Effects of peroxisome proliferator-activated receptor- activation in endothelin-dependent hypertension

Aims We analysed the chronic effects of the peroxisome proliferator-activated receptor β/δ (PPAR-β) agonist GW0742 on the renin-independent hypertension induced by deoxycorticosterone acetate (DOCA)-salt. Methods and results Rats were treated for 5 weeks with: control-vehicle, control-GW0742 (5 or 20 mg kg−1 day−1), DOCA-vehicle, DOCA-GW0742 (5 or 20 mg kg−1 day−1), DOCA-GSK0660 (1 mg kg−1 day−1), and DOCA-GSK0660-GW0742. Rats receiving DOCA-vehicle showed increased systolic blood pressure, left ventricular and kidney weight indices, endothelin-1 (ET-1), and malondialdehyde plasma levels, urinary iso-PGF2α excretion, impaired endothelium-dependent relaxation to acetylcholine, and contraction to ET-1 when compared with controls. Aortic reactive oxygen species content, NADPH oxidase activity, and p47phox, p22phox, NOX-4, glutathione peroxidase 1, hemeoxygenase-1, and preproET-1 expression were increased, whereas catalase and regulators of G protein-coupled signalling proteins (RGS)5 expression were decreased in the DOCA-vehicle group. GW0742 prevented the development of hypertension in a dose-dependent manner but the reduction of renal and cardiac hypertrophy, systemic and vascular oxidative stress markers, and improvement of endothelial dysfunction were only observed after the higher dose. GW0742, at 20 mg kg−1 day−1, attenuated ET-1 contraction by increasing RGS5 expression and restored the intracellular redox balance by reducing NADPH-oxidase activity, and by increasing the antioxidant genes expression. The PPAR-β antagonist GSK0660 prevented all vascular changes induced by GW0742 but not its antihypertensive effects. Conclusion Vascular protective effects of GW0742 operate via PPAR-β by interference with the ET-1 signalling as a result of increased expression of RGS5 and up-regulation of antioxidant genes and via PPAR-β-independent mechanisms to decrease blood pressure

Levels and patterns of objectively assessed physical activity and compliance with different public health guidelines in university students

ArticleBackground Physical activity (PA) is associated with health enhancement. The aim of this study was to assess: 1) levels and patterns of PA in university students by using accelerometers; and 2) the percentage of fulfilment of PA recommendations for adults, according to different public health guidelines. Methods Observational cross-sectional study (Cuenca’s Adults Study) involving 296 (206 women) healthy Spanish university students aged 18–25 years old. Participants wore the ActiGraph GT1M accelerometer for seven consecutive days. Total PA, steps and time spent in sedentary time, light, moderate, vigorous, and moderate to vigorous PA (MVPA) was assessed, and the prevalence of sufficient PA was calculated according to various public health guidelines. Results No sex differences in total PA were found. University students were more sedentary during weekend days than weekdays (p<0.05). Only 30.3% of participants accumulated 30 min/day at least five days a week of MVPA. A total of 5.4% of students met the recommendation of 150 min/week of MVPA or 75 min/week of vigorous PA, in PA bouts of at least 10 min. using the same definition, but on five or more days a week, only 0.5% students were found to meet the recommendation. In addition, only 0.5% of students met the recommendation of 30 min/day of MVPA, at least five days a week and in bouts of at least 10 min. Finally, 28.1% of the students met the recommendation of 10,000 steps/day. Conclusions Our study shows a high incidence of sedentary time in university students. The number of students meeting PA recommendations significantly differed depending on the recommendation proposed. Specific strategies to promote PA in this population are necessary as well as an agreement as to which PA guidelines should be used.Fundación para la Investigación SanitariaMinistry of Health and Consumer AffairsInstituto de Salud Carlos IIIRed de Investigación en Actividades Preventivas y de Promoción de Salu

Stakeholder opinion-led study to identify canine priority diseases for surveillance and control in the UK

BackgroundMany pathogens cause disease in dogs; however, meaningful surveillance in small companion animals is often only possible for the most impactful diseases. We describe the first stakeholder opinion-led approach to identify which canine infectious diseases should be prioritised for inclusion in surveillance and control strategies in the UK.MethodsParticipants were identified through a stakeholder analysis. A multicriteria decision analysis was undertaken to establish and weight epidemiological criteria for evaluating diseases, and a Delphi technique was employed to achieve a consensus among participants on the top-priority canine diseases.ResultsNineteen stakeholders from multiple backgrounds participated in this study. Leptospirosis and parvovirus were identified as the top two endemic diseases of concern, while leishmaniosis and babesiosis were the top two exotic diseases. Respiratory and gastrointestinal diseases were identified as the top two syndromes of concern.LimitationsDue to the COVID-19 pandemic, the number of participants was reduced. Despite this, a representative multidisciplinary sample of relevant stakeholders contributed to the present study.ConclusionsFindings from this study are being used to inform the development of a future UK-wide epidemic response strategy. This methodology could provide a blueprint for other countries

Effects of an exercise program on brain health outcomes for children with overweight or obesity

Importance Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. Objectives To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. Design, Setting, and Participants All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70% or more of the recommended exercise sessions and were included in per-protocol analyses. Interventions All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. Main Outcomes and Measures Intelligence, executive function (cognitive flexibility, inhibition, and working memory), and academic performance were assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. Results The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95% CI, 0.44-0.80]) compared with the control group (mean z score, –0.10 [95% CI, –0.28 to 0.09]; difference between groups, 0.72 SDs [95% CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95% CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, –0.14 to 0.28]; difference between groups, 0.62 SDs [95% CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, –0.17 [95% CI, –0.39 to 0.04]; difference between groups, 0.42 SDs [95% CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95% CI, 0.18-0.44]; control group, 0.10 [95% CI, –0.04 to 0.24]; difference between groups, 0.21 SDs [95% CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95% CI, 0.27-0.82]; control group, 0.13 [95% CI, –0.16 to 0.41]; difference between groups, 0.42 SDs [95% CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. Conclusions and Relevance In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvements were not identified

Modular framework to assess the risk of African swine fever virus entry into the European Union

BACKGROUND The recent occurrence and spread of African swine fever (ASF) in Eastern Europe is perceived as a serious risk for the pig industry in the European Union (EU). In order to estimate the potential risk of ASF virus (ASFV) entering the EU, several pathways of introduction were previously assessed separately. The present work aimed to integrate five of these assessments (legal imports of pigs, legal imports of products, illegal imports of products, fomites associated with transport and wild boar movements) into a modular tool that facilitates the visualization and comprehension of the relative risk of ASFV introduction into the EU by each analyzed pathway. RESULTS The framework's results indicate that 48% of EU countries are at relatively high risk (risk score 4 or 5 out of 5) for ASFV entry for at least one analyzed pathway. Four of these countries obtained the maximum risk score for one pathway: Bulgaria for legally imported products during the high risk period (HRP); Finland for wild boar; Slovenia and Sweden for legally imported pigs during the HRP. Distribution of risk considerably differed from one pathway to another; for some pathways, the risk was concentrated in a few countries (e.g., transport fomites), whereas other pathways incurred a high risk for 4 or 5 countries (legal pigs, illegal imports and wild boar). CONCLUSIONS The modular framework, developed to estimate the risk of ASFV entry into the EU, is available in a public domain, and is a transparent, easy-to-interpret tool that can be updated and adapted if required. The model's results determine the EU countries at higher risk for each ASFV introduction route, and provide a useful basis to develop a global coordinated program to improve ASFV prevention in the EU

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Role of Physical Activity and Fitness in the Characterization and Prognosis of the Metabolically Healthy Obesity Phenotype: a Systematic Review and Meta-Analysis

The aims of the present article are to systematically review and meta-analyze the existing evidence on: 1) differences in physical activity (PA), sedentary behavior (SB), cardiorespiratory fitness (CRF) and muscular strength (MST) between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO); and 2) the prognosis of all-cause mortality and cardiovascular disease (CVD) mortality/morbidity in MHO individuals, compared with the best scenario possible, i.e., metabolically healthy normal-weight (MHNW), after adjusting for PA, SB, CRF or MST. Our systematic review identified 67 cross-sectional studies to address aim 1, and 11 longitudinal studies to address aim 2. The major findings and conclusions from the current meta-analysis are: 1) MHO individuals are more active, spend less time in SB, and have a higher level of CRF (yet no differences in MST) than MUO individuals, suggesting that their healthier metabolic profile could be at least partially due to these healthier lifestyle factors and attributes. 2) The meta-analysis of cohort studies which accounted for PA (N = 10 unique cohorts, 100% scored as high-quality) support the notion that MHO individuals have a 24-33% higher risk of all-cause mortality and CVD mortality/morbidity compared to MHNW individuals. This risk was borderline significant/non-significant, independent of the length of the follow-up and lower than that reported in previous meta-analyses in this topic including all type of studies, which could be indicating a modest reduction in the risk estimates as a consequence of accounting for PA. 3) Only one study has examined the role of CRF in the prognosis of MHO individuals. This study suggests that the differences in the risk of all-cause mortality and CVD mortality/morbidity between MHO and MHNW are largely explained by differences in CRF between these two phenotypes

NSAIDs Modulate CDKN2A, TP53, and DNA Content Risk for Progression to Esophageal Adenocarcinoma

BACKGROUND: Somatic genetic CDKN2A, TP53, and DNA content abnormalities are common in many human cancers and their precursors, including esophageal adenocarcinoma (EA) and Barrett's esophagus (BE), conditions for which aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as possible chemopreventive agents; however, little is known about the ability of a biomarker panel to predict progression to cancer nor how NSAID use may modulate progression. We aimed to evaluate somatic genetic abnormalities with NSAIDs as predictors of EA in a prospective cohort study of patients with BE. METHODS AND FINDINGS: Esophageal biopsies from 243 patients with BE were evaluated at baseline for TP53 and CDKN2A (p16) alterations, tetraploidy, and aneuploidy using sequencing; loss of heterozygosity (LOH); methylation-specific PCR; and flow cytometry. At 10 y, all abnormalities, except CDKN2A mutation and methylation, contributed to EA risk significantly by univariate analysis, ranging from 17p LOH (relative risk [RR] = 10.6; 95% confidence interval [CI] 5.2–21.3, p < 0.001) to 9p LOH (RR = 2.6; 95% CI 1.1–6.0, p = 0.03). A panel of abnormalities including 17p LOH, DNA content tetraploidy and aneuploidy, and 9p LOH was the best predictor of EA (RR = 38.7; 95% CI 10.8–138.5, p < 0.001). Patients with no baseline abnormality had a 12% 10-y cumulative EA incidence, whereas patients with 17p LOH, DNA content abnormalities, and 9p LOH had at least a 79.1% 10-y EA incidence. In patients with zero, one, two, or three baseline panel abnormalities, there was a significant trend toward EA risk reduction among NSAID users compared to nonusers (p = 0.01). The strongest protective effect was seen in participants with multiple genetic abnormalities, with NSAID nonusers having an observed 10-y EA risk of 79%, compared to 30% for NSAID users (p < 0.001). CONCLUSIONS: A combination of 17p LOH, 9p LOH, and DNA content abnormalities provided better EA risk prediction than any single TP53, CDKN2A, or DNA content lesion alone. NSAIDs are associated with reduced EA risk, especially in patients with multiple high-risk molecular abnormalities

Comunicación corta. Primera detección del virus de la parálisis aguda israelita (IAPV) en España

Spanish bee samples were analyzed for the presence of Israel Acute Paralysis Virus (IAPV). Some of these samples were collected from colonies presenting compatible symptoms with the colony collapse disorder (CCD, 240 out of 484) and the rest were asymptomatic. Only one of these samples was diagnosed as positive to IAPV by employing a one step RT-PCR that targets the ORF 2 of the IAPV genome. Specificity of the RT-PCR assay was evaluated by sequence analysis of size specific amplification products. IAPV nucleotide sequences already published in GeneBank were used to construct a phylogenetic tree that included the new Spanish IAPV sequence (FJ821506). They segregated in two main lineages and the Spanish isolate was mainly related with the American ones. As IAPV was detected in Spain in a very low frequency, no causal relation between IAPV and CCD in Spain was found.Se analizaron muestras de abejas espa&ntilde;olas para detectar el virus de la par&aacute;lisis aguda israelita (IAPV). Parte de las muestras (240 de 484) proced&iacute;an de colmenas que mostraban s&iacute;ntomas compatibles con el s&iacute;ndrome de despoblamiento (SDC), el resto de las muestras eran asintom&aacute;ticas. Solo una de las muestras fue diagnosticada como positiva frente a IAPV utilizando la t&eacute;cnica RT-PCR, que amplifica una parte del ORF 2 del genoma viral. La especificidad de la prueba fue confirmada por secuenciaci&oacute;n del producto amplificado que presentaba el tama&ntilde;o espec&iacute;fico. Se emplearon secuencias de IAPV ya publicadas en GeneBank para construir un &aacute;rbol filogen&eacute;tico que incluye la secuencia de IAPV detectada en muestras espa&ntilde;olas (FJ821506). Se observaron dos grupos principales y la muestra espa&ntilde;ola est&aacute; agrupada con varias americanas. Debido a que en Espa&ntilde;a IAPV fue detectado en muy baja frecuencia, no se encuentra relaci&oacute;n causal entre el SDC y la presencia de IAPV