Protective effect of ethosuximide on hearing in NOD/LtJ mice via blockage of endogenous apoptosis

Purpose: To determine the protective effect of ethosuximide on the hearing of NOD/LtJ mice, and the underlying mechanism of action. Methods: The mice were randomly assigned to control and treatment groups (20 mice per group). Mice in the treatment group were administered ethosuximide intraperitoneally at a dose of 200mg/kg body weight (bwt), while those in the control group received an equivalent dose of saline via the same route. Both groups were subjected to auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) tests, as well as determination of mRNA expressions of α1G, α1H, α1I, m-calpain, μ-calpain, and caspase-3. Results: At ages of 6 and 9 weeks, ABR values were significantly lower in the treatment group than those in the control group (p < 0.05). At age 3, 6 and 9 weeks, control group DPOAE values were much lower than those in the treatment group. However, at signal frequency of 35344 Hz, DPOAE value was significantly reduced in the treatment group (p < 0.05). There was significant down-regulation in mRNA expressions of α1G, α1H, α1I, m-calpain, μ-calpain and caspase-3, in the treatment group, when compared with the control group (p < 0.05). Conclusion: Ethosuximide delays mice hearing loss and protects their hearing via a mechanism involving blockage of endogenous apoptotic pathways. This mechanism may provide guidance in the search for suitable new drugs. Keywords: Ethosuximide, Endogenous apoptosis, Hearing, Protectio

Occurrence of False Positive Results for the Detection of Carbapenemases in Carbapenemase-Negative Escherichia coli and Klebsiella pneumoniae Isolates

Adequate detection of the production of carbapenemase in Enterobacteriaceae isolates is crucial for infection control measures and the appropriate choice of antimicrobial therapy. In this study, we investigated the frequency of false positive results for the detection of carbapenemases in carbapenemase-negative Escherichia coli and Klebsiella pneumoniae clinical isolates by the modified Hodge test (MHT). Three hundred and one E. coli and K. pneumoniae clinical isolates were investigated. All produced extended spectrum β-lactamases (ESBLs) but were susceptible to carbapenems. Antimicrobial susceptibility testing was performed by the disk diffusion and agar dilution methods. The MHT was performed using the standard inoculum of test organisms recommended by the CLSI. Genes that encoded ESBLs and carbapenemases were identified by PCR and DNA sequencing. Among the 301 clinical isolates, none of the isolates conformed to the criteria for carbapenemase screening recommended by the CLSI. The susceptibility rates for imipenem, meropenem, and ertapenem all were 100.0%, 100.0%, and 100.0%, respectively. Of the 301 E. coli and K. pneumoniae isolates, none produced carbapenemase. The MHT gave a positive result for 3.3% (10/301) of the isolates. False positive results can occur when the MHT is used to detect carbapenemase in ESBL-producing isolates and clinical laboratories must be aware of this fact

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Validation of mHealth Applications for Behaviour Change : A Mixed-Method Study

Context: The amount of Mobile Health (mHealth) applications to cultivate a healthy lifestyle or rehabilitate patients with physical or mental disabilities are increasingly available on app stores[1]. However, without a validation process, satisfactory results may not be obtained, especially for behaviour change apps.  Objectives: Discover validation tools with high adaptability and design a validation process of mHealth apps for behaviour change involving theoretical frameworks.  Methods: The author conducted a literature review of previous behaviour change theories, validation tools, and research methods to design a validation process for behaviour change apps. A mixed research method of preliminary questionnaire followed by semi-structured interview for limited amount of participants was proposed to empathy with users and evaluate features in the app. Lastly, a case study of a smoking cessation app (Myli) was practiced to examine the feasibility of the designed validation process. Results: A four-step validation process was designed as an instruction to validate mHealth apps step by step, especially behaviour change apps. From the case study, we obtained the knowledge and opinions through the survey and interview such as smoking behaviours, expectations and requirements on user experience, recommendations on features,etc, with five elder smokers and five younger medical students.  Conclusions: This paper contributes a validation study of mHealth apps that applying behaviour change theories and validation tools. Furthermore, the proposed validation process allows app developers or medical professions to adapt their own requirements in validation to meet the app users’ needs. Sammanhang: Mobile Health (mHealth) applikationer för att bilda hälsosam livsstil eller att rehabilitera patienter med fysiska eller psykiska funktionsnedsättningar är alltmer tillgängliga i appbutiker [1]. Men utan en valideringsprocess kan tillfredsställande resultat inte erhållas, särskilt i appar för beteendeförändringar. Mål: Upptäcka valideringsverktyg med hög anpassningsförmåga och designa en valideringsprocess för mHealth-appar för beteendeförändringar som involverar teoretiska ramverk. Metoder: Författaren genomförde en litteraturgenomgång av tidigare beteendeförändringsteorier, valideringsverktyg och forskningsmetoder för att utforma en valideringsprocess för appar avsedda till beteendeförändringar. En blandad forskningsmetod av ett preliminärt frågeformulär som följs upp med en semistrukturerad intervju med ett begränsat antal deltagare föreslogs för att bättre förstå användare och utvärdera funktioner i appen. Slutligen praktiserades en fallstudie av en rökavvänjningsapp (Myli) för att undersöka genomförbarheten av den designade valideringsprocessen. Resultat: En valideringsprocess i fyra steg utformades som en instruktion för att validera mHealth-appar steg för steg, särskilt appar avsedda för beteendeförändringar. Genom fallstudien fick vi kunskaper och åsikter såsom rökbeteenden, förväntningar och krav på användarupplevelse, rekommendationer om funktioner etc genom enkäten och intervjun med fem äldre rökare och fem yngre läkarstudenter. Slutsatser: Denna artikel bidrar med en valideringsstudie av mHealth-appar som tillämpar teorier för beteendeförändringar och valideringsverktyg. Dessutom möjliggör den föreslagna valideringsprocessen apputvecklare eller de medicinska yrkesverksamma att anpassa sina krav i validering för att möta appanvändarnas behov.

Validation of mHealth Applications for Behaviour Change : A Mixed-Method Study

Context: The amount of Mobile Health (mHealth) applications to cultivate a healthy lifestyle or rehabilitate patients with physical or mental disabilities are increasingly available on app stores[1]. However, without a validation process, satisfactory results may not be obtained, especially for behaviour change apps.  Objectives: Discover validation tools with high adaptability and design a validation process of mHealth apps for behaviour change involving theoretical frameworks.  Methods: The author conducted a literature review of previous behaviour change theories, validation tools, and research methods to design a validation process for behaviour change apps. A mixed research method of preliminary questionnaire followed by semi-structured interview for limited amount of participants was proposed to empathy with users and evaluate features in the app. Lastly, a case study of a smoking cessation app (Myli) was practiced to examine the feasibility of the designed validation process. Results: A four-step validation process was designed as an instruction to validate mHealth apps step by step, especially behaviour change apps. From the case study, we obtained the knowledge and opinions through the survey and interview such as smoking behaviours, expectations and requirements on user experience, recommendations on features,etc, with five elder smokers and five younger medical students.  Conclusions: This paper contributes a validation study of mHealth apps that applying behaviour change theories and validation tools. Furthermore, the proposed validation process allows app developers or medical professions to adapt their own requirements in validation to meet the app users’ needs. Sammanhang: Mobile Health (mHealth) applikationer för att bilda hälsosam livsstil eller att rehabilitera patienter med fysiska eller psykiska funktionsnedsättningar är alltmer tillgängliga i appbutiker [1]. Men utan en valideringsprocess kan tillfredsställande resultat inte erhållas, särskilt i appar för beteendeförändringar. Mål: Upptäcka valideringsverktyg med hög anpassningsförmåga och designa en valideringsprocess för mHealth-appar för beteendeförändringar som involverar teoretiska ramverk. Metoder: Författaren genomförde en litteraturgenomgång av tidigare beteendeförändringsteorier, valideringsverktyg och forskningsmetoder för att utforma en valideringsprocess för appar avsedda till beteendeförändringar. En blandad forskningsmetod av ett preliminärt frågeformulär som följs upp med en semistrukturerad intervju med ett begränsat antal deltagare föreslogs för att bättre förstå användare och utvärdera funktioner i appen. Slutligen praktiserades en fallstudie av en rökavvänjningsapp (Myli) för att undersöka genomförbarheten av den designade valideringsprocessen. Resultat: En valideringsprocess i fyra steg utformades som en instruktion för att validera mHealth-appar steg för steg, särskilt appar avsedda för beteendeförändringar. Genom fallstudien fick vi kunskaper och åsikter såsom rökbeteenden, förväntningar och krav på användarupplevelse, rekommendationer om funktioner etc genom enkäten och intervjun med fem äldre rökare och fem yngre läkarstudenter. Slutsatser: Denna artikel bidrar med en valideringsstudie av mHealth-appar som tillämpar teorier för beteendeförändringar och valideringsverktyg. Dessutom möjliggör den föreslagna valideringsprocessen apputvecklare eller de medicinska yrkesverksamma att anpassa sina krav i validering för att möta appanvändarnas behov.

Environmental Regulation, Government R&D Funding and Green Technology Innovation: Evidence from China Provincial Data

The “environmental pollution–economic development” circle is a problem in the process of national sustainable development. As a complex concept of environmental protection and technology innovation, green technology innovation is the key to cracking this strange circle. This paper divides green technology innovation into green product innovation and green process innovation and measures green technology innovation based on the perspective of energy saving and emission reduction. Furthermore, we examine the effects of environmental regulation and government R&D funding on green technology innovation. The empirical findings are as follows: (1) from the dynamic point of view, we test whether there is a significant ”U-shaped” relationship between environmental regulation and green technological innovation, and we find there exists an “inflection point” in the role of environmental regulation in green technology innovation, and China is at the stage of inhibition before the “inflection point”; (2) direct government funding and tax incentives can promote green technology innovation, but the promotion of government tax incentives to green technology innovation is not significant; (3) the interaction between environmental regulation and government R&D will promote green product innovation and inhibit green process innovation, which is closely related to the imbalance of environmental regulation intensity in energy saving and emission reduction. In addition, this paper also gives out three kinds of control variables (the level of regional development, the proportion of the regional manufacturing industry, and the development level of regional export-oriented economy) and presents their effects on green technology innovation

Pathogenic Implication of a Fibrinogen-Binding Protein of Staphylococcus epidermidis in a Rat Model of Intravascular-Catheter-Associated Infection▿

The involvement of Fbe, a fibrinogen-binding protein of Staphylococcus epidermidis, in the pathogenesis of catheter-associated infection was investigated. An fbe (gene encoding Fbe protein) mutant was constructed by allelic replacement, wherein an erythromycin resistance gene replaced a portion of the A region of fbe. Meanwhile, a rat central venous catheter (CVC) infection model was established to assess the importance of Fbe in the pathogenesis of CVC-associated infection due to S. epidermidis. Fbe-positive S. epidermidis strain HB was significantly more likely to cause a CVC-associated infection resulting in bacteremia and metastatic disease than its isogenic Fbe-deficient mutant (100% versus 20%, P < 0.01). These results confirm the importance of adherence associated with Fbe in the pathogenesis of CVC-associated infection caused by S. epidermidis

Fabrication and Characterization of Novel Electrothermal Self-Healing Microcapsules with Graphene/Polymer Hybrid Shells for Bitumenious Material

Self-healing bituminous material has been a hot research topic in self-healing materials, and this smart self-healing approach is a promising a revolution in pavement material technology. Bitumen has a self-healing naturality relating to temperature, healing time, and aging degree. To date, heat induction and microencapsulation rejuvenator are two feasible approaches, which have been put into real applications. However, both methods have disadvantages limiting their practical results and efficiency. It will be an ideal method combining the advantages and avoiding the disadvantages of the above two methods at the same time. The aim of this work was to synthesize and characterize electrothermal self-healing microcapsules containing bituminous rejuvenator with graphene/organic nanohybrid structure shells. The microcapsules owned electric conductivity capability because of the advent of graphene, and realized the self-healing through the two approaches of heat induction and rejuvenation. The microcapsule shells were fabricated using a strength hexamethoxymethylmelamine (HMMM) resin and graphene by two-step hybrid polymerization. Experimental tests were carried out to character the morphology, integrity, and shell structure. It was found that the electric charge balance determined the graphene/HMMM microstructure. The graphene content in shells could not be greatly increased under an electrostatic balance in emulsion. X-ray photoelectron spectroscopy (XPS), Energy dispersive spectrometer (EDS), Transmission electron microscope (TEM) and Atomic force microscopy (AFM) results indicated that the graphene had deposited on shells. TGA/DTG tests implied that the thermal decomposition temperature of microcapsules with graphene had increased to about 350 &deg;C. The thermal conductivity of microcapsules had been sharply increased to about 8.0 W/m2&middot;K with 2.0 wt % graphene in shells. At the same time, electrical resistivity of microcapsules/bitumen samples had a decrease with more graphene in bitumen

The Synergistic Mechanism of Total Saponins and Flavonoids in Notoginseng–Safflower against Myocardial Infarction Using a Comprehensive Metabolomics Strategy

Notoginseng and safflower are commonly used traditional Chinese medicines for benefiting qi and activating blood circulation. A previous study by our group showed that the compatibility of the effective components of total saponins of notoginseng (NS) and total flavonoids of safflower (SF), named NS–SF, had a preventive effect on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. However, the therapeutic effect on MI and the synergistic mechanism of NS–SF are still unclear. Therefore, integrated metabolomics, combined with immunohistochemistry and other pharmacological methods, was used to systematically research the therapeutic effect of NS–SF on MI rats and the synergistic mechanism of NS and SF. Compared to NS and SF, the results demonstrated that NS–SF exhibited a significantly better role in ameliorating myocardial damage, apoptosis, easing oxidative stress and anti-inflammation. NS–SF showed a more significant regulatory effect on metabolites involved in sphingolipid metabolism, glycine, serine, and threonine metabolism, primary bile acid biosynthesis, aminoacyl-tRNA biosynthesis, and tricarboxylic acid cycle, such as sphingosine, lysophosphatidylcholine (18:0), lysophosphatidylethanolamine (22:5/0:0), chenodeoxycholic acid, L-valine, glycine, and succinate, than NS or SF alone, indicating that NS and SF produced a synergistic effect on the treatment of MI. This study will provide a theoretical basis for the clinical development of NS–SF