We investigated changes in Na(+) currents (I(Na)) in permanent (or chronic) atrial fibrillation (AF) and the effects of I(Na) inhibition using ranolazine (Ran) on arrhythmias and contractility in ...human atrial myocardium.
Electrical remodeling during AF is typically associated with alterations in Ca(2+) and K(+) currents. It remains unclear whether I(Na) is also altered.
Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied.
Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I(Na) density ( approximately 16%) in AF compared with SR, which was accompanied by a 26% lower expression of Nav1.5 (p < 0.05). In contrast, late I(Na) was significantly increased in myocytes from AF atria by approximately 26%. Ran (10 mumol/l) decreased late I(Na) by approximately 60% (p < 0.05) in myocytes from patients with AF but only by approximately 18% (p < 0.05) in myocytes from SR atria. Proarrhythmic activity was elicited in atrial trabeculae exposed to high Ca(2+)(o) or isoprenaline, which was significantly reversed by Ran (by 83% and 100%, respectively). Increasing pacing rates from 0.5 to 3.0 Hz led to an increase in diastolic tension that could be significantly decreased by Ran in atria from SR and AF patients.
Na(+) channels may contribute to arrhythmias and contractile remodeling in AF. Inhibition of I(Na) with Ran had antiarrhythmic effects and improved diastolic function. Thus, inhibition of late I(Na) may be a promising new treatment option for patients with atrial rhythm disturbances and diastolic dysfunction.
Purpose
The purpose of this paper is to draw on social exchange theory and heuristic–systematic model to examine how peer-to-peer (P2P) lending firms can enhance their customer acquisition by ...achieving mobile social media popularity.
Design/methodology/approach
Content data collected from multiple sources (websites and mobile applications) were employed to validate the research model.
Findings
The mobile social media popularity of P2P lending firms positively influences their customer acquisition. Furthermore, the heuristic cues (i.e. source credibility and content freshness) and the systematic cue (i.e. transaction relevance) potentially affect the firms’ mobile social media popularity.
Research limitations/implications
Mobile social media is not only a platform for firms’ image-building but a critical means of acquiring actual customers. The appropriate use of heuristic–systematic cues in a mobile interface is useful for firms to achieve high user popularity despite the challenges derived from the mobile context.
Practical implications
To achieve higher user popularity in the competitive online world, firms should dedicate greater effort in determining the adequate heuristic–systematic cues designed for the interface of their mobile social media account. The effect of popularity can then help the firms acquire more customers.
Originality/value
This study extends the understanding of social exchange in the context of mobile social media accounts and enriches the knowledge on business value of mobile social media popularity. This paper also contributes to the literature by relating heuristic–systematic cues to firms’ mobile social media popularity.
BACKGROUND:Successful bowel preparation is important for safe, efficacious, cost-effective colonoscopy procedures; however, poor preparation is common.
OBJECTIVE:We sought to determine whether there ...was an association between health literacy and comprehension of typical written instructions on how to prepare for a colonoscopy to enable more targeted interventions in this area.
DESIGN:This is a cross-sectional observational study.
SETTING:This study was performed at primary care clinics and federally qualified health centers in Chicago, Illinois.
PATIENTS:Seven hundred sixty-four participants (mean age, 63 years; SD, 5.42) were recruited. The sample was from a mixed sociodemographic background, and 71.9% of the participants were classified as having adequate health literacy scores.
INTERVENTION:Seven hundred sixty-four participants were presented with an information leaflet outlining the bowel preparatory instructions for colonoscopy.
MAIN OUTCOME MEASURES:Five questions were used to assess participants’ comprehension of the instructions in an “open book” test.
RESULTS:Comprehension scores on the bowel preparation items were low. The mean number of items correctly answered was 3.2 (SD, 1.2) of a possible 5. Comprehension scores overall and for each individual item differed significantly by health literacy level (all p < 0.001). After controlling for sex, age, race, socioeconomic status, and previous colonoscopy experience in a multivariable model, health literacy was a significant predictor of comprehension (inadequate vs adequateβ = −0.2; p < 0.001; marginal vs adequateβ = −0.2; p < 0.001).
LIMITATIONS:The outcome represents a simulated task and not actual comprehension of preparation instructions for participants’ own recommended behavior.
CONCLUSIONS:Comprehension of a written colonoscopy preparation leaflet was generally low and significantly lower among people with low health literacy. Poor comprehension has implications for the safety and economic impact of gastroenterological procedures such as colonoscopy. Therefore, future interventions should aim to improve comprehension of complex medical information by reducing literacy-related barriers.
Traces of life are nearly ubiquitous on Earth. However, a central unresolved question is whether these traces always indicate an active microbial community or whether, in extreme environments, such ...as hyperarid deserts, they instead reflect just dormant or dead cells. Although microbial biomass and diversity decrease with increasing aridity in the Atacama Desert, we provide multiple lines of evidence for the presence of an at times metabolically active, microbial community in one of the driest places on Earth. We base this observation on four major lines of evidence: (i) a physico-chemical characterization of the soil habitability after an exceptional rain event, (ii) identified biomolecules indicative of potentially active cells e.g., presence of ATP, phospholipid fatty acids (PLFAs), metabolites, and enzymatic activity, (iii) measurements of in situ replication rates of genomes of uncultivated bacteria reconstructed from selected samples, and (iv) microbial community patterns specific to soil parameters and depths. We infer that the microbial populations have undergone selection and adaptation in response to their specific soil microenvironment and in particular to the degree of aridity. Collectively, our results highlight that even the hyperarid Atacama Desert can provide a habitable environment for microorganisms that allows them to become metabolically active following an episodic increase in moisture and that once it decreases, so does the activity of the microbiota. These results have implications for the prospect of life on other planets such as Mars, which has transitioned from an earlier wetter environment to today’s extreme hyperaridity.
RATIONALE:Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in ...human heart failure, but its role in the heart is unknown.
OBJECTIVE:To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction.
METHODS AND RESULTS:Pharmacological inhibition of phosphodiesterase 2 (BAY 60–7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor activation in healthy mice. Under pathological conditions induced by chronic catecholamine infusions, BAY reversed both the attenuated β-adrenoceptor–mediated inotropy and chronotropy. Conversely, ECG telemetry in heart-specific phosphodiesterase 2-transgenic (TG) mice showed a marked reduction in resting and in maximal heart rate, whereas cardiac output was completely preserved because of greater cardiac contraction. This well-tolerated phenotype persisted in elderly TG with no indications of cardiac pathology or premature death. During arrhythmia provocation induced by catecholamine injections, TG animals were resistant to triggered ventricular arrhythmias. Accordingly, Ca-spark analysis in isolated TG cardiomyocytes revealed remarkably reduced Ca leakage and lower basal phosphorylation levels of Ca-cycling proteins including ryanodine receptor type 2. Moreover, TG demonstrated improved cardiac function after myocardial infarction.
CONCLUSIONS:Endogenous phosphodiesterase 2 contributes to heart rate regulation. Greater phosphodiesterase 2 abundance protects against arrhythmias and improves contraction force after severe ischemic insult. Activating myocardial phosphodiesterase 2 may, thus, represent a novel intracellular antiadrenergic therapeutic strategy protecting the heart from arrhythmia and contractile dysfunction.
Mayaro virus (MAYV) is responsible for a mosquito-borne tropical disease with clinical symptoms similar to dengue or chikungunya virus fevers. In addition to the recent territorial expansion of MAYV, ...this virus may be responsible for an increasing number of outbreaks. Currently, no vaccine is available. Aedes aegypti is promiscuous in its viral transmission and thus an interesting model to understand MAYV-vector interactions. While the life-cycle of MAYV is known, the mechanisms by which this arbovirus affects mosquito host cells are not clearly understood.
After defining the best conditions for cell culture harvesting using the highest virus titer, Ae. aegypti Aag-2 cells were infected with a Brazilian MAYV isolate at a MOI of 1 in order to perform a comparative proteomic analysis of MAYV-infected Aag-2 cells by using a label-free semi-quantitative bottom-up proteomic analysis. Time-course analyses were performed at 12 and 48 h post-infection (hpi). After spectrum alignment between the triplicates of each time point and changes of the relative abundance level calculation, the identified proteins were annotated and using Gene Ontology database and protein pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes.
After three reproducible biological replicates, the total proteome analysis allowed for the identification of 5330 peptides and the mapping of 459, 376 and 251 protein groups, at time 0, 12 hpi and 48 hpi, respectively. A total of 161 mosquito proteins were found to be differentially abundant during the time-course, mostly related to host cell processes, including redox metabolism, translation, energy metabolism, and host cell defense. MAYV infection also increased host protein expression implicated in viral replication.
To our knowledge, this first proteomic time-course analysis of MAYV-infected mosquito cells sheds light on the molecular basis of the viral infection process and host cell response during the first 48 hpi. Our data highlight several mosquito proteins modulated by the virus, revealing that MAYV manipulates mosquito cell metabolism for its propagation.
The increasing trend of exposing patients seeking health advice to numerical information has the potential to adversely impact patient-provider relationships especially among individuals with low ...literacy and numeracy skills. We used the HINTS 2007 to provide the first large scale study linking statistical confidence (as a marker of subjective numeracy) to demographic variables and a health-related outcome (in this case the quality of patient-provider interactions). A cohort of 7,674 individuals answered sociodemographic questions, a question on how confident they were in understanding medical statistics, a question on preferences for words or numbers in risk communication, and a measure of patient-provider interaction quality. Over thirty-seven percent (37.4%) of individuals lacked confidence in their ability to understand medical statistics. This was particularly prevalent among the elderly, low income, low education, and non-White ethnic minority groups. Individuals who lacked statistical confidence demonstrated clear preferences for having risk-based information presented with words rather than numbers and were 67% more likely to experience a poor patient-provider interaction, after controlling for gender, ethnicity, insurance status, the presence of a regular health care professional, and the language of the telephone interview. We will discuss the implications of our findings for health care professionals.
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