Infographic. How does exercise treatment compare with antihypertensive medications?

High systolic blood pressure (SBP) remains the major cause of premature death globally despite advances in pharmacological treatment.1 2 The global direct medical costs associated with hypertension treatment are estimated at $370 billion/year worldwide, with the healthcare savings from effective management of this condition projected at about$100 billion/year.3 Unfortunately, relatively little attention is given to non-pharmacological strategies, including structured exercise interventions. A recent network meta-analysis of randomised controlled trials (RCTs) published in the BJSM4 aimed to compare the effects of exercise interventions and medications on SBP. We highlight the key findings of this network meta-analysis that are particularly relevant for clinical practice and health policy.Sin financiación12.022 JCR (2019) Q1, 1/85 Sport Sciences3.712 SJR (2019) Q1, 48/2754 Medicine (miscellaneous), 1/284 Orthopedics and Sports Medicine, 1/207 Physical Therapy, Sports Therapy and Rehabilitation, 2/125 Sports ScienceNo data IDR 2019UE

Preferential Localization of Human Origins of DNA Replication at the 5′-Ends of Expressed Genes and at Evolutionarily Conserved DNA Sequences

Replication of mammalian genomes requires the activation of thousands of origins which are both spatially and temporally regulated by as yet unknown mechanisms. At the most fundamental level, our knowledge about the distribution pattern of origins in each of the chromosomes, among different cell types, and whether the physiological state of the cells alters this distribution is at present very limited.We have used standard λ-exonuclease resistant nascent DNA preparations in the size range of 0.7–1.5 kb obtained from the breast cancer cell line MCF–7 hybridized to a custom tiling array containing 50–60 nt probes evenly distributed among genic and non-genic regions covering about 1% of the human genome. A similar DNA preparation was used for high-throughput DNA sequencing. Array experiments were also performed with DNA obtained from BT-474 and H520 cell lines. By determining the sites showing nascent DNA enrichment, we have localized several thousand origins of DNA replication. Our major findings are: (a) both array and DNA sequencing assay methods produced essentially the same origin distribution profile; (b) origin distribution is largely conserved (>70%) in all cell lines tested; (c) origins are enriched at the 5′ends of expressed genes and at evolutionarily conserved intergenic sequences; and (d) ChIP on chip experiments in MCF-7 showed an enrichment of H3K4Me3 and RNA Polymerase II chromatin binding sites at origins of DNA replication.Our results suggest that the program for origin activation is largely conserved among different cell types. Also, our work supports recent studies connecting transcription initiation with replication, and in addition suggests that evolutionarily conserved intergenic sequences have the potential to participate in origin selection. Overall, our observations suggest that replication origin selection is a stochastic process significantly dependent upon local accessibility to replication factors

Early rise in central venous pressure during a spontaneous breathing trial: A promising test to identify patients at high risk of weaning failure?

Background The spontaneous breathing trial (SBT) assesses the risk of weaning failure by evaluating some physiological responses to the massive venous return increase imposed by discontinuing positive pressure ventilation. This trial can be very demanding for some critically ill patients, inducing excessive physical and cardiovascular stress, including muscle fatigue, heart ischemia and eventually cardiac dysfunction. Extubation failure with emergency reintubation is a serious adverse consequence of a failed weaning process. Some data suggest that as many as 50% of patients that fail weaning do so because of cardiac dysfunction. Unfortunately, monitoring cardiovascular function at the time of the SBT is complex. The aim of our study was to explore if central venous pressure (CVP) changes were related to weaning failure after starting an SBT. We hypothesized that an early rise on CVP could signal a cardiac failure when handling a massive increase on venous return following a discontinuation of positive pressure ventilation. This CVP rise could identify a subset of patients at high risk for extubation failure. Methods Two-hundred and four mechanically ventilated patients in whom an SBT wa

Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis

Background: Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF. Methods: Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI ( 5%) using random coefficient regression. Results: In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 [SE 22.4], − 207.9 [20.9] and − 104.5 [21.4] in patients with BMI 5% than ≤5% weight loss over 52 weeks (− 312.7 [SE 32.2] versus − 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups. Conclusions: In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not. Trial registration: ClinicalTrials.gov; Nos. NCT01335464 and NCT01335477; URL: www.clinicaltrials.gov

Association Between Race/Ethnicity and COVID-19 Outcomes in Systemic Lupus Erythematosus Patients From the United States: Data From the COVID-19 Global Rheumatology Alliance

OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36–5.53]) and Hispanic (OR 2.76 [95% CI 1.34–5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population

Plasmonic response of complex nanoparticle assemblies

Optical properties of nanoparticle assemblies reflect distinctive characteristics of their building blocks and spatial organization, giving rise to emergent phenomena. Integrated experimental and computational studies have established design principles connecting the structure to properties for assembled clusters and superlattices. However, conventional electromagnetic simulations are too computationally expensive to treat more complex assemblies. Here we establish a fast, materials agnostic method to simulate the optical response of large nanoparticle assemblies incorporating both structural and compositional complexity. This many-bodied, mutual polarization method resolves limitations of established approaches, achieving rapid, accurate convergence for configurations including thousands of nanoparticles, with some overlapping. We demonstrate these capabilities by reproducing experimental trends and uncovering far- and near-field mechanisms governing the optical response of plasmonic semiconductor nanocrystal assemblies including structurally complex gel networks and compositionally complex mixed binary superlattices. This broadly applicable framework will facilitate the design of complex, hierarchically structured, and dynamic assemblies for desired optical characteristics.This research was primarily supported by the National Science Foundation through the Center for Dynamics and Control of Materials: an NSF Materials Research Science and Engineering Center (NSF MRSEC) under Cooperative Agreement DMR-1720595. E.V.A. acknowledges support from the Welch Regents Chair (F-0046). D.J.M. and T.M.T. acknowledge support from the Welch Foundation (F-1696 and F-1848) and NSF (CHE-1905263). This work was supported by an NSF Graduate Research Fellowship (DGE-1610403) to S.A.V. and Arnold O. Beckman Postdoctoral Fellowship to Z.M.S. We acknowledge the Texas Materials Institute for use of the SAXSLAB Ganesha, acquired using an NSF MRI grant CBET-1624659.Center for Dynamics and Control of Material

Individual Shrink Wrapping of Zucchini Fruit Improves Postharvest Chilling Tolerance Associated with a Reduction in Ethylene Production and Oxidative Stress Metabolites

We have studied the effect of individual shrink wrapping (ISW) on the postharvest performance of refrigerated fruit from two zucchini cultivars that differ in their sensitivity to cold storage: Sinatra (more sensitive) and Natura (more tolerant). The fruit was individually shrink wrapped before storing at 4°C for 0, 7 and 14 days. Quality parameters, ethylene and CO2 productions, ethylene gene expression, and oxidative stress metabolites were assessed in shrink wrapped and non-wrapped fruit after conditioning the fruit for 6 hours at 20°C. ISW decreased significantly the postharvest deterioration of chilled zucchini in both cultivars. Weight loss was reduced to less than 1%, pitting symptoms were completely absent in ISW fruit at 7 days, and were less than 25% those of control fruits at 14 days of cold storage, and firmness loss was significantly reduced in the cultivar Sinatra. These enhancements in quality of ISW fruit were associated with a significant reduction in cold-induced ethylene production, in the respiration rate, and in the level of oxidative stress metabolites such as hydrogen peroxide and malonyldialdehyde (MDA). A detailed expression analysis of ethylene biosynthesis, perception and signaling genes demonstrated a downregulation of CpACS1 and CpACO1 genes in response to ISW, two genes that are upregulated by cold storage. However, the expression patterns of six other ethylene biosynthesis genes (CpACS2 to CpACS7) and five ethylene signal transduction pathway genes (CpCTR1, CpETR1, CpERS1, CpEIN3.1 and CpEN3.2), suggest that they do not play a major role in response to cold storage and ISW packaging. In conclusion, ISW zucchini packaging resulted in improved tolerance to chilling concomitantly with a reduction in oxidative stress, respiration rate and ethylene production, as well as in the expression of ethylene biosynthesis genes, but not of those involved in ethylene perception and sensitivity.This work was supported by grants AGL2011-30568-C02/ALI from the Spanish Ministry of Science and Innovation, and AGR1423 from the Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, Spain. Z.M. acknowledges FPU program scholarships from MEC, Spain. S.M. is funded by grant PTA2011-479-I from the Spanish Ministry of Science and Innovation

Results From the Global Rheumatology Alliance Registry

Funding Information: We acknowledge financial support from the ACR and EULAR. The ACR and EULAR were not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.Objective: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. Methods: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. Results: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. Conclusion: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.publishersversionepub_ahead_of_prin

Commentaries on viewpoint : physiology and fast marathons

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