Padron RI. Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling. Am J Physiol Heart Circ Physiol 306: H641-H653, 2014. First published January 10, 2014; doi:10.1152/ajpheart.00641.2013.-Aging has been associated with pathological vascular remodeling and increased neointimal hyperplasia. The understanding of how aging exacerbates this process is fundamental to prevent cardiovascular complications in the elderly. This study proposes a mechanism by which aging sustains leukocyte adhesion, vascular inflammation, and increased neointimal thickness after injury. The effect of aging on vascular remodeling was assessed in the rat balloon injury model using microarray analysis, immunohistochemistry, and LINCOplex assays. The injured arteries in aging rats developed thicker neointimas than those in younger animals, and this significantly correlated with a higher number of tissue macrophages and increased vascular IL-18. Indeed, IL-18 was 23-fold more abundant in the injured vasculature of aged animals compared with young rats, while circulating levels were similar in both groups of animals. The depletion of macrophages in aged rats with clodronate liposomes ameliorated vascular accumulation of IL-18 and significantly decreased neointimal formation. IL-18 was found to inhibit apoptosis of vascular smooth muscle cells (VSMC) and macrophages, thus favoring both the formation and inflammation of the neointima. In addition, injured arteries of aged rats accumulated 18-fold more fibrinogen-␥ than those of young animals. Incubation of rat peritoneal macrophages with immobilized IL-18 increased leukocyte adhesion to fibrinogen and suggested a proinflammatory positive feedback loop among macrophages, VSMC, and the deposition of fibrinogen during neointimal hyperplasia. In conclusion, our data reveal that concentration changes in vascular cytokine and fibrinogen following injury in aging rats contribute to local inflammation and postinjury neointima formation. inflammation; vascular injury; aging; neointima; vascular smooth muscle cells AGING IS RECOGNIZED AS A MAJOR and independent risk factor for the development of vascular restenosis (29). This risk can be explained by profound, age-dependent changes in vascular structure and physiology that lead to endothelial dysfunction (18) and a chronic inflammatory stage (53), which impair healing and render a vascular system prone to develop occlusive neointimas in response to injury. However, even when this notion is largely accepted, the mechanisms by which aging alters vascular physiology and repair have remained understudied to date.The process of aging increases and sustains inflammation within the vascular wall (52). Macrophages are commonly recognized as the most important cell type in the chronicity of this process (37). Indeed, inflammation in arteries of aged individuals is evidenced by an excessive accumulation of macrophages in the inner layer of the arterial wall (intima), and this occurs in the presence o...

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Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1–2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.

Results from the present study showed that haemophilia was associated with a higher frequency of LBMD. Severity of haemophilia, haemophilic arthropathy, and elevated C-reactive protein levels was directly associated with LBMD.

Chagas disease (CD) is a protozoan zoonosis caused by Trypanosoma cruzi . Reactivation of CD occurs via drug-induced immunosuppression before and during transplantation. Here, we report the case of a 62-year-old man diagnosed with classic Hodgkin lymphoma who received highly aggressive conditioning chemotherapy before undergoing stem cell transplantation (SCT). The patient tested positive for CD in pre-transplantation evaluation. The patient exhibited persistent fever and elevated C-reactive protein levels before and after SCT, and was treated with antibiotics. Micro-Strout test showed evidence of trypomastigotes and he was treated with benznidazole until tested negative. Post-transplantation seropositive patients should be screened for possible reactivation.

Adenosine 59-monophosphate (AMP) bronchoprovocation reproduces the lung function abnormalities that occur spontaneously during acute asthma and detects peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone.The present authors investigated whether AMP induced a greater imbalance in the ventilation/ perfusion ratio than methacholine (MCh), at an equivalent degree of bronchoconstriction, with and without salbutamol pre-medication. In total, 36 asthmatics were studied in three randomised, doubleblind, crossover studies: 1) before and after AMP or MCh; 2) before and 30 min after salbutamol or placebo, followed by AMP; or 3) MCh challenge. Sputum was collected before and 4 h post-challenge.Compared with MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (forced expiratory volume in one second decrease of 28-44%). While salbutamol blocked AMP-or MCh-induced bronchoconstriction, arterial oxygen tension (Pa,O 2 ) and alveolar-arterial oxygen tension difference (PA-a,O 2 ) disturbances induced by AMP and MCh were only partially blocked (Pa,O 2 by 46 and 42%, respectively; PA-a,O 2 by 58 and 57%, respectively). Compared with MCh, AMP increased the percentage of neutrophils (mean¡SE increased from 28¡4% to 38¡4%), but this increase did not occur after salbutamol pre-treatment.Both adenosine 59-monophosphate and methacholine induced similar peripheral airway dysfunction. The fully inhibited adenosine 59-monophosphate-induced neutrophilia with residual hypoxaemia observed after salbutamol treatment is probably related to b 2 -agonists acting on both bronchial and pulmonary circulation.

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Introducción y Objetivos. Las NMPC son relativamente raras, con incidencias que varían entre 0,47-1,03/100.000 habitantes, es importante para el país conocer las características clínicas de estos pacientes. Se presenta el primer reporte del trabajo del registro colombiano de NMPC. Materiales y métodos. Estudio observacional multicéntrico retrospectivo y prospectivo en ocho centros del país, de abril de 2013 a diciembre de 2014. Las variables cualitativas se presentan con frecuencias absolutas y relativas; y las cuantitativas se resumen en medidas de tendencia central y dispersión. Resultados. 11 centros fueron aprobados, 8 ingresaron pacientes. En los primeros 179 casos reportados el 50 % eran hombres, la edad promedio al diagnóstico 58,7 años (rango: 19-92). 93 son Trombocitemia Esencial (TE), 55 Policitemia Vera (PV), 31 Mielofibrosis (MF). 41% tenían esplenomegalia al diagnóstico. 20% tuvieron complicaciones trombóticas y 12,85% sangrado. Solo en 57,5% se realizó JAK, de ellos en 53,5% positivo, en especial solo 60% de las PV. 8% de los casos no tenían estudio de médula ósea, 29,3% tiene algún grado de fibrosis. El hallazgo más frecuente fue hiperplasia megacariocítica en 59,78%. Más del 50% de pacientes estaban sintomáticos al diagnóstico. Solo 11% no recibieron tratamiento farmacológico; los más frecuentes fueron Hidroxiurea en 149 y ASA en 79 casos. Con promedio de seguimiento de 52,6 meses; 97,21% de los pacientes están vivos. Conclusiones. Los hallazgos sugieren que algunas características de las NMPC podrían ser diferentes a lo reportado en otras series, lo que valida la importancia del esfuerzo de recoger información local.