Supervised Group-Based Exercise for Preventing Falls Among Older Adults in the Community: A Systematic Review and Meta-Analysis.

BACKGROUND: Supervised group exercise may have greater health benefits than no exercise or exercise alone. PURPOSE: The purpose of this systematic review and meta-analysis was to investigate the effectiveness of supervised group-based exercise on the risk of falls among community-dwelling older adults compared to no exercise or exercise alone. METHODS: Four databases were searched up to March 1, 2024 for eligible randomized controlled trials. RESULTS: Seventeen randomized controlled trials were eligible for this meta-analysis. Meta-analyses showed that compared with no exercise, supervised group-based exercise had a significant effect on preventing falls, injurious falls, and fall-related fractures. Compared with exercise alone, supervised group-based exercise significantly reduced falls and injurious falls. CONCLUSIONS: Moderate-quality evidence suggests that compared with no exercise or exercise alone, supervised group-based exercise is more effective at preventing falls among community-dwelling older adults.

Unraveling Differences in the Effects of Ammonium/Amine-Based Additives on the Performance and Stability of Inverted Perovskite Solar Cells.

Additive engineering, with its excellent ability to passivate bulk or surface perovskite defects, has become a common strategy to improve the performance and stability of perovskite solar cells (PVSCs). Among the various additives reported so far, ammonium salts are considered an important branch. It is worth noting that although both ammonium-based additives (R-NH3 +) and amine-based additives (R-NH2) are derivatives of ammonia (NH3), the functions of the two can be easily confused due to their structural similarities. Moreover, there is no comprehensive comparative analysis of them in the literature. Here, the differences between phenethylammonium iodide (PEA+) and phenethylamine (PEA) additives are revealed experimentally and theoretically. The results clearly show that PEA outperforms PEA+ in terms of device performance and stability based on the following three factors: i) PEA's defect passivation capability is superior to that of PEA+; ii) PEA has better hydrophobicity to hinder water ingress; and iii) PEA completely improves the stability of PVSCs by enhancing thermal stability and inhibiting iodide migration in perovskite more effectively than PEA+. As a result, the power conversion efficiency (PCE) of the inverted methylammonium triiodide (MAPbI3) device using PEA increases by ≈15% to over 21%. More importantly, this device exhibits greater ability to prevent water invasion, thermal-induce degradation, and inhibit iodide ion migration, resulting in better long-term stability.

Long-term prevention of hereditary angioedema attacks with lanadelumab in adolescents.

BACKGROUND: Lanadelumab was well-tolerated and effective in preventing hereditary angioedema (HAE) attacks in the phase 3, double-blind, placebo-controlled HELP Study and subsequent open-label extension study, HELP OLE (NCT02741596). OBJECTIVE: To evaluate outcomes from HELP OLE for adolescent patients aged 12 to 17 years. METHODS: HELP OLE comprised patients who completed the HELP Study (rollovers) and new eligible (lanadelumab-naive) patients. Rollovers received a single dose of lanadelumab 300 mg at the last HELP Study visit (day 0). Treatment was then paused until patients experienced their first investigator-confirmed HAE attack, following which lanadelumab 300 mg was administered every 2 weeks (Q2W) for up to 33 months (4 weeks/month). Lanadelumab-naive patients received lanadelumab 300 mg Q2W from day 0. Patient-reported outcomes included Angioedema Quality of Life Questionnaire (AE-QoL). Safety was monitored throughout the study. RESULTS: The subgroup analysis included 21 patients (8 rollovers, 13 lanadelumab-naive patients); 95.2% completed ≥ 30 months on study. Mean (SD) monthly attack rates decreased from 1.58 (1.0) at baseline to 0.11 (0.2) during treatment (mean 94.7% reduction). Eight (38.1%) patients were attack-free during treatment and, on average, 99.1% of days were attack-free (mean 27.7 days/month). Patients reported a mean (SD) AE-QoL total score of 27.5 (17.5) at baseline vs 7.5 (13.2) at end of study. Twelve (57.1%) patients reported treatment-related treatment-emergent adverse events; however, there were no treatment-related serious adverse events. CONCLUSION: Lanadelumab provided long-term efficacy in preventing HAE attacks, was associated with clinically meaningful improvements in health-related quality of life and high levels of treatment satisfaction, and was well-tolerated in adolescent patients.

ST6GALNAC1-mediated sialylation in uterine endometrial epithelium facilitates the epithelium-embryo attachment.

INTRODUCTION: Embryo implantation requires synergistic interaction between the embryo and the receptive endometrium. Glycoproteins and glycan-binding proteins are involved in endometrium-embryo attachment. Sialyl Tn (sTn), a truncated O-glycan, is catalyzed by ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) and can be detected by specific Sialic-acid-binding immunoglobulin-like lectins (Siglecs). Whether the sTn-Siglecs axis supports embryo implantation remains unknown. OBJECTIVES: This paper aims to study the role of ST6GALNAC1/sTn-Siglecs axis in embryo implantation. METHODS: ST6GALNAC1 and sTn in human endometrium were analyzed by immunohistochemistry. An in vitro implantation model was conducted to evaluate the effects of ST6GALNAC1/sTn on the receptivity of human endometrial AN3CA cells to JAR spheroids. Immunoprecipitation combined with mass spectrometry analysis was carried out to identify the key proteins modified by sTn in endometrial cells. Siglec-6 in human embryos was analyzed by published single-cell RNA sequencing (scRNA-seq) datasets. Protein interaction assay was applied to verify the bond between the Siglec-6 with sTn-modified CD44. St6galnac1 siRNAs and anti-sTn antibodies were injected into the uterine horn of the mouse at the pre-implantation stage to evaluate the role of endometrial St6galnac1/sTn in embryo implantation. Siglec-G in murine embryos was analyzed by immunofluorescence staining. The function of Siglec-G is evidenced by uterine horn injection and protein interaction assay. RESULTS: Both human and murine endometrium at the receptive stage exhibit higher ST6GALNAC1 and sTn levels compared to the non-receptive stage. Overexpression of ST6GALNAC1 significantly enhanced the receptivity of AN3CA cells to JAR spheroids. Inhibition of endometrial ST6GALNAC1/sTn substantially impaired embryo implantation in vivo. CD44 was identified as a carrier for sTn in the endometrial cells of both species. Siglec-6 and Siglec-G, expressed in the embryonic trophectoderm, were found to promote embryo attachment, which may be achieved through binding with sTn-modified CD44. CONCLUSION: ST6GALNAC1-regulated sTn in the endometrium aids in embryo attachment through interaction with trophoblastic Siglecs.

Neuronal double-stranded DNA accumulation induced by DNase II deficiency drives tau phosphorylation and neurodegeneration.

BACKGROUND: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. METHODS: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. RESULTS: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. CONCLUSIONS: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

[Anti-myocardial ischemic injury effects and mechanisms of cryptotanshinone in regulating macrophage polarisation through Dectin-1 signalling pathway].

The aim of this study was to investigate the potential mechanism by which cryptotanshinone(CTS) may exert its anti-myo-cardial ischemic effect through the regulation of macrophage polarization via the dendritic cell-associated C-type lectin 1(Dectin-1) signaling pathway. Male C57BL/6 mice, aged six weeks, were utilized to establish myocardial ischemia models and were subsequently divided into five groups: sham, model, CTS low-dose(21 mg·kg~(-1)·d~(-1)), CTS high-dose(84 mg·kg~(-1)·d~(-1)), and dapagliflozin(0.14 mg·kg~(-1)·d~(-1)). The cardiac function, serum enzyme levels, Dectin-1 expression, macrophage polarization, and neutrophil infiltration in the myocardial infarction area were assessed in each group. An in vitro model of M1-type macrophages was constructed using lipopolysaccharide/interfe-ron-γ(LPS/IFN-γ) stimulated RAW264.7 cells to investigate the impact of CTS on macrophage polarization and to examine alterations in key proteins within the Dectin-1 signaling pathway. In the CTS group, compared to the model group mice, there was a significant improvement in the cardiac function and myocardial injury, along with a notable increase in the ratio of M2/M1-type macrophages in the myocardial infarcted area and a decrease in neutrophil infiltration. Additionally, Dectin-1 exhibited low expression. The results of in vitro experiments demonstrated that CTS can decrease the expression of M1-type marker genes and increase the expression of M2-type marker genes. Besides, it can decrease the levels of Dectin-1 and the phosphorylation of its associated proteins, including spleen tyrosine kinase(Syk), protein kinase B(Akt), nuclear factor-kappaB p65(NF-κB p65), and extracellular signal-regulated protein kinases(ERK1/2). Additionally, CTS was found to enhance the phosphorylation of signal transducer and activator of transcription-6(STAT6). The above results suggest that CTS exerts its anti-myocardial ischemic injury effect by regulating macrophage polarization through the Dectin-1 signaling pathway.

Metabolic dysfunction-associated steatotic liver disease and diabetes: the cross-talk between hepatologist and diabetologist.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (DM) are the most prevalent metabolic disorders globally. The numbers affected in both disorders are also rapidly increasing with alarming trends in children and young adults. AREAS COVERED: Insulin resistance (IR) and the subsequent metabolic dysregulation are the fundamental pathogenesis pathways of the prevalent metabolic disorders. The interaction and impacts are bidirectional between MASLD and DM in terms of disease mechanisms, disease course, risks, and prognosis. There's a pressing issue for highlighting the links between MASLD and DM for both care specialists and primary care providers. The review collected the scientific evidence addressing the mutual interactions between the two disorders. The strategies for surveillance, risk stratification, and management are discussed in a practical manner. It also provides individualized viewpoints of patient care in hepatology and diabetology. EXPERT OPINION: Both MASLD and DM shared similar disease mechanisms, and affected the disease development and progression in a bidirectional manner. The high prevalence and the cross-link between the two disorders raise clinical issues from awareness, screening, risk stratification, optimal referral, to appropriate management for primary care providers.

Efficacy and Safety of Thermal Ablation for Solitary Low-Risk T2N0M0 Papillary Thyroid Carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of thermal ablation in treating solitary low-risk T2N0M0 papillary thyroid cancer (PTC) and compare the outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA). MATERIALS AND METHODS: This retrospective, single center study involved 34 patients (age: 40.0 ± 13.9 years; 28 female) who had low-risk T2N0M0 PTC with a maximum diameter >2 cm and ≤4 cm and underwent MWA (n = 15) or RFA (n = 19) from November 2016 to April 2023. The primary outcomes were the cumulative rate of disease progression and delayed surgery rates. In contrast, the secondary outcomes included changes in tumor size, cumulative rate of complete tumor disappearance, and complication rates. RESULTS: The median follow-up period was 18.0 months (interquartile range [IQR]: 9.0-40.0 months). At 12 months, the median volume reduction rate of the ablation zone was 74.2% (IQR: 53.7%-86.0%). Disease progression was noted in two patients within 1 year, including one patient with local tumor progression post-RFA and one with a new tumor post-MWA, resulting in a constant cumulative disease progression rate of 8.8% (95% confidence interval [CI]: 0%-19.8%) throughout the remaining follow-up period. Both patients were subsequently treated with additional ablation and did not require surgery. The cumulative rates of complete tumor disappearance at 1, 3, and 5 years were 4.0% (95% CI: 0%-11.4%), 26.8% (95% CI: 2.7%-44.9%), and 51.2% (95% CI: 0%-79.1%), respectively. No significant differences were observed in the disease progression (P = 0.829) or complete tumor disappearance (P = 0.633) rates between the MWA and RFA groups. Complications occurred in 14.7% (5/34) of patients presenting with transient hoarseness. RFA had a higher but not statistically significant complication rate than MWA did (21.1% [4/19] vs. 6.7% [1/15]; P = 0.355). CONCLUSION: Both MWA and RFA demonstrated promising short-term outcomes in terms of efficacy and safety in treating solitary low-risk T2N0M0 PTC, with no significant differences.

Dual-etiology MAFLD: the interactions between viral hepatitis B, viral hepatitis C, alcohol, and MAFLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

Clofazimine and QT prolongation in the treatment of rifampicin-resistant tuberculosis: Findings of aDSM in Taiwan.

BACKGROUND: Bedaquiline, delamanid and fluoroquinolones are associated with increased QTcF. Whether clofazimine is associated with QTcF prolongation is less clear. METHODS: All patients with rifampicin-resistant TB enrolled between May 2017 and Dec 2019 were included. ECGs were performed at baseline, month 1, month 3 and month 6 for patients treated with conventional regimens, and at additional timepoint for patients treated with bedaquiline, delamanid and short regimen. We estimated the maximum increase of QTcF and constructed cox proportional hazards models to assess factors associated with QTcF≥501ms. RESULTS: Among 321 patients, 59 (18.4%) patients had QTcF≥501ms during a mean follow-up of 242 days (median 189, range 4-1091). The median maximum increase of QTcF was 43.4 ms (IQR 31.3-65.9) in patients treated with clofazimine. Treatment with clofazimine was significantly associated with QTcF≥501ms as compared to without clofazimine (adjusted hazards ratio (adjHR) 4.35, 95% confidence interval (CI) 2.01-9.44). Among patients not treated with bedaquiline and delamanid, those treated with clofazimine and a fluoroquinolone (adjHR 3.43, 95% CI 1.61-7.34) and those treated with clofazimine and high dose moxifloxacin (adjHR 6.54, 95% CI 2.43-17.60) had a significantly higher risk of QTcF≥501ms as compared to those treated with a fluoroquinolone without other QTcF prolonging agents. Four (1.6%) patients had documented ventricular tachycardia, in which one was Torsade de pointes. One patient was found to have sudden death during hospitalization. CONCLUSIONS: Clofazimine was significantly associated with an increased risk of QTcF prolongation. QTcF≥501ms was potentially associated with fatal event and needed to be managed cautiously.

PPARß/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells.

The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator-activated receptor ß/δ (PPARß/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8+ T cells. PPARß/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARß/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARß/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.

An Innovative Methodology: The Submental Island Flap Offers Enhanced Soft Tissue Coverage to the Vascularized Iliac Crest Flap.

The vascularized iliac crest flap has garnered widespread acclaim within the field of mandibular reconstruction attributable to its sufficient bone mass and congruent curved morphology. However, when the precise orientation of the iliac crest is imperative during mandibular reconstruction and there exists an accompanying defect within the oral soft tissue, the indispensability of an additional flap to facilitate concurrent defect repair becomes evident. In such instances, the submental island flap emerges as an exemplary candidate.

Estimating the risk of major adverse cardiac events following radiotherapy for left breast cancer using a modified generalized Lyman normal-tissue complication probability model.

BACKGROUND: We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT). MATERIALS AND METHODS: Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups. RESULTS: Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D50 = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D50 = 30 Gy) compared to the low-comorbidity group (D50 = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively. CONCLUSION: Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT.

Associations of the EAT-Lancet reference diet with metabolic dysfunction-associated steatotic liver disease and its severity: A multicohort study.

BACKGROUND AND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. APPROACH AND RESULTS: This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß = -5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

Erythrocyte Very Long-Chain Saturated Fatty Acids, Gut Microbiota-Bile Acid Axis, and Incident Coronary Artery Disease in Adults: A Prospective Cohort Study.

BACKGROUND: Prior research has highlighted inverse associations between concentrations of circulating very long-chain saturated fatty acids (VLCSFAs) and coronary artery disease (CAD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored. OBJECTIVES: This study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids. METHODS: This 10-y prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs [arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)] were measured using gas chromatography at baseline, and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S ribosomal ribonucleic acid sequencing and ultra-performance liquid chromatography-tandem mass spectrometry at middle-term. RESULTS: The multivariable-adjusted hazard ratios (95% confidence interval) for CHD incidence in highest compared with lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42, 0.96) for C22:0, 0.59 (0.41, 0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA concentrations exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These 5 genera generated overlapping differential microbial scores (ODMSs) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation = 0.018). Bile acids tauro_α_ and tauro_ß_muricholic acid were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid and glycodeoxycholic acid. Mediation analyses indicated that glycolithocholic acid, glycodeoxycholic acid, and tauro_α_ and tauro_ß_muricholic acid explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation = 0.002, 0.008, and 0.020). CONCLUSIONS: Elevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies. This trial was registered at registry name as NCT03179657.

The nucleus accumbens in reward and aversion processing: insights and implications.

The nucleus accumbens (NAc), a central component of the brain's reward circuitry, has been implicated in a wide range of behaviors and emotional states. Emerging evidence, primarily drawing from recent rodent studies, suggests that the function of the NAc in reward and aversion processing is multifaceted. Prolonged stress or drug use induces maladaptive neuronal function in the NAc circuitry, which results in pathological conditions. This review aims to provide comprehensive and up-to-date insights on the role of the NAc in motivated behavior regulation and highlights areas that demand further in-depth analysis. It synthesizes the latest findings on how distinct NAc neuronal populations and pathways contribute to the processing of opposite valences. The review examines how a range of neuromodulators, especially monoamines, influence the NAc's control over various motivational states. Furthermore, it delves into the complex underlying mechanisms of psychiatric disorders such as addiction and depression and evaluates prospective interventions to restore NAc functionality.

Quantitative diagnosis of early acute compartment syndrome using two-dimensional shear wave elastography in a rabbit model.

PURPOSE: This study explored the association of the elasticity modulus and shear wave velocity (SWV) of the tibialis anterior muscle, as measured by two-dimensional shear wave elastography (2D-SWE), with the intracompartmental pressure (ICP) determined using the Whitesides method in a New Zealand rabbit model of acute compartment syndrome (ACS). Additionally, it evaluated the viability of 2D-SWE as a noninvasive, quantitative tool for the early detection of ACS. METHODS: An ACS model was established through direct external compression by applying pressure bandaging to the lower legs of 15 New Zealand rabbits using neonatal blood pressure cuffs. Another five animals represented a non-modeled control group. To measure the elasticity modulus and SWV of the tibialis anterior muscles, 2D-SWE was employed. Blood oxygen saturation, serum creatine kinase (CK), and myoglobin levels were monitored. Subsequently, the anterior tibial compartment was dissected, and the tibialis anterior was removed for hematoxylin and eosin staining to assess muscle injury. RESULTS: The elasticity modulus and SWV of the tibialis anterior muscle increased with compression duration, as did serum CK and myoglobin levels. ICP was strongly positively correlated with these parameters, particularly mean velocity (r=0.942, P<0.001) and CK (r=0.942, P<0.001). Blood oxygen saturation was negatively correlated with ICP (r=-0.887, P<0.001). Histological analysis indicated progressive muscle cell swelling over time, with damage transitioning from reversible to irreversible and culminating in necrosis. CONCLUSION: In a rabbit ACS model, ICP was strongly positively correlated with muscle elasticity modulus/SWV. Consequently, 2D-SWE may represent a novel tool for assessing early-phase ACS.