Tuesday, November 10, 2020

Low-dose or no aspirin administration in acute-phase Kawasaki disease: a meta-analysis and systematic review

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Objective

To compare the efficacy of low-dose or no aspirin with conventional high-dose aspirin for the initial treatment in the acute-phase of Kawasaki disease (KD).

Design

A meta-analysis and systematic review of randomised control trials and cohort studies.

Methods

All available articles that compared different dosage of aspirin in the acute-phase of KD published until 20 September 2019 were included from the databases of PubMed, Embase and Cochrane Central Register of Controlled Trials Central witho ut language restrictions. Extracted data from eligible studies were reviewed by two authors independently and analysed by using RStudio software.

Results

Nine cohorts with a total of 12 182 children were enrolled. We found that low-dose (3–5 mg/kg/day) or no aspirin in the acute-phase KD was associated with reducing the risk of coronary artery lesions (CALs, OR=0.81, 95% CI 0.69 to 0.95). No differences were observed in intravenous immunoglobulin resistance, length of hospital stay and fever days after admission (OR=1.35, 95% CI 0.91 to 1.98; standard mean difference (SMD)=0.17, 95% CI –1.07 to 1.4; SMD=0.3, 95% CI –1.51 to 2.11) in the low-dose/no aspirin subgroup compared with the high-dose (≥30 mg/kg/day) aspirin subgroup. We did not identify any potential factors affecting the homogeneity of CAL risk as well as clinical important effects in all included studies.

Conclusions

Prescribing low-dose or no aspirin in the acute-phase of KD might be associated with a d ecreased incidence of CAL. However, additional well-designed prospective trials are required to support the theory.

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Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

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Background

Pathogenic variants of GNB5 encoding the β5 subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia.

Methods

We used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse.

Results

We delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5–/– mice were smaller and had a smaller heart than Gnb5+/+ and Gnb5+/–, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5–/– mice. In contrast, Gnb5–/– mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the ID DCA cohort to 44 patients.

Conclusions

Our data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5/– mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening.

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Induced Pluripotent Stem Cell-Differentiated Chondrocytes Repair Cartilage Defect in a Rabbit Osteoarthritis Model

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The aim of this study was to explore the therapeutic effect of iPSC-mesenchymal stem cell (MSC)-derived chondrocytes in a rabbit osteoarthritis (OA) model. The iPSCs were characterized by gene expressions, immunostaining of pluripotent markers, and in vivo teratoma formation. iPSC-differentiated MSCs were characterized by flow cytometry and trilineage differentiation. A rabbit OA model was established by the transection of the anterior cruciate ligament. The therapeutic effect of transplanted iPSC-MSC-chondrocytes on the OA was evaluated by the histology, immunostaining, and qPCR of defective cartilage. The results showed iPSC could express pluripotency markers such as OCT4, SOX2, and NANOG and form an embryoid body and a teratoma. After differentiation of iPSCs for 30 days, MSCs were established. The iPSC-MS C could express typical MSC markers such as CD29, CD44, CD90, CD105, and HLA-ABC. They could differentiate into adipocytes, osteocytes, and chondrocytes. In this model, iPSC-MSC-chondrocytes significantly improved the histology and ICRS (International Cartilage Repair Society) scores. The transplanted cartilage expressed less IL-1β, TNF-α, and MMP13 than control cartilage. In conclusion, the iPSCs we derived might represent an emerging source for differentiated MSC-chondrocyte and might rescue cartilage defects through its anti-inflammatory and anti-catabolic effects.
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Dercum’s Disease: A Case Report of a Patient Having Both Type 1 and Type 2 Dercum’s Disease

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Dercum's disease, or adiposis dolorosa, is a rare disorder which consists of multiple, painful lipomas within the subcutaneous tissue and has a distribution mainly in the abdomen and extremities. Dercum's disease can be defined as in combination with chronic painful adipose tissue. Although the etiology of Dercum's disease is not clear, it is thought to be a combination of a neurological and endocrine disorder. Treatment for this disease is centered at managing pain. Although there is no standard of care for managing pain, there are different pain management regimes that are promising.
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So-Ochim-Tang-Gamibang, a Traditional Herbal Formula, Ameliorates Depression by Regulating Hyperactive Glucocorticoid Signaling In Vitro and In Vivo

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So-ochim-tang-gamibang (SOCG) is a Korean traditional medicine; it has previously been shown to be safe and effective against depression. Persistently increased levels of circulating glucocorticoids have been considered as a pathological mechanism for depression and associated with decreased neurotrophic factors in the hippocampus. This study investigated whether SOCG controls the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and the molecular mechanisms underlying its effects in vivo and in vitro. Wistar Kyoto (WKY) rats were subjected to restraint stress, where SOCG was orally administered to the animals for 2 weeks. An open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were performed to explore the antidepressant activity of SOCG in WKY rats. Plasma lev els of HPA axis hormones were measured by ELISA or western blotting analysis. The expression levels or activation of HPA axis-related signaling molecules such as brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), extracellular regulated kinase (ERK), and glucocorticoid receptors (GRs) in the brain were determined by real-time PCR and western blotting analysis. Furthermore, a corticosterone- (CORT-) induced cell injury model was established using SH-SY5Y cells to explore the antidepressive effects of SOCG in vitro. The results of the OFT, FST, and SPT revealed that SOCG ameliorated depressive-like behaviors in the WKY rats. The blood plasma levels of HPA axis hormones such as CORT, CORT-releasing hormone (CRH), and adrenocorticotrophic hormone were downregulated by SOCG. On the other hand, SOCG upregulated the phosphorylation of CREB and ERK in both the rat hippocampus and CORT-treated SH-SY5Y cells. Moreover, it also increased the GR expression. These results suggested that SOCG may improve depression by controlling hyperactive glucocorticoid signaling via the downregulation of HPA axis hormones and upregulation of GR.
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Identification of Genetic Biomarkers for Diagnosis of Myocardial Infarction Compared with Angina Patients

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Background. Myocardial infarction (MI) is the most terrible appearance of cardiovascular disease. The incidence of heart failure, one of the complications of MI, has increased in the past few decades. Therefore, the identification of MI from angina patients and the determination of new diagnoses and therapies of MI are increasingly important. The present study was aimed at identifying differentially expressed genes and miRNAs as biomarkers for the clinical and prognosis factors of MI compared with angina using microarray data analysis. Methods. Differentially expressed miRNAs and genes were manifested by GEO2R. The biological function of differentially expressed genes (DEGs) was examined by GO and KEGG. The construction of a protein-protein network was explored by STRING. cytoHubba was utilized to screen h ub genes. Analysis of miRNA-gene pairs was executed by the miRWalk 3.0 database. The miRNA-target pairs overlapped with hub genes were seen as key genes. Logistic regressive analysis was performed by SPSS. Results. A number of 779 DEGs were recorded. The biological function containing extracellular components, signaling pathways, and cell adhesion was enriched. Twenty-four hub genes and three differentially expressed miRNAs were noted. Eight key genes were demonstrated, and 6 out of these 8 key genes were significantly related to clinical and prognosis factors following MI. Conclusions. CALCA, CDK6, MDM2, NRXN1, SOCS3, VEGFA, SMAD4, NCAM1, and hsa-miR-127-5p were thought to be potential diagnosis biomarkers for MI. Meanwhile, CALCA, CDK6, NRXN1, SMAD4, SOCS3, and NCAM1 were further identified to be potential diagnosis and therapy targets for MI.
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Exosomal Long Noncoding RNAs: Insights into Emerging Diagnostic and Therapeutic Applications in Lung Cancer

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Lung cancer is the most common cause of cancer-related deaths worldwide. Annually, millions of people die from lung cancer because of late detection and ineffective therapies. Recently, exosomes have been introduced as new therapeutic players with the potential to improve upon current diagnostic and treatment options. Exosomes are small membranous vesicles produced during endosomal merging. This allows for cell packaging of nucleic acids, proteins, and lipids and transfer to adjacent or distant cells. While exosomes are a part of normal intercellular signaling, they also allow malignant cells to transfer oncogenic material leading to tumor spread and metastasis. Exosomes are an interesting field of discovery for biomarkers and therapeutic targets. Among exosomal materials, lncRNAs have priority; lncRNAs are a cl ass of noncoding RNAs longer than 200 base pairs. In the case of cancer, primary interest regards their oncogene and tumor suppressor functions. In this review, the advantages of exosomal lncRNAs as biomarkers and therapeutic targets will be discussed in addition to reviewing studies of their application in lung cancer.
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Ecological Evaluation of Industrial Parks Using a Comprehensive DEA and Inverted-DEA Model

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Data envelopment analysis (DEA) and inverted data envelopment analysis (inverted-DEA) are used so that the desirable and undesirable outputs of decision-making units (DMUs) exist simultaneously. We developed a new approach based on the concept of utilizing both DEA and inverted-DEA to enhance the discrimination power of DMUs with undesirable outputs. DMUs are ranked by the Z-score method and classified based on the efficiency scores of DEA and inverted-DEA. Then, the characteristics of the DMUs are analyzed based on the classification result. This paper performs an efficiency evaluation of 21 industrial parks in China in 2017 using this new approach. The overall evaluation results indicate that the proposed new approach increases the discrimination ability in this empirical study.
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In Vitro Determination of Antimicrobial and Hypoglycemic Activities of Mikania cordata (Asteraceae) Leaf Extracts

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Infectious diseases and diabetes mellitus are counted responsible for a substantial amount of mortality among the human population. The current study was performed to detect the antimicrobial activities and hypoglycemic potential of Mikania cordata (Asteraceae) leaves extracted into aqueous media and several organic solvents (ethyl acetate and methanol). The ethyl acetate extract of Mikania cordata (MEA) leaves was observed to possess significantly () greater antimicrobial capabilities (susceptible against Bacillus cereus ATCC 11778 and Staphylococcus aureus ATCC 25923) when compared with that of the methanol (MME) and aqueous extracts (MDW) which were assessed based on Kirby-Bauer disk diffusion assay. The minimum inhibitory concentration of MEA (against B. cereus, S. aureus, and Escherichia coli ATCC 25922) and MME (against B. cereus, S. aureus, E. coli, and Candida albicans ATCC 10231) lies in a similar range of 1.13 > MIC>0.56 mg/ml. In the present study, a single compound (from MEA) of Rf value 0.64 was isolated by thin-layer chromatography (TLC) that was responsible for the zone of inhibition against B. cereus (20.3 ± 0.3 mm). The results of this study also depicted the antihyperglycemic properties of M. cordata leaves which followed the same trend as the commercial drug Metformin in a glucose concentration-independent manner when tested in a glucose uptake assay by yeast cells. Therefore, it is evident that Mikania cordata is a reservoir of useful bioactive compounds which with further research will be paving the path for drug commercialization. This is the first record of TLC-based isolation of antimicrobial compounds of M. cordata and analysis of the hypoglycemic properties of M. cordata leaves.
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Large Uterine Fibroids in Pregnancy with Successful Caesarean Myomectomy

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Uterine fibroid is the commonest benign tumour of the female reproductive tract. It occurs in 20–40% of women, whereas the estimated incidence in pregnancy is 0.1–3.9%. Uterine fibroid in pregnancy is usually asymptomatic with complications occurring in 10–30% of cases. The first line of management is conservative with counselling for myomectomy after delivery. However, in the presence of intractable symptoms, both antepartum myomectomy and caesarean myomectomy have been reported to be successfully performed in carefully selected cases. We report a case of large subserous uterine fibroid in pregnancy that was referred to our centre at 14 weeks of gestation. She developed generalized body weakness, backache, and breathlessness at 27 weeks gestation. Thus, she was admitted and managed conservatively for eight weeks with significant relief of symptoms. She eventually had a caesarean myomectomy at 35 weeks of gestation; the outcome was a live female baby with a birth weight of 2.3 kg and a large subserous fibroid weighing 9.5 kg. We can therefore say that caesarean myomectomy can be safely performed in carefully selected cases.
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The Use of System Dynamics Methodology in Building a COVID-19 Confirmed Case Model

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Researchers used a hybrid model (a combination of health resource demand model and disease transmission model), Bayesian model, and susceptible-exposed-infectious-removed (SEIR) model to predict health service utilization and deaths and mixed-effect nonlinear regression. Further, they used the mixture model to predict the number of confirmed cases and deaths or to predict when the curve would flatten. In this article, we show, through scenarios developed using system dynamics methodology, besides close to real-world results, the detrimental effects of ignoring social distancing guidelines (in terms of the number of people infected, which decreased as the percentage of noncompliance decreased).
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Utilizing Technology-Enabled Intervention to Improve Blood Glucose Self-Management Outcome in Type 2 Diabetic Patients Initiated on Insulin Therapy: A Retrospective Real-World Study

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Background. The aim of this study was to assess the benefits of a mobile-enabled app through Lilly Connected Care Program (LCCP) in achieving blood glucose control and adhering to self-monitoring of blood glucose in patients with type 2 diabetes mellitus (T2DM). Methods. This retrospective study included T2DM patients who were initiated on insulin therapy (mostly premixed insulin) after failure to respond to oral antidiabetic drugs. Patients were provided with glucometers enabled with synchronous data transmission to healthcare providers and family members. The primary objective was to assess the benefits of LCCP based on changes in fasting blood glucose (FBG) and postprandial glucose (PPG) levels from baseline to 12 weeks. Paired t-test was used to assess the change in blood glucose (BG) from baseline to wee k 12. Results. In total, 14,085 T2DM patients were recruited. Compared with baseline, significant reductions in FBG and PPG were evident at week 12 (FBG: -0.39 mmol/L; PPG: −0.79 mmol/L; both ). Furthermore, at week 12, the proportion of patients attaining a target glucose level of FBG
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