Exercise offers short-term and long-term health benefits, including an increased metabolic rate and energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates ...conversion of white into brown adipocytes as well as increased mitochondrial biogenesis and energy expenditure. Remarkably, irisin is highly expressed in myocardium, but its physiological effects in the heart are unknown. The objective of this work is to investigate irisin's potential multifaceted effects on cardiomyoblasts and myocardium. For this purpose, H9C2 cells were treated with recombinant irisin produced in yeast cells (r-irisin) and in HEK293 cells (hr-irisin) for examining its effects on cell proliferation by MTT 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and on gene transcription profiles by qRT-PCR. R-irisin and hr-irisin both inhibited cell proliferation and activated genes related to cardiomyocyte metabolic function and differentiation, including myocardin, follistatin, smooth muscle actin, and nuclear respiratory factor-1. Signal transduction pathways affected by r-irisin in H9C2 cells and C57BL/6 mice were examined by detecting phosphorylation of PI3K-AKT, p38, ERK or STAT3. We also measured intracellular Ca2+ signaling and mitochondrial thermogenesis and energy expenditure in r-irisin-treated H9C2 cells. The results showed that r-irisin, in a certain concentration rage, could activate PI3K-AKT and intracellular Ca2+ signaling and increase cellular oxygen consumption in H9C2 cells. Our study also suggests the existence of irisin-specific receptor on the membrane of H9C2 cells. In conclusion, irisin in a certain concentration rage increased myocardial cell metabolism, inhibited cell proliferation and promoted cell differentiation. These effects might be mediated through PI3K-AKT and Ca2+ signaling, which are known to activate expression of exercise-related genes such as follistatin and myocardin. This work supports the value of exercise, which promotes irisin release.
Single-phase far-red-emitting ZnAl2O4:Cr3+ phosphor has been successfully synthesized by a sol-gel method. The phosphor can be well excited by NUV, violet, and green lights, and it strongly emits ...multi-peak broadband emissions in the far-red region peaking at 687 and 698 nm, matching well with the absorption band of phytochrome. The maximum PL intensity is achieved for the ZnAl2O4:0.8%Cr3+ phosphor annealed at 1400 °C. The lifetime and activation energy of the optimal ZnAl2O4:0.8%Cr3+ phosphor annealed at 1400 °C are 25.3 ms and 0.302 eV, respectively. Three types of far-red-emitting LEDs have been successfully fabricated by coating the optimal ZnAl2O4:0.8%Cr3+ phosphor on the surface of NUV (395 nm), violet (410 nm), and green (510 nm) chips. The chromatic coordinates of the corresponding LEDs are (0.2990; 0.2199), (0.2725; 0.1594), (0.2703; 0.5743), respectively. The quantum efficiency of the ZnAl2O4:Cr3+ phosphor excited by different LEDs is calculated and reported for the first time. The obtained results indicate that the ZnAl2O4:Cr3+ phosphor has a high potential for pc-converted plant growth LED application.
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•Single crystal far-red emitting Cr3+-doped ZnAl2O4 phosphor was synthesized by sol-gel method.•The local environment around the Cr3+ ions and the origins of all the emissions are elucidated.•Three type of pc(ZnAl2O4:Cr3+)-converted LEDs were fabricated based on 395, 410 and 520 nm chips.•The quantum efficiency of the pc-NUV-LED, pc-violet-LED and pc-green-LED are 16.2%, 15.1% and 30.4%, respectively.•ZnAl2O3:Cr3+ phosphors have potential application in plant growth lighting.
Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord.
To assess the efficacy of duloxetine, a dual reuptake ...inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP).
In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed.
Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient's Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered.
This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.
This study sought to monitor the presence of carbapenem-resistant Enterobacteriaceae (CRE) and the proportion New Delhi metallo-beta-lactamase 1 (NDM-1)-producing bacteria between August 2010 and ...December 2012 in a surgical hospital in Vietnam. We identified 47 CRE strains from a total of 4,096 Enterobacteriaceae isolates (1.1 %) that were NDM-1-positive from 45 patients admitted to 11 different departments, with the majority being from the urology department. The NDM-1 gene was found in seven different species. Genotyping revealed limited clonality of NDM-1-positive isolates. Most of the isolates carried the NDM-1 gene on a plasmid and 17.8 % (8/45) of those were readily transferable. We found five patients at admission and one patient at discharge with NDM-1-positive bacteria in their stool. From 200 screening environmental hospital samples, five were confirmed to be NDM-1-positive and included
Acinetobacter
species (
n
= 3) and
Enterobacter aerogenes
(
n
= 2). The results reveal that NDM-1-producing Enterobacteriaceae are commonly isolated in patients admitted to a Vietnamese surgical hospital and are also detected in the hospital environment.
Tuberculous meningitis kills or disables more than half of those affected with the disease. Previous studies have been too small to determine whether adjunctive treatment with corticosteroids can ...reduce the risk of disability or death among adults with tuberculous meningitis, and the effect of coinfection with the human immunodeficiency virus (HIV) is unclear.
We performed a randomized, double-blind, placebo-controlled trial in Vietnam in patients over 14 years of age who had tuberculous meningitis, with or without HIV infection, to determine whether adjunctive treatment with dexamethasone reduced the risk of death or severe disability after nine months of follow-up. We conducted prespecified subgroup analyses and intention-to-treat analyses.
A total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients (1.8 percent) had been lost to follow-up at nine months of treatment. Treatment with dexamethasone was associated with a reduced risk of death (relative risk, 0.69; 95 percent confidence interval, 0.52 to 0.92; P=0.01). It was not associated with a significant reduction in the proportion of severely disabled patients (34 of 187 patients 18.2 percent among survivors in the dexamethasone group vs. 22 of 159 patients 13.8 percent in the placebo group, P=0.27) or in the proportion of patients who had either died or were severely disabled after nine months (odds ratio, 0.81; 95 percent confidence interval, 0.58 to 1.13; P=0.22). The treatment effect was consistent across subgroups that were defined by disease-severity grade (stratified relative risk of death, 0.68; 95 percent confidence interval, 0.52 to 0.91; P=0.007) and by HIV status (stratified relative risk of death, 0.78; 95 percent confidence interval, 0.59 to 1.04; P=0.08). Significantly fewer serious adverse events occurred in the dexamethasone group than in the placebo group (26 of 274 patients vs. 45 of 271 patients, P=0.02).
Adjunctive treatment with dexamethasone improves survival in patients over 14 years of age with tuberculous meningitis but probably does not prevent severe disability.
Primary hypokalemic periodic paralysis (HypoPP), a rare skeletal muscle channelopathy resulting in episodic muscle weakness or paralysis under hypokalemic conditions, is caused by autosomal-dominant ...genetic mutations. HypoPP limits physical activity, and cardiac arrhythmias during paralytic attacks have been reported. We describe a rare familial HypoPP case complicated by sinus arrest and syncope requiring urgent temporary pacemaker implantation.
A 27-year-old Vietnamese man with a family history of periodic paralysis presented with his third attack of muscle weakness triggered by intense football training the previous day. Clinical and laboratory features justified a HypoPP diagnosis. During intravenous potassium replacement, the patient experienced syncopal sinus arrest requiring urgent temporary pacemaker implantation. The patient gradually improved, responding favorably to oral potassium supplements. Genetic testing revealed an Arg1132Gln mutation in the sodium ion channel (SCN4A, chromosome 17: 63947091). At discharge, the patient received expert consultation regarding nonpharmacological preventive strategies, including avoidance of vigorous exercise and carbohydrate-rich diet.
No evidence has established a relationship between hypokalemia and sinus arrest, and no specific treatment exists for familial HypoPP due to SCN4A mutation. Clinician awareness of this rare condition will promote appropriate diagnostic approaches and management strategies for acute paralytic attacks. Treatment should be tailored according to HypoPP phenotypes and genotypes.
Maintenance of a delicate haemostatic balance or a balance between clotting and bleeding is critical to human health. Irrespective of administration route, nanoparticles can reach the bloodstream and ...might interrupt the haemostatic balance by interfering with one or more components of the coagulation, anticoagulation, and fibrinolytic systems, which potentially lead to thrombosis or haemorrhage. However, inadequate understanding of their effects on the haemostatic balance, along with the fact that most studies mainly focus on the functionality of nanoparticles while forgetting or leaving behind their risk to the body's haemostatic balance, is a major concern. Hence, our review aims to provide a comprehensive depiction of nanoparticle-haemostatic balance interactions, which has not yet been covered. The synergistic roles of cells and plasma factors participating in haemostatic balance are presented. Possible interactions and interference of each type of nanoparticle with the haemostatic balance are comprehensively discussed, particularly focusing on the underlying mechanisms. Interactions of nanoparticles with innate immunity potentially linked to haemostasis are mentioned. Various physicochemical characteristics that influence the nanoparticle-haemostatic balance are detailed. Challenges and future directions are also proposed. This insight would be valuable for the establishment of nanoparticles that can either avoid unintended interference with the haemostatic balance or purposely downregulate/upregulate its key components in a controlled manner.
The shrimp sector has been one of the fastest growing agri-food systems in the last decades, but its growth has entailed negative social and environmental impacts. Sustainable intensification will ...require innovation in multiple elements of the shrimp production system and its value chain. We use the case of the shrimp sector in the Mekong Delta in Vietnam to explore the constraints in the transition to sustainable intensification in shrimp farming, using an analytical framework based on innovation systems thinking, i.e., an aquaculture innovation systems framework. Using this framework, we conduct a systemic diagnostic of blocking mechanisms, interrelated sets of constraints within the aquaculture sector that hinder a transition toward sustainable intensification. Our findings show that the major constraints are institutional, with limited enforcement of the regulatory framework for input quality control, disease control, and wastewater management, and a lack of coordination between government bodies to design and enforce this framework. At farm level, limited access to capital favors pond mismanagement and the use of low-quality inputs. The absence of multi-stakeholder initiatives to foster dialog between actors in the value chain constrains the response to new regulations dictated by international market demand. Because of shrimp farming’s connectivity with the wider ecosystem, sustainable intensification in shrimp farming will require collective management of water resources at the landscape level for disease and water pollution control. Ecological principles for pond management need to be promoted to farmers in order to reduce farmers’ inefficient practices and build their capacity to understand new techniques and inputs available in the Vietnamese market. Our paper demonstrates for the utility of a multi-level, multi-dimension, and multi-stakeholder aquaculture innovation systems approach to analyze and address these blocking mechanisms in the transition to sustainable intensification in shrimp farming and aquaculture more broadly.
Extracellular vesicles (EVs) are emerging as a promising drug delivery vehicle as they are biocompatible and capable of targeted delivery. However, clinical translation of EVs remains challenging due ...to the lack of standardized and scalable manufacturing protocols to consistently isolate small EVs (sEVs) with both high yield and high purity. The heterogenous nature of sEVs leading to unknown composition of biocargos causes further pushback due to safety concerns. In order to address these issues, we developed a robust quality‐controlled multi‐stage process to produce and isolate sEVs from human embryonic kidney HEK293F cells. We then compared different 2‐step and 3‐step workflows for eliminating protein impurities and cell‐free nucleic acids to meet acceptable limits of regulatory authorities. Our results showed that sEV production was maximized when HEK293F cells were grown at high‐density stationary phase in semi‐continuous culture. The novel 3‐step workflow combining tangential flow filtration, sucrose‐cushion ultracentrifugation and bind‐elute size‐exclusion chromatography outperformed other methods in sEV purity while still preserved high yield and particle integrity. The purified HEK293F‐derived sEVs were thoroughly characterized for identity including sub‐population analysis, content profiling including proteomics and miRNA sequencing, and demonstrated excellent preclinical safety profile in both in‐vitro and in‐vivo testing. Our rigorous enrichment workflow and comprehensive characterization will help advance the development of EVs, particularly HEK293F‐derived sEVs, to be safe and reliable drug carriers for therapeutic applications.
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