Prognosis prediction and immunotherapy optimisation for cryptogenic new-onset refractory status epilepticus.

BACKGROUND: Cryptogenic new-onset refractory status epilepticus (cNORSE) currently lacks comprehensive knowledge regarding its clinical dynamics, prognostic factors and treatment guidance. Here we present the longitudinal clinical profiles, predictive factors for outcomes and the optimal duration of immunotherapy in patients with cNORSE. METHODS: This retrospective secondary endpoint analysis investigated patients with cNORSE identified from a prospective autoimmune encephalitis cohort at a national referral centre in Korea. The main outcomes included longitudinal functional scales, seizure frequency and the number of antiseizure medications. Measures encompassed NORSE-related clinical parameters such as the duration of unconsciousness, immunotherapy profiles, cytokine/chemokine analysis, and serial MRI scans. RESULTS: A total of 74 patients with cNORSE were finally analysed (mean age: 38.0±18.2; 36 (48.6%) male). All patients received first-line immunotherapy, and 91.9% (68/74) received second-line immunotherapy. A total of 83.8% (62/74) regained consciousness within a median duration of 30 days (14-56), and 50% (31/62) achieved good outcome (mRS ≤2) at 2 years. Poor 1-year outcomes (mRS ≥3) were predicted by the presence of mesial temporal lobe (mTL) and extra-mTL lesions at 3-month MRI, and prolonged unconsciousness (≥60 days). Those with mTL atrophy exhibited a higher seizure burden post-NORSE. The optimal duration of immunotherapy appeared to be between 18 weeks and 1-year post-NORSE onset. CONCLUSIONS: This study elucidates longitudinal clinical dynamics, functional outcomes, prognostic factors and immunotherapy response in patients with cNORSE. These findings might contribute to a more standardised understanding and clinical decision-making for cNORSE.

Bioconversion of agriculture by-products with functionally enhanced Streptomyces sp. SCUT-3: Fish skin as a model.

With the global population continuously rising, efficient bioconversion of inedible agricultural by-products is crucial for human food and energy sustainability. We here propose solid-state fermentation approaches to efficiently convert biopolymers into oligomers/monomers by accelerating the natural degradation process of the versatile Streptomyces sp. strain SCUT-3. Using fish skin as a representative by-product, 54.3 g amino acids and 14.7 g peptides (91 % < 2500 Da) were recovered from 89.0 g protein in 100 g tilapia skin sample by collagenase-overexpressed SCUT-3 for seven days at a 1:4 substrate:liquid ratio. Fish skin collagen hydrolysates exhibited excellent anti-oxidation, anti-hypertension, scratch-repairing, anti-aging, anti-ultraviolet radiation, and anti-inflammation effects on human skin fibroblasts In vitro and zebrafish larvae in vivo, indicating their potential applications in healthcare/skincare and anti-atopic dermatitis. As Laozi said, the divine law follows nature. This study underscores the efficacy of genetically engineered SCUT-3 according to its natural biomass utilization laws in large-scale biopolymer conversion.

Development of a Standardized Suicide Prevention Program for Gatekeeper Intervention in Korea (Suicide CARE Version 2.0) to Prevent Adolescent Suicide: Version for Teachers.

OBJECTIVE: The increasing concern over adolescent suicide necessitates suicide prevention training for school teachers, as students spend a significant portion of their time at school. This study's objective is to develop a suicide prevention program tailored for teachers. METHODS: The program was developed by a multidisciplinary research team, drawing on a review of both domestic and international suicide prevention programs, related scholarly articles, and Korean psychological autopsy interviews of adolescents. This was complemented by a survey of teachers to assess the program's practicality and usability. RESULTS: The developed program comprises three parts, consistent with other versions: Careful Observation, Active Listening, and Risk Evaluation and Expert Referral. Careful Observation focuses on training teachers to recognize verbal, behavioral, and situational warning signs of suicidal ideation in students; Active Listening involves strategies for encouraging students to express their suicidal thoughts and techniques for being an empathetic and attentive listener; Risk Evaluation and Expert Referral provides instruction on how to assess suicide risk and assist students safely. CONCLUSION: It is anticipated that this program will equip teachers with valuable knowledge and skills, contributing to a reduction in adolescents suicide rates.

Clinical characteristics and phenoconversion in isolated REM sleep behavior disorder: a prospective single-center study in Korea, compared with Montreal cohort.

STUDY OBJECTIVES: Isolated rapid-eye movement behavior disorder (iRBD) is a prodromal synucleinopathy, but its conversion rate and subtypes can vary among different cohorts. We report the clinical characteristics and phenoconversion rate of the large single-center iRBD cohort in Korea and compared it to the Montreal cohort. METHODS: This prospective cohort study examined 238 patients with polysomnography confirmed iRBD from Seoul National University Hospital (SNUH) who completed at least one follow-up evaluation. We compared the baseline and phenoconversion data of the SNUH cohort to those of 242 iRBD patients in the Montreal cohort. RESULTS: In the SNUH cohort, age at RBD diagnosis was similar (66.4±7.8 vs 65.6±8.4, p=0.265), but the proportion of men was lower (63.0% vs. 74.0%, p=0.001), and the duration of follow-up was shorter than that in the Montreal cohort (3.7±2.0 vs. 4.8±3.6 years, p<0.001). During follow-up, 34 (11.8%) patients in the SNUH cohort converted to neurodegenerative disease: 18 (52.9%) to Parkinson's disease, 9 (26.5%) to dementia with Lewy bodies (DLB), and 7 (20.6%) to multiple system atrophy. The conversion rate in the SNUH cohort was 15% after 3 years, 22% after 5 years, and 32% after 7 years, which was significantly lower than that of the Montreal cohort (log-rank test, p=0.002). Among phenoconversion subtype, fewer subjects in the SNUH group than in the Montreal group converted to DLB (Gray's test p=0.001). CONCLUSIONS: Through a comparative analysis between the SNUH and Montreal cohorts, we identified a significant difference in phenoconversion rates, particularly for DLB patients. These findings underscore the importance of further research into the underlying factors, such as racial and geographical factors contributing to such disparities.

Integrative Analysis of the Microbiome and Metabolome of Broiler Intestine: Insights into the Mechanisms of Probiotic Action as an Antibiotic Substitute.

Antibiotic substitutes have become a research focus due to restrictions on antibiotic usage. Among the antibiotic substitutes on the market, probiotics have been extensively researched and used. However, the mechanism by which probiotics replace antibiotics remains unclear. In this study, we aimed to investigate this mechanism by comparing the effects of probiotics and antibiotics on broiler growth performance and intestinal microbiota composition. Results shown that both probiotics and antibiotics increased daily weight gain and reduced feed conversion rate in broilers. Analysis of ileum and cecum microorganisms via 16S rRNA gene sequencing revealed that both interventions decreased intestinal microbial diversity. Moreover, the abundance of Bacteroides increased in the mature ileum, while that of Erysipelatoclostridium decreased in the cecum in response to both probiotics and antibiotics. The main metabolites of probiotics and antibiotics in the intestine were found to be organic acids, amino acids, and sugars, which might play comparable roles in growth performance. Furthermore, disaccharides and trisaccharides may be essential components in the ileum that enable probiotics to replace antibiotics. These findings provide important insights into the mechanisms underlying the use of probiotics as antibiotic substitutes in broiler breeding.

Mediation Effect of Social Distancing on Neonatal Vitamin D Status and Related Clinical Outcomes during the Coronavirus Disease-19 Pandemic.

BACKGROUND: We analyzed the impact of social distancing (SD) on vitamin D status and associated morbidity in neonates during the coronavirus disease (COVID-19) pandemic. METHODS: Serum levels of 25-hydroxy vitamin D (25OHD) and clinical characteristics of newborn infants before (2019) and during SD (2021) were compared. RESULTS: A total of 526 neonates (263 in 2019 and 263 in 2021) were included. The rate of vitamin D deficiency in neonates (47.1% vs. 35.4 %, p = 0.008) decreased and the rate of maternal vitamin D intake increased (6.8% vs. 37.6%, p < 0.001), respectively, during SD compared to those in 2019. The rates of hypocalcemia (12.5% vs. 3.8%, p < 0.001) and respiratory illness (57.0% vs. 43.0%, p = 0.002) decreased during SD. Neonatal vitamin D deficiency during SD was associated with maternal vitamin D supplementation (odds ratio [OR] = 0.463, p = 0.003) but was not associated with SD (OR = 0.772, p = 0.189). The mediation effect of SD on neonatal morbidity by neonatal vitamin D status was statistically insignificant. CONCLUSIONS: SD might affect the increased maternal vitamin D intake and decreased neonatal vitamin D deficiency. However, neonatal morbidity was not affected by SD, even with neonatal vitamin D status changes.

Effect of nicotinamide mononucleotide on osteogenesis in MC3T3-E1 cells against inflammation-induced by lipopolysaccharide.

OBJECTIVE: Nicotinamide mononucleotide (NMN) is extensively utilized as an anti-aging agent and possesses anti-inflammatory properties. Lipopolysaccharide (LPS) activates Toll-like receptor 4, a process modulated by intracellular signaling pathways such as the Wnt/ß-catenin pathway. This study investigated the impact of NMN on osteogenesis in the presence of LPS. METHODS: To elucidate the role of NMN in osteogenesis in the context of Gram-negative bacterial infection after LPS treatment, we cultured a mouse pre-osteoblast cell line (MC3T3-E1) and subsequently incubated it with NMN and/or LPS. We then evaluated osteogenic activity by measuring alkaline phosphatase activity, assessing gene expression and protein levels, and performing Alizarin Red S staining and immunocytochemistry. RESULTS: MC3T3-E1 cells underwent successful differentiation into osteoblasts following treatment with osteogenic induction medium. LPS diminished features related to osteogenic differentiation, which were subsequently partially reversed by treatment with NMN. The restorative effects of NMN on LPS-exposed MC3T3-E1 cells were further substantiated by elucidating the role of Wnt/ß-catenin signaling, as confirmed through immunocytochemistry. CONCLUSION: This study showed that infection with Gram-negative bacteria disrupted the osteogenic differentiation of MC3T3-E1 cells. This adverse effect was partially reversed by administering a high-dose of NMN. Drawing on these results, we propose that NMN could serve as a viable therapeutic strategy to preserve bone homeostasis in elderly and immunocompromised patients.

Identification of Autoantigens in Pediatric Gastric Juices.

Purpose: This study aimed to investigate the presence of autoantigens in the gastric juices of children. Methods: Gastric juice and serum samples were obtained from 53 children <15 years of age who underwent gastric endoscopy. Among these, 8, 22, and 23 participants were in the age groups 0-5, 6-10, and 11-15 years, respectively. These samples were analyzed using two-dimensional electrophoresis (2-DE), immunoblot analysis, and matrix-assisted laser desorption ionization-time of-flight mass spectrometry. Furthermore, we reviewed the histopathological findings and urease test results and compared them with the results of 2-DE and immunoblot analysis. Results: There were no statistically significant differences in urease test positivity, grades of chronic gastritis, active gastritis, or Helicobacter pylori infiltration of the antrum and body among the three age groups. Three distinct patterns of gastric juice were observed on 2-DE. Pattern I was the most common, and pattern III was not observed below the age of 5 years. Histopathological findings were significantly different among active gastritis (p=0.037) and H. pylori infiltration (p=0.060) in the gastric body. The immunoblots showed large spots at an approximate pH of 3-4 and molecular weights of 31-45 kDa. These distinct, large positive spots were identified as gastric lipase and pepsin A and C. Conclusion: Three enzymes, which are normally secreted under acidic conditions were identified as autoantigens. Further investigation of the pathophysiology and function of autoantigens in the stomach is required.

Comprehensive lifestyle modification interventions for metabolic syndrome: A systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews and meta-analyses have mainly focused on improvements in the number of metabolic syndrome risk factors and individual changes in each risk factor, making it challenging to examine the impact of comprehensive lifestyle modification interventions on adherence to recommended health behaviors. To address this gap, we conducted a systematic and meta-analysis aimed at identifying clinical parameter levels associated with lifestyle modification outcomes and adherence to recommended health behaviors for individuals with metabolic syndrome. METHODS: A total of seven studies retrieved from four databases (CINAHL, Medline via PubMed, American Psychological Association PsycINFO, and Embase) were included in the review. The selected studies, which demonstrated improvements in health behaviors, all included diet and exercise as main factors of comprehensive lifestyle modification in home settings. RESULTS: Our findings suggest that a 6-month comprehensive intervention including diet and exercise can be effective in decreasing glucose levels and systolic blood pressure. However, given the limited available data, further studies investigating the efficacy of interventions of varying durations are needed. DISCUSSION: Although our review included a small number of studies, comprehensive lifestyle modifications consisting of at least two components (primarily diet and exercise) can improve health behaviors and some clinical parameters among individuals with metabolic syndrome. Future studies are needed to investigate the long-term effects of lifestyle modifications on health behavior adherence and explore effective interventions to address certain clinical parameters, such as high-density lipoprotein levels. Also, we recommend using objective and quantifiable measure to compare adherence to recommended lifestyle modifications across studies. CLINICAL RELEVANCE: This research provides empirical evidence of the effectiveness of comprehensive lifestyle modification and emphasizes the need to develop long-term nursing strategies in public health that can be used to effectively manage metabolic syndrome.

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p

BACKGROUND@#Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilagederived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. @*METHODS@#The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. @*RESULTS@#F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and b-catenin. @*CONCLUSION@#F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.

Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone–Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model

BACKGROUND@#Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone–tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. @*METHODS@#Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including TGF-b-only, CTGF-only, and TGF-b + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. @*RESULTS@#Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-band CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. @*CONCLUSION@#Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

Sustainable valorizing high-protein feather waste utilization through solid-state fermentation by keratinase-enhanced Streptomyces sp. SCUT-3 using a novel promoter.

Feather waste, a rich source of proteins, has traditionally been processed through high-temperature puffing and acid-base hydrolysis, contributing to generation of greenhouse gases and H2S. To address this issue, we employed circular economy techniques to recover the nutritional value of feather waste. Streptomyces sp. SCUT-3, an efficient proteolytic and chitinolytic bacterium, was isolated for feather degradation previously. This study aimed to valorize feather waste for feed purposes by enhancing its feather transformation ability through promoter optimization. Seven promoters were identified through omics analysis and compared to a common Streptomyces promoter ermE*p. The strongest promoter, p24880, effectively enhanced the expression of three candidate keratinases (Sep39, Sep40, and Sep53). The expression efficiency of double-, triple-p24880 and sandwich p24880-sep39-p24880 promoters were further verified. The co-overexpression strain SCUT-3-p24880-sep39-p24880-sep40 exhibited a 16.21-fold increase in keratinase activity compared to the wild-type. Using this strain, a solid-state fermentation process was established that increased the feather/water ratio (w/w) to 1:1.5, shortened the fermentation time to 2.5 days, and increased soluble peptide and free amino acid yields to 0.41 g/g and 0.14 g/g, respectively. The resulting has high protein content (90.49 %), with high in vitro digestibility (94.20 %). This method has the potential to revolutionize the feather waste processing industry.

Health Care Support Worker Status, Health Behaviors, Mental Health, and Preventive Health Care Use.

This cross-sectional study compares the health behaviors, mental health status, and preventive health care usage of health care support workers (HSWs) with clinicians and the general population.

Enzyme Activity and Lipogenesis Inhibition by Fermented Grain Using Natural Enzymes.

This study aims to compare the effects of three enzyme-rich foods, including one fermented (grain enzyme) and two non-fermented foods (enzyme foods 1 and 2), by investigating their antioxidant, anti-inflammatory, and anti-adipogenic properties. Grain enzyme exhibited the highest radical scavenging activity and was rich in antioxidant components, including total polyphenol and total flavonoid contents. Grain enzyme and enzyme foods 1 and 2 inhibited nitric oxide production by 27, 34, and 17%, respectively, at a concentration of 200 µg/mL in LPS-stimulated macrophages. Among the tested enzymes, grain enzyme demonstrated the strongest inhibition on the expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1ß, while Enzyme Food 2 exhibited the most significant suppression of IL-6 mRNA levels. Furthermore, Grain Enzyme demonstrated a stronger inhibitory effect compared to Enzyme Food 1 and 2. Grain Enzyme decreased the mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, and fatty acid-binding protein (FABP)4 by 28, 21, and 30%, respectively, at a concentration of 400 µg/mL. In summary, fermented grain enzymes outperformed non-fermented enzymes in suppressing inflammation and adipogenesis. This study highlights the anti-inflammatory and anti-adipogenic effects of grain enzyme, suggesting its potential as a valuable dietary supplement for managing metabolic disorders.

Effects of physical exercise interventions on cognitive function in Parkinson's disease: An updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether physical exercise interventions can improve cognitive function, including overall performance and specific domains, in patients with Parkinson's disease (PD) and to provide potential evidence on how cognitive benefits can be optimized by exercise prescriptions. METHODS: Using PubMed, Web of Science, and Cochrane Library (from inception to August 2022), four independent reviewers screened the search results and extracted data from randomized controlled trials of physical exercise interventions in patients with PD with an outcome measure of cognitive function. Random-effects meta-analysis models were used to report standardized mean differences (SMDs) with 95 % confidence intervals (CIs). RESULTS: Twenty-one randomized controlled trials including 761 patients with PD were eligible for inclusion. Physical exercise interventions led to significant improvements in global cognitive function (SMD = 0.69; 95 % CI = 0.31 to 1.06; P < 0.001). With respect to cognitive domains, the significant effect of exercise was found on executive function (SMD = 0.94; 95 % CI = 0.05 to 1.83; P = 0.039), but not on attention/working memory, language, memory, and visuospatial function. In moderator variable analyses, the effect on global cognition was observed in combined exercise programs (SMD = 0.79; 95 % CI = 0.46 to 1.12; P < 0.001), whereas there were no significant positive effects in aerobic exercise programs, strength exercise programs, and flexibility exercise programs. In addition, exercise interventions of light-to-moderate intensity with at least 60 min in duration, and of any frequency or period, were beneficial to the global cognitive function. CONCLUSION: This updated systematic review and meta-analysis suggests that physical exercise interventions are effective in improving global cognitive function and, to a lesser extent, executive function in patients with PD. At least 60 min a day of combined exercise programs on as many days of the week as feasible may be recommended as the non-pharmacological therapeutic option to improve cognitive function.

Incidence and Risk Factors for Wound Revision after Surgical Treatment of Spinal Metastasis: A National Population-Based Study in South Korea.

Wound complications are commonly seen after surgeries for metastatic spine tumors. While numerous studies have pinpointed various risk factors, there is ongoing debate. Therefore, this study aimed to verify various factors that are still under debate utilizing the comprehensive Korean National Health Insurance Service database. We identified and retrospectively reviewed a cohort of 3001 patients who underwent one of five surgical treatments (corpectomy, decompression and instrumentation, instrumentation only, decompression only, and vertebroplasty) for newly diagnosed spinal metastasis between 2009 and 2017. A Cox regression analysis was performed to determine the risk factors. A total of 197 cases (6.6%) of wound revision were found. Only the surgical method and Charlson comorbidity index were significantly different between the group that underwent wound revision and the group that did not. Regarding surgical methods, the adjusted hazard ratios for decompression only, corpectomy, instrumentation and decompression, and instrumentation only were 1.3, 2.2, 2.2, and 2.4, with these ratios being compared to the vertebroplasty group (p for trend = 0.02). In this regard, based on a sizable South Korean cohort, both surgical methods and medical comorbidity were found to be associated with the wound revision rate among spinal surgery patients for spinal metastasis.

Enhancement of preimplantation mouse embryo development with optimized in vitro culture dish via stabilization of medium osmolarity.

OBJECTIVE: We evaluated the efficacy of the newly developed optimized in vitro culture (OIVC) dish for cultivating preimplantation mouse embryos. This dish minimizes the need for mineral oil and incorporates microwells, providing a stable culture environment and enabling independent monitoring of individual embryos. METHODS: Mouse pronuclear (PN) zygotes and two-cell-stage embryos were collected at 18 and 46 hours after human chorionic gonadotropin injection, respectively. These were cultured for 120 hours using potassium simplex optimized medium (KSOM) to reach the blastocyst stage. The embryos were randomly allocated into three groups, each cultured in one of three dishes: a 60-mm culture dish, a microdrop dish, and an OIVC dish that we developed. RESULTS: The OIVC dish effectively maintained the osmolarity of the KSOM culture medium over a 5-day period using only 2 mL of mineral oil. This contrasts with the significant osmolarity increase observed in the 60-mm culture dish. Additionally, the OIVC dish exhibited higher blastulation rates from two-cell embryos (100%) relative to the other dish types. Moreover, blastocysts derived from both PN zygotes and two-cell embryos in the OIVC dish group demonstrated significantly elevated mean cell numbers. CONCLUSION: Use of the OIVC dish markedly increased the number of cells in blastocysts derived from the in vitro culture of preimplantation mouse embryos. The capacity of this dish to maintain medium osmolarity with minimal mineral oil usage represents a breakthrough that may advance embryo culture techniques for various mammals, including human in vitro fertilization and embryo transfer programs.

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up.

OBJECTIVE: Although orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DESIGN: An 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. SETTING AND PARTICIPANTS: A total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. METHODS: The patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. RESULTS: The prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (ß = -0.11, 95% CI -0.20 to -0.02, t = -2.44, P = .015) and Semantic Fluency Test (SFT) (ß = -0.44, 95% CI -0.81 to -0.08, t = -2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (ß = -0.08, 95% CI -0.14 to -0.01, t = -2.20, P = .028) and SFT (ß = -0.36, 95% CI -0.63 to -0.08, t = -2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. CONCLUSIONS AND IMPLICATIONS: Both OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.