Nutritional and functional roles of ß-mannanase on intestinal health and growth of newly weaned pigs fed two different types of feeds.

This study aimed to investigate the nutritional and functional roles of ß-mannanase on the intestinal health and growth of newly weaned pigs fed a typical or low-cost formulated feeds. Twenty-four newly weaned pigs at 6.2 kg ± 0.4 body weight (BW) were allotted to three dietary treatments based on a randomized complete block design with sex and initial body weight as blocks. Three dietary treatments are as follows: Control, typical nursery feeds including animal protein supplements and enzyme-treated soybean meal; LCF, low-cost formulated feeds with increased amounts of soybean meal, decreased amounts of animal protein supplements, and no enzyme-treated soybean meal; LCF+, low-cost formulated feed with ß-mannanase at 100 g/t, providing 800 thermostable ß-mannanase unit (TMU) per kg of feed. Pigs were fed based on a three-phase feeding program for a total of 37 d. On d 37 of feeding, all pigs were euthanized and the gastrointestinal tract was removed for sample collection to analyze intestinal health parameters, mucosa-associated microbiota, and gene expression of tight junction proteins. Pigs fed LCF increased (P < 0.05) the relative abundance of Proteobacteria and Helicobacter in the jejunal mucosa, tended to decrease (P = 0.097; P = 0.098) the concentration of malondialdehyde (MDA) and the expression of zona occluden 1 (ZO-1) gene in the jejunum, tended to decrease average daily gain (ADG; P = 0.084) and final BW (P = 0.090), and decreased (P < 0.05) average daily feed intake (ADFI). Pigs fed LCF+ tended to decrease (P = 0.088) digesta viscosity, decreased (P < 0.05) the relative abundance of Helicobacter, and increased (P < 0.05) Lactobacillus in the jejunal mucosa compared to LCF. Additionally, LCF+ tended to increase final BW (P = 0.059) and ADG (P = 0.054), increased (P < 0.05) gain to feed ratio (G:F), and reduced (P < 0.05) fecal score compared to LCF. Low-cost formulated feeds with decreased amounts of animal protein supplements and increased amounts of soybean meal had negative effects on the composition of the mucosa-associated microbiota, intestinal integrity, and growth performance of nursery pigs. Beta-mannanase supplementation to low-cost formulated feeds decreased digesta viscosity, increased the relative abundance of potentially health-benefitting microbiota such as Lactobacillus, and improved growth and fecal score, thus reflecting its efficacy in low cost formulated feeds with increased amounts of soybean meal.

Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.

Effect of diabetes on mortality and liver transplantation in alcoholic liver cirrhotic patients with acute decompensation.

BACKGROUND: Previous studies have investigated the influence of diabetes on alcoholic liver cirrhosis patients, leaving its impact unclear. Thus, we conducted a study to reveal the association of diabetes and clinical outcomes of such patients. MATERIALS AND METHODS: We prospectively collected data from multicenter pertaining to 965 patients diagnosed with alcoholic liver cirrhosis, all of whom were admitted due to acute decompensation between 2015 and 2019. Risk of major precipitating factors and incidences of death or liver transplantation in patients with and without diabetes was comparatively assessed. Propensity score (PS) matching was performed at a 1:2 ratio for accurate comparisons. RESULTS: The mean age was 53.4 years, and 81.0% of the patients were male. Diabetes was prevalent in 23.6% of the cohort and was positively correlated with hepatic encephalopathy and upper gastrointestinal bleeding, although not statistically significant. During a median follow-up of 903.5 person-years (PYs), 64 patients with and 171 without diabetes died or underwent liver transplantation, with annual incidence of 33.6/100 PYs and 24.0/100 PYs, respectively. In the PS-matched cohort, the incidence of death or liver transplantation was 36.8/100 PYs and 18.6/100 PYs in the diabetes and matched control group, respectively. After adjusting for various factors, coexisting diabetes significantly heightened the risk of death or liver transplantation in the short and long term, in addition to prolonged prothrombin time, low serum albumin, elevated total bilirubin and creatinine, and decreased serum sodium levels. CONCLUSIONS: Diabetes increases the risk of death or liver transplantation in patients with alcoholic liver cirrhosis.

The Current Incidence and Future Projection of Acetabular Fractures in Korea.

BACKGROUND: As one of the most challenging fractures to orthopedic surgeons, acetabular fractures show a wide range of incidence among countries and regions with even more variance in the treatment modalities. In this study, we aimed to investigate the epidemiology of acetabular fractures, and to compare the rate of subsequent total hip arthroplasty (THA) between nonoperative and operative treatments in South Korea using a medical claims database. METHODS: This was a retrospective study using the Korean Health Insurance Review and Assessment database. Patients admitted for acetabular fractures from January 2007 to December 2018 were identified using International Classification of Diseases-10 codes. Kaplan-Meier survival analysis was used to compare the cumulative incidence of THA between two groups. We also evaluated the survivorship of operative group according to the type of institutions. RESULTS: The incidence rate of acetabular fractures increased by 28% between 2007 and 2018. Acetabular fractures were more common in men (62%) than women (38%), and most common in the patients older than 80 years. The number of acetabular fractures was estimated to increase 1.7-fold in 2030 compared to 2018. Operative treatment accounted for 16% of cases, and nonoperative treatment for 84%. The incidence of subsequent THA was higher in the operative treatment group than in the nonoperative group (P < 0.001). The higher rate in the operative treatment group is probably related with the severity of the fracture type. The rate of subsequent THA was higher in patients who initially treated in general hospitals compared with those who were initially treated in tertiary hospitals. CONCLUSION: The incidence of acetabular fractures is increasing in South Korea, in line with global trends. Most acetabular fractures are treated conservatively, and those who receive surgery are more likely to require a subsequent THA. Patients who were operated in general hospitals had highest possibility of subsequent THA after acetabular fractures.

A Rare Case of Delayed Ventriculoperitoneal Shunt Catheter Migration Into the Heart: A Case Report.

The treatment of hydrocephalus with a ventriculoperitoneal (VP) shunt can lead to complications such as shunt migration. A 67-year-old male, who had previously undergone VP shunt surgery for normal-pressure hydrocephalus, presented approximately five years later with symptoms of general weakness and abdominal pain. Imaging revealed shunt malpositioning, with the catheter passing through an abnormal route to the heart. The catheter was successfully removed under fluoroscopic guidance while monitoring patient's electrocardiogram to prevent potential secondary complications. Although rare, cardiac migration of VP shunts can lead to life-threatening secondary complications. Our case highlights the possibility of delayed upward migration of the shunt catheter in patients with VP shunts, emphasizing the need for various strategies to address and manage this issue.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Catalytic enantioselective [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones.

A highly efficient asymmetric [3+2] and [4+2]-annulation of cyclic N-sulfonyl ketimines with γ- or δ-hydroxy-α,ß-unsaturated ketones has been developed. This innovative reaction employs an organocatalytic approach, utilizing a hydrogen-bonding bifunctional squaramide-based catalyst. The process enables precise synthesis of chiral polyheterotricyclic oxazolidines and 1,3-oxazinane derivatives, revealing intricate structures with incorporated chiral quaternary centers. Remarkably, this method delivers high yields and exceptional enantioselectivities and diastereoselectivities, achieving up to 99% yield, >20 : 1 dr, and >99% ee.

Red ginseng extract inhibits lipopolysaccharide-induced platelet-leukocyte aggregates in mice.

Background: Platelet-leukocyte aggregates (PLAs) play important roles in cardiovascular disease and sepsis. Red ginseng extract (RGE) has been well-studied for its antiplatelet and anti-inflammatory activities. However, the potential inhibitory effects of RGE on PLA have not been investigated. Methods: Six-week-old ICR mice were given oral gavage of RGE for 7 days, followed by an intraperitoneal injection of 15 mg/kg of lipopolysaccharide. Mice were euthanized 24 h later, and blood samples were collected for further analysis. Flow cytometry was utilized to sort populations of PLAs and platelet-neutrophil aggregates (PNAs). By using confocal microscopy, PNAs were validated. Morphological changes in platelets and leukocytes were visualized with scanning electron microscopy. Expressions of tissue factor (TF) and platelet factor 4 (PF4) were investigated using enzyme-linked immunosorbent assay. Results: Populations of activated platelets, PLAs and PNAs, were significantly increased with LPS-induction. Treatment with 200 and 400 mg/kg of RGE decreased platelet activation. Moreover, the populations of PLAs and PNAs were reduced. PNAs were visible in the blood of septic mice, and this was attenuated by treatment with 400 mg/kg of RGE. Morphologically, sepsisinduced platelet activation and fibrin formation in the blood. This was reduced with RGE treatment. Sepsis-induced increase in the plasma levels of TF and PF4 was also reduced with RGE treatment. Conclusion: This study shows that RGE is a potential therapeutic that reduces the activation of platelets and targets PLA and PNA formation. Detailed inhibitory mechanisms of RGE should be studied.

LMT AMI Caused by a Valve-Like Ridge in a 9-Year-Old Boy Successfully Treated With PCI.

A 9-year-old boy was suspected of having acute myocardial infarction and emergency coronary angiogram was performed. No signs of flow limitation in either coronary artery was detected. We performed intravascular ultrasonography from the ascending aorta, which showed a ridge on the left main trunk acting like a valve, resulting in significant stenosis. Percutaneous coronary intervention with stent deployment was performed with good result.

Complete genome sequence of Pseudomonas aeruginosa strain NCTR 501 isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media.

We report the circularized 6,427,509-bp genome of Pseudomonas aeruginosa isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media. The genome of P. aeruginosa NCTR 501 has a circular chromosome of 6,420,288 bp and two plasmids of 4,042 and 3,179 bp, respectively.

Real-world incidence of incident noninfectious uveitis in patients treated with BRAF inhibitors: a nationwide clinical cohort study.

PURPOSE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy. DESIGN: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration. RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < 0.001 and 95% CI 2.81-11.47, P < 0.001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = 0.001 and 95% CI 1.76-141.00, P = 0.014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = 0.046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis. CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

Trastuzumab deruxtecan versus trastuzumab emtansine in Asian patients with HER2-positive metastatic breast cancer.

The global phase 3 DESTINY-Breast03 study (ClinicalTrials.gov; NCT03529110) showed statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) with trastuzumab deruxtecan (T-DXd) over trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. Here, we report a subgroup analysis of Asian patients enrolled in DESTINY-Breast03. In total, 309 patients (149 in the T-DXd arm and 160 in the T-DM1 arm) from Asian countries and regions were randomized. At data cutoff (July 25, 2022), the median duration of follow-up in the Asian subpopulation was 29.0 months with T-DXd and 26.0 months with T-DM1. The PFS (determined by blinded independent central review) hazard ratio was 0.30 (95% confidence interval 0.22-0.41) favoring T-DXd over T-DM1 (median PFS 25.1 vs. 5.4 months). Median OS was not reached in the T-DXd arm and was 37.7 months in the T-DM1 arm. The median treatment duration was 15.4 months with T-DXd and 5.5 months with T-DM1. The incidence of grade ≥3 drug-related treatment-emergent adverse events was similar between both treatment arms (49.0% vs. 46.5%) and was consistent with the overall DESTINY-Breast03 population. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 12.9% of patients treated with T-DXd and 2.5% treated with T-DM1, with a higher incidence in Japanese patients; none of these were grade ≥4 events. These efficacy and safety data reinforce the favorable benefit-risk profile of T-DXd in HER2-positive mBC, including in the Asian subgroup.

Resistance to FOXM1 inhibitors in breast cancer is accompanied by impeding ferroptosis and apoptotic cell death.

PURPOSE: Cancer treatments often become ineffective because of acquired drug resistance. To characterize changes in breast cancer cells accompanying development of resistance to inhibitors of the oncogenic transcription factor, FOXM1, we investigated the suppression of cell death pathways, especially ferroptosis, in FOXM1 inhibitor-resistant cells. We also explored whether ferroptosis activators can synergize with FOXM1 inhibitors and can overcome FOXM1 inhibitor resistance. METHODS: In estrogen receptor-positive and triple-negative breast cancer cells treated with FOXM1 inhibitor NB73 and ferroptosis activators dihydroartemisinin and JKE1674, alone and in combination, we measured suppression of cell viability, motility, and colony formation, and monitored changes in gene and protein pathway expressions and mitochondrial integrity. RESULTS: Growth suppression of breast cancer cells by FOXM1 inhibitors is accompanied by increased cell death and alterations in mitochondrial morphology and metabolic activity. Low doses of FOXM1 inhibitor strongly synergize with ferroptosis inducers to reduce cell viability, migration, colony formation, and expression of proliferation-related genes, and increase intracellular Fe+2 and lipid peroxidation, markers of ferroptosis. Acquired resistance to FOXM1 inhibition is associated with increased expression of cancer stem-cell markers and proteins that repress ferroptosis, enabling cell survival and drug resistance. Notably, resistant cells are still sensitive to growth suppression by low doses of ferroptosis activators, effectively overcoming the acquired resistance. CONCLUSION: Delineating changes in viability and cell death pathways that can overcome drug resistance should be helpful in determining approaches that might best prevent or reverse resistance to therapeutic targeting of FOXM1 and ultimately improve patient clinical outcomes.

Topological Fermi-arc surface state covered by floating electrons on a two-dimensional electride.

Two-dimensional electrides can acquire topologically non-trivial phases due to intriguing interplay between the cationic atomic layers and anionic electron layers. However, experimental evidence of topological surface states has yet to be verified. Here, via angle-resolved photoemission spectroscopy (ARPES) and scanning tunnelling microscopy (STM), we probe the magnetic Weyl states of the ferromagnetic electride [Gd2C]2+·2e-. In particular, the presence of Weyl cones and Fermi-arc states is demonstrated through photon energy-dependent ARPES measurements, agreeing with theoretical band structure calculations. Notably, the STM measurements reveal that the Fermi-arc states exist underneath a floating quantum electron liquid on the top Gd layer, forming double-stacked surface states in a heterostructure. Our work thus not only unveils the non-trivial topology of the [Gd2C]2+·2e- electride but also realizes a surface heterostructure that can host phenomena distinct from the bulk.

Impact of linkage level on inferences from big data analyses in health and medical research: an empirical study.

BACKGROUND: Linkage errors that occur according to linkage levels can adversely affect the accuracy and reliability of analysis results. This study aimed to identify the differences in results according to personally identifiable information linkage level, sample size, and analysis methods through empirical analysis. METHODS: The difference between the results of linkage in directly identifiable information (DII) and indirectly identifiable information (III) linkage levels was set as III linkage based on name, date of birth, and sex and DII linkage based on resident registration number. The datasets linked at each level were named as databaseIII (DBIII) and databaseDII (DBDII), respectively. Considering the analysis results of the DII-linked dataset as the gold standard, descriptive statistics, group comparison, incidence estimation, treatment effect, and moderation effect analysis results were assessed. RESULTS: The linkage rates for DBDII and DBIII were 71.1% and 99.7%, respectively. Regarding descriptive statistics and group comparison analysis, the difference in effect in most cases was "none" to "very little." With respect to cervical cancer that had a relatively small sample size, analysis of DBIII resulted in an underestimation of the incidence in the control group and an overestimation of the incidence in the treatment group (hazard ratio [HR] = 2.62 [95% confidence interval (CI): 1.63-4.23] in DBIII vs. 1.80 [95% CI: 1.18-2.73] in DBDII). Regarding prostate cancer, there was a conflicting tendency with the treatment effect being over or underestimated according to the surveillance, epidemiology, and end results summary staging (HR = 2.27 [95% CI: 1.91-2.70] in DBIII vs. 1.92 [95% CI: 1.70-2.17] in DBDII for the localized stage; HR = 1.80 [95% CI: 1.37-2.36] in DBIII vs. 2.05 [95% CI: 1.67-2.52] in DBDII for the regional stage). CONCLUSIONS: To prevent distortion of the analyses results in health and medical research, it is important to check that the patient population and sample size by each factor of interest (FOI) are sufficient when different data are linked using DBDII. In cases involving a rare disease or with a small sample size for FOI, there is a high likelihood that a DII linkage is unavoidable.

Meditation-type specific reduction in infra-slow activity of electroencephalogram.

Purpose: Meditation is renowned for its positive effects on cognitive abilities and stress reduction. It has been reported that the amplitude of electroencephalographic (EEG) infra-slow activity (ISA, < 0.1 Hz) is reduced as the stress level decreases. Consequently, we aimed to determine if EEG ISA amplitude decreases as a result of meditation practice across various traditions. Methods: To this end, we analyzed an open dataset comprising EEG data acquired during meditation sessions from experienced practitioners in the Vipassana tradition-which integrates elements of focused attention and open monitoring, akin to mindfulness meditation-and in the Himalayan Yoga and Isha Shoonya traditions, which emphasize focused attention and open monitoring, respectively. Results: A general trend was observed where EEG ISA amplitude tended to decrease in experienced meditators from these traditions compared to novices, particularly significant in the 0.03-0.08 Hz band for Vipassana meditators. Therefore, our analysis focused on this ISA frequency band. Specifically, a notable decrease in EEG ISA amplitude was observed in Vipassana meditators, predominantly in the left-frontal region. This reduction in EEG ISA amplitude was also accompanied by a decrease in phase-amplitude coupling (PAC) between the ISA phase and alpha band (8-12 Hz) amplitude, which implied decreased neural excitability fluctuations. Conclusion: Our findings suggest that not only does EEG ISA amplitude decrease in experienced meditators from traditions that incorporate both focused attention and open monitoring, but this decrease may also signify a diminished influence of neural excitability fluctuations attributed to ISA.

Endohepatology in clinical practice: EUS-guided portal pressure measurement combined with EUS-guided liver biopsy and variceal screening and treatment in outpatients.

Background and Objectives: EUS-guided portal pressure gradient (PPG) is a novel technique that permits a true, direct measure of portal vein pressure and hepatic vein pressure. This article details our experience and lessons learned from 20 consecutive outpatient EUS-PPG procedures performed at a single center, along with simultaneous EUS-guided liver biopsy, variceal screening, and variceal banding. Methods: Data on the first 20 patients who underwent EUS-PPG at a single center were retrospectively viewed and analyzed. The effects of various liver diseases or other patient-related factors on the clinical and technical success of EUS-PPG measurements, as well as EUS-guided liver biopsy (EUS-LB), were evaluated. During the procedure, if esophageal varices were encountered, they were assessed, and if felt to be clinically indicated, endoscopic variceal ligation was performed. Results: The 20 patients included 10 male and 10 female patients. All procedures were technically successful. In all patients, the portal vein and hepatic veins could be easily identified. One adverse event of bleeding occurred during the EUS-PPG measuring procedure. All 20 EUS-LBs were technically successful and yielded adequate samples for histological evaluations, with an average of 25 complete portal tracts per sample. Among patients with esophageal varices, 40% of patients underwent banding. The mean EUS-PPG among 5 patients with esophageal varices was 11.6 mm Hg, compared with 3.2 mm Hg among 15 patients without esophageal varices. Conclusion: This study demonstrates that EUS-PPG is a novel, safe, reproducible, and effective technique. Also, the fact that EUS-PPG, EUS-LB, variceal screening, and variceal banding could be performed in 1 session and on an outpatient basis speaks to the growing relevance and impact of the nascent field of endohepatology.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials.

This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1ß) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-ß) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.