Learning curve analysis for hand-assisted laparoscopic living donor nephrectomy: an analysis of 96 consecutive cases performed by a trained gastrointestinal surgeon.

Purpose: This study aims to analyze the learning curve of hand-assisted laparoscopic living donor nephrectomy (HLDN) conducted by a trained gastrointestinal surgeon. Methods: A retrospective analysis was performed on the perioperative clinical data of 96 consecutive patients who underwent HLDN from May 2013 to March 2023. The learning curve was evaluated using the cumulative sum (CUSUM) test based on operation time and risk-adjusted CUSUM for postoperative complications. Patients were divided into three groups (novice, development, and competency phases) based on changes in operation time. Patient demographics and perioperative outcomes were compared between each group. Results: Among the patients, 35 were male, with a mean age of 48.9 ± 11.3 years and a mean body mass index (BMI) of 24.5 ± 3.2 kg/m2. The novice phase (phase 1) included the first 30 cases, with the development phase (phase 2) up to the 65th case. Operation times were significantly different across phases, averaging 263.2 ± 33.4, 211.1 ± 34.4, and 161.1 ± 31.3 minutes for phases 1, 2, and 3, respectively (P < 0.001). Blood loss decreased gradually across phases (phase 1, 264.7 ± 144.4 mL; phase 2, 239.7 ± 166.3 mL; phase 3, 198.8 ± 103.5 mL), though not statistically significant. BMI impacted operation time only in phase 1. Overall postoperative complications occurred in 13 cases (Clavien-Dindo grade I, 4 cases; grade II, 9 cases), with no significant differences across phases. Conclusion: HLDN can be safely performed by a trained gastrointestinal surgeon, with approximately 30 cases needed to achieve proficiency.

Galectin 3-binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor-ß1 (TGF-ß1) availability and inhibits hepatocarcinogenesis.

BACKGROUND: Increased Galectin 3-binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-ß1 (TGF-ß1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF-ß1 signaling pathway. METHODS: The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA-sequencing, transposase-accessible chromatin-sequencing assay, and liquid chromatography-tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP-TGF-ß1 axis. The effects of altered TGF-ß1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice. RESULTS: In patients with MASH and HCC, the levels of LGALS3BP and TGFB1 exhibited positive correlations. Stimulation of LGALS3BP by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice, with increased TGFB1 levels. LGALS3BP directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF-ß1 from extracellular latent complex with the rearranged F-actin cytoskeleton. The released TGF-ß1 activated JunB transcription factor, which in turn promoted the TGF-ß1 positive feedback loop. LGALS3BP deletion in the hepatocytes downregulated TGF-ß1 signaling and CCl4 induced fibrosis. Moreover, LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-ß1. CONCLUSION: LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-ß1 signaling pathway, making it a promising therapeutic target in TGF-ß1-related diseases.

Relationship between crustacean consumption and serum perfluoroalkyl substances (PFAS): the Korean National Environmental Health Survey (KoNEHS) cycle 4.

Background: Perfluoroalkyl substances (PFASs) are non-aromatic organic compounds, whose hydrogen atoms in the carbon chain substituted by fluorine atoms. PFASs exhibit developmental toxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, immunotoxicity, and hormone toxicity. PFASs are used in the production of disposable food packages, aircraft and automobile devices, cooking utensils, outdoor gear, furniture and carpets, aqueous film forming foam (AFFF), cables and wires, electronics, and semiconductors. This study aimed to determine the association between crustacean consumption and serum PFASs. Methods: Adult participants (2,993) aged ≥ 19 years were extracted from the 4th cycle data of the Korean National Environmental Health Survey (KoNEHS). Based on the 50th percentile concentrations of serum PFASs, participants were divided into the low-concentration group (LC) and the high-concentration group (HC). General characteristics, dietary factors, coated product usage, and personal care product usage, an independent t-test and χ2 test were analyzed. The odds ratio (OR) of serum PFAS concentration against crustacean consumption was estimated via logistic regression analysis adjusting for general characteristics, dietary factors, coated product usage, and personal care product usage. Results: The OR for the HC of serum PFASs was higher in individuals with ≥once a week crustacean consumption than in those with < once a week crustacean consumption. Estimated ORs were perfluorohexanesulfonic acid 2.15 (95% confidence interval [CI]: 1.53-3.02), perfluorononanoic acid (PFNA) 1.23 (95% CI: 1.07-1.41), and perfluorodecanoic acid (PFDeA) 1.42 (95% CI: 1.17-1.74) in males, and perfluorooctanoic acid 1.48 (95% CI: 1.19-1.84), perfluorooctanesulfonic acid 1.39 (95% CI: 1.27-1.52), PFNA 1.70 (95% CI: 1.29-2.26) and PFDeA 1.43 (95% CI: 1.32-1.54) in females. Conclusions: This study revealed the association between the crustacean consumption and concentrations of serum PFASs in general Korean population.

The application of enhanced recovery after surgery protocol after distal gastrectomy for patients with gastric cancer: a prospective randomized clinical trial.

BACKGROUND: This study aimed to evaluate the clinical outcomes and efficacy of enhanced recovery after surgery (ERAS) protocol in patients undergoing distal gastrectomy for gastric cancer (GC). METHODS: Patients were randomly assigned to the ERAS group (EG) and the conventional care group (CG) by stratified randomization according to age and sex. The primary endpoint was adjusted postoperative hospital stay, calculated using discharge criteria developed to evaluate recovery. Nutritional data and quality of life (QoL) (European Organisation for Research and Treatment of Cancer [EORTC] C30 and STO22) during the perioperative period were also analyzed. RESULTS: We enrolled 198 eligible patients with GC for the study between June 2017 and January 2019. A total of 147 patients were finally enrolled in this study (full analysis set) and were assigned to EG (n = 71) and CG (n = 76). First flatus was faster significantly in EG (3.6 ± 1.5 vs 4.1 ± 1.2 days, P = .019). EG showed a faster start of the sips and soft diet than CG (1.3 ± 0.7 vs 3.1 ± 0.4 days, P < .001; 2.4 ± 0.9 vs 5.2 ± 0.7 days, P < .001) according to the protocol. The recorded hospital stay was not significantly different; however, adjusted hospital stay was significantly shorter in EG than in CG (6.5 ± 3.1 vs 7.8 ± 2.1 days, P = .005). There was no difference in morbidity, and no mortality occurred in both groups. EG did not show significant superiority in nutritional outcome and QoL improvement, except for pain scale in EORTC-STO22. CONCLUSION: The application of the ERAS protocol could reduce the adjusted hospital stay without an increase in postoperative complications. There was no significant difference in long-term nutritional outcome and QoL of the 2 groups.

Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.

Metformin, a primary anti-diabetic medication, has been anticipated to provide benefits for Alzheimer's disease (AD), also known as "type 3 diabetes". Nevertheless, some studies have demonstrated that metformin may trigger AD pathology and even elevate AD risk in humans. Despite this, limited research has elucidated the behavioral outcomes of metformin treatment, which would hold significant translational value. Thus, we aimed to perform thorough behavioral research on the prolonged administration of metformin to mice: We administered metformin (300 mg/kg/day) to transgenic 3xTg-AD and non-transgenic (NT) C57BL/6 mice over 1 and 2 years, respectively, and evaluated their behaviors across multiple domains via touchscreen operant chambers, including motivation, attention, memory, visual discrimination, and cognitive flexibility. We found metformin enhanced attention, inhibitory control, and associative learning in younger NT mice (≤16 months). However, chronic treatment led to impairments in memory retention and discrimination learning at older age. Furthermore, metformin caused learning and memory impairment and increased levels of AMPKα1-subunit, ß-amyloid oligomers, plaques, phosphorylated tau, and GSK3ß expression in AD mice. No changes in potential confounding factors on cognition, including levels of motivation, locomotion, appetite, body weight, blood glucose, and serum vitamin B12, were observed in metformin-treated AD mice. We also identified an enhanced amyloidogenic pathway in db/db mice, as well as in Neuro2a-APP695 cells and a decrease in synaptic markers, such as PSD-95 and synaptophysin in primary neurons, upon metformin treatment. Our findings collectively suggest that the repurposing of metformin should be carefully reconsidered when this drug is used for individuals with AD.

Automated prediction of acute promyelocytic leukemia from flow cytometry data using a graph neural network pipeline.

OBJECTIVES: Our study aimed to develop a machine learning (ML) model to accurately classify acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (other AML) using multicolor flow cytometry (MFC) data. Multicolor flow cytometry is used to determine immunophenotypes that serve as disease signatures for diagnosis. METHODS: We used a data set of MFC files from 27 patients with APL and 41 patients with other AML, including those with uncommon immunophenotypes. Our ML pipeline involved training a graph neural network (GNN) to output graph-level labels and identifying the most crucial MFC parameters and cells for predictions using an input perturbation method. RESULTS: The top-performing GNN achieved 100% accuracy on the training/validation and test sets on classifying APL from other AML and used MFC parameters similarly to expert pathologists. Pipeline performance is amenable to use in a clinical decision support system, and our deep learning architecture readily enables prediction explanations. CONCLUSIONS: Our ML pipeline shows robust performance on predicting APL and could be used to screen for APL using MFC data. It also allowed for intuitive interrogation of the model's predictions by clinicians.

Workout with a Smartwatch: A Cross-Sectional Study of the Effects of Smartwatch Attributes on Flow Experience and Exercise Intentions Depending on Exercise Involvement.

Smartwatches are emerging as effective tools to promote exercise and physical activities in the healthcare industry. However, little is known about how smartwatch attributes facilitate exercise and for whom such attributes are more effective for exercise. Accordingly, the purpose of this study was to explore the structural relationship between smartwatch attributes, flow experience, and continued exercise intentions and to examine the moderating role of exercise involvement in the structural relationship. For this, a total of 600 participants were recruited via a professional survey firm in South Korea based on a multi-stage random sampling method and used for data analyses, including confirmatory factor analysis (CFA), structural equation modeling (SEM), and multi-group SEM. All survey items were adopted from the existing literature on healthcare, flow experience, and wearable device technologies. The results revealed that smartwatch attributes, including interactivity (γ = 0.234, p < 0.001/γ = 0.235, p < 0.001), autonomy (γ = 0.225, p < 0.001/γ = 0.172, p < 0.001), wearability (γ = 0.104, p < 0.05/γ = 0.106, p < 0.05), convenience (γ = 0.209, p < 0.001/γ = 0.214, p < 0.001), and experiential novelty (γ = 0.221, p < 0.001/γ = 0.281, p < 0.001) enhanced flow experience (absorption/enjoyment) during exercise. Furthermore, flow experience (absorption/enjoyment) was found to positively influence exercise intention (ß = 0.511, p < 0.001/ß = 0.239, p < 0.001). Lastly, exercise involvement was found to modulate the structural relationships among smartwatch attributes, flow experience, and exercise intention (∆χ2 = 23.231, ∆df = 12, p < 0.05). By investigating these dynamics, this study contributes to shared knowledge not only in the healthcare literature but also in the wearable-technology literature. The results of the current study also provide useful guidelines for practitioners in the wearable-device and healthcare industries to develop optimal features of smartwatches for exercise and physical activities.

Effects of a supportive workplace environment on the success rate for smoking cessation camp.

Background: This study was conducted to identify the success rate for smoking cessation over time after participation in a therapeutic smoking cessation camp, and to identify how participant characteristics, including a supportive workplace environment for smoking cessation (SWESC), affect the success rate for smoking cessation. Methods: In all, 296 participants at smoking cessation camps in Ulsan between 2015 and 2020 were investigated. The success rates of smoking cessation after weeks 4, 6, 12, and 24 at camp were investigated. The participants were grouped as workers with an SWESC, and workers without an SWESC, and variables (age, education, household income, marital status, drinking, exercise, body mass index, morbidity, job, number of counseling sessions, cigarettes smoked per day and smoking initiation age) were investigated. Multiple logistic regression analysis was conducted at each time point. In addition, Cox regression analysis was performed to evaluate the variables affecting the success rate for smoking cessation over time. Results: The smoking cessation success rate of workers with an SWESC at week 24 (90.7%) was higher than that for workers without an SWESC (60.5%). Multiple logistic regression was performed to determine the relationship between each variable and the success rates for smoking cessation at week 6, 12, and 24. SWESC was confirmed as significant (p < 0.05) variables for increased success rate for smoking cessation at all 3 time points. After adjusting for all variables, the Cox proportional hazards survival analysis showed a hazard ratio of 6.17 for SWESC (p < 0.001,; 95% confidence interval: 3.08-12.38). Conclusions: At a professional treatment smoking cessation camp, participants with an SWESC showed a significantly higher success rate for smoking cessation. Supportive workplace environment for workers' health is expected to be an important factor for smoking cessation projects as well as other health promotion projects at workplace.

High-throughput chemogenetic drug screening reveals PKC-RhoA/PKN as a targetable signaling vulnerability in GNAQ-driven uveal melanoma.

Uveal melanoma (UM) is the most prevalent cancer of the eye in adults, driven by activating mutation of GNAQ/GNA11; however, there are limited therapies against UM and metastatic UM (mUM). Here, we perform a high-throughput chemogenetic drug screen in GNAQ-mutant UM contrasted with BRAF-mutant cutaneous melanoma, defining the druggable landscape of these distinct melanoma subtypes. Across all compounds, darovasertib demonstrates the highest preferential activity against UM. Our investigation reveals that darovasertib potently inhibits PKC as well as PKN/PRK, an AGC kinase family that is part of the "dark kinome." We find that downstream of the Gαq-RhoA signaling axis, PKN converges with ROCK to control FAK, a mediator of non-canonical Gαq-driven signaling. Strikingly, darovasertib synergizes with FAK inhibitors to halt UM growth and promote cytotoxic cell death in vitro and in preclinical metastatic mouse models, thus exposing a signaling vulnerability that can be exploited as a multimodal precision therapy against mUM.

Pharmacokinetic profiles and egg residue patterns of levamisole in laying hens at two dosing rates and two routes of administration.

The levamisole maximum residue limit for edible fat, kidney, and muscle of chickens is 0.01 mg/kg. However, no maximum residue limit has been established for eggs. In the present study, the pharmacokinetic profile and levamisole residue in the eggs from laying hens were investigated using ultra-performance liquid chromatography-tandem mass spectrometry. A single dose of levamisole (30 mg/kg) was administered via the intramuscular or oral route, and an additional egg residue study was performed with 300 or 600 mg/kg commercial LEV drug (30 or 60 mg/kg as levamisole) orally. The limit of quantification was 0.0056 µg/mL and 0.0015 mg/kg for plasma and eggs, respectively. The plasma concentration was below the limit of quantification 10 and 12 h after intramuscular and oral administration, respectively. The half-life of the absorption phase was comparable between the intramuscular and oral routes, which was approximately 1 h, and the mean maximum concentration value was significantly higher in intramuscular (2.29 ± 0.30 µg/mL) than in oral (1.45 ± 0.38 µg/mL) route. The relative oral bioavailability after intramuscular administration was 92.3%. In the egg residue study, dose-dependent area under concentration and maximum concentration were observed after single oral administration of 30 and 60 mg/kg egg residue, and the calculated withdrawal period for both 30 and 60 mg/kg groups based on the positive list system standard (0.01 mg/kg) was 7 d after the treatment.

Endocytosis gated by emergent properties of membrane-clathrin interactions.

Clathrin-mediated endocytosis (CME), the major cellular entry pathway, starts when clathrin assembles on the plasma membrane into clathrin-coated pits (CCPs). Two populations of CCPs are detected within the same cell: 'productive' CCPs that invaginate and pinch off, forming clathrin-coated vesicles (CCVs) [1, 2], and 'abortive' CCPs [3, 4, 5] that prematurely disassemble. The mechanisms of gating between these two populations and their relations to the functions of dozens of early-acting endocytic accessory proteins (EAPs) [5, 6, 7, 8, 9] have remained elusive. Here, we use experimentally-guided modeling to integrate the clathrin machinery and membrane mechanics in a single dynamical system. We show that the split between the two populations is an emergent property of this system, in which a switch between an Open state and a Closed state follows from the competition between the chemical energy of the clathrin basket and the mechanical energy of membrane bending. In silico experiments revealed an abrupt transition between the two states that acutely depends on the strength of the clathrin basket. This critical strength is lowered by membrane-bending EAPs [10, 11, 12]. Thus, CME is poised to be shifted between abortive and productive events by small changes in membrane curvature and/or coat stability. This model clarifies the workings of a putative endocytic checkpoint whose existence was previously proposed based on statistical analyses of the lifetime distributions of CCPs [4, 13]. Overall, a mechanistic framework is established to elucidate the diverse and redundant functions of EAPs in regulating CME progression.

Diagnostic performance of F-18 FDG PET or PET/CT for detection of recurrent gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigated the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (PET/CT) for the detection of disease recurrence after curative resection of gastric cancer. METHODS: The PubMed and Embase databases, from the earliest available date of indexing through November 30, 2019, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT to detect recurrent disease after gastric cancer surgery. RESULTS: Across 17 studies (1,732 patients), the pooled sensitivity for F-18 FDG PET or PET/CT was 0.82 (95% confidence interval [CI], 0.74-0.88) with heterogeneity of I2=76.5 (p<0.001), and the specificity was 0.86 (95% CI, 0.78-0.91) with heterogeneity of I2=94.2 (p<0.001). Likelihood ratio (LR) tests gave an overall positive LR of 6.0 (95% CI, 3.6-9.7) and negative LR of 0.2 (95% CI, 0.14-0.31). The pooled diagnostic odds ratio was 29 (95% CI, 13-63). The summary receiver operating characteristic curve indicates that the area under the curve was 0.91 (95% CI, 0.88-0.93). CONCLUSION: The current meta-analysis showed good sensitivity and specificity of F-18 FDG PET or PET/CT for detecting recurrent disease after curative resection of gastric cancer despite heterogeneity in ethnicity, recurrence rate, histology, and interpretation method.

Enhanced Photoelectrochemical Water Oxidation Using TiO2-Co3O4 p-n Heterostructures Derived from in Situ-Loaded ZIF-67.

Exposing catalytically active metal sites in metal-organic frameworks (MOFs) while maintaining porosity is beneficial for increasing electron transport to achieve better electrochemical energy conversion performance. Herein, we propose an in situ method for MOF formation and loading onto TiO2 nanorods (NR) using a simple solution-processable method followed by annealing to obtain TiO2-Co3O4. The as-prepared TiO2-ZIF-67 based photoanodes were annealed at 350, 450, and 550 °C to study the effect of carbonization on photo-electrochemical water oxidation. The successful loading of ZIF-67 on TiO2 and the formation of TiO2-Co3O4 heterojunction were confirmed by XRD, XPS, FE-SEM, and HRTEM analyses. TiO2-Co3O4-450 (the sample annealed at 450 °C) showed an enhanced photocurrent of 2.4 mA/cm2, which was 2.6 times larger than that of pristine TiO2. The improved photocurrent might be ascribed to the prepared p-n heterostructures (Co3O4 and TiO2), which promote electron-hole separation and charge transfer within the system and improve the photoelectrochemical performance. Moreover, the preparation of Co3O4 from the MOF carbonization process improved the electrical conductivity and significantly increased the number of exposed active sites and enhanced the photoresponse performance. The as-prepared ZIF-67 derived TiO2-Co3O4 based photoanodes demonstrate high PEC water oxidation, and the controlled carbonization method paves the way toward the synthesis of low-cost and efficient electrocatalysts.

Patency of arteriovenous fistulas and grafts for dialysis access: An analysis using the Korean National Health Insurance Service database from 2008 to 2019.

BACKGROUND: Arteriovenous (AV) access practice and its outcomes vary internationally. To provide a better understanding of the patterns and outcomes of AV access creation, we investigated the patency and risk factors of arteriovenous fistulas (AVFs) and grafts (AVGs) as initial AV access in the Korean adult population using data from the last 10 years. METHODS: The National Health Insurance Service database was queried retrospectively to identify patients undergoing hemodialysis with AVFs and AVGs as well as their clinical characteristics and outcomes from 2008 to 2019. AV access patency and its associated risk factors were evaluated. RESULTS: During the study period, 64,179 AVFs and 21,857 AVGs were placed. The mean patient age was 62.6 ± 13.6 years (21.5% were ⩾75 years old), and 39.3% patients were women. More than half of the patients underwent AV access creation at tertiary care hospitals. At 1 year, the primary, primary assisted, and secondary patency rates were 62.2%, 80.7%, and 94.2% for AVFs, and 46.0%, 68.4%, and 86.8% for AVGs, respectively. AVG, older age, female sex, diabetes, and creation at general hospitals (vs tertiary hospitals) were associated with decreased patency outcomes (all, p < 0.05). CONCLUSION: This study using national data showed that three quarters of patients with AV access had AVF and AVF showed superior performance to AVG and identified several patient and center factors related to AV access patency in Korea.

Added Breathing Resistance during Exercise Impairs Pulmonary Ventilation and Exaggerates Exercise-Induced Hypoxemia Leading to Impaired Aerobic Exercise Performance.

Protective masks impose variable breathing resistance (BR) on the wearer and may adversely affect exercise performance, yet existing literature shows inconsistent results under different types of masks and metabolic demands. The present study was undertaken to determine whether added BR impairs cardiopulmonary function and aerobic performance during exercise. Sixteen young healthy men completed a graded exercise test on a cycle ergometer under the four conditions of BR using a customized breathing resistor at no breathing resistance (CON), 18.9 (BR1), 22.2 (BR2), and 29.9 Pa (BR3). The results showed that BR significantly elevates respiratory pressure (p < 0.001) and impairs ventilatory response to graded exercise (reduced VE; p < 0.001) at a greater degree with an increased level of BR which caused mild to moderate exercise-induced hypoxemia (final mean SpO2: CON = 95.6%, BR1 = 94.4%, BR2 = 91.6%, and BR3 = 90.6%; p < 0.001). Especially, such a marked reduction in SpO2 was significantly correlated with maximal oxygen consumption at the volitional fatigue (r = 0.98, p < 0.001) together with exaggerated exertion and breathing discomfort (p < 0.001). In conclusion, added BR commonly experienced when wearing tight-fitting facemasks and/or respirators could significantly impair cardiopulmonary function and aerobic performance at a greater degree with an increasing level of BR.

A Single Bout of Remote Ischemic Preconditioning Suppresses Ischemia-Reperfusion Injury in Asian Obese Young Men.

Remote ischemic preconditioning (RIPC) has been shown to minimize subsequent ischemia-reperfusion injury (IRI), whereas obesity has been suggested to attenuate the efficacy of RIPC in animal models. The primary objective of this study was to investigate the effect of a single bout of RIPC on the vascular and autonomic response after IRI in young obese men. A total of 16 healthy young men (8 obese and 8 normal weight) underwent two experimental trials: RIPC (three cycles of 5 min ischemia at 180 mmHg + 5 min reperfusion on the left thigh) and SHAM (the same RIPC cycles at resting diastolic pressure) following IRI (20 min ischemia at 180 mmHg + 20 min reperfusion on the right thigh). Heart rate variability (HRV), blood pressure (SBP/DBP), and cutaneous blood flow (CBF) were measured between baseline, post-RIPC/SHAM, and post-IRI. The results showed that RIPC significantly improved the LF/HF ratio (p = 0.027), SBP (p = 0.047), MAP (p = 0.049), CBF (p = 0.001), cutaneous vascular conductance (p = 0.003), vascular resistance (p = 0.001), and sympathetic reactivity (SBP: p = 0.039; MAP: p = 0.084) after IRI. However, obesity neither exaggerated the degree of IRI nor attenuated the conditioning effects on the measured outcomes. In conclusion, a single bout of RIPC is an effective means of suppressing subsequent IRI and obesity, at least in Asian young adult men, does not significantly attenuate the efficacy of RIPC.

Prevalence of feline chronic gingivostomatitis in feral cats and its risk factors.

OBJECTIVES: This study investigated the prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea and analysed its risk factors. METHODS: Three hundred and forty-five feral cats that visited the hospital for neutering using a trap-neuter-return approach were screened for feline chronic gingivostomatitis based on clinical criteria. In addition, we determined if body weight, sex and the presence of tongue lesions are risk factors for feline chronic gingivostomatitis. The difference in severity due to the presence or absence of risk factors, and the relationship between gross findings and histopathological lesions, were analysed by grading lesion severity. RESULTS: Feline chronic gingivostomatitis was diagnosed in 92 cats. Disease prevalence did not significantly differ with body weight and sex but was significantly related to tongue lesions. CONCLUSIONS AND RELEVANCE: The prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea was 26.6%. It was significantly more prevalent in cats that had tongue lesions. Severity was also significantly associated with tongue lesions. Feline chronic gingivostomatitis may be associated with an infectious agent that causes tongue lesions.

Comprehensive Characterization of Mutant Pichia stipitis Co-Fermenting Cellobiose and Xylose through Genomic and Transcriptomic Analyses.

The development of a yeast strain capable of fermenting mixed sugars efficiently is crucial for producing biofuels and value-added materials from cellulosic biomass. Previously, a mutant Pichia stipitis YN14 strain capable of co-fermenting xylose and cellobiose was developed through evolutionary engineering of the wild-type P. stipitis CBS6054 strain, which was incapable of cofermenting xylose and cellobiose. In this study, through genomic and transcriptomic analyses, we sought to investigate the reasons for the improved sugar metabolic performance of the mutant YN14 strain in comparison with the parental CBS6054 strain. Unfortunately, comparative wholegenome sequencing (WGS) showed no mutation in any of the genes involved in the cellobiose metabolism between the two strains. However, comparative RNA sequencing (RNA-seq) revealed that the YN14 strain had 101.2 times and 5.9 times higher expression levels of HXT2.3 and BGL2 genes involved in cellobiose metabolism, and 6.9 times and 75.9 times lower expression levels of COX17 and SOD2.2 genes involved in respiration, respectively, compared with the CBS6054 strain. This may explain how the YN14 strain enhanced cellobiose metabolic performance and shifted the direction of cellobiose metabolic flux from respiration to fermentation in the presence of cellobiose compared with the CBS6054 strain.

BNT162b2-induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 diminish with age.

Each severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant renews concerns about decreased vaccine neutralization weakening efficacy. However, while prevention of infection varies, protection from disease remains and implicates immunity beyond neutralization in vaccine efficacy. Polyclonal antibodies function through Fab domains that neutralize virus and Fc domains that induce non-neutralizing responses via engagement of Fc receptors on immune cells. To understand how vaccines promote protection, we leverage sera from 51 SARS-CoV-2 uninfected individuals after two doses of the BNT162b2 mRNA vaccine. We show that neutralizing activities against clinical isolates of wild-type and five SARS-CoV-2 variants, including Omicron BA.2, link to FcγRIIIa/CD16 non-neutralizing effector functions. This is associated with post-translational afucosylation and sialylation of vaccine-specific antibodies. Further, polyfunctional neutralizing and non-neutralizing breadth, magnitude, and coordination diminish with age. Thus, studying Fc functions in addition to Fab-mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations, such as the elderly, against SARS-CoV-2 and novel variants.