The impact of co-exposure to air and noise pollution on the incidence of metabolic syndrome from a health checkup cohort.

Previous studies have found associations between the incidence of metabolic syndrome (MetS) and exposure to air pollution or road traffic noise. However, investigations on environmental co-exposures are limited. This study aimed to investigate the association between co-exposure to air pollution and road traffic noise and MetS and its subcomponents. Participants living in Taipei City who underwent at least two health checkups between 2010 and 2016 were included in the study. Data were sourced from the MJ Health database, a longitudinal, large-scale cohort in Taiwan. The monthly traffic noise exposure (Lden and Lnight) was computed using a dynamic noise map. Monthly fine particulate data at one kilometer resolution were computed from satellite imagery data. Cox proportional hazards regression models with month as the underlying time scale were used to estimate hazard ratios (HRs) for the impact of PM2.5 and road traffic noise exposure on the risk of developing MetS or its subcomponents. Data from 10,773 participants were included. We found significant positive associations between incident MetS and PM2.5 (HR: 1.88; 95% CI 1.67, 2.12), Lden (HR: 1.10; 95% CI 1.06, 1.15), and Lnight (HR: 1.07; 95% CI 1.02, 1.13) in single exposure models. Results further showed significant associations with an elevated risk of incident MetS in co-exposure models, with HRs of 1.91 (95% CI 1.69, 2.16) and 1.11 (95% CI 1.06, 1.16) for co-exposure to PM2.5 and Lden, and 1.90 (95% CI 1.68, 2.14) and 1.08 (95% CI 1.02, 1.13) for co-exposure to PM2.5 and Lnight. The HRs for the co-exposure models were higher than those for models with only a single exposure. This study provides evidence that PM2.5 and noise exposure may elevate the risk of incident MetS and its components in both single and co-exposure models. Therefore, preventive approaches to mitigate the risk of MetS and its subcomponents should consider reducing exposure to PM2.5 and noise pollution.

Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.

Boosting 2000-Fold Hypergolic Ignition Rate of Carborane by Substitutes Migration in Metal Clusters.

Hypergolic propellants rely on fuel and oxidizer that spontaneously ignite upon contact, which fulfill a wide variety of mission roles in launch vehicles and spacecraft. Energy-rich carboranes are promising hypergolic fuels, but triggering their energy release is quite difficult because of their ultrastable aromatic cage structure. To steer the development of carborane-based high-performance hypergolic material, carboranylthiolated compounds integrated with atomically precise copper clusters are presented, yielding two distinct isomers, Cu14B-S and Cu14C-S, both possessing similar ligands and core structures. With the migration of thiolate groups from carbon atoms to boron atoms, the ignition delay (ID) time shortened from 6870 to 3 ms when contacted with environmentally benign oxidizer high-test peroxide (HTP, with a H2O2 concentration of 90%). The extraordinarily short ignition ID time of Cu14B-S is ranking among the best of HTP-active hypergolic materials. The experimental and theoretical findings reveal that benefitting from the migration of thiolate groups, Cu14B-S, characterized by an electron-rich metal kernel, displays enhanced reducibility and superior charge transfer efficiency. This results in exceptional activation rates with HTP, consequently inducing carborane combustion and the simultaneous release of energy. This fundamental investigation shed light on the development of advanced green hypergolic propulsion systems.

Construction of novel Ag(0)-containing silver nanoclusters by regulating auxiliary phosphine ligands.

Controlled synthesis of metal clusters through minor changes in surface ligands holds significant interest because the corresponding entities serve as ideal models for investigating the ligand environment's stereochemical and electronic contributions that impact the corresponding structures and properties of metal clusters. In this work, we obtained two Ag(0)-containing nanoclusters (Ag17 and Ag32) with near-infrared emissions by regulating phosphine auxiliary ligands. Ag17 and Ag32 bear similar shells wherein Ag17 features a trigonal bipyramid Ag5 kernel while Ag32 has a bi-icosahedral interpenetrating an Ag20 kernel. Ag17 and Ag32 showed a near-infrared emission (NIR) of around 830 nm. Benefiting from the rigid structure, Ag17 displayed a more intense near-infrared emission than Ag32. This work provides new insight into the construction of novel superatomic silver nanoclusters by regulating phosphine ligands.

Association of JAK2V617F allele burden and clinical correlates in polycythemia vera: a systematic review and meta-analysis.

Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.

Therapeutic targeting of thioredoxin reductase 1 causes ferroptosis while potentiating anti-PD-1 efficacy in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) faces low response rates to anti-PD-1 immunotherapies, highlighting the need for enhanced treatment strategies. Auranofin, which inhibits thioredoxin reductase (TrxR) through its gold-based composition, has shown potential in cancer treatment. It targets the TrxR system, essential for safeguarding cells from oxidative stress. The overproduction of TrxR in cancerous cells supports their proliferation. However, auranofin's interference with this system can upset the cellular redox equilibrium, boost levels of reactive oxygen species, and trigger the death of cancer cells. This study is the first to highlight TXNRD1 as a crucial factor contributing to resistance to anti-PD-1 treatment in HNSCC. In this study, we identified targetable regulators of resistance to immunotherapy-induced ferroptosis in HNSCC. We observed a link of thioredoxin reductase 1 (TXNRD1) with tumoral PD-L1 expression and ferroptosis suppression in HNSCC. Moreover, HNSCC tumors with aberrant TXNRD1 expression exhibited a lack of PD-1 response, NRF2 overexpression, and PD-L1 upregulation. TXNRD1 inhibition promoted ferroptosis in HNSCC cells with NRF2 activation and in organoid tumors derived from patients lacking a PD-1 response. Mechanistically, TXNRD1 regulated PD-L1 transcription and maintained the redox balance by binding to ribonucleotide reductase regulatory subunit M2 (RRM2). TXNRD1 expression disruption sensitized HNSCC cells to anti-PD-1-mediated Jurkat T-cell activation, promoting tumor killing through ferroptosis. Moreover, TXNRD1 inhibition through auranofin cotreatment synergized with anti-PD-1 therapy to potentiate immunotherapy-mediated ferroptosis by mediating CD8+ T-cell infiltration and downregulating PD-L1 expression. Our findings indicate that targeting TXNRD1 is a promising therapeutic strategy for improving immunotherapy outcomes in patients with HNSCC.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids.

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M-1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

[A novel periodontal endoscopy-aided non-incisional periodontal regeneration technique：a case series study].

PURPOSE: To investigate the effect of endoscopy-aided non-incisional periodontal regeneration technique (NIT) in the treatment of alveolar bone angular resorption. METHODS: Thirteen patients with severe periodontitis(13 diseased teeth) were selected. All patients had alveolar bone angular resorption on adjacent surface. The patients received NIT treatment 6 weeks after periodontal primary therapy. The visualization of subgingival environment was acquired by the periodontal endoscopy. Following the removal of the subgingival plaque, calculus and intra-bony granulation tissue, bone grafting materials were placed into the intra-bony defects with the assistance of a delicate gingival protector. No flap was elevated and no sutures were applied. Probing depth (PD), gingival recession (GR), clinical attachment level (CAL), as well as radiographic parameters were evaluated at baseline and 2 years after treatment. SPSS 22.0 software package was used for data analysis. RESULTS: At 2-years follow-up, an average CAL gain of (3.65±2.10) mm (P＜0.001), PD reduction of (4.42±1.66) mm (P＜0.001), and minimal increase in GR of (0.38±0.87) mm (P=0.25) were observed. Alveolar bone was significantly improved at 2-years follow-up on radiographs (P＜0.001). CONCLUSIONS: For angular resorption site of alveolar bone, NIT treatment can obtain good periodontal regeneration results without flap inversion.

[Evaluating the dietary quality of 454 rural elderly aged 65 years and above in Luzhou City in 2023].

OBJECTIVE: To evaluate the dietary quality of the rural elderly aged 65 years and above. METHODS: In February-March 2023, a convenience sampling method was adopted to select 454 rural elderly aged 65 years and above in a township of Luzhou City. The dietary survey was conducted using a semi-quantitative food frequency questionnaire(FFQ-25), and the questionnaire information was collected by face-to-face interviews. Dietary quality was evaluated using the Dietary Balance Index-16(DBI-16) score. RESULTS: The proportion of older people in the region with moderate and high dietary imbalances was 79.7%. Inadequate and excessive dietary intake coexisted. The average daily intake of cereals and potatoes and livestock and meat foods were 356.7 g and 76.2 g, exceeding the recommended intake. The average daily intake of fruit, milk and fish and shrimp intake was 22.8 g, 36 g and 3.7 g, respectively, which was only 10% of the recommended amount, and the intake was seriously insufficient. In addition, the degree of food diversity is relatively low, with most of the average daily intake of food types ranging from five to eight, and only 4.6% of the elderly having more than eight. A total of seven dietary patterns were found among the rural elderly in the region, including a certain degree of under-consumption pattern, a severe under-consumption pattern, a certain degree of over-consumption pattern, and a pattern of both under-consumption and over-consumption. That was dominated by the pattern of severe underconsumption and the pattern of some degree of underconsumption and higher degree of overconsumption, which accounted for 72.3% of the total. CONCLUSION: The rural elderly aged 65 years and above in Luzhou City have a serious dietary imbalance, with a high proportion of insufficient intake of vegetables, fruits and milk, as well as aquatic products and eggs; and excessive intake of livestock, poultry, meat and cereals and potatoes.

Cayratia albifolia C.L.Li exerts anti-rheumatoid arthritis effect by inhibiting macrophage activation and neutrophil extracellular traps (NETs).

BACKGROUND: Cayratia albifolia C.L.Li (CAC), commonly known as "Jiao-Mei-Gu" in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. RESULTS: CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. CONCLUSIONS: We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation.

Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: Triglyceride-glucose (TyG) index values are a new surrogate marker for insulin resistance. This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). METHODS: A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this study. The participants were grouped based on cumulative TyG index values tertiles within 3 months after ablation. Cox regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF recurrence. The predictive value of all risk factors was assessed by receiver operating curve analysis. RESULTS: There were 375 patients completed the study (age: 63.23 ± 10.73 years, 64.27% male). The risk of AF recurrence increased with increasing cumulative TyG index values tertiles. After adjusting for potential confounders, patients in the medium cumulative TyG index group [hazard ratio (HR) = 4.949, 95% CI: 1.778-13.778, P = 0.002] and the high cumulative TyG index group (HR = 8.716, 95% CI: 3.371-22.536, P < 0.001) had a higher risk of AF recurrence than those in the low cumulative TyG index group. The restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index values. When considering cumulative TyG index values, left atrial diameter, and lactate dehydrogenase levels as a comprehensive factor, the model could effectively predict AF recurrence after RFCA [area under the curve (AUC) = 0.847, 95% CI: 0.797-0.897, P < 0.001]. CONCLUSIONS: Cumulative TyG index values were a risk factor for AF recurrence after RFCA. Monitoring longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

Novel Stereo-Induction Pattern in Pudovik Addition/Phospha-Brook Rearrangement Towards Chiral Trisubstituted Allenes.

Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity of reports on axially chiral allenyl phosphorus compounds. Here, we disclosed an efficient and straightforward cascade reaction between ethynyl ketones and phosphine oxides, resulting in a broad array of trisubstituted allenes incorporating a phosphorus moiety in high yields with excellent stereoselectivities facilitated by peptide-mimic phosphonium salt (PPS) catalysis, Additionally, comprehensive series of mechanistic experiments have been conducted to elucidate that this cascade reaction proceeds via an asymmetric Pudovik addition reaction followed by a subsequent phospha-Brook rearrangement that occurs concomitantly with kinetic resolution, representing a stereospecific rearrangement and protonation process facilitating central-to-axial chirality transfer in a cascade manner. We anticipate that our research will pave the way for a promising exploration of novel stereo-induction pattern in the Pudovik addition/phospha-Brook rearrangement cascade reaction.

GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation.

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41-/-) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41-/- mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ+ T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41-/- mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41-/- mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D.

Comparison of six screening methods for sarcopenia among rural community-dwelling older adults: a diagnostic accuracy study.

OBJECTIVE: The objective of this analysis was to determine the diagnostic efficacy of the Ishii test, SarSA-Mod, SARC-F, SARC-Calf, SARC-F+AC, and SARC-Calf+AC for screening for sarcopenia among rural community-dwelling older adults. METHODS: The AWGS 2019 diagnostic criteria was a diagnostic reference for sarcopenia. There were six screening tools whose accuracy was determined through the use of metrics, including specificity, sensitivity, negative and positive predictive values, and the receiver operating characteristic (ROC) curve. RESULTS: The study included 551 participants (304 women, age 70.9 ± 4.9 years). The prevalence of sarcopenia was 44.5% in men and 39.1% in women. In males, the sensitivity/specificity of the Ishii test, SarSA-Mod, SARC-F, SARC-Calf, SARC-F+AC, and SARC-Calf+AC screening sarcopenia were 87.3%/65.7%, 98.2%/21.9%, 6.4%/98.5%, 28.2%/91.2%, 33.6%/83.9%, and 84.6%/43.8%, and in females, they were 68.1%/82.2, 100%/23.2%, 16.0%/90.3%, 35.3%/84.3%, 58.8%/61.1%, and 89.9%/42.2%, respectively. In males, the area under the curves of the Ishii test, SarSA-Mod, SARC-F, SARC-Calf, SARC-F+AC, and SARC-Calf+AC were 0.846 (95% CI 0.795-0.889), 0.800 (95% CI 0.745-0.848), 0.581 (95% CI 0.516-0.643), 0.706 (95% CI 0.645-0.762), 0.612 (95% CI 0.548-0.673), and 0.707 (95% CI 0.646-0.763), respectively, and in females, they were 0.824 (95% CI 0.776-0.865), 0.845 (95% CI 0.799-0.883), 0.581 (95% CI 0.524-0.637), 0.720 (95% CI 0.666-0.770), 0.632 (95% CI 0.575-0.686), and 0.715 (95% CI 0.661-0.765), respectively. CONCLUSION: Our findings demonstrate that the overall accuracy of the Ishii test was best among the six screening tools for sarcopenia screening in rural community-dwelling older adults.

Associations between community green view index and fine particulate matter from Airboxes.

Urban greenery can help to improve air quality, reduce health risks and create healthy livable urban communities. This study aimed to explore the role of urban greenery in reducing air pollution at the community level in Tainan City, Taiwan, using air quality sensors and street-view imagery. We also collected the number of road trees around each air quality sensor site and identified the species that were best at absorbing PM2.5. Three greenness metrics were used to assess community greenery in this study: two Normalized Difference Vegetation Indices (NDVI) from different satellites and the Green View Index (GVI) from Google Street View (GSV) images. Land-use Regression (LUR) was used for statistical analysis. The results showed that a higher GVI within a 500 m buffer was significantly associated with decreased PM2.5. Neither NDVI metrics within a 500 m circular buffer were significantly associated with decreased PM2.5. Evergreen trees were significantly associated with lower ambient PM2.5, compared with deciduous and semi-deciduous trees. Because localized changes in air quality profoundly affect public health and environmental equity, our findings provide evidence for future urban community greenspace planning and its beneficial impacts on reducing air pollution.

Neural specialization with generalizable representations underlies children's cognitive development of attention.

From childhood to adulthood, the human brain develops highly specialized yet interacting neural modules that give rise to nuanced attention and other cognitive functions. Each module can specialize over development to support specific functions, yet also coexist in multiple neurobiological modes to support distinct processes. Advances in cognitive neuroscience have conceptualized human attention as a set of cognitive processes anchored in highly specialized yet interacting neural systems. The underlying mechanisms of how these systems interplay to support children's cognitive development of multiple attention processes remain unknown. Leveraging developmental functional magnetic resonance imaging with attention network test paradigm, we demonstrate differential neurocognitive development of three core attentional processes from childhood to adulthood, with alerting reaching adult-like level earlier, followed by orienting and executive attention with more protracted development throughout middle and late childhood. Relative to adults, young children exhibit immature specialization with less pronounced dissociation of neural systems specific to each attentional process. Children manifest adult-like distributed representations in the ventral attention and cingulo-opercular networks, but less stable and weaker generalizable representations across multiple processes in the dorsal attention network. Our findings provide insights into the functional specialization and generalization of neural representations scaffolding cognitive development of core attentional processes from childhood to adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enhancement of LC3-associated efferocytosis for the alleviation of intestinal inflammation.

LC3-associated phagocytosis (LAP) is an instrumental machinery for the clearance of extracellular particles including apoptotic cells for the alleviation of inflammation. While pharmacological approaches to modulate LAP for inflammation regulation have been poorly explored, in our study we identified a novel compound, columbamine (COL), which can trigger LAP and enhance efferocytosis in an animal model of colitis to attenuate inflammation. We found that COL directly binds to and biasedly activates FPR2 (formyl peptide receptor 2) to promote efferocytosis and alleviate colitis. Biochemically, COL induces an interaction between RAC1 and the PIK3C3/VPS34-RUBCN/RUBICON complex, stimulating LC3-associated efferocytosis. These findings provide a novel interpretation of the potential roles of LAP in regulating inflammatory bowel disease (IBD), reveal the relationship between G protein-coupled receptors (GPCRs) and LAP, and highlight the role of RAC1 in regulating the PIK3C3/VPS34-RUBCN complex in LAP.

Full adherence to cirrhosis quality indicators is associated with lower mortality in acute variceal bleeding: Nationwide audit.

BACKGROUND AND AIMS: Acute variceal bleeding (AVB) is a major complication in patients with cirrhosis. Using a nationwide AVB audit, we performed a nested cohort study to determine whether full adherence to the AVB quality indicator (QI) improves clinical outcomes in patients with cirrhosis and AVB. APPROACH AND RESULTS: We assessed real-world adherence to AVB QI among patients with cirrhosis admitted for AVB in all public hospitals in Singapore between January 2015 and December 2020. Full adherence was considered when all 5 QIs were fulfilled: prophylactic antibiotics, vasoactive agents, timely endoscopy, endoscopic hemostasis during index endoscopy, and nonselective beta-blockers after AVB. We compare 6-week mortality between the full adherence and suboptimal adherence groups using a propensity-matched cohort.A total of 989 patients with AVB were included. Full adherence to all AVB QI was suboptimal (56.5%). Analysis of the propensity-matched cohort with comparable baseline characteristics showed that full adherence was associated with a lower risk of early infection (20.0% vs. 26.9%), early rebleeding (5.2% vs. 10.2%), and mortality at 6 weeks (8.2% vs. 19.7%) and 1 year (21.3% vs. 35.4%) ( p <0.05 for all). While full adherence was associated with a lower 6-week mortality regardless of the MELD score, nonadherence was associated with a higher 6-week mortality despite a lower predicted risk of 6-week mortality. Despite high adherence to the recommended process measures, patients with CTP-C remain at a higher risk of rebleeding, 6-week and 1-year mortality. CONCLUSIONS: Full adherence to the AVB QI should be the target for quality improvement in patients with cirrhosis.

Association of emotional and behavioral problems with the development of the substantia nigra, subthalamic nucleus, and red nucleus volumes and asymmetries from childhood to adolescence: A longitudinal cohort study.

The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) have been widely studied as important biomarkers of degenerative diseases. However, how they develop in childhood and adolescence and are affected by emotional behavior has not been studied thus far. This population-based longitudinal cohort study used data from a representative sample followed two to five times. Emotional and behavioral problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were used to map developmental trajectories and behavioral regulation. Using an innovative automated image segmentation technique, we quantified the volumes and asymmetries of the SN, STN and RN with 1226 MRI scans of a large longitudinal sample of 667 subjects aged 6-15 years and mapped their developmental trajectories. The results showed that the absolute and relative volumes of the bilateral SN and right STN showed linear increases, while the absolute volume of the right RN and relative volume of the bilateral RN decreased linearly, these effects were not affected by gender. Hyperactivity/inattention weakened the increase in SN volume and reduced the absolute volume of the STN, conduct problems impeded the RN volume from decreasing, and emotional symptoms changed the direction of SN lateralization. This longitudinal cohort study mapped the developmental trajectories of SN, STN, and RN volumes and asymmetries from childhood to adolescence, and found the association of emotional symptoms, conduct problems, and hyperactivity/inattention with these trajectories, providing guidance for preventing and intervening in cognitive and emotional behavioral problems.

Meta-analysis: Prevalence and impact of alcohol abstinence in alcohol-associated cirrhosis.

BACKGROUND: Although alcohol abstinence may be an effective intervention for alcohol-associated cirrhosis, its association with prognosis has not been systematically assessed or quantified. AIMS: To determine the prevalence of alcohol abstinence, factors associated with alcohol abstinence and the impact of abstinence on morbidity and overall survival in people with alcohol-associated cirrhosis. METHODS: We searched Medline and Embase from inception to 15 April 2023 for prospective and retrospective cohort studies describing alcohol abstinence in people with known alcohol-associated cirrhosis. Meta-analysis of proportions for pooled estimates was performed. The method of inverse variance, employing a random-effects model, was used to pool the hazard ratio (HR) comparing outcomes of abstinent against non-abstinent individuals with alcohol-associated cirrhosis. RESULTS: We included 19 studies involving 18,833 people with alcohol-associated cirrhosis. The prevalence of alcohol abstinence was 53.8% (CI: 44.6%-62.7%). Over a mean follow-up duration of 48.6 months, individuals who continued to consume alcohol had significantly lower overall survival compared to those who were abstinent (HR: 0.611, 95% CI: 0.506-0.738). These findings remained consistent in sensitivity/subgroup analysis for the presence of decompensation, study design and studies that assessed abstinence throughout follow-up. Alcohol abstinence was associated with a significantly lower risk of hepatic decompensation (HR: 0.612, 95% CI: 0.473-0.792). CONCLUSIONS: Alcohol abstinence is associated with substantial improvement in overall survival in alcohol-associated cirrhosis. However, only half of the individuals with known alcohol-associated cirrhosis are abstinent.