Association between single-person household wage workers in South Korea and insomnia symptoms: the 6th Korean Working Conditions Survey (KWCS).

BACKGROUND: The rise in single-person households is a global phenomenon with well-documented implications for both physical and mental well-being. However, there remains a scarcity of studies focusing specifically on the health impacts of single-person households on workers. This study aims to address this gap by comparing insomnia symptoms between single- and multi-person household workers, shedding light on the health implications of household composition. METHODS: This study utilized data from the Sixth Korean Working Conditions Survey. Insomnia symptoms were categorized into normal sleep and insomnia symptom groups utilizing the 3-item Minimal Insomnia Symptom Scale. Multiple logistic regression analysis was employed to examine the association between single-person household wage workers and insomnia symptoms. RESULTS: In comparison to wage workers from multi-person households, those from single-person households exhibited heightened risks of reporting insomnia symptoms. In the fully adjusted model, the odds ratios for symptoms of insomnia among single-person household wage workers was 1.173 (95% confidence interval: 1.020-1.349). CONCLUSIONS: This study underscores that single-person household wage workers in Korea face an elevated risk of insomnia symptoms compared to their counterparts in multi-person households.

Prognostic impact of intraoperative rupture in early-stage epithelial ovarian cancer: an ancillary study of GORILLA-3002.

OBJECTIVE: To evaluate whether intraoperative rupture affects oncological outcomes in patients with early-stage epithelial ovarian cancer (EOC). METHODS: A multicenter retrospective study was conducted on patients with early-stage EOC based on surgical and final pathological reports between 2007 and 2021. Oncologic outcomes were compared between the unruptured group (International Federation of Gynaecology and Obstetrics [FIGO] stage IA/IB) and ruptured group (FIGO stage IC1). The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) was performed to adjust for the imbalance in prognostic factors between the groups. RESULTS: Overall, 197 (58.3 %) patients comprised the unruptured group (FIGO stage IA/IB), and 141 (41.7 %) were in the intraoperatively ruptured group (FIGO stage IC1). No significant difference in the 5-year PFS was observed between the two groups before PSM (92.65 % vs. 92.80 %, P = 0.93). After PSM, the 5-year PFS showed a noticeable decrease in the ruptured group compared to the unruptured group, although this difference showed borderline statistical significance (96.90 % vs. 89.82 %, P = 0.061). This trend was particularly discernible in cases with aggressive tumor characteristics; intraoperative rupture remained an independent prognostic factor for shorter PFS in patients with high-grade histology (adjusted hazard ratio = 14.4, 95 % confidence interval = 2.8-74.1). CONCLUSIONS: Although not statistically significant, intraoperative rupture may negatively affect PFS in these patients after PSM. Therefore, rupture during surgery should be avoided as it can cause upstaging and unnecessary chemotherapy.

Feasibility Assessment of Robotic Major Hepatectomy and Bile Duct Resection in Klatskin Type IIIB Tumor with Concomitant Gallbladder Cancer.

BACKGROUND: Radical resection is the only curative treatment for perihilar cholangiocarcinoma (Klatskin tumor), the most common type of bile duct cancer.1,2 Because Klatskin tumors require major hepatectomy including segment 1, extensive lymphadenectomy, and bile duct reconstruction, laparoscopic surgery has technical challenges, especially with small and multiple bile ducts.2-5 The robotic platform has great freedom of movement, making it effective for dissection and suturing in minimally invasive Klatskin tumor resection.2,3,6 However, few cases have been reported, prompting this video demonstration. METHODS: A 74-year-old woman was referred to surgery after biliary drainage due to obstructive jaundice. Adenocarcinoma was diagnosed via endobiliary brushing, with magnetic resonance imaging and computed tomography (CT) showing a polypoid mass in the gallbladder and a 3-cm enhancing mass in the perihilar area. No signs of distant metastasis were present. Thus, robotic left hepatectomy including segment 1, partial hepatectomy of segment 5, and bile duct resection were performed (see video). RESULTS: The total operative time was 419 min, with an estimated blood loss of 300 ml. Computed tomography on postoperative day 5 showed no abnormal findings, and the patient was discharged on postoperative day 10 without complications. The final pathologic results confirmed the double primary adenocarcinomas with clear resection margins of 6.4 cm and 3.8 cm, respectively, and 11 lymph nodes all were negative for malignancy. CONCLUSIONS: This case exemplifies the safety and effectiveness of robotic surgery for Klatskin tumors, even with concomitant gallbladder cancer, and demonstrates the benefits and potential of this technique in complex surgical procedures.

Protective Role of Astaxanthin in Regulating Lipopolysaccharide-Induced Inflammation and Apoptosis in Human Neutrophils.

Astaxanthin, a keto-carotenoid, is known to have potent antioxidant properties. This study aims to investigate the anti-inflammatory effect of astaxanthin and its mechanism in human neutrophils. The effects of astaxanthin on lipopolysaccharide (LPS)-stimulated human neutrophils were investigated in vitro. Neutrophils were isolated from healthy volunteers and stimulated with LPS in the presence and absence of astaxanthin. We assessed cytokine production, signaling pathway activation via mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB), and apoptosis. Astaxanthin's impact was evaluated at different concentrations, and both pretreatment and cotreatment protocols were tested. The results demonstrated that astaxanthin significantly reduced the production of pro-inflammatory cytokines TNF-α and IL-1ß in LPS-stimulated neutrophils. It effectively inhibited the phosphorylation of ERK1/2 MAPK, without notably affecting p38 MAPK or NF-κB pathways. Furthermore, astaxanthin promoted apoptosis in neutrophils, counteracting the apoptosis-delaying effects of LPS. These effects were more pronounced with pretreatment. In conclusion, astaxanthin has protective effects on inflammatory responses in neutrophils by reducing cytokine production and enhancing apoptosis while selectively modulating intracellular signaling pathways. Astaxanthin demonstrates significant potential as a therapeutic agent in the management of severe inflammatory conditions.

Relationship between continuity of primary care and hospitalisation for patients with COPD: population-based cohort study from South Korea.

OBJECTIVES: The existing evidence for the impacts of continuity of care (COC) in patients with chronic obstructive pulmonary disease (COPD) is low to moderate. This study aimed to investigate the associations between relational COC within primary care and COPD-related hospitalisations using a robust methodology. DESIGN: Population-based cohort study. SETTING: National Health Insurance Service database, South Korea. PARTICIPANTS: 92 977 adults (≥40 years) with COPD newly diagnosed between 2015 and 2016 were included. The propensity score (PS) matching approach was used. PSs were calculated from a multivariable logistic regression that included eight baseline characteristics. EXPOSURE: COC within primary care. MAIN OUTCOME MEASURES: The primary outcome was the incidence of COPD-related hospitalisations. Cox proportional hazard models were used to estimate HRs and 95% CIs. RESULTS: Out of 92 977 patients, 66 677 of whom were cared for continuously by primary doctors (the continuity group), while 26 300 were not (the non-continuity group). During a 4-year follow-up period, 2094 patients (2.25%) were hospitalised; 874 (1.31%) from the continuity group and 1220 (4.64%) from the non-continuity group. After adjusting for confounding covariates, patients in the non-continuity group exhibited a significantly higher risk of hospital admission (adjusted HR (aHR) 2.43 (95% CI 2.22 to 2.66)). This risk was marginally reduced to 2.21 (95% CI 1.99 to 2.46) after PS matching. The risk of emergency department (ED) visits, systemic corticosteroid use and costs were higher for patients in the non-continuity group (aHR 2.32 (95% CI 2.04 to 2.63), adjusted OR 1.25 (95% CI 1.19 to 1.31) and expß=1.89 (95% CI 1.82 to 1.97), respectively). These findings remained consistent across the PS-matched cohort, as well as in the sensitivity and subgroup analyses. CONCLUSIONS: In patients with COPD aged over 40, increased continuity of primary care was found to be associated with less hospitalisation, fewer ED visits and lower healthcare expenditure.

Development of a biomarker-based platform for comprehensive skin characterization using minimally invasive skin sampling and quantitative real-time PCR.

BACKGROUND: Classifying diverse skin types is crucial for promoting skin health. However, efficiently identifying and analyzing relevant biomarkers from a vast array of available genetic data is challenging. Therefore, this study aimed to develop a precise and efficient platform for analyzing specific skin biomarkers using quantitative real-time PCR (qRT-PCR) with the minimal invasive skin sampling method (MISSM). MATERIALS AND METHODS: MISSM was used for RNA extraction from skin samples, followed by qRT-PCR analysis to quantify the expression of 20 biomarkers associated with skin characteristics (four biomarkers each for five skin characteristics). Noninvasive measurements from 299 Korean participants were utilized to correlate biomarker expression with skin parameters. Statistical analyses were conducted between biomarker expression levels and noninvasive skin measurements to select the relatively best-performing biomarker for each skin characteristic. RESULTS: Collagen type 1 alpha 1 (COL1A1) and moesin (MSN) were identified as skin aging biomarkers. Krüppel-like factor 4 (KLF4) and serine peptidase inhibitor Kazal type 5 (SPINK5) were identified as skin dryness biomarkers, whereas melan-A (MLANA) was selected as a biomarker for understanding pigmentation dynamics. Myelin protein zero like 3 (MPZL3) and high mobility group box 2 (HMGB2) were identified as markers of oily skin and skin sensitivity, respectively. Statistically significant correlations were found between the biomarker expression levels and noninvasive skin characteristic measurements. CONCLUSION: This study successfully developed a platform for the precise evaluation of individual skin characteristics using MISSM and qRT-PCR biomarker analysis. By selecting biomarkers that correlate with noninvasive measurements of skin characteristics, we demonstrated the platform's efficacy in assessing diverse skin conditions.

The association of shift work and TyG index among male workers in a chemical plant of Korea: a cross-sectional study.

Background: Disturbance of circadian rhythms caused by shift work has adverse effects on insulin resistance. Many previous studies have confirmed that shift work and insulin resistance are related using homeostasis model assessment-insulin resistance, one of the insulin resistance indicators. However, the triglycerides and glucose index (TyG index) has recently been studied as an insulin resistance indicator. The aim of this study is to investigate the association of shift work and TyG index, one of the indirect indicators of insulin resistance, using results of health checkups in one workplace. Methods: Based on medical examination data collected in February 2019, a total of 3,794 subjects from one chemical plant in Korea were selected for this study. Cut-off value of TyG index for predicting development of diabetes mellitus (DM) was 4.69. A multiple logistic regression analysis was performed after adjusting for age, employment period, obesity, abdominal obesity, smoking, drinking, physical activity, hypertension, stroke, heart disease. Results: As a result of logistic regression analysis, compared to day workers, odds ratio (OR) with a TyG index above cut-off value for predicting development of DM in shift workers was 1.220 after adjusting for age, employment period, obesity, abdominal obesity, smoking, drinking, physical activity, hypertension, stroke, heart disease (Model 1, OR: 1.276; 95% confidence interval [CI]: 1.099-1.482; Model 2, OR: 1.232; 95% CI: 1.055-1.438; Model 3, OR: 1.220, 95% CI: 1.030-1.444). Conclusions: There was a significant association between shift work and TyG index among male workers in a chemical plant. More research studies on the association between shift work and TyG index are needed in the future.

Anatomical Feasibility of Percutaneous Arteriovenous Fistula Formation in Korea.

INTRODUCTION: Currently, there are two types of percutaneous arteriovenous fistula (pAVF) formation systems approved by the FDA: Ellipsys and WavelinQ. Although these systems are already in use in Europe or the United States, they have not been approved for use in Korea yet. For this reason, this study aimed to check anatomical feasibility of these systems for Korean population prior to their actual use. METHODS: Consecutive patients who received ultrasound vein mapping for arteriovenous fistula formation from June 2021 to June 2022 were included. The anatomical feasibility of each system was confirmed according to the manufacturer's instructions for use (IFU). RESULTS: Upper extremity ultrasonography was performed for a total of 83 patients to determine their feasibility for pAVF formation. Of these patients, 65.1% were feasible for pAVF formation with appropriate deep communicating vein (DCV) and outflow. Among them, 57.8% were feasible for the Ellipsys system and 54.2% were feasible for the WavelinQ system. Most patients who were infeasible for pAVF formation had a DCV of small size. Ulnar vessels were more suitable than radial vessel for WavelinQ (54.2% vs 33.7%, P-value = .012). The most common reason for not meeting the criteria was a small vein size at the access site. CONCLUSIONS: More than half of all patients were feasible for pAVF formation in this study. Ellipsys had a higher feasibility than WavelinQ, although they showed no significant difference in the feasibility. If these devices are imported into Korea, it will be a good opportunity for many patients to reduce the surgical burden and create AVFs more easily through these procedures.

Comparison of Clinical Outcomes and Postoperative Nutritional Status Between Early and Late Oral Feeding After Esophagectomy: An Open Labeled Randomized Controlled Trial.

OBJECTIVE: To compare nutritional and postoperative outcomes between early oral feeding and late oral feeding with jejunostomy feeding support after esophagectomy. SUMMARY BACKGROUND DATA: Esophagectomy is associated with substantial body weight loss and malnutrition, impacting the prognosis of esophageal cancer patients. Despite many studies on post-esophagectomy nutritional support, optimal strategies remain elusive. This study investigates the impact of jejunostomy feeding with late oral feeding compared to conventional oral feeding on nutritional and postoperative outcomes. METHODS: We performed a single-center prospective open-labelled randomized controlled trial between 2020 and 2022. Patients aged 18 to 75 years with resectable esophageal cancer were randomly assigned to undergo either early oral feeding (early group) or late oral feeding with jejunostomy feeding support (late group) after esophagectomy. The primary endpoint was body weight loss from preoperative body weight at postoperative 4-5 weeks and 4 months. Other perioperative and nutritional outcomes were also evaluated. RESULTS: We randomly assigned 29 patients to the early group and 29 patients to the late group. The late group exhibited significantly less body weight loss at both postoperative 4-5 weeks (8.3% vs. 5.6%; P =0.002) and 4 months (15.0% vs. 10.5%; P =0.003). The total calorie intake and protein intake were higher in the late group for both postoperative 4-5 weeks (1800 kcal/day vs. 1100 kcal/day; P <0.001) and 4 months (1565 kcal/day vs. 1200 kcal/day; P =0.010). Sixty percentage of early group changed to malnutrition state, while 40% of the late group changed to malnutrition. The complication rate and length of hospital stays were similar. CONCLUSIONS: The late group demonstrated prevention of significant body weight loss, enhanced nutritional intake, and reduces malnutrition without compromising short-term surgical outcomes.

In vitro antifungal and physicochemical properties of polymerized acrylic resin containing strontium-modified phosphate-based glass.

Acrylic resins are widely used as the main components in removable orthodontic appliances. However, poor oral hygiene and maintenance of orthodontic appliances provide a suitable environment for the growth of pathogenic microorganisms. In this study, strontium-modified phosphate-based glass (Sr-PBG) was added to orthodontic acrylic resin at 0% (control), 3.75%, 7.5%, and 15% by weight to evaluate the surface and physicochemical properties of the novel material and its in vitro antifungal effect against Candida albicans (C. albicans). Surface microhardness and contact angle did not vary between the control and 3.75% Sr-PBG groups (p > 0.05), and the flexural strength was lower in the experimental groups than in the control group (p < 0.05), but no difference was found with Sr-PBG content (p > 0.05). All experimental groups showed an antifungal effect at 24 and 48 h compared to that in the control group (p < 0.05). This study demonstrated that 3.75% Sr-PBG exhibits antifungal effects against C. albicans along with suitable physicochemical properties, which may help to minimize the risk of adverse effects associated with harmful microbial living on removable orthodontic appliances and promote the use of various materials.

Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.

Effects of the Synthetic Cathinone α-Pyrrolidinobutiothiophenone (α-PBT) on Discriminative Stimulus Effects and Intracranial Self-Stimulation Thresholds in Male Rats.

Recently, the abuse of synthetic cathinones is increasing among young people. α-Pyrrolidinobutiothiophenone (α-PBT), a synthetic cathinone, is a designer drug that is freely traded online with no legal restrictions. Moreover, there is currently no scientific basis for legal regulation. Here, we examined the addictive properties of α-PBT using a drug discrimination (DD) task. We also investigated the role of α-PBT in brain stimulation reward (BSR) using an intracranial self-stimulation (ICSS) paradigm in rats. Initially, the rats were trained to discriminate between cocaine and saline. After the discrimination training criteria were met, we determined the dose-effect curves of cocaine and conducted generalization tests with α-PBT and α-pyrrolidinopentiothiophenone (α-PVT) using a cumulative dosing protocol. In a separate set of studies, we examined the dopaminergic mechanisms underlying the function of α-PBT as an interoceptive stimulus (17.8 mg/kg) by intraperitoneally injecting either the dopamine (DA) D1 antagonist SCH23390 (0.06 and 0.12 mg/kg) or the D2 antagonist eticlopride (0.05 and 0.1 mg/kg) 15 min before DD testing. Brain reward function was measured using an ICSS procedure to examine the effects of α-PBT on ICSS threshold under the frequency-rate procedure. Our results showed that α-PBT functioned as a discriminative cue similar to cocaine in rats. More importantly, SCH23390 abolished the effects of α-PBT as an interoceptive stimulus in a dose-dependent manner in rats trained to press a lever to receive cocaine. Similarly, eticlopride dose-dependently attenuated the effect of α-PBT used as a discriminative cue. Additionally, cumulative α-PBT administration dose-dependently lowered ICSS thresholds compared with those in saline-treated rats. Furthermore, α-PBT-induced potentiation of BSR was abolished by pretreatment with both SCH23390 and eticlopride. Taken together, our results suggest that α-PBT can function as a cocaine-like discriminative cue via the activation of D1 and D2 receptors. α-PBT also appears to influence BSR by reducing the brain reward threshold via changes in D1 and D2 receptors. The present study suggests that α-PBT could have addictive properties through DA D1 and D2 receptors and thus poses a threat to humans.

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

The method of using robotic Harmonic ACE curved shears for parenchymal transection in robotic hepatectomy.

Robotic liver surgery is emerging as a minimally invasive surgery to overcome the disadvantages of laparoscopy. The two biggest barriers to the uptake of robotic hepatectomy are the high cost and instrument limitations. Transection of the liver parenchyma is the main issue in robotic hepatectomy. Nonetheless, with adequate experience and the aid of reliable and enhanced three-dimensional visualization, many robotic surgeons have successfully used robotic Harmonic ACE curved shears (Intuitive Surgical Inc.) for parenchymal transection of the liver. Herein, we share a method of using robotic Harmonic ACE curved shears for parenchymal transection using a video clip.

The neuropharmacological properties of α-pyrrolidinobutiothiophenone, a new synthetic cathinone, in rodents; role of the dopaminergic system.

BACKGROUND AND PURPOSE: α-Pyrrolidinobutiothiophenone (α-PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α-PBT. EXPERIMENTAL APPROACH: We examined the abuse potential of α-PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine-like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self-administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D1 receptor or D2 receptors in α-PBT-induced hyperlocomotor activity, conditioned place preference, and the methamphetamine-like discriminative stimulus effect of α-PBT in rodents. KEY RESULTS: α-PBT promoted hyperlocomotor activity in mice. α-PBT induced drug-paired place preference in mice and supported self-administration in rats. In a drug discrimination experiment, α-PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α-PBT increased dopamine levels and c-Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D1 receptor antagonist SCH23390 or the D2 receptors antagonist eticlopride significantly attenuated acute or repeated α-PBT-induced hyperlocomotor activity, place preference, and the methamphetamine-like discriminative stimulus effects in rodents. CONCLUSIONS AND IMPLICATIONS: These findings suggest that α-PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α-PBT.

Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis.

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

Advancing treatment for perihilar cholangiocarcinoma: role of hepatopancreaticoduodenectomy in small-volume centers.

Hepatopancreaticoduodenectomy (HPD) is a controversial surgical technique for the treatment of perihilar cholangiocarcinoma. This study aimed to clarify the mortality, morbidity, and survival outcomes in patients with perihilar cholangiocarcinoma who underwent HPD at a small-volume hepatobiliary-pancreatic center. This retrospective study included 78 patients with perihilar cholangiocarcinoma who underwent HPD (n = 18) or major liver resection with bile duct resection (n = 60) at our center between October 2013 and December 2022. The primary endpoints were the in-hospital morbidity and 90-day mortality rates. The secondary endpoints included the recurrence-free and overall survival rates in both groups. Major complications (Clavien-Dindo grade ≥3) were more common in the HPD group (Group 1, 61.1%) than in the major liver resection group (Group 2; 23.3%, p = 0.03). The 1-, 3- and 5-year overall survival rates for Groups 1 and 2 were 66.7%, 41.7%, and 27.8% and 79.9%, 44.5%, and 22.7%, respectively (p = 0.89). The 1-, 3-, and 5-year recurrence-free survival rates for Groups 1 and 2 were 64.2%, 53.5%, and 35.6% and 85.3%, 46.8%, and 25.0%, respectively (p = 0.41). Although morbidity and mortality after HPD are higher than those after other surgeries, our findings suggest that HPD is a feasible treatment option for perihilar cholangiocarcinoma, even in small-volume centers. However, meticulous pre- and perioperative evaluation of the patient's overall health status, quality of life, and prospective advantages are required.

Antifungal mechanisms investigation of lactic acid bacteria against Aspergillus flavus: through combining microbial metabolomics and co-culture system.

AIMS: To develop antifungal lactic acid bacteria (LAB) and investigate their antifungal mechanisms against Aspergillus flavus in aflatoxin (AF) production. METHODS AND RESULTS: We isolated 179 LABs from cereal-based fermentation starters and investigated their antifungal mechanism against A. flavus through liquid chromatography-mass spectrometry and co-culture analysis techniques. Of the 179 isolates, antifungal activity was identified in Pediococcus pentosaceus, Lactobacillus crustorum, and Weissella paramesenteroides. These LABs reduced AF concentration by (i) inhibiting mycelial growth, (ii) binding AF to the cell wall, and (iii) producing antifungal compounds. Species-specific activities were also observed, with P. pentosaceus inhibiting AF production and W. paramesenteroides showing AF B1 binding activity. In addition, crucial extracellular metabolites for selecting antifungal LAB were involved in the 2',3'-cAMP-adenosine and nucleoside pathways. CONCLUSIONS: This study demonstrates that P. pentosaceus, L. crustorum, and W. paramesenteroides are key LAB strains with distinct antifungal mechanisms against A. flavus, suggesting their potential as biological agents to reduce AF in food materials.

Long-Term Epigenetic Regulation of Foxo3 Expression in Neonatal Valproate-Exposed Rat Hippocampus with Sex-Related Differences.

Perinatal exposure to valproic acid is commonly used for autism spectrum disorder (ASD) animal model development. The inhibition of histone deacetylases by VPA has been proposed to induce epigenetic changes during neurodevelopment, but the specific alterations in genetic expression underlying ASD-like behavioral changes remain unclear. We used qPCR-based gene expression and epigenetics tools and Western blotting in the hippocampi of neonatal valproic acid-exposed animals at 4 weeks of age and conducted the social interaction test to detect behavioral changes. Significant alterations in gene expression were observed in males, particularly concerning mRNA expression of Foxo3, which was significantly associated with behavioral changes. Moreover, notable differences were observed in H3K27ac chromatin immunoprecipitation, quantitative PCR (ChIP-qPCR), and methylation-sensitive restriction enzyme-based qPCR targeting the Foxo3 gene promoter region. These findings provide evidence that epigenetically regulated hippocampal Foxo3 expression may influence social interaction-related behavioral changes. Furthermore, identifying sex-specific gene expression and epigenetic changes in this model may elucidate the sex disparity observed in autism spectrum disorder prevalence.

Continuity of care between dyslipidemia patients and multiple providers: A cohort study.

OBJECTIVE: This study aimed to investigate the impacts of continuity of care (COC) between patients and multiple providers, i.e., doctors and community pharmacists, on clinical and economic outcomes. METHODS: This is a retrospective cohort study and analyzed Korean national claims data for ambulatory care setting between 2007 and 2018. Patients with dyslipidemia newly diagnosed in 2008 were identified. COC between providers and patients was computed using the continuity of care index (COCI). Based on COCIs, the study patients were allocated to four groups: HM/HP, HM/LP, LM/HP, and LM/LP. Each symbol represents H for high, L for low, M for doctor, and P for pharmacist. The primary study outcome was the incidence of atherosclerotic cardiovascular disease (ASCVD). RESULTS: 126,710 patients were included. Percentages of patients in the four study groups were as follows: HM/HP 35%, HM/LP 19%, LM/HP 12%, and LM/LP 34%. During the seven-year outcome period, 8,337 patients (6.6%) developed an ASCVD, and percentages in the study groups were as follows; HM/HP 6.2%, HM/LP 6.3%, LM/HP 6.8%, and LM/LP 7.1%. After adjusting for confounding covariates, only the LM/LP group had a significantly higher risk of ASCVD than the reference group, HM/HP (aHR = 1.16 [95% confidence interval = 1.10~1.22]). The risk of inappropriate medication adherence gradually increased 1.03-fold in the HM/LP group, 1.67-fold in the LM/HP, and 2.26-fold in the LM/LP group versus the HM/HP group after adjusting for covariates. Disease-related costs were lower in the HM/HP and LM/HP groups. CONCLUSIONS: The study shows that patients with high relational care continuity with doctors and pharmacists achieved better clinical results and utilized health care less, resulting in reduced expenses. Further exploration for the group that exhibits an ongoing relationship solely with pharmacists is warranted.