Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Prevalence, proportions of elevated liver enzyme levels, and long-term cardiometabolic mortality of patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIM: This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated. METHODS: We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020. RESULTS: The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001). DISCUSSION: Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

Gain of C-Ala enables AlaRS to target the L-shaped tRNAAla.

Unlike many other aminoacyl-tRNA synthetases, alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout biology. While Caenorhabditis elegans cytoplasmic AlaRS (CeAlaRSc) retains the prototype structure, its mitochondrial counterpart (CeAlaRSm) contains only a residual C-terminal domain (C-Ala). We demonstrated herein that the C-Ala domain from CeAlaRSc robustly binds both tRNA and DNA. It bound different tRNAs but preferred tRNAAla. Deletion of this domain from CeAlaRSc sharply reduced its aminoacylation activity, while fusion of this domain to CeAlaRSm selectively and distinctly enhanced its aminoacylation activity toward the elbow-containing (or L-shaped) tRNAAla. Phylogenetic analysis showed that CeAlaRSm once possessed the C-Ala domain but later lost most of it during evolution, perhaps in response to the deletion of the T-arm (part of the elbow) from its cognate tRNA. This study underscores the evolutionary gain of C-Ala for docking AlaRS to the L-shaped tRNAAla.

Frame-based versus robot-assisted stereo-electro-encephalography for drug-resistant epilepsy.

BACKGROUND: Stereoelectroencephalography (SEEG) is an effective presurgical invasive evaluation for drug-resistant epilepsies. The introduction of robotic devices provides a simplified, accurate, and safe alternative to the conventional SEEG technique. We report our institutional experience with robot-assisted SEEG and compare its in vivo accuracy, operation efficiency, and safety with the more traditional SEEG workflow. METHODS: All patients with medically refractory focal epilepsy who underwent SEEG depth electrode implantation between 2014 and 2022 were included in this study. Technical advancements of the robot-assisted technique are described. Analyses of patient demographics, electrode implantation accuracy, operation time, and procedure-related complications were performed. RESULTS: One hundred and sixty-six patients underwent 167 SEEG procedures. The first 141 procedures were performed using a conventional approach involving a Leksell stereotactic system, and the last 26 procedures were robot-assisted. Among the 1726 depth electrodes that were inserted, the median entry point localization error was as follows: conventional (1.0 mm; range, 0.1-33.5 mm) and robot-assisted (1.1 mm; range, 0-4.8 mm) (P = 0.17). The median target point localization error was as follows: conventional (2.8 mm; range, 0.1-49 mm) and robot-assisted (1.8 mm; range, 0-30.3 mm) (P < 0.001). The median operation time was significantly reduced with the robot-assisted workflow (90 min vs. 77.5 min; P < 0.01). Total complication rates were as follows: conventional (17.7%) and robot-assisted (11.5%) (P = 0.57). Major complication rates were 3.5% and 7.7% (P = 0.77), respectively. CONCLUSIONS: SEEG is a safe and highly accurate method that provides essential guidance for epilepsy surgery. Implementing SEEG in conjunction with multimodal planning systems and robotic devices can further increase safety margin, surgical efficiency, and accuracy.

Evaluation of the Feasibility of In Vitro Metabolic Interruption of Trimethylamine with Resveratrol Butyrate Esters and Its Purified Monomers.

Resveratrol (RSV), obtained from dietary sources, has been shown to reduce trimethylamine oxide (TMAO) levels in humans, and much research indicates that TMAO is recognized as a risk factor for cardiovascular disease. Therefore, this study investigated the effects of RSV and RSV-butyrate esters (RBE) on the proliferation of co-cultured bacteria and HepG2 cell lines, respectively, and also investigated the changes in trimethylamine (TMA) and TMOA content in the medium and flavin-containing monooxygenase-3 (FMO3) gene expression. This study revealed that 50 µg/mL of RBE could increase the population percentage of Bifidobacterium longum at a rate of 53%, while the rate was 48% for Clostridium asparagiforme. In contrast, co-cultivation of the two bacterial strains effectively reduced TMA levels from 561 ppm to 449 ppm. In addition, regarding TMA-induced HepG2 cell lines, treatment with 50 µM each of RBE, 3,4'-di-O-butanoylresveratrol (ED2), and 3-O-butanoylresveratrol (ED4) significantly reduced FMO3 gene expression from 2.13 to 0.40-1.40, which would also contribute to the reduction of TMAO content. This study demonstrated the potential of RBE, ED2, and ED4 for regulating TMA metabolism in microbial co-cultures and cell line cultures, which also suggests that the resveratrol derivative might be a daily dietary supplement that will be beneficial for health promotion in the future.

Treatment Landscape of Renal Cell Carcinoma.

OPINION STATEMENT: The treatment landscape of renal cell carcinoma (RCC) has evolved significantly over the past three decades. Active surveillance and tumor ablation are alternatives to extirpative therapy in appropriately selected patients. Stereotactic body radiation therapy (SBRT) is an emerging noninvasive alternative to treat primary RCC tumors. The advent of immune checkpoint inhibitors (ICIs) has greatly improved the overall survival of advanced RCC, and now the ICI-based doublet (dual ICI-ICI doublet; or ICI in combination with a vascular endothelial growth factor tyrosine kinase inhibitor, ICI-TKI doublet) has become the standard frontline therapy. Based on unprecedented outcomes in the metastatic with ICIs, they are also being explored in the neoadjuvant and adjuvant setting for patients with high-risk disease. Adjuvant pembrolizumab has proven efficacy to reduce the risk of RCC recurrence after nephrectomy. Historically considered a radioresistant tumor, SBRT occupies an expanding role to treat RCC with oligometastasis or oligoprogression in combination with systemic therapy. Furthermore, SBRT is being investigated in combination with ICI-doublet in the advanced disease setting. Lastly, given the treatment paradigm is shifting to adopt ICIs at earlier disease course, the prospective studies guiding treatment sequencing in the post-ICI setting is maturing. The effort is ongoing in search of predictive biomarkers to guide optimal treatment option in RCC.

Incidence, prescription patterns and risk factors of antipsychotic initiation in elderly stroke survivors.

OBJECTIVES: Epidemiological data regarding antipsychotic initiation in elderly patients with stroke are limited. We aimed to investigate the incidence, prescription patterns and determinants of antipsychotic initiation in elderly patients with stroke. METHODS: We conducted a retrospective cohort study to identify patients aged above 65 years who had been admitted for stroke from the National Health Insurance Database (NHID). The index date was defined as the discharge date. The incidence and prescription pattern of antipsychotics were estimated using the NHID. To evaluate the determinants of antipsychotic initiation, the cohort identified from the NHID was linked to the Multicenter Stroke Registry (MSR). Demographics, comorbidities and concomitant medications were obtained from the NHID. Information including smoking status, body mass index, stroke severity and disability was retrieved by linking to the MSR. The outcome was antipsychotic initiation after the index date. Hazard ratios for antipsychotic initiation were estimated using the multivariable Cox model. RESULTS: In terms of prognosis, the first 2 months after a stroke was the highest-risk period for antipsychotic use. A high burden of coexisting diseases carried an increased risk of antipsychotic use; in particular, chronic kidney disease (CKD) had the highest adjusted hazard ratio (aHR = 1.73; 95% CI 1.29-2.31) as compared with other risk factors. Furthermore, stroke severity and disability were significant risk factors for antipsychotic initiation. CONCLUSIONS: Our study indicated that elderly stroke patients with chronic medical conditions, particularly CKD, and a higher stroke severity and disability were at greater risk of psychiatric disorders during the first 2 months after a stroke. CLINICAL TRIAL REGISTRATION: NA.

Rotablation for Octogenarians in a Modern Cathlab: Short- and Intermediate-Term Results.

Background: There are limited reports on the treatment of complex calcified lesions using rotational atherectomy (RA) in octogenarians, particularly in high-risk patients. Objective: To evaluate procedural and clinical outcomes of RA in octogenarians. Methods: Consecutive RA patients from 2010 to 2018 were selected from our catheterization laboratory database, stratified into two groups (≥ or < 80 years old), and analyzed. Results: A total of 411 patients (269 males and 142 females) with a mean age of 73.8 ± 11.3 years were enrolled, of whom 153 were ≥ 80 years old and 258 were < 80 years old. Most of the patients displayed high-risk features. The baseline Syntax scores were high in both groups, and most lesions were heavily calcified (96.1% vs. 97.3%, p = 0.969, respectively). The use of hemodynamic support intra-aortic balloon pump was more frequent in the octogenarians (21.6% vs. 11.6%, p = 0.007), but the RA completion rate was similarly high (95.9% vs. 99.1%, p = 0.842). There was no difference in acute complications. The total/cardiovascular (CV) death rate within one year was higher in the octogenarians, along with higher major adverse cardiovascular event (MACE)/CV MACE rates in the first month. Cox regression analysis showed that age ≥ 80 years, acute coronary syndrome, ischemic cardiomyopathy/shock, multi-vessel disease and serum creatinine were all predictors of MACE, and that these factors plus peripheral artery disease were predictors of all-cause mortality in these patients. Conclusions: RA is feasible with a very high success rate in high-risk octogenarians with complex anatomies, and with equal safety and no increase in complications. The higher rates of all-cause death and MACE were attributed to an older age and other traditional risk factors.

Allogeneic adipose tissue-derived stem cells ELIXCYTE® in chronic kidney disease: A phase I study assessing safety and clinical feasibility.

The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue-derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible CKD patients with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE® ), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment-related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR â‰§ 30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2  group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single-dose intravenous ELIXCYTE was well tolerated in moderate-to-severe CKD patients and its preliminary efficacy warrants future studies.

Rotablation in Patients with Advanced Renal Insufficiency through End-Stage Renal Disease: Short- and Intermediate-Term Results.

Objective: Patients with advanced renal insufficiency are at high risk of coronary artery disease (CAD) and complex lesions. Treating complex calcified lesion with rotational atherectomy (RA) in these patients might be associated with higher risks and poorer outcomes. This study was set to evaluate features and outcomes of RA in these patients. Method: Consecutive patients who received coronary RA from April 2010 to April 2018 were queried from the Cath Lab database. The procedural details, angiography, and clinical information were reviewed in detail. Results: A total of 411 patients were enrolled and divided into Group A (baseline serum creatinine <5 mg/dl, n = 338) and Group B (baseline serum creatinine ≥ 5 mg/dl through ESRD, n = 73). Most patients had high-risk features (65.7% of acute coronary syndrome (ACS), 14.1% of ischemic cardiomyopathy, and 5.1% of cardiogenic shock). Group B patients were significantly younger (66.8 ± 11.4 vs. 75.2 ± 10.7 years, p < 0.001) and had more RCA and LCX but less LAD treated with RA. No difference was found in lesion location, vessel tortuosity, bifurcation lesions, chronic total occlusion, total lesion length, or total lesion numbers between the two groups. Less patients in Group B obtained completion of RA (95.9% vs 99.1%, p=0.037). There was no difference in the incidence of procedural complication or acute contrast-induced nephropathy. Group B patients had more deaths and MACE while in the hospital. The MACE and CV MACE were also higher in Group B patients at 180 days and one year, mostly due to TLR and TVR. Multivariate regression analysis showed that ACS, age, peripheral artery disease (PAD), advanced renal insufficiency, ischemic cardiomyopathy/shock, and high residual SYNTAX score were independent risk factors for in-hospital MACE, whereas ACS, advanced renal insufficiency, ischemic cardiomyopathy/shock, triple-vessel disease, and PAD independently predicted MACE at 6 months. Conclusions: Rotablation is feasible, safe, and could be carried out with very high success rate in very-high-risk patients with advanced renal dysfunction through ESRD without an increase in procedural complication.

Approaches to First-Line Therapy for Metastatic Clear Cell Renal Cell Carcinoma.

PURPOSE OF REVIEW: Four immuno-oncology (IO)-based combinations have demonstrated overall survival benefit as frontline treatment of metastatic clear cell renal cell carcinoma (mccRCC). Choosing among the available combinations depends on treating physician's interpretation of existing data without level I evidence to inform choice of therapy. Landmark trials of mccRCC are reviewed and perspective on treatment options is provided. RECENT FINDINGS: The four IO-based combinations reviewed are ipilimumab/nivolumab (IO/IO), pembrolizumab/axitinib (IO/TKI), nivolumab/cabozantinib (IO/TKI), and pembrolizumab/lenvatinib (IO/TKI). The ipilimumab/nivolumab combination is notable for durable efficacy after extended 4-year follow-up. IO/TKI combinations have clinical efficacy across all IMDC risk groups with higher response rates and longer progression-free survival (PFS) but also had higher ≥ grade 3 adverse events rate. Patient tumor burden, performance status, and IMDC risk group are factors in choosing an IO-based treatment. IO/IO and IO/TKI combinations for mccRCC have distinct efficacy and toxicity profiles. Future studies are needed to identify biomarkers to optimize patient outcomes.

Cerebrospinal fluid diversion and outcomes for lung cancer patients with leptomeningeal carcinomatosis.

OBJECTIVE: To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC). METHODS: A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications. RESULTS: The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2). CONCLUSION: CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.

Health promotion challenges for young adults living with intellectual disability and type 1 diabetes.

BACKGROUND: Self-management of type 1 diabetes mellitus (T1DM) can be challenging for people with intellectual disability. Often, parents provide health support due to lack of appropriate services outside the home. The study aim was to identify barriers and facilitators to T1DM self-management for young adults with intellectual disability and the implications for health promotion. METHODS: Five male participants with intellectual disability, aged 17-26 years, and seven parents were interviewed between October 2017 and February 2019. Interview data were descriptively analysed. FINDINGS: Two categories for barriers and facilitators were identified: 1) Diabetes self-management is complex (carbohydrate counting, blood glucose level monitoring, insulin therapy); 2) support for diabetes care (reliance on parents and carers, the National Disability Insurance Scheme, mainstream diabetes service support). CONCLUSIONS: Parents are critical for the support of people with intellectual disability and T1DM in the absence of disability staff with appropriate health skills.

Impact of dialysis modality on major adverse cardiovascular events and all-cause mortality: a national population-based study.

BACKGROUND: Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective assessment of survival benefits a greater challenge. METHODS: Data were retrieved from Taiwan's National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities. RESULTS: For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 [95% confidence interval (CI) 0.89-1.02] in the propensity score study design and 1.06 (95% CI 1.01-1.12) in the time-varying study design. For all-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05-1.13) in the propensity score study design and 1.13 (95% CI 1.09-1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15-1.28), patients ≥65 years old (1.30, 95% CI 1.24-1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22-1.34). CONCLUSIONS: The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.

Does the Diffuseness of the Nidus Affect the Outcome of Stereotactic Radiosurgery in Patients with Unruptured Cerebral Arteriovenous Malformations?

BACKGROUND: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS). OBJECTIVES: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes. METHODS: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS. RESULTS: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS. CONCLUSIONS: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.

Riverside underwater noise pollution threaten porpoises and fish along the middle and lower reaches of the Yangtze River, China.

The Yangtze River exhibits a high biodiversity and plays an important role in global biodiversity conservation. As the world's busiest inland river in regard to shipping, little attention has been paid to underwater noise pollution. In 2017, the underwater noise level in 25 riverside locations along the middle and lower reaches of the Yangtze River mainly at night time were investigated by using passive acoustic monitoring method. Approximately 88% and 40% of the sampled sites exhibit noise levels exceeding the underwater acoustic thresholds of causing responsiveness and temporary threshold shift, respectively, in cetacean. Noise pollution may impose a high impact on fish with physostomous swim bladders and Weberian ossicles, such as silver carp, bighead carp, goldfish and common carp, whereas it may affect fish with physoclistous swim bladders and without Weberian ossicles, such as lake sturgeon and paddlefish, to a lesser extent. Noise levels reductions of approximately 10 and 20 dB were observed in the middle and lower reaches, respectively, of the Yangtze River over the 2012 level. The green development mode of the ongoing construction of green shipping in the Yangtze River Economic Belt, including the development of green shipping lanes, ports, ships and transportation organizations, may account for the alleviated underwater noise pollution. Follow-up noise mitigation endeavors, such as the extension of ship speed restrictions and the study and implementation of the optimal navigation speed in ecologically important areas, are required to further reduce the noise level in the Yangtze River to protect local porpoises and fish.

Diagnosis and Treatment for embolic stroke of undetermined source: Consensus statement from the Taiwan stroke society and Taiwan society of cardiology.

Cryptogenic stroke comprises about one-quarter of ischemic strokes with high recurrence rate; however, studies specifically investigating the features and treatment of this stroke subtype are rare. The concept of 'embolic stroke of undetermined source' (ESUS) may facilitate the development of a standardized approach to diagnose cryptogenic stroke and improve clinical trials. Since recent large randomized control trials failed to demonstrate a reduction in stroke recurrence with anticoagulants, anti-platelet agents remain the first-line treatment for ESUS patients. Nevertheless, patients with high risk of stroke recurrence (e.g., those with repeated embolic infarcts despite aspirin treatment) require a more extensive survey of stroke etiology, including cardiac imaging and prolonged cardiac rhythm monitoring. Anticoagulant treatments may still benefit some subgroups of high-risk ESUS patients, such as those with multiple infarcts at different arterial territories without aortic atheroma, the elderly, or patients with high CHA2D2-VASc or HOVAC scores, atrial cardiopathy or patent foramen ovale. Several important ESUS clinical trials are ongoing, and the results are anticipated. With rapid progress in our understanding of ESUS pathophysiology, new subcategorizations of ESUS and assignment of optimal treatments for each ESUS subgroup are expected in the near future.

Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota.

Resveratrol can affect the physiology or biochemistry of offspring in the maternal-fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4-8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut-liver axis in the offspring.

Separation and Identification of Resveratrol Butyrate Ester Complexes and Their Bioactivity in HepG2 Cell Models.

Resveratrol butyrate ester (RBE) complexes have demonstrated higher antioxidant capacity and anti-fat accumulation activity in previous studies. In this study, silica gel, high-performance liquid chromatography, and 1H nuclear magnetic resonance were used for separation and identification of RBE complex components. With the exception of resveratrol, five different structures of ester derivatives were separated from silica gel: 3,4'-di-O-butanoylresveratrol (ED2, 18.8%), 3-O-butanoylresveratrol (ED4, 35.7%), 4'-O-butanoylresveratrol (ED5, 4.4%), 3,5,4'-tri-O-butanoylresveratrol (ED6, 1.5%), and 3,5-di-O-butanoylresveratrol (ED7, 0.7%). Among the ester derivatives obtained, ED2 and ED4 were the main ester derivatives in the RBE complex. Thus, the cellular antioxidant activities of the RBE mixture, ED2, and ED4 were evaluated. Results showed that the antioxidant capacity of ED2 and ED4 was higher than that of the RBE mixture, demonstrating that the number and position of butyrate esterification sites are related to cell survival rate and antioxidant capacity. This study is the first to report the successful isolation, structural identification, and cellular biological antioxidant activity of RBE complex derivatives, which are key characteristics for the potential practical application of RBE complexes.

Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats.

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.