Liquid Nitrogen Exfoliation and Nanodispersion of WS2 for Thermocatalysts.

The efficient and clean exfoliation of single and/or few-layer nanosheets of WS2, a two-dimensional transition metal dichalcogenides, remains a significant challenge. In this study, a simple exfoliation method was proposed to produce ultrathin WS2 nanosheets by combining the liquid nitrogen exfoliation and nanodispersion techniques. This approach efficiently exfoliated WS2 into several layers of nanosheets via rapid temperature changes and mechanical stress without inducing defects or contamination. After five cycles of heating/liquid nitrogen and nanodispersion, the resulting WS2 nanosheets (WS2-5N ND) were confirmed to have been successfully exfoliated into 1-4 layers. When applied as a promoter in a thermocatalyst for the selective catalytic reduction of NOX using NH3, 2V3WS2/Ti (WS2-5N ND) exhibited excellent NOX conversion and N2 selectivity, along with excellent durability even in the presence of SO2. This result was greater than 2V3WS2/Ti (WS2-5N) subjected to only liquid nitrogen exfoliation, proving the importance of the simultaneous action of both methods. This method is expected to be an important contribution to ongoing research on high-performance WS2-based catalysts, thereby opening up potential opportunities for a wide range of applications.

The therapeutic effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on chemically induced atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. However, it is still urgent to develop innovative treatments that can effectively manage refractory patients with unpredictable chronic disease courses. In this study, we evaluated the therapeutic efficacy of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a novel agent for AD treatment using a human-like mouse model of AD. PLAG significantly improved 2,4-dinitrochlorobenzene (DNCB)-induced AD skin lesions compared to those in mice treated with DNCB alone. PLAG substantially modulated the AD-induced infiltration of monocytes and eosinophils into skin lesions and humoral systemic responses involving immunoglobulin E (IgE), interleukin (IL)-4, and IL-13, restoring them to a normal state. Next, we compared the therapeutic efficacy of PLAG and abrocitinib for severe AD treatment. PLAG exhibited a significant therapeutic effect on AD skin lesions compared to abrocitinib. Unlike abrocitinib, PLAG significantly reduced AD-induced eosinophil infiltration to a level similar to that observed in untreated negative controls. Notably, both PLAG and abrocitinib downregulated IgE, IL-4, and IL-13 in a similar pattern, reaching levels similar to those in the untreated negative controls. Our findings strongly suggest that PLAG may serve as a therapeutic agent for AD with an efficacy comparable to that of abrocitinib.

Conductive single enzyme nanocomposites prepared by in-situ growth of nanoscale polyaniline for high performance enzymatic bioelectrode.

Enzyme-based electrochemical biosensors hold great promise for applications in health/disease monitoring, drug discovery, and environmental monitoring. However, inherently non-conductive nature of proteinaceous enzymes often hampers effective electron transfer at enzyme-electrode interface, limiting biosensor performance of enzyme bioelectrodes. To address this problem, we present an approach to synthesize polyaniline (PAN)-based conductive single enzyme nanocomposites of glucose oxidase (GOx) (denoted as PAN-GOx). To prevent multimerization of enzymes during nanocomposite synthesis and enable single enzyme wrapping, we activate GOx surface with phenylamine groups based on the programmed diffusion of reactants in the reaction solution. Subsequent in-situ polymerization enables the synthesis of nanoscale conductive PAN layer (∼2.7 nm thickness) grafted from individual GOx molecule. PAN-GOx retains 83% and 74% of its specific activity and catalytic efficiency, respectively, compared to free GOx, while demonstrating a ∼500% improved conductivity. Furthermore, PAN-GOx-based glucose biosensors show an approximately 16- and 3-fold higher sensitivity compared to biosensors prepared by using free GOx and a mixture of PAN and GOx, respectively. This study provides a facile method to fabricate conductive single enzyme nanocomposites with enhanced electron transfer, which can potentially be further modified and/or compounded with conductive materials for demonstrating high performance enzymatic bioelectrodes.

Ketogenic diet with aerobic exercise can induce fat browning: potential roles of ß-hydroxybutyrate.

Introduction: Despite evidence suggesting that metabolic intermediates like ß-HB influence white adipose tissue (WAT) metabolism, the precise molecular mechanisms remain unclear. The aim of this study was to investigate the impact of beta-hydroxybutyrate (ß-HB) on the fat browning program and to explore the underlying molecular mechanisms using both in vitro and in vivo models. We assessed the effects of ß-HB on fat browning in adipocytes using 3T3-L1 cells and rat models. Methods: We evaluated the effects of ß-HB on fat browning, thermogenesis, lipid accumulation, adipokine expression, and mitochondrial biogenesis by treating mature 3T3-L1 adipocytes with sodium ß-HB for 24 h or by continuously exposing preadipocytes to ß-HB during the 8-day differentiation process. Male Sprague Dawley rats were divided into control, exercise only (EX), ketogenic diet only (KD), and combined exercise and ketogenic diet (KE) groups for an 8-week intervention involving diet and/or exercise. After intervention, we evaluated WAT histology, plasma lipids and adipokines, and the expression of markers related to fat browning, thermogenesis and mitochondrial biogenesis in WAT of rats. Results: In our adipocyte culture experiments, ß-HB reduced intracellular lipid accumulation by enhancing lipolysis and stimulated the expression of thermogenic and fat browning genes like uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), and adipokines such as fibroblast growth factor 21 (FGF21) and Fibronectin type III domain-containing protein 5 (FDNC5). Additionally, ß-HB activated the AMPK-SIRT1-PGC-1α pathway, with UCP1 and PRDM16 upregulation mediated by ß-HB intracellular action and SIRT1 activity. In animal experiments, KE group raised ß-HB levels, decreasing body weight and blood lipids. KD with EX promoted WAT browning possibly via AMPK-SIRT1-PGC-1α, augmenting PRDM16, UCP1, FGF21, and FNDC5 expression. Conclusion: ß-HB induction via KD and/or EX shows potential in promoting WAT browning by activating mitochondrial biogenesis, lipolysis, and thermogenesis, suggesting that dietary and physical intervention inducing ß-HB may benefit metabolic health.

Long-term tracking of glycosylated hemoglobin levels across the lifespan in type 1 diabetes: from infants to young adults.

PURPOSE: Glycosylated hemoglobin (HbA1c) is commonly used as a monitoring tool in diabetes. Due to the potential influence of insulin resistance (IR), HbA1c level may fluctuate over a person's lifetime. This study explores the long-term tracking of HbA1c level in individuals diagnosed with type 1 diabetes mellitus (T1DM) from infancy to early adulthood. METHODS: The HbA1c levels in 275 individuals (121 males, 43.8%) diagnosed with T1DM were tracked for an average of 9.4 years. The distribution of HbA1c levels was evaluated according to age with subgroups divided by gender, use of continuous glucose monitoring (CGM), and the presence of complications. RESULTS: HbA1c levels were highest at the age of 1 year and then declined until age 4, followed by a significant increase, reaching a maximum at ages 15-16 years. The levels subsequently gradually decreased until early adulthood. This pattern was observed in both sexes, but it was more pronounced in females. Additionally, HbA1c levels were higher in CGM nonusers compared with CGM users; however, regardless of CGM usage, an age-dependent pattern was observed. Furthermore, diabetic complications occurred in 26.8% of individuals, and the age-dependent pattern was observed irrespective of diabetic complications, although HbA1c levels were higher in individuals with diabetic complications. CONCLUSION: HbA1c levels vary throughout the lifespan, with higher levels during adolescence. This trend is observed regardless of sex and CGM usage, potentially due to physiological IR observed during adolescence. Hence, physiological IR should be considered when interpretating HbA1c levels during adolescence.

Enhancement of Intracellular Cholesterol Efflux in Chondrocytes Leading to Alleviation of Osteoarthritis Progression.

OBJECTIVE: Osteoarthritis (OA) is the most common degenerative disease worldwide, with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol-lowering drugs in suppressing OA development in mice, and uncover the cholesterol-lowering mechanisms that effectively impede OA progression. METHODS: Five clinically approved cholesterol-lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to mice with OA who underwent destabilization of the medial meniscus induction and were fed a 2% high-cholesterol diet. Gene expression linked to cholesterol metabolism was determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra-articular injection of either its inhibitor or adenovirus. RESULTS: Logistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol-lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high-density lipoprotein cholesterol that are crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via down-regulation of apolipoprotein A1-binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression. CONCLUSION: Our results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for patients with OA.

Thyroid Carcinoma With NSD3::NUTM1 Fusion and Secondary TERT Promoter Mutation: A Case Report and Literature Review.

Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive tumor characterized by translocation of the NUTM1 gene. To date, only about 20 NUT carcinomas arising from the thyroid have been reported in the literature, with the majority showing immunohistochemical markers indicative of squamous differentiation. We present a 29-year-old man with NUT carcinoma arising from thyroid follicular cells. Notably, the tumor cells expressed markers characteristic of thyroid follicular cells such as thyroglobulin, TTF1 and PAX8, without obvious histological and immunohistochemical features of squamous differentiation. Molecular analysis revealed a concurrent TERT promoter mutation (C228T) together with the NSD3::NUTM1 fusion, a combination not previously documented in NUT carcinoma. The tumor highlights the need to include NUT carcinoma in the differential diagnosis of thyroid cancer, especially when it presents with unconventional histopathological features, even in the absence of signs of squamous differentiation.

Effect of Inter-Hospital Transfer on Mortality in Patients Admitted through the Emergency Department.

Background: Despite advancements in emergency medical systems, inter-hospital transfer (IHT) remains a critical component. Several studies have analyzed the impact of IHT on patient outcomes. Some studies have reported positive effects, indicating that transfers can improve patient prognosis. However, other studies have suggested that transfers may worsen outcomes. We investigated whether IHT is associated with in-hospital mortality. Methods: This retrospective observational study utilized data on patient outcomes from the National Emergency Department Information System (NEDIS) from 2016 to 2018, focusing on patients admitted to hospitals after visiting the emergency department (ED). The primary outcome was the in-hospital mortality rate. Results: This study included 2,955,476 adult patients admitted to emergency medical centers, with 832,598 (28.2%) undergoing IHT. The in-hospital mortality rate was significantly higher in the transfer group (6.9%) than in the non-transfer group (4.8%). Multiple logistic regression analysis revealed that IHT was an independent predictor of in-hospital mortality (adjusted odds ratio [aOR] 1.114, 95% confidence interval [CI] 1.101-1.128) after adjusting for variables. Sub-analysis indicated that higher severity scores, shorter symptom onset-to-arrival duration, and diagnoses of infectious or respiratory diseases were significantly associated with increased in-hospital mortality among transferred patients. Conclusions: This study identifies IHT as a significant factor associated with increased in-hospital mortality. Additionally, it suggested the need for policies to mitigate the risks associated with IHT, particularly in critically ill patients, those with the acute phase response, and those with infectious, genitourinary, and respiratory diseases.

Effect of Sortilin1 on promoting angiogenesis and systemic metastasis in hepatocellular carcinoma via the Notch signaling pathway and CD133.

Hepatocellular carcinoma (HCC) is known to be lethal disease. However, its prognosis remains poor, primarily because the precise oncogenic mechanisms underlying HCC progression remain elusive, thus hampering effective treatment. Here, we aimed to identify the potential oncogenes in HCC and elucidate the underlying mechanisms of their action. To identify potential candidate genes, an integrative analysis of eight publicly available genomic datasets was performed, and the functional implications of the identified genes were assessed in vitro and in vivo. Sortilin 1 (SORT1) was identified as a potential candidate oncogene in HCC, and its overexpression in HCC cells was confirmed by analyzing spatial transcriptomic and single-cell data. Silencing SORT1 in Huh-7 and Hep3B cells significantly reduced HCC progression in vitro and in vivo. Functional analyses of oncogenic pathways revealed that SORT1 expression regulated the Notch signaling pathway activation and CD133 expression. Furthermore, analysis of epigenetic regulation of the candidate gene and its clinical implications using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) and our HCC cohort (AJOU_HCC cohort) data demonstrated an inverse correlation between the methylation status of the SORT1 promoter region, specifically at the cg16988986 site, and SORT1 mRNA expression, indicating the epigenetic regulation of SORT1 in HCC. In addition, the distinct methylation status of cg16988986 was significantly associated with patient survival. In conclusion, SORT1 plays a pivotal role in HCC by activating the Notch signaling pathway and increasing CD133 expression. These findings suggest SORT1 as a promising therapeutic target for HCC.

Functional loss of ERBB receptor feedback inhibitor 1 (MIG6) promotes glioblastoma tumorigenesis by aberrant activation of epidermal growth factor receptor (EGFR).

Dysregulation of epidermal growth factor receptor (EGFR) is one of the most common mechanisms associated with the pathogenesis of various cancers. Mitogen-inducible gene 6 [MIG6; also known as ERBB receptor feedback inhibitor 1 (ERRFI1)], identified as a feedback inhibitor of EGFR, negatively regulates EGFR by directly inhibiting its kinase activity and facilitating its internalization, subsequently leading to degradation. Despite its proposed role as an EGFR-dependent tumor suppressor, the functional consequences and clinical relevance in cancer etiology remain incompletely understood. Here, we identify that the stoichiometric balance between MIG6 and EGFR is crucial in promoting EGFR-dependent oncogenic growth in various experimental model systems. In addition, a subset of ERRFI1 (the official gene symbol of MIG6) mutations exhibit impaired ability to suppress the enzymatic activation of EGFR at multiple levels. In summary, our data suggest that decreased or loss of MIG6 activity can lead to abnormal activation of EGFR, potentially contributing to cellular transformation. We propose that the mutation status of ERRFI1 and the expression levels of MIG6 can serve as additional biomarkers for guiding EGFR-targeted cancer therapies, including glioblastoma.

Phrenic Ampulla Emptying Dysfunction in Patients with Esophageal Symptoms.

Background/Aims: Pharyngeal pump, esophageal peristalsis, and phrenic ampulla emptying play important roles in the propulsion of bolus from the mouth to the stomach. There is limited information available on the mechanism of normal and abnormal phrenic ampulla emptying. The goal of our study is to describe the relationship between bolus flow and esophageal pressure profiles during the phrenic ampulla emptying in normal subjects and patient with phrenic ampulla dysfunction. Methods: Pressure (using topography) and bolus flow (using changes in impedance) relationship through the esophagus and phrenic ampulla were determined in 15 normal subjects and 15 patients with retrograde escape of bolus from the phrenic ampulla into esophagus during primary peristalsis. Results: During the phrenic ampulla phase, 2 high pressure peaks (proximal, related to lower esophageal sphincter and distal, related to crural diaphragm) were observed in normal subjects and patients during the phrenic ampulla emptying phase. The proximal was always higher than the distal one in normal subjects; in contrast, reverse was the case in patients with the retrograde escape of bolus from the phrenic ampulla into the esophagus. Conclusions: We propose that a strong after-contraction of the lower esophageal sphincter plays an important role in the normal phrenic ampullary emptying. A defective lower esophageal after-contraction, along with high crural diaphragm pressure are responsible for the phrenic ampulla emptying dysfunction.

Immediate effects of insoles applied to the sound side lower extremity of patients with chronic hemiplegia during walking.

Background: Asymmetric gait patterns are mostly observed in hemiplegic stroke patients. These abnormal gait patterns resulting in abnormal speed, and decreased ability in daily of activity living. Objective: This study aimed to determine the immediate changes in gait parameters and plantar pressure during elevation by wearing an insole on the sound side lower extremity of patients with hemiplegia. Methods: Thirty-six participants were recruited, comprising those with a post-stroke follow-up of ≥3 months and a functional ambulation category score of ≥2. The participants were asked to walk with and without a 1 cm insole in the shoe of their sound side, and the order of wearing or not wearing the insole was randomized. Gait parameters, bilateral gait parameters, and dynamic plantar pressure were measured using the GAITRite Walkway System. Results: Paired t-test was used to examine immediate changes in gait parameters and plantar pressure with and without insoles during walking in the same group. Overall, gait velocity and step length significantly decreased (p < 0.05), whereas step time significantly increased (p < 0.05). The swing phase of the affected sidelower extremities significantly increased (p < 0.05), and the stance phase significantly decreased (p < 0.05). Double-support unloading phase (pre-swing phase) significantly increased (p < 0.05). The changes in plantar pressure were significantly increased in some lateral zones and significantly decreased in the medial zone of the mid-hindfoot, both in terms of pressure per time and peak pressure (p < 0.05). Conclusion: Although this study did not show immediate positive effects on gait parameters and gait cycle, it is expected that sensory input from the sole of the foot through changes in plantar pressure may help improve gait asymmetry and regulate postural symmetry.

Disability-related disparities in health outcomes among newly diagnosed diabetic patients: A retrospective cohort.

BACKGROUND: A distinct gap in the literature persists regarding the health outcome of individuals with Type 2 diabetes who also have disabilities. This study aimed to investigate potential disparities in events occurrence among diabetes patients across various disability stages. METHODS: We conducted a retrospective cohort study on patients newly diagnosed with diabetes in 2013 and 2014, aged ≥ 18 years, and followed them until December 2021, using data from the Korean National Health Insurance database. All-cause mortality and hospitalization for diabetes mellitus and cardio-cerebrovascular diseases (CVD) was assessed. RESULTS: The study included 26,085 patients, encompassing individuals without disabilities and those with physical, visual, hearing and speech, intellectual and developmental, and mental disabilities. After adjustment, individuals with disabilities had a higher risk of all-cause death (adjusted hazard ratio [aHR]: 1.25, 95% CI: 1.07-1.48) compared to those without disabilities. In particular, severe disabilities and hearing and speech disabilities showed significantly higher risks of all-cause death (aHR: 1.40, 95% CI: 1.06-1.85 and aHR: 1.58, 95% CI: 1.17-2.15, respectively), with marginal significance for mild disabilities (aHR: 1.20, 95% CI: 0.99-1.45) and mental disorders (aHR: 1.92, 95% CI: 0.98-3.73). Patients with disabilities also had significantly increased risks of CVD-related first admissions (aHR: 1.30, 95% CI: 1.07-1.56) and diabetes-related first admissions (aHR: 1.31, 95% CI: 1.20-1.43) compared to those without disabilities. CONCLUSIONS: This study underscores the urgent need for public health policies to prioritize individuals with disabilities and diabetes, addressing the disparities in health outcome.

Innate immune signatures in the nasopharynx after SARS-CoV-2 infection and links with the clinical outcome of COVID-19 in Omicron-dominant period.

While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is characterized by impaired induction of interferons (IFNs) and IFN-stimulated genes (ISGs), the IFNs and ISGs in upper airway is essential to restrict the spread of respiratory virus. Here, we identified the prominent IFN and ISG upregulation in the nasopharynx (NP) of mild and even severe coronavirus disease 2019 (COVID-19) patients (CoV2+) in Omicron era and to compare their clinical outcome depending on the level of IFNs and ISGs. Whereas the induction of IFNB was minimal, transcription of IFNA, IFNG, and IFNLs was significantly increased in the NP of CoV2 + patients. IFNs and ISGs may be more upregulated in the NP of CoV2 + patients at early phases of infection according to viral RNA levels and this is observed even in severe cases. IFN-related innate immune response might be characteristic in macrophages and monocytes at the NP and the CoV2 + patients with higher transcription of IFNs and ISGs in the NP showed a correlation with good prognosis of COVID-19. This study presents that IFNs and ISGs may be upregulated in the NP, even in severe CoV2 + patients depending on viral replication during Omicron-dominant period and the unique IFN-responsiveness in the NP links with COVID-19 clinical outcomes.

Nasal symbiont Staphylococcus epidermidis restricts influenza A virus replication via the creation of a polyamine-deficient cellular environment.

Studies on the immune-regulatory roles played by the commensal microbes residing in the nasal mucosa consider the contribution of antiviral immune responses. Here, we sought to identify the nasal microbiome, Staphylococcus epidermidis-regulated antiviral immune responses and the alteration of polyamine metabolites in nasal epithelium. We found that polyamines were required for the life cycle of influenza A virus (IAV) and depletion of polyamines disturbed IAV replication in normal human nasal epithelial (NHNE) cells. Inoculation of S. epidermidis also suppressed IAV infection and the concentration of polyamines including putrescine, spermidine, and spermine was completely attenuated in S. epidermidis-inoculated NHNE cells. S. epidermidis activated the enzyme involved in the production of ornithine from arginine and downregulated the activity of the enzyme involved in the production of putrescine from ornithine in nasal epithelium. S. epidermidis also induced the activation of enzymes that promote the extracellular export of spermine and spermidine in NHNE cells. Our findings demonstrate that S. epidermidis is shown to be able of creating an intracellular environment lacking polyamines in the nasal epithelium and promote the balance of cellular polyamines in favor of the host to restrict influenza virus replication.

Clinical efficacy of multigene panels in the management of congenital hypothyroidism with gland in situ.

Congenital hypothyroidism (CHT) is a diverse condition with various genetic etiologies. This study aimed to investigate the utility of next-generation sequencing (NGS) analysis in guiding treatment decisions and predicting prognosis for CHT patients with gland in situ (GIS). A retrospective analysis was conducted on 33 CHT patients with GIS who underwent NGS analysis at a single institution between 2018 and 2023. Patients were classified as having permanent (PCH), transient congenital hypothyroidism, or ambiguous congenital hypothyroidism (ACH) CHT based on their response to levothyroxine discontinuation at 3 years of age. Among the 33 patients, genetic variants were identified in 26, with the most prevalent variants found in DUOX2 (26.92%), TSHR (30.77%), TG (19.35%), and DUOXA2 (19.23%). Patients with high initial thyroid-stimulating hormone levels (>50 mIU/L) and low free thyroxine levels (<0.89 ng/dL) at diagnosis tended to have compound heterozygous or homozygous variants in DUOX2, DUOXA2, and TG, and were more likely to develop PCH. In contrast, patients with heterozygous variants in these genes often exhibited ACH. TSHR variants were associated with diverse clinical manifestations, ranging from PCH to ACH, and were more common in patients with initial thyroid-stimulating hormone levels <50 mIU/L. The study highlights the potential utility of NGS analysis in predicting the clinical course and guiding treatment decisions for CHT patients with GIS. Genetic analysis may aid in determining the appropriate duration of levothyroxine therapy and monitoring strategies, particularly in cases where traditional clinical indicators are inconclusive.

Efficacy of Mobile App-Based Cognitive Behavioral Therapy for Insomnia: Multicenter, Single-Blind Randomized Clinical Trial.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBTi) is the first-line therapy for chronic insomnia. Mobile app-based CBTi (MCBTi) can enhance the accessibility of CBTi treatment; however, few studies have evaluated the effectiveness of MCBTi using a multicenter, randomized controlled trial design. OBJECTIVE: We aimed to assess the efficacy of Somzz, an MCBTi that provides real-time and tailored feedback to users, through comparison with an active comparator app. METHODS: In our multicenter, single-blind randomized controlled trial study, participants were recruited from 3 university hospitals and randomized into a Somzz group and a sleep hygiene education (SHE) group at a 1:1 ratio. The intervention included 6 sessions for 6 weeks, with follow-up visits over a 4-month period. The Somzz group received audiovisual sleep education, guidance on relaxation therapy, and real-time feedback on sleep behavior. The primary outcome was the Insomnia Severity Index score, and secondary outcomes included sleep diary measures and mental health self-reports. We analyzed the outcomes based on the intention-to-treat principle. RESULTS: A total of 98 participants were randomized into the Somzz (n=49, 50%) and SHE (n=49, 50%) groups. Insomnia Severity Index scores for the Somzz group were significantly lower at the postintervention time point (9.0 vs 12.8; t95=3.85; F2,95=22.76; ηp2=0.13; P<.001) and at the 3-month follow-up visit (11.3 vs 14.7; t68=2.61; F2,68=5.85; ηp2=0.03; P=.01) compared to those of the SHE group. The Somzz group maintained their treatment effect at the postintervention time point and follow-ups, with a moderate to large effect size (Cohen d=-0.62 to -1.35; P<.01 in all cases). Furthermore, the Somzz group showed better sleep efficiency (t95=-3.32; F2,91=69.87; ηp2=0.41; P=.001), wake after sleep onset (t95=2.55; F2,91=51.81; ηp2=0.36; P=.01), satisfaction (t95=-2.05; F2,91=26.63; ηp2=0.20; P=.04) related to sleep, and mental health outcomes, including depression (t95=2.11; F2,94=29.64; ηp2=0.21; P=.04) and quality of life (t95=-3.13; F2,94=54.20; ηp2=0.33; P=.002), compared to the SHE group after the intervention. The attrition rate in the Somzz group was 12% (6/49). CONCLUSIONS: Somzz outperformed SHE in improving insomnia, mental health, and quality of life. The MCBTi can be a highly accessible, time-efficient, and effective treatment option for chronic insomnia, with high compliance. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) KCT0007292; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22214&search_page=L.

Prediction of insulin resistance and elevated liver transaminases using serum uric acid and derived markers in children and adolescents.

OBJECTIVE: To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases. RESULTS: Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC. CONCLUSIONS: Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.

Investigating the impact of environmental enrichment on proteome and neurotransmitter-related profiles in an animal model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non-pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter-related analyses. Wild-type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aß accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography-tandem mass spectrometry showed that EE enhanced synapse- and neurotransmitter-related networks and upregulated synapse- and neurotransmitter-related proteins in the AD brain. Furthermore, neurotransmitter-related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse-related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.