass with endobronchial obstruction, and biopsy confirmed squamous cell carcinoma. The hypercalcemia was presumed to be mediated by tumor-derived parathyroid hormone-related peptide (PTHrP). This case highlights the value of recognizing paraneoplastic hypercalcemia as an early red flag for occult lung malignancy in high-risk patients, even with modest smoking exposure, thereby preventing diagnostic delay due to anchoring on infection.
Pediatric primary orbital lymphomas are exceptionally rare entities and represent a very small subset of both childhood orbital tumors and extra-nodal non-Hodgkin lymphomas. They often present with non-specific clinical features that can closely mimic inflammatory or other malignant orbital conditions, thereby posing significant diagnostic challenges. We report a rare case of an orbital lymphoma in an infant presenting with rapidly progressive, painless unilateral eyelid swelling. Magnetic resonance imaging demonstrated a well-defined extraconal orbital mass that appeared isointense on T1-weighted images and iso- to hypointense on T2-weighted sequences, with homogeneous post-contrast enhancement. The lesion exhibited marked diffusion restriction with significantly reduced apparent diffusion coefficient (ADC) values, indicative of a highly cellular neoplasm and in this context, most favorable diagnosis of lymphoma was considered. Histopathological evaluation, supported by immunohistochemistry and flow cytometry, confirmed an aggressive B-cell lymphoma, and molecular analysis revealed features consistent with Burkitt lymphoma. Staging fluorodeoxyglucose positron emission tomography demonstrated residual metabolically active disease confined to the orbit without evidence of systemic involvement. The patient was initiated on intensive multi-agent chemotherapy with an early favorable clinical response. A systematic review of the literature was subsequently done, which highlighted the extreme rarity of primary pediatric orbital lymphomas, with a predominance of high-grade B-cell histology, particularly Burkitt lymphoma. This case highlights the critical role of diffusion-weighted imaging and low ADC values in differentiating orbital lymphomas from other pediatric orbital masses, thereby facilitating early diagnosis, accurate lesion characterization, and timely initiation of therapy. Radiological awareness of these characteristic imaging features is essential to avoid diagnostic delay and to improve clinical outcomes in this rare but aggressive disease, given its marked responsiveness to treatment.
Socioeconomic status (SES) significantly influences the incidence and severity of chronic obstructive pulmonary disease. This study investigated the impact of SES on incidence of airflow obstruction and lung function decline within a general population cohort in Republic of Korea (South Korea). We utilized data from the Korean Genome and Epidemiology Study Ansan-Ansung Cohort, collected between 2001 and 2014. A total of 10,030 participants were included in the longitudinal analysis. Socioeconomic status was classified using four key indicators: area of residence (urban, n = 5,012; rural, n = 5,018), marital status (single, n = 974; married, n = 8,987), education level (elementary school, n = 3,355; middle or high school, n = 5,287; college or above, n = 1,305), and income (< $1,460, n = 6,413; $1,460-2,920, n = 2,705; > $2,920, n = 729), among participants with available data. Over a 12-year follow-up period, individuals living in rural areas experienced a more rapid decline in both mean forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) compared to those in urban areas (P < 0.001). Participants with the lowest levels of education and income experienced significantly faster declines in both FVC and FEV₁ (all P < 0.001, except for medium vs. high income). The risk of developing airflow obstruction was significantly higher for participants from rural areas, with lower education levels, and lower income. This study demonstrated a significant association between lower SES and incidence of airflow obstruction and progression in Korea. Lower SES, characterized by rural residence, lower educational status, and lower income, was associated with poorer baseline health, higher comorbidity rates, and more rapid lung function decline over a 12-year period.
Erdheim-Chester disease is a rare, aggressive non-Langerhans cell histiocytosis characterized by multisystem infiltration of histiocytes. It commonly affects middle-aged men and is driven by acquired mutations in the MAPK signaling pathway. This essential cellular pathway relays extracellular signals to the nucleus and regulates cell proliferation and survival. We report the case of a 39-year-old male who presented with progressive, severe left-sided frontal and temporal headaches. Imaging revealed a symptomatic craniocervical mass, a nonsecreting pituitary lesion, and bilateral perinephric soft tissue infiltration extending throughout the retroperitoneum. Histopathologic evaluation demonstrated foamy histiocytes consistent with Erdheim-Chester disease, and molecular testing identified a BRAF mutation. Notably, no FDG-avid skeletal involvement was identified on available whole-body FDG PET/CT imaging, an uncommon feature in Erdheim-Chester disease. The patient was treated with the BRAF inhibitor vemurafenib, with dose reduction due to dermatologic toxicity, and subsequently tolerated therapy well. He has maintained a stable disease course at one-year follow-up. This report demonstrates the variable clinical manifestations of Erdheim-Chester disease and emphasizes the importance of molecular profiling in directing targeted therapeutic strategies.
Crohn's disease (CD) is a chronic immune-mediated inflammatory disorder in which extraintestinal manifestations occur in up to 40% of patients. Metastatic Crohn's disease (MCD), characterized by noncaseating cutaneous granulomas anatomically remote from the gastrointestinal tract, is among the rarest of these manifestations. Its coexistence with occult acute myeloid leukemia (AML) and secondary hemophagocytic lymphohistiocytosis (sHLH) in a treatment-naïve patient constitutes an exceptional clinical triad with profound diagnostic and therapeutic implications. We report a 56-year-old woman without prior immunosuppressive exposure who presented with severe panenteric CD, MCD manifesting as necrotic lower-extremity nodules, and a submandibular abscess. Profound bicytopenia (hemoglobin: 5.3 g/dL, reference range: 13-18 g/dL; platelets: 12,000/μL, reference range: 150,000-450,000/μL) prompted a bone marrow evaluation, which revealed hypercellularity with 9% myeloid blasts (CD34+, CD117+). Although these findings required an urgent repeat marrow evaluation, cytogenetic/molecular testing, and hematology clearance due to the high risk of an indeterminate or pre-leukemic state, the presence of active, refractory gastrointestinal bleeding prompted the immediate initiation of infliximab induction. Given the absence of prior therapy and the presence of marked systemic inflammation, including concurrent pneumonia and active CD, these findings were initially attributed to reactive myelodysplastic mimicry. However, while systemic inflammation from pneumonia and active CD can mimic myelodysplasia, a 9% blast count with severe cytopenias should not be safely dismissed as merely reactive. Within days of the first infliximab infusion, the patient developed explosive leukocytosis (40,000/μL). Repeat flow cytometry demonstrated 37% immature myeloid blasts (CD34+, CD117++, HLA-DR+, CD123+), establishing a diagnosis of AML without maturation (FAB M1). Concurrently, overt hemophagocytosis with extreme hyperferritinemia confirmed concomitant sHLH (HScore: 227). This case highlights a critical and underrecognized risk: TNF-α may act as an endogenous immunological brake against clonal expansion. In our patient, TNF-alpha blockade may have contributed to the loss of immune control over an occult myeloid clone, dismantling this surveillance mechanism and precipitating a rapid transition to fulminant leukemia while triggering sHLH. Although causality cannot be proven from this single case and a direct triggering effect by infliximab remains speculative unless other potential triggers are thoroughly evaluated, the temporal association is striking. Severe systemic inflammation can create a reactive bone marrow phenotype indistinguishable from early myeloid neoplasia or myelodysplastic syndrome, posing a life-threatening diagnostic trap. Comprehensive hematologic evaluation-including repeat bone marrow assessment under controlled inflammatory conditions-should be considered mandatory before initiating biologic therapy in patients with CD and unexplained cytopenias or borderline blast counts.
To evaluate the association between the healthy lifestyle score (HLS) and metabolic syndrome (MetS) among Japanese male workers. This cross-sectional study included 940 participants aged 20-63 years. The longitudinal analysis included 744 participants without MetS at baseline who completed at least one follow-up examination between 2013 and 2019. The HLS was derived from ten lifestyle-related factors: body mass index, smoking, alcohol consumption, current physical activity, sleep quality, weight change, meal skipping, snacking, eating speed, and family history of non-communicable diseases. MetS was defined according to the Japanese criteria. In the cross-sectional analysis, multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for MetS, after adjusting for potential confounders. In the longitudinal analysis, generalized estimating equations were used to estimate ORs and 95% CIs for incident MetS during follow-up per 1-point increase in baseline HLS, with adjustment for potential confounders. In the cross-sectional analysis, HLS was inversely associated with MetS (p < 0.001). Consistent findings were observed in the longitudinal analysis, in which each 1-point increase in baseline HLS was associated with lower odds of MetS during follow-up (OR: 0.676, 95% CI: 0.600-0.762; p < 0.001). These cross-sectional and longitudinal findings suggest that adherence to healthy lifestyle factors may help prevent MetS among Japanese male workers. The online version contains supplementary material available at 10.1007/s40200-026-01985-6.
Background Hip fractures represent a major public health concern among elderly individuals, with annual cases projected to exceed six million globally by 2050 due to population aging. Patients with atrial fibrillation (AF) may be at increased risk due to multiple comorbidities. Identifying those predictors of hip fracture in this population is essential for early risk stratification and prevention. Therefore, this study aimed to determine the predictors of hip fracture among patients with AF. Methods This retrospective study included all eligible 189 patients aged ≥50 years with confirmed atrial fibrillation, enrolled using consecutive sampling according to predefined inclusion and exclusion criteria. Demographic and clinical data were collected via a self-designed form. Patients were categorized into fracture and non-fracture groups. Statistical analysis was performed in the Statistical Package for the Social Sciences (SPSS) software, version 25 (Released 2017; IBM Corp., Armonk, New York) using independent t-tests and chi-square tests for group comparisons. Variables with clinical relevance were further analyzed using multivariate logistic regression to identify independent predictors. Results The mean age of participants was 67.60±8.26 years, and 27 (14.28%) patients developed hip fractures. Patients with fractures were significantly older and more likely to be female with lower BMI. Univariate analysis identified multiple significant associations (p<0.05). On further analysis, multivariate logistic regression confirmed age ≥65 years (odds ratio (OR)= 2.32, p=0.037), female gender (OR= 2.14, p=0.047), BMI <22 kg/m² (OR= 2.17, p=0.046), osteoporosis (OR= 4.37, p<0.001), vitamin D deficiency (OR=2.02, p=0.040), history of stroke (OR=2.24 , p=0.047), chronic kideny disease (CKD) (OR=2.12, p=0.048), polypharmacy (OR= 2.82, p=0.012), and prolonged anticoagulation (OR 3.14, p=0.007) as independent predictors. In contrast, smoking, physical inactivity, coronary artery disease, diabetes mellitus, and hypertension, lacked independent association with hip fracture within this population. Conclusion Hip fracture risk in patients with atrial fibrillation is independently associated with several demographic, clinical, and treatment-related factors. Advanced age, female gender, low BMI, osteoporosis, vitamin D deficiency, history of stroke, CKD, polypharmacy, and long-term anticoagulation are key independent predictors. Early identification and targeted management of these factors may help reduce fracture risk in this high-risk population.
This study aimed to examine whether chronic obstructive pulmonary disease (COPD) is associated with the subsequentdevelopment of chronic rhinosinusitis (CRS) among Korean adults. Using the 2002-2019 Korean National Health Insurance database, we conducted a retrospective cohort study. Individuals with COPD, definted by relevant ICD-10 codes recorded on at least two occasions together with at least two prescriptions for COPD-related medicines (n=615,706), were matched with control participants (n=2,184,000) by age, sex, income, and region of residence. The incidence of CRS with and without nasal polyps was evaluated in both COPD and control groups. Hazard ratios (HRs) were estimated using stratified Cox proportional hazards models, and prespecified subgroup analyses were conducted. The incidence rate of CRS was higher in patients with COPD than in control participants. After adjustment, the HR for CRS was significantly higher in the COPD group compared with the control group. Likewise, the HRs for CRS with nasal polyps and CRS without nasal polyps were also significantly higher in the COPD group than in the control group. Statistical significance was observed in all subgroups according to age, sex, income, and region of residence. Kaplan-Meier analyses showed a higher cumulative incidence in participants with COPD. In this nationwide Korean cohort, COPD was associated with a higher incidence of CRS, both with and without nasal polyps.
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) accumulation, impaired proteostatic clearance, and oxidative damage, all of which contribute to neuronal dysfunction and disease progression. Fucoxanthin (FX), a marine-derived carotenoid abundant in brown algae, has shown antioxidant and neuroprotective potential. However, its role in autophagy-lysosome dysfunction and ferroptosis-associated oxidative injury under amyloidogenic conditions remains unclear. In this study, the effects of FX were investigated in APP Swedish mutant-expressing Neuro2a (SweAPP N2a) cells treated with 0.1-5 μM FX and in 5XFAD transgenic mice orally administered FX at 200 mg kg-1. FX treatment increased LC3-II expression and reduced p62 accumulation in SweAPP N2a cells, indicating enhanced autophagic degradation. FX also increased the expression of the lysosomal markers LAMP1 and cathepsin D (CTSD), suggesting enhanced lysosome-associated degradative capacity. These responses were accompanied by AMPK activation and suppression of mTOR signaling, together with increased autophagic flux as confirmed by bafilomycin A1-based analysis. Moreover, FX significantly reduced intracellular ROS levels and lipid peroxidation marker 4-hydroxynonenal (4-HNE), while modulating ferroptosis-associated proteins, including GPX4 and FTH1. Consistent with the cellular findings, FX administration in 5XFAD mice modulated autophagy-lysosome-related and ferroptosis-associated proteins in the brain and significantly reduced ThS-positive amyloid plaque burden. Collectively, these findings demonstrate that FX enhances autophagy-lysosome-associated proteostatic regulation through AMPK/mTOR signaling and attenuates ferroptosis-linked oxidative injury under amyloidogenic conditions. These results provide mechanistic evidence supporting the role of FX as a marine-derived bioactive compound for modulating AD-related pathological processes.
Surgical resection remains the primary treatment modality for well-differentiated thyroid carcinoma. However, hypoglossal nerve injury following thyroidectomy represents a rare complication. We report a case of bilateral hypoglossal nerve palsy in a 57-year-old female patient who underwent bilateral total thyroidectomy with neck dissection and thyroglossal duct cyst excision under general anesthesia. Comprehensive imaging and electrophysiological studies confirmed bilateral hypoglossal nerve dysfunction, although surgical re-exploration revealed anatomically intact nerves. Despite empirical steroid treatment, neurological improvement was limited. The patient subsequently underwent intensive, multidisciplinary neurorehabilitation. Over the following months, swallowing function gradually improved, allowing a return to oral intake, although mild dysarthria persisted. This case presents a complex and rare neurological complication following thyroid surgery. Although thyroidectomy techniques are well-established, preoperative assessment should carefully consider the potential risk factors for hypoglossal nerve injury to optimize surgical outcomes.
Background From mid-June into late December 2025, China experienced its largest-ever Chikungunya virus (CHIKV) outbreak across Guangdong Province, a densely populated region of southeast China with extensive international travel and established Aedes mosquito populations. CHIKV, dengue virus (DENV), and Zika virus (ZIKV) share the same Aedes vectors, overlap in clinical presentation, and exhibit serologic cross-reactivity. We describe the epidemiology and integrated public health response to this outbreak, as well as future arboviral risks and mitigation strategies. Materials and methods We synthesized weekly surveillance data from the Guangdong Provincial Center for Disease Control and Prevention, national epidemiological and genomic data from the China CDC and World Health Organization, Hong Kong Observatory climate records, published literature, and government bulletins. Outbreak dynamics were analyzed using confirmed-case counts disaggregated by prefecture-level city and reporting week. Results Guangdong reported over 25,800 locally transmitted CHIKV cases across all 21 prefecture-level cities, with nationwide cases exceeding 29,500. The outbreak occurred in two distinct waves: an initial wave centered on Foshan City (July-August; 8,948 cases) that was successfully contained through a rapid, multi-level public health response; and a second, larger wave in Jiangmen City (September-October; 10,035 cases) temporally coincident with three tropical cyclones that made landfall within a 16-day span, creating widespread Aedes breeding habitat. No deaths were reported in Guangdong. The causative lineage was the Middle African Lineage within the East/Central/South African genotype, carrying Aedes albopictus-adaptive mutations (E1-A226V, E2-L210Q, E2-I211T) independently acquired through convergent evolution with the Indian Ocean Lineage. The persistence of cases into mid-December, combined with the warmest winter on record in the Pearl River Delta, raises concerns about overwintering mosquitoes and an early resurgence in 2026. Conclusions The 2025 Guangdong outbreak suggests that extreme weather events can overwhelm even well-executed arboviral responses and that the climate-vector-arbovirus interface represents a systems-level vulnerability requiring anticipatory preparedness. We advocate for typhoon-landfall-triggered vector control deployment, intensified genomic and entomological surveillance beginning in spring 2026, multiplex molecular diagnostics for concurrent CHIKV/DENV/ZIKV detection, obstetric and neonatal arboviral screening, and cross-jurisdictional coordination across the Pearl River Delta and beyond.