Enhancing Prognostication and Treatment Response Evaluation in Primary CNS Lymphoma with 18F-FDG PET/CT.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. METHODS: We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). RESULTS: The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥17.0 cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). CONCLUSION: Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

The Association of Vitamin B12 Plasma Concentration with Stroke Incidence According to Sex.

BACKGROUND: Previous studies reported that vitamin B12 deficiency is associated with an increased risk of stroke. However, studies examining the association between excessive vitamin B12 and stroke risk are limited. Our study aimed to investigate the relationship between excessive vitamin B12 levels and the risk of stroke and explore whether this association varies according to sex. METHODS: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were vitamin B12 plasma concentration and sex. The occurrence of stroke served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. An interaction analysis was conducted to assess the interaction effect of vitamin B12 and sex on stroke incidence. RESULTS: Cox proportional logistic regression analysis, adjusting for confounders, showed that excessive vitamin B12 did not significantly alter stroke risk (HR 1.22, 95% CI: 0.82-1.71) and revealed no significant sex-based differences in stroke risk (HR 0.90, 95% CI: 0.75-1.04). However, interaction analysis indicated that excessive vitamin B12 was linked to a significant increase in stroke risk in males (HR 1.81, 95% CI: 1.10-2.99), but not in females (HR 1.04, 95% CI: 0.66-1.60), with statistically significant interaction effect (p<0.01). CONCLUSION: Our study demonstrated that while excessive vitamin B12 alone does not significantly increase stroke risk, it increases the risk in males when considering the interaction with sex.

Clinical implications of six-minute walk test in patients with idiopathic pulmonary fibrosis: a retrospective cohort study.

BACKGROUND: A six-minute walk test (6MWT) is a reproducible, easily performed test, and is widely used to determine functional exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). However, there is currently a paucity of data on the clinical significance of baseline and serial 6-minute walk tests in patients with IPF, especially in Asian patients. OBJECTIVES: We aimed to investigate the clinical significance of serial 6MWT in patients with IPF, especially in Asian patients. DESIGN: This is a single-center retrospective cohort study. METHODS: Clinical data of patients diagnosed with IPF at a tertiary center in Korea were retrospectively analyzed. IPF diagnosis was defined according to the clinical guidelines of the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society/Latin American Thoracic Association. RESULTS: There were 216 patients diagnosed with IPF from December 2012 to January 2022, of whom 198 had a baseline of 6MWT data. The mean age of the cohort was 66.9 ± 8.6, and 89% were male. The non-survivors showed significantly lower six-minute walk distance (6MWD), minimum saturation of peripheral oxygen (SpO2) during 6MWT, forced vital capacity, and diffusing capacity of the lung for carbon monoxide than survivors at baseline. A multivariate Cox analysis demonstrated that lower minimum SpO2 was independently associated with increased mortality rates (Hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.024-1.142, p = 0.005). Higher mortality rates were also associated with echocardiographic-determined pulmonary hypertension (HR: 2.466, 95% CI: 1.149-5.296, p = 0.021) at diagnosis. Among 144 patients with 6MWT results at 12 months, patients with a decline of 50 m or more in the 6MWD showed poorer overall survival than others (median survival: 45.0 months vs 58.0 months, p < 0.001). CONCLUSIONS: Baseline lower minimum SpO2 during 6MWT was an independent prognostic factor in patients with IPF, and a decline in 6MWD in serial follow-up was also associated with a poorer prognosis. These findings suggest that both baseline 6MWT and follow-up data are important in the prognostication of patients with IPF.

Mapping Tumor Habitats in IDH-Wild Type Glioblastoma: Integrating MR Imaging, Pathologic, and RNA Data from Ivy Glioblastoma Atlas Project.

BACKGROUND: To spatially validate intratumoral subregions (tumor habitat) using physiologic MRI on pathology of the isocitrate dehydrogenase (IDH)-wildtype whole-glioblastoma sample. METHODS: Data of 20 patients (168 slides) were obtained from the Ivy Glioblastoma Atlas Project. On MRI, tumor habitats were defined using voxel-wise clustering of apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps for contrast-enhancing lesion (CEL) and non-enhancing lesion (NEL). On pathology slides, normalized areas of leading edge (LE), infiltrating tumor (IT), cellular tumor (CT), hypervascular lesion (CThypervascular), and perinecrotic lesion (CTperinecrotic) were obtained. Gross specimen was co-registered on MRI and correlation between pathology-MRI habitats was calculated. RNA sequencing of 67 samples was assessed using 4 Neftel subtypes and further correlated with pathology. RESULTS: Six tumor habitats were identified: hypervascular, hypovascular cellular, and hypovascular hypocellular habitats for CEL and NEL. CT was correlated with hypovascular cellular habitat in CEL (r= 0.238, p =.005). IT was correlated with hypovascular cellular habitat in NEL (r= 0.294, p =.017). CThypervascular was correlated with hypervascular habitat in NEL (r= 0.195, p = .023). CTperinecrotic was correlated with imaging necrosis (r= 0.199, p =.005). Astrocyte-like subtypes were correlated with IT (r= 0.256, p <.001), while mesenchymal-like subtypes were correlated with CTperinecrotic area (r= 0.246, p <.001). CONCLUSION: Pathologically matched tumor subregions were cellular tumor with hypovascular cellular habitat in CEL and infiltrative tumor with hypovascular cellular habitat in NEL. Identification of the most aggressive as well as infiltrative tumor portion can be achieved using non-invasive MRI tumor habitats.

Hydrothermal dechlorination strategy for high-quality oil recovery from polyvinyl chloride.

The global production of PVC is around 3.5 million tons each year. Unfortunately, the disposal of PVC waste releases toxic substances such as hydrochloric acid, polychlorinated dioxins, and furans, which can harm the environment. Therefore, there is an urgent need for a safe and environmentally friendly thermochemical treatment method that reduces the damage caused by HCl gas produced during PVC pyrolysis and improves the quality of pyrolysis oil. Hydrothermal treatment technology is one of the potential dechlorination strategies for PVC. However, its efficiency is reduced in the supercritical region, while the additives used result in secondary pollution and increased operating costs. This study is pioneering in its approach, aiming to produce high-quality oil with reduced chlorine through low-temperature hydrothermal treatment of PVC, all without additives. The results are promising, indicating that by administering steam at 250 °C with a 2.0-3.0 g-steam/g-feed ratio, we can significantly reduce chlorine content to 0.13 % while achieving an oil yield of up to 14.9 % from PVC. The hydrothermal process can reduce CO2 emissions by 15-43 % compared to pyrolysis methods, providing a simultaneous opportunity for carbon neutrality and resource recovery.

Enhancing drug administration flexibility: evaluation of pharmacokinetic properties of tegoprazan orally disintegrating tablet (ODT) administered via nasogastric tube or oral dosing.

Tegoprazan orally disintegrating tablet (ODT) formulation is a novel formulation to improve a convenience in comparison to taking the conventional tablet of tegoprazan, a potassium-competitive acid blocker. The purpose of this study was to evaluate the pharmacokinetic and safety profiles of tegoprazan ODT when administered via two routes: nasogastric tube or oral dosing. This study is expected to expand the administration route of tegoprazan ODT. The study was conducted in an open-label, randomized, single-dose, two-way crossover design with a 1-week washout period. Healthy subjects aged 19 to 45 years were administered 50 mg of tegoprazan ODT orally or dissolved in water via nasogastric tube. Tegoprazan, the active ingredient, was quantified using a ultra-high performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS), and pharmacokinetic parameters were determined through non-compartmental analysis. Safety was monitored throughout the study. A total of 48 subjects, successfully completed the trial. The geometric mean ratios for log-transformed Cmax and AUCt, representing the ratio of nasogastric tube group to oral dosing group, along with 90% confidence intervals, were 1.1087 (1.0243-1.2000) and 1.0023 (0.9620-1.0442), respectively. All adverse events were unrelated to tegoprazan and mild in intensity. The pharmacokinetic profiles of tegoprazan ODT were equivalent between the nasogastric tube and oral administration. Considering the demonstrated linear pharmacokinetics and concentration-dependent pharmacodynamics of tegoprazan, the administration via nasogastric tube is expected to yield effects equivalent to those of oral administration. This approach offers a viable alternative, especially beneficial for patients with oral intake difficulties.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Purpose: Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion: Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Spatiotemporal variation of sterols in sediment as markers of primary production and ocean sewage dumping in the southwestern East Sea (Japan Sea).

The sedimentation of organic carbon in the Ulleung Basin, in the southwestern East Sea (Japan Sea) was investigated using radiocarbon and sterols. The accumulation rates of organic carbon and the contents of brassicasterol and dinosterol were higher on the slope than in the central basin, reflecting the surface water productivity, whereas cholesterol showed similar or higher contents in the central basin. The coprostanol concentration in surface sediments reflected the dispersion of sewage dumped in this region. The vertical distribution showed that the coprostanol concentration was the highest in the top 5-cm layer near the Korea Strait, close to one of the two dumping sites. A high coprostanol concentration was also found near the coast further north, where the content peaked at ∼10 cm depth. The vertical distribution of coprostanol helped to estimate the sediment accumulation rate at sites where radiocarbon gradient was too small or the values were too variable.

Mitral valve repair with leaflet resection versus preservation for degenerative posterior leaflet prolapse.

OBJECTIVES: The optimal technique for repairing posterior mitral valve leaflet prolapse remains undetermined. We aimed to compare leaflet resection and neochordae implantation in patients undergoing mitral valve repair for posterior leaflet prolapse, focusing on transmitral pressure gradient and recurrence of mitral regurgitation. METHODS: We enrolled patients undergoing mitral valve repair using either leaflet resection or neochordae implantation for single-segment prolapse of posterior mitral valve leaflet between 2000 and 2021 at our institution. Longitudinal outcomes were evaluated after adjustments with inverse-probability-of-treatment weighting. Repeat echocardiographic measurements (n = 3473, 5.4/patient) of transmitral pressure gradient and significant (moderate or severe) mitral regurgitation recurrence were estimated using nonlinear mixed-effect models. Subgroup analyses were conducted based on the size and type of prosthesis. RESULTS: Among 639 patients, leaflet resection was used in 479 (75.0%) and neochordae implantation was used in 160 (25.0%). In the inverse-probability-of-treatment weighting adjusted cohort, the risk of death (P = .623) and mitral valve reoperation (P = .340) did not significantly differ between the 2 groups during a median follow-up of 97.3 months. Echocardiographic data showed comparable mean (at 5 years, 3.8 vs 4.0 mm Hg; P = .442) and peak (9.6 vs 10.4 mm Hg; P = .131) pressure gradients between groups, which persisted in most subgroup analyses. However, neochordae implantation was associated with a higher probability of significant mitral regurgitation recurrence compared with leaflet resection (at 5 years, 16.1% vs 7.0%; P < .001). CONCLUSIONS: Leaflet resection yielded similar clinical outcomes and transmitral pressure gradients compared with neochordae implantation after mitral valve repair, with a lower mitral regurgitation recurrence rate. These findings underscore the need to reassess the efficacy of neochordae implantation relative to leaflet resection.

Is Hooke's law applicable to an orthodontic cantilever?

INTRODUCTION: This study aimed to analyze the load-deflection characteristics of an orthodontic cantilever by using the large deflection elastic model. METHODS: We experimentally measured the vertical deflections of a cantilever with round or rectangular cross-sections, with lengths of 20 mm and 30 mm, and made of either stainless steel or titanium molybdenum alloy. The measurements were obtained under clinically relevant loading ranges (20-60 g of force for round and 20-140 g of force for rectangular wires) and compared with theoretical predictions derived from small and large deflection elastic models. Load-deflection and tangent stiffness curves were subsequently plotted. RESULTS: The impact of a permanent deformation was clinically insignificant. The stiffness of the cantilever increased with the load or deflection rather than remaining constant. Within the clinical loading range, we identified stiffness reversal loading values at which the stiffness of titanium molybdenum alloy surpassed that of stainless steel. The textbook guidelines on cantilevers can apply only when the vertical deflection remains within 16% of its length. CONCLUSIONS: Within the typical clinical loading range, the load-deflection relationship of a cantilever deviates from Hooke's law because of the prominent deflection trait. The conventional model remains effective when the vertical deflection is within 16% of the cantilever length. Otherwise, it is advisable to determine the load and stiffness on the basis of actual measurements rather than relying on theoretical predictions.

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.

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT).

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

N-terminal truncated trehalose-6-phosphate synthase 1 gene (△NIbTPS1) enhances the tolerance of sweet potato to abiotic stress.

Sweet potato [Ipomoea batatas (L.) Lam], the crop with the seventh highest annual production globally, is susceptible to various adverse environmental influences, and the study of stress-resistant genes is important for improving its tolerance to abiotic stress. The enzyme trehalose-6-phosphate synthase (TPS) is indispensable in the one pathway for synthesizing trehalose in plants. TPS is known to participate in stress response in plants, but information on TPS in sweet potato is limited. This study produced the N-terminal truncated IbTPS1 gene (△NIbTPS1) overexpression lines of Arabidopsis thaliana and sweet potato. Following salt and mannitol-induced drought treatment, the germination rate, root elongation, and fresh weight of the transgenic A. thaliana were significantly higher than that in the wild type. Overexpression of △NIbTPS1 elevated the photosynthetic efficiency (Fv/Fm) and the activity of superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase in sweet potato during drought and salt treatments, while reducing malondialdehyde and O2∙- contents, although expression of the trehalose-6-phosphate phosphatase gene IbTPP and trehalose concentrations were not affected. Thus, overexpressing the △NIbTPS1 gene can improve the stress tolerance of sweet potato to drought and salt by enhancing the photosynthetic efficiency and antioxidative enzyme system. These results will contribute to understand the functions of the △NIbTPS1 gene and trehalose in the response mechanism of higher plants to abiotic stress.

Discovery of urinary biosignatures for tuberculosis and nontuberculous mycobacteria classification using metabolomics and machine learning.

Nontuberculous mycobacteria (NTM) infection diagnosis remains a challenge due to its overlapping clinical symptoms with tuberculosis (TB), leading to inappropriate treatment. Herein, we employed noninvasive metabolic phenotyping coupled with comprehensive statistical modeling to discover potential biomarkers for the differential diagnosis of NTM infection versus TB. Urine samples from 19 NTM and 35 TB patients were collected, and untargeted metabolomics was performed using rapid liquid chromatography-mass spectrometry. The urine metabolome was analyzed using a combination of univariate and multivariate statistical approaches, incorporating machine learning. Univariate analysis revealed significant alterations in amino acids, especially tryptophan metabolism, in NTM infection compared to TB. Specifically, NTM infection was associated with upregulated levels of methionine but downregulated levels of glutarate, valine, 3-hydroxyanthranilate, and tryptophan. Five machine learning models were used to classify NTM and TB. Notably, the random forest model demonstrated excellent performance [area under the receiver operating characteristic (ROC) curve greater than 0.8] in distinguishing NTM from TB. Six potential biomarkers for NTM infection diagnosis, including methionine, valine, glutarate, 3-hydroxyanthranilate, corticosterone, and indole-3-carboxyaldehyde, were revealed from univariate ROC analysis and machine learning models. Altogether, our study suggested new noninvasive biomarkers and laid a foundation for applying machine learning to NTM differential diagnosis.

Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study.

Introduction: The use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality. Methods: Forty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed. Results: No significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera Blautia and Ruminococcus increased in fecal samples from the LTC-022 group. Conclusion: These results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep duration and an appropriate bedtime. Additionally, changes in the gut microbiota may be linked to changes in sleep patterns resulting from the consumption of Lactium and L-theanine. Clinical trial registration: https://cris.nih.go.kr/cris/search/detailSearch.do/22841, KCT0007750.

The Role of Prolactin in Amniotic Membrane Regeneration: Therapeutic Potential for Premature Rupture of Membranes.

Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.

Extracellular C1qbp inhibits myogenesis by suppressing NFATc1.

Aging and lack of exercise are the most important etiological factors for muscle loss. We hypothesized that new factors that contribute to muscle loss could be identified from ones commonly altered in expression in aged and exercise-limited skeletal muscles. Mouse gastrocnemius muscles were subjected to mass spectrometry-based proteomic analysis. The muscle proteomes of hindlimb-unloaded and aged mice were compared to those of exercised and young mice, respectively. C1qbp expression was significantly upregulated in the muscles of both hindlimb-unloaded and aged mice. In vitro myogenic differentiation was not affected by altering intracellular C1qbp expression but was significantly suppressed upon recombinant C1qbp treatment. Additionally, recombinant C1qbp repressed the protein level but not the mRNA level of NFATc1. NFATc1 recruited the transcriptional coactivator p300, leading to the upregulation of acetylated histone H3 levels. Furthermore, NFATc1 silencing inhibited p300 recruitment, downregulated acetylated histone H3 levels, and consequently suppressed myogenic differentiation. The expression of C1qbp was inversely correlated with that of NFATc1 in the gastrocnemius muscles of exercised or hindlimb-unloaded, and young or aged mice. These findings demonstrate a novel role of extracellular C1qbp in suppressing myogenesis by inhibiting the NFATc1/p300 complex. Thus, C1qbp can serve as a novel therapeutic target for muscle loss.

Apple Watch 6 vs. Galaxy Watch 4: A Validity Study of Step-Count Estimation in Daily Activities.

The purpose of this study was to examine the validity of two wearable smartwatches (the Apple Watch 6 (AW) and the Galaxy Watch 4 (GW)) and smartphone applications (Apple Health for iPhone mobiles and Samsung Health for Android mobiles) for estimating step counts in daily life. A total of 104 healthy adults (36 AW, 25 GW, and 43 smartphone application users) were engaged in daily activities for 24 h while wearing an ActivPAL accelerometer on the thigh and a smartwatch on the wrist. The validities of the smartwatch and smartphone estimates of step counts were evaluated relative to criterion values obtained from an ActivPAL accelerometer. The strongest relationship between the ActivPAL accelerometer and the devices was found for the AW (r = 0.99, p < 0.001), followed by the GW (r = 0.82, p < 0.001), and the smartphone applications (r = 0.93, p < 0.001). For overall group comparisons, the MAPE (Mean Absolute Percentage Error) values (computed as the average absolute value of the group-level errors) were 6.4%, 10.5%, and 29.6% for the AW, GW, and smartphone applications, respectively. The results of the present study indicate that the AW and GW showed strong validity in measuring steps, while the smartphone applications did not provide reliable step counts in free-living conditions.