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Pharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145.
Eight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred.
AP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.
AP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.Although best practice recommendations exist regarding school-based healthy eating and physical activity policies, practices, and programs, research indicates that implementation is poor. As the field of implementation science is rapidly evolving, an update of the recent review of strategies to improve the implementation of healthy eating and physical activity interventions in schools published in the Cochrane Library in 2017 was required. The primary aim of this review was to examine the effectiveness of strategies that aim to improve the implementation of school-based policies, practices, or programs to address child diet, physical activity, or obesity. A systematic review of articles published between August 31, 2016 and April 10, 2019 utilizing Cochrane methodology was conducted. In addition to the 22 studies included in the original review, eight further studies were identified as eligible. The 30 studies sought to improve the implementation of healthy eating (n = 16), physical activity (n = 11), or both healthy eating and physical activity (n = 3). The narrative synthesis indicated that effect sizes of strategies to improve implementation were highly variable across studies. For example, among 10 studies reporting the proportion of schools implementing a targeted policy, practice, or program versus a minimal or usual practice control, the median unadjusted effect size was 16.2%, ranging from -0.2% to 66.6%. Findings provide some evidence to support the effectiveness of strategies in enhancing the nutritional quality of foods served at schools, the implementation of canteen policies, and the time scheduled for physical education.With the surge of COVID-19 cases worldwide, it is essential that vaccination be prioritized to facilitate herd immunity. However, there is vaccine hesitancy reflected in religiosity. This correspondence aims to understand religiosity as a factor that plays a role in vaccination hesitancy. Medical and scientifically sound evidence is influenced by religious beliefs resulting in varied responses toward getting vaccinated such as vaccination hesitancy.Control of the COVID-19 pandemic relies heavily on behavioral mitigation strategies such as physical distancing, hand washing and mask wearing. Even with the availability of SARS-CoV-2 vaccines, the extraordinary effort to distribute the vaccines must be paired with continued adherence to behavioral recommendations as well as vaccine confidence. To facilitate rapid and equitable uptake of the vaccines, there is a need for responsive, trustworthy, and evidence-informed communication about vaccination, enhanced trust in science, and engaging populations disproportionately affected by the pandemic. Efforts to address vaccine hesitancy and increase vaccine confidence will address the emerging gaps between vaccine availability and actual vaccination. Although these gaps are attributable, in part, to challenges with logistics and access, social and behavioral drivers of vaccination decision making also have a significant role in vaccination uptake. As federal, state, and local health and public health agencies coordinate vaccine dissemination, there will be a continuous need to adapt to an evolving landscape of SARS-CoV-2 vaccines, new scientific information, and the spread of COVID-19- and vaccine-related misinformation. Facilitating widespread vaccination and maintaining a focus on equity requires thoughtful and compassionate approaches to reach and address the needs of those who are disproportionately affected by the pandemic such as underserved, vulnerable, and racial/ethnic minority populations. This commentary focuses on several National Institutes of Health initiatives that are supporting behavioral and social science research to address SARS-CoV-2 vaccine communication and increase the uptake of vaccination. We conclude with implications for future research.Borage oil that is extracted from (Borago officinalis Linn.) is a well-known medicinal plant having various medicinal benefits. In this work, an affordable, simple, reliable, rapid and easily accessible high-performance thin-layer chromatography (HPTLC) method was developed for the estimation of gamma-linolenic acid (GLA) in borage oil. click here HPTLC method employs thin-layer chromatography (TLC) aluminum plates precoated with silica gel (G60F254) as the stationary phase, and the mixture of hexanetouleneglacial acetic acid (371, v/v/v) was used as the mobile phase. Densitometric analysis of the TLC plates was carried out at 200 nm. The developed method showed well-resolved spots with retention factor (Rf) value of 0.53 ± 0.04 for GLA. Various experimental conditions like saturation time for chamber, solvent phase migration and width of the band were studied intensely for selecting the optimum conditions. The method validation was performed for parameters like linearity, accuracy, specificity and precision. The values of limit of detection and limit of quantification for GLA were found to be 0.221 and 0.737 μg/band, respectively. In nutshell, the developed HPTLC method was found to be highly sensitive for the estimation of GLA in the herbal oil samples and formulations.
To quantify Guinness-related branding in the 2019 Guinness Six Nations Championship.
Content analysis of Guinness-related branding ('Guinness' and the alibi brand 'Greatness') was shown during active play throughout all 15 games of the 2019 Guinness Six Nations Championship. The duration of each appearance was timed to the nearest second to provide information on the amount of time that Guinness-related branding was shown on screen. Census data and viewing figures were used to estimate gross and per capita alcohol impressions.
Our coding identified a total of 3719 appearances of two logos of which 3415 (92%) were for 'Guinness' and 304 (8%) were for 'Greatness'. 'Guinness' imagery was present for 13,640s (227.3min or 3.8h, 16% of total active play time), 'Greatness' was present for 944s (15.7min, 1% of total active play time), with a combined total of 14,584s across all games (243 min or 4.05h, 17% of active play time). The 15 games delivered an estimated 122.4 billion Guinness-related branded impressions to the UK population, including 758 million to children aged under 16.
Alcohol marketing was highly prevalent during the 2019 Guinness Six Nations Championship and was a significant source of exposure to alcohol marketing and advertising for children, likely influencing youth alcohol experimentation and uptake.
Alcohol marketing was highly prevalent during the 2019 Guinness Six Nations Championship and was a significant source of exposure to alcohol marketing and advertising for children, likely influencing youth alcohol experimentation and uptake.Several Alzheimer's disease (AD) atrophy subtypes were identified, but their brain network properties are unclear. We analyzed data from two independent datasets, including 166 participants (103 AD/63 controls) from the DZNE-longitudinal cognitive impairment and dementia study and 151 participants (121 AD/30 controls) from the AD neuroimaging initiative cohorts, aiming to identify differences between AD atrophy subtypes in resting-state functional magnetic resonance imaging intra-network connectivity (INC) and global and nodal network properties. Using a data-driven clustering approach, we identified four AD atrophy subtypes with differences in functional connectivity, accompanied by clinical and biomarker alterations, including a medio-temporal-predominant (S-MT), a limbic-predominant (S-L), a diffuse (S-D), and a mild-atrophy (S-MA) subtype. S-MT and S-D showed INC reduction in the default mode, dorsal attention, visual and limbic network, and a pronounced reduction of "global efficiency" and decrease of the "clustering coefficient" in parietal and temporal lobes. Despite severe atrophy in limbic areas, the S-L exhibited only marginal global network but substantial nodal network failure. S-MA, in contrast, showed limited impairment in clinical and cognitive scores but pronounced global network failure. Our results contribute toward a better understanding of heterogeneity in AD with the detection of distinct differences in functional connectivity networks accompanied by CSF biomarker and cognitive differences in AD subtypes.
The burden and treatment landscape of rheumatoid arthritis (RA) is poorly understood. This research aimed to identify evidence on quality of life, caregiver burden, economic burden, treatment patterns and clinical outcomes for patients with moderate RA in the United Kingdom.
A systematic literature review was performed across multiple databases and screened against pre-defined inclusion criteria.
2,610 records were screened; seven studies presenting evidence for moderate RA were included. These patients were found to incur substantial burden, with moderate to severe levels of disability. Compared with patients in remission, moderate RA patients reported higher levels of disability and decreased EQ-5D utility scores. The majority of patients did not feel that their current therapy adequately controlled their disease or provided sufficient symptom relief. In the United Kingdom, NICE have not approved advanced therapies (such as biological disease-modifying anti-rheumatic drugs) for patients with moderate disease, which restricts access for these patients.
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