This study summarizes the evidence from quantitative systematic reviews that assessed the association between urban environment attributes and physical activity. It also documents sociopolitical ...barriers and facilitators involved in urban interventions linked with active living in the ten most populated urban settings of Latin America. The synthesis of evidence indicates that several attributes of urban environments are associated with physical activity, including land-use mix and cycling infrastructure. The documentary analysis indicated that despite the benefits and opportunities provided by the programs and existing infrastructure in the examined cities, an overall concern is the rising inequality in the coverage and distribution of the initiatives in the region. If these programs and initiatives are to achieve a real population level effect that helps to reduce health disparities, they need to examine their social and spatial distribution within the cities so they can reach underserved populations and develop to their full potential.
•Most research on physical activity and the environment was in high income countries.•There is an unequal distribution of supportive urban environments in Latin American.•The Ciclovia program may offset urban inequalities existing in public green areas.•Strong civil society leadership is needed for sustainable policy and programs.
Mechanical signaling through cell-matrix interactions plays a major role in progressive vascular remodeling in pulmonary arterial hypertension (PAH). MMP-8 (matrix metalloproteinase-8) is an ...interstitial collagenase involved in regulating inflammation and fibrosis of the lung and systemic vasculature, but its role in PAH pathogenesis remains unexplored.
To evaluate MMP-8 as a modulator of pathogenic mechanical signaling in PAH.
MMP-8 levels were measured in plasma from patients with pulmonary hypertension (PH) and controls by ELISA. MMP-8 vascular expression was examined in lung tissue from patients with PAH and rodent models of PH. MMP-8
and MMP-8
mice were exposed to normobaric hypoxia or normoxia for 4-8 weeks. PH severity was evaluated by right ventricular systolic pressure, echocardiography, pulmonary artery morphometry, and immunostaining. Proliferation, migration, matrix component expression, and mechanical signaling were assessed in MMP-8
and MMP-8
pulmonary artery smooth muscle cells (PASMCs).
MMP-8 expression was significantly increased in plasma and pulmonary arteries of patients with PH compared with controls and induced in the pulmonary vasculature in rodent PH models. Hypoxia-exposed MMP-8
mice had significant mortality, increased right ventricular systolic pressure, severe right ventricular dysfunction, and exaggerated vascular remodeling compared with MMP-8
mice. MMP-8
PASMCs demonstrated exaggerated proliferation and migration mediated by altered matrix protein expression, elevated integrin-β3 levels, and induction of FAK (focal adhesion kinase) and downstream YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif) activity.
MMP-8 is a novel protective factor upregulated in the pulmonary vasculature during PAH pathogenesis. MMP-8 opposes pathologic mechanobiological feedback by altering matrix composition and disrupting integrin-β3/FAK and YAP/TAZ-dependent mechanical signaling in PASMCs.
Abstract
The development of effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines has been a significant accomplishment. Adverse events are extremely ...rare, but continued surveillance is important, especially in at-risk populations. In 5 patients with preexisting immune dysregulation, hyperinflammatory syndromes, including hemophagocytic lymphohistiocytosis, developed after SARS-CoV-2 mRNA vaccination. Early recognition of this rare condition is essential.
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