Objective
The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS).
Methods
We ...prospectively recruited 3 independent cohorts of patients with RCVS and age‐matched and sex‐matched controls in a single medical center. Next‐generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross‐validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis.
Results
We identified a panel of miRNAs including miR‐130a‐3p, miR‐130b‐3p, let‐7a‐5p, let‐7b‐5p, and let‐7f‐5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve AUC was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let‐7a‐5p, let‐7b‐5p, and let‐7f‐5p, but not miR‐130a‐3p nor miR‐130b‐3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor‐β signaling pathway and endothelin‐1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients’ cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR‐130a‐3p was associated with imaging‐proven disruption of the blood‐brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model.
Interpretation
We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459–473
CDGSH iron-sulfur domain-containing protein 2 (Cisd2) is pivotal to mitochondrial integrity and intracellular Ca2+ homeostasis. In the heart of Cisd2 knockout mice, Cisd2 deficiency causes ...intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Furthermore, Cisd2 deficiency disrupts Ca2+ homeostasis via dysregulation of sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) activity, resulting in an increased level of basal cytosolic Ca2+ and mitochondrial Ca2+ overload in cardiomyocytes. Most strikingly, in Cisd2 transgenic mice, a persistently high level of Cisd2 is sufficient to delay cardiac aging and attenuate age-related structural defects and functional decline. In addition, it results in a younger cardiac transcriptome pattern during old age. Our findings indicate that Cisd2 plays an essential role in cardiac aging and in the heart's electromechanical functioning. They highlight Cisd2 as a novel drug target when developing therapies to delay cardiac aging and ameliorate age-related cardiac dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute kidney injury (AKI) is a common complication of extracorporeal membrane oxygenation (ECMO) treatment. The aim of this study was to elucidate the long-term outcomes of adult patients with AKI ...who receive ECMO.
The study analyzed encrypted datasets from Taiwan's National Health Insurance Research Database. The data of 3251 patients who received first-time ECMO treatment between January 1, 2003, and December 31, 2013, were analyzed. Characteristics and outcomes were compared between patients who required dialysis for AKI (D-AKI) and those who did not in order to evaluate the impact of D-AKI on long-term mortality and major adverse kidney events.
Of the 3251 patients, 54.1% had D-AKI. Compared with the patients without D-AKI, those with D-AKI had higher rates of all-cause mortality (52.3% vs. 33.3%; adjusted hazard ratio aHR 1.82, 95% confidence interval CI 1.53-2.17), chronic kidney disease (13.7% vs. 8.1%; adjusted subdistribution HR aSHR 1.66, 95% CI 1.16-2.38), and end-stage renal disease (5.2% vs. 0.5%; aSHR 14.28, 95% CI 4.67-43.62). The long-term mortality of patients who survived more than 90 days after discharge was 22.0% (153/695), 32.3% (91/282), and 50.0% (10/20) in the patients without D-AKI, with recovery D-AKI, and with nonrecovery D-AKI who required long-term dialysis, respectively, demonstrating a significant trend (Pfor trend <0.001).
AKI is associated with an increased risk of long-term mortality and major adverse kidney events in adult patients who receive ECMO.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims The relationship between pyogenic liver abscess (PLA) and gastrointestinal (GI) cancer was first reported more than 20 years ago, yet little is known about this connection. We ...evaluated this association in a population-based, retrospective, cohort study. Methods Using Taiwan National Health Insurance claims data, we collected data on a cohort of 14,690 patients with PLA diagnosed from 2000 to 2007. A reference cohort of 58,760 persons without PLA (controls) was selected from the same database, frequency matched by age, sex, and index year. Both cohorts were followed up until the end of 2009, and incidences of GI cancer were calculated. Results The incidence of GI cancer was 4.30-fold higher among patients with PLA compared with controls (10.8 vs 2.51/1000 person-years). Site-specific analysis showed that the highest incidence of colorectal cancer was among patients with PLA and diabetes mellitus, followed by patients with PLA without diabetes and controls with diabetes (9.58, 5.76, and 1.49/10,000 person-years, respectively). The PLA cohort also had a high risk of small intestine cancer (adjusted hazard ratio aHR, 12.7; 95% confidence interval CI, 5.79–27.7) and biliary tract cancer (aHR, 9.56; 95% CI, 6.68–13.7). Their risk of pancreatic cancer (aHR, 2.51; 95% CI, 1.68–3.76) was also significant. However, patients with PLA did not have an increased risk of gastric cancer compared with controls. Conclusions In a population-based study, we found that the incidence of GI cancer is increased more than 4-fold among patients with PLA compared with controls. PLA might therefore be an indicator of GI cancer. Patients with PLA had the highest incidence of colorectal cancer, followed by cancers of the biliary tract, pancreas, and small intestine.
The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical ...treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.
Summary
Purpose: Schizophrenia and epilepsy may share a mutual susceptibility. This study examined the bidirectional relation between the two disorders.
Methods: We used claims data obtained from ...the Taiwan National Health Insurance database to conduct retrospective cohort analyses. Analysis 1 compared 5,195 patients with incident schizophrenia diagnosed in 1999–2008 with 20,776 controls without the disease randomly selected during the same period, frequency matched with sex and age. Analysis 2 comprised a similar method to compare 11,527 patients with newly diagnosed epilepsy with 46,032 randomly selected sex‐ and age‐matched controls. At the end of 2008, analysis 1 measured the incidence and risk of developing epilepsy and analysis 2 measured the incidence and risk of developing schizophrenia.
Key Findings: In analysis 1, the incidence of epilepsy was higher in the schizophrenia cohort than in the nonschizophrenia cohort (6.99 vs. 1.19 per 1,000 person‐years) with an adjusted hazard ratio (aHR) of 5.88 95% confidence interval (CI) 4.71–7.36 for schizophrenia patients. In analysis 2, the incidence of schizophrenia was higher in the epilepsy cohort than in the nonepilepsy comparison cohort (3.53 vs. 0.46 per 1,000 person‐years) with an aHR of 7.65 (95% CI 6.04–9.69) for epilepsy patients. The effect of schizophrenia on subsequent epilepsy was greater for women, but the association between epilepsy and elevated incidence of schizophrenia was more pronounced in men.
Significance: We found a strong bidirectional relation between schizophrenia and epilepsy. These two conditions may share common causes. Further studies on the mechanism are required.
Using claims data from the universal health insurance program of Taiwan, we conducted a retrospective cohort study to investigate whether endometriosis and hormone therapy are associated with the ...risk of developing hyperlipidemia. We selected 9,155 women aged 20-55 years with endometriosis diagnosed during the period 2000-2013 and 212,641 women without endometriosis with a median follow-up time of 7 years. Among patients with endometriosis, 86% of cases were identified on the basis of diagnosis codes with an ultrasound claim, and 14% were defined by diagnostic laparoscopy or surgical treatments. In a Cox proportional hazards model, the adjusted hazard ratio was 1.30 (95% confidence interval (CI): 1.19, 1.41) for all women, 1.04 (95% CI: 0.81, 1.32) for women under 35 years of age, 1.17 (95% CI: 1.03, 1.32) for women aged 35-44 years, and 1.34 (95% CI: 1.18, 1.52) for women aged 45-54 years. Hysterectomy and/or bilateral oophorectomy accounted for 46.9% of the association between endometriosis and hyperlipidemia, and hormone therapy accounted for 21.6%. Among women with endometriosis, the marginal structural model approach adjusting for time-varying hysterectomy/bilateral oophorectomy showed no association between use of hormone medications and risk of hyperlipidemia. We concluded that women with endometriosis are at increased risk of hyperlipidemia; use of hormone therapy by these women was not independently associated with the development of hyperlipidemia.
Myocarditis can be classified into 2 categories: fulminant myocarditis (FM) and nonfulminant myocarditis. FM is the most severe type, characterized by its acute and explosive nature, posing a sudden ...and life-threatening risk with a high fatality rate. Limited research has been conducted on FM characteristics using cluster analysis. This study introduces the following-leading clustering algorithm (`) as a unique method and utilizes it to generate a dual map and timeline view of FM themes, aiming to gain a better understanding of FM.
The metadata were obtained from the Web of Science (WoS) database using an advanced search strategy based on the topic (TS= (("Fulminant") AND ("Myocarditis"))). The analysis comprised 3 main components: descriptive analytics, which involved identifying the most influential entities using CJAL scores and analyzing publication trends, author collaborations using the FLCA algorithm, and generating a dual map and timeline view of FM themes using the FLCA algorithm. The visualizations included radar plots divided into 4 quadrants, stacked bar and line charts, network charts, chord diagrams, a dual map overlay, and a timeline view.
The findings reveal that the prominent entities in terms of countries, institutes, departments, and authors were the United States, Huazhong University of Science and Technology (China), Cardiology, and Enrico Ammirati from Italy. A dual map, based on the research category, was created to analyze the relationship between citing and cited articles. It showed that articles related to cells and clinical medicine/surgery were frequently cited by articles in the fields of general health/public/nursing and clinical medicine/surgery. Additionally, a visual timeline view was presented on Google Maps, showcasing the themes extracted from the top 100 cited articles. These visualizations were successfully and reliably generated using the FLCA algorithm, offering insights from various perspectives.
A new FLCA algorithm was utilized to examine bibliometric data from 1989 to 2022, specifically focusing on FM. The results of this analysis can serve as a valuable guide for researchers, offering insights into the thematic trends and characteristics of FM research development. This, in turn, can facilitate and promote future research endeavors in this field.
Although many companies in the hotel industry aim to pursue more sustainable and socially responsible practices, the present literature shows mixed results with regard to tourist reactions to such ...moves, especially for the service quality perception impacted by implemented green practices and the willingness to pay more for such actions. Unlike previous research examining tourists' preferences for separate green hotel attributes, this study identifies the determinants of tourists' choice of green hotel attributes. Additionally, the study measures the willingness to pay (WTP) for such services, in the context of the Taiwanese market, using the stated preference of combined green hotel attribute scenarios. A multinomial logit (MNL) model is employed to estimate the relative influence of behavioral and facility attributes on choice behavior. Furthermore, the study examines determinants influencing respondents' choice of green hotel attributes. A latent variable class model (LVCM) approach is applied in the estimation of the unobserved heterogeneity, and a total of 390 valid respondents were used in the analysis. The empirical MNL results indicate that while tourists prefer luxury rooms and the provision of personal toiletries, they are also willing to accept reduced service quality. Additionally, sex, income, and age have significant influences on tourist choice behavior. The results of the LVCM model demonstrate that respondents with high levels of the green consumption trait are more likely to choose hotels that have a greater number of environmentally friendly attributes. The implicit amount that tourists are willing to pay for room quality is around US$13, for the provision of personal toiletries is about US$22, and for service quality is US$12, but they also require a discount of approximately US$11 in order to accept the common practices of green hotels. This study is useful in providing the hotel industry and government with quantitative information that can be used to develop and implement better green hotel policies.
Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. ...Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (LDHA) or acetyl-CoA by Pyruvate Dehydrogenase E1 component α subunit (PDHA1) catalytic complex. In tumor cells, accumulating lactate is produced whereas the conversion of pyruvate into mitochondrial acetyl-CoA is less active compared with their normal counterparts. This reciprocal molecular association makes pyruvate metabolism a potential choice of anti-cancer target. Cellular and molecular changes were herein assayed in Head and Neck Squamous Cell Carcinoma (HNSCC) cells in response to LDHA and PDHA1 loss in vitro, in vivo and in clinic. By using various human cancer databases and clinical samples, LDHA and PDHA1 levels exhibit reversed prognostic roles. In vitro analysis demonstrated that decreased cell growth and motility accompanied by an increased sensitivity to chemotherapeutic agents was found in cells with LDHA loss whereas PDHA1-silencing exhibited opposite phenotypes. At the molecular level, it was found that oncogenic Protein kinase B (PKB/Akt) and Extracellular signal-regulated kinase (ERK) singling pathways contribute to pyruvate metabolism mediated HNSCC cell growth. Furthermore, LDHA/PDHA1 changes in HNSCC cells resulted in a broad metabolic reprogramming while intracellular molecules including polyunsaturated fatty acids and nitrogen metabolism related metabolites underlie the malignant changes. Collectively, our findings reveal the significance of pyruvate metabolic fates in modulating HNSCC tumorigenesis and highlight the impact of metabolic plasticity in HNSCC cells.
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