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BackgroundOur objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP).MethodsWe performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1 ). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility.ResultsWe evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1 % predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1 % predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility.ConclusionsLung function, that is FEV1 % predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.

Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P = .047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P = .039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.

To understand how extracellular vesicle (EV) subtypes differentially activate monocytes, a series of in vitro studies were performed. We found that plasma-EVs biased monocytes toward an M1 profile. Culturing monocytes with granulocyte-, monocyte-, and endothelial-EVs induced several pro-inflammatory cytokines. By contrast, platelet-EVs induced TGF-β and GM-CSF, and red blood cell (RBC)-EVs did not activate monocytes in vitro. The scavenger receptor CD36 was important for binding of RBC-EVs to monocytes, while blockade of CD36, CD163, CD206, TLR1, TLR2, and TLR4 did not affect binding of plasma-EVs to monocytes in vitro. To identify mortality risk factors, multiple soluble factors and EV subtypes were measured in patients' plasma at intensive care unit admission. Of 43 coagulation factors and cytokines measured, two were significantly associated with mortality, tissue plasminogen activator and cystatin C. Of 14 cellular markers quantified on EVs, 4 were early predictors of mortality, including the granulocyte marker CD66b. In conclusion, granulocyte-EVs have potent pro-inflammatory effects on monocytes in vitro. Furthermore, correlation of early granulocyte-EV levels with mortality in critically ill patients provides a potential target for intervention in management of the pro-inflammatory cascade associated with critical illness.

Summary: Background: Family based treatment is an effective, multipronged approach to address obesity as it plagues families. Objective: To investigate the relationships among sociodemographic characteristics (e.g., education and income), body mass index (BMI) and race/ethnicity with readiness to change for parents enrolled in the Primary care pediatrics, Learning, Activity and Nutrition (PLAN) study. Methods: Multivariate linear regressions tested two hypotheses: (1) White parents will have higher levels of baseline readiness to change, when compared to Black parents; (2) parents with higher income and education will have higher levels of readiness to change at baseline. Results: A positive relationship exists between baseline parent BMI and readiness to change (Pearson correlation, 0.09, p < 0.05); statistically significant relationships exist between parent education level (−0.14, p < 0.05), income (0.04, p < 0.05) and readiness to change. Additionally, a statistically significant relationship exists, with both White (β, −0.10, p < 0.05), and Other, non‐Hispanic (−0.10, p < 0.05) parents exhibiting lower readiness to change than Black, non‐Hispanic parents. Child data did not indicate significant relationships between race/ethnicity and readiness to change. Conclusions: Results demonstrate that investigators should consider sociodemographic characteristic factors and different levels of readiness to change in participants enrolling in obesity interventions. [ABSTRACT FROM AUTHOR]

Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. Methods and findings Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 [mu]g/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were [greater than or equal to]5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. Conclusions In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. Trial registration Clinicaltrials.gov registration number: NCT02899936, Author(s): Gary J. Weil 1,*, Joshua Bogus 1, Michael Christian 2, Christine Dubray 3, Yenny Djuardi 2, Peter U. Fischer 1, Charles W. Goss 1, Myra Hardy 4, Purushothaman Jambulingam [...]

Aging is associated with decreases in aerobic capacity, cardiac function, and insulin sensitivity as well as alterations in myocardial substrate metabolism. Endurance exercise training (EET) improves cardiac function in a gender-specific manner, and EET has been shown to improve whole body glucose tolerance, but its effects on myocardial metabolism are unclear. Accordingly, we studied the effect of EET on myocardial substrate metabolism in older men and women. Twelve healthy older individuals (age: 60-75 yr; 6 men and 6 women) underwent PET with [[sup.15]O]water, [[sup.11]C]acetate, [[sup.11]C]glucose, and [[sup.11]C]palmitate for the assessment of myocardial blood flow (MBF), myocardial [O.sub.2] consumption ([MVo.sub.2]), myocardial glucose utilization (MGU), and myocardial fatty acid utilization (MFAU), respectively, at rest and during dobutamine infusion (10 [micro]g * [kg.sup.-1] * [min.sup.-1]). Measurements were repeated after 11 mo of EET. Maximal 02 uptake ([Vo.sub.2max]) increased (P = 0.005) after EET. MBF was unaffected by training, as was resting MVoe; however, posttraining dobutamine [MVo.sub.2] was significantly higher (P = 0.05), as was MGU (P < 0.04). Although overall dobutamine MFAU was unchanged, posttraining dobutamine MFAU increased in women (P = 0.01) but decreased in men (P = 0.03). Thus, EET in older individuals improves the catecholamine response of myocardial glucose metabolism. Moreover, gender differences exist in the myocardial fatty acid metabolic response to training. These findings suggest a role for altered myocardial substrate metabolism in modulating the cardiovascular benefits of EET in older individuals. aging; catecholamine; fatty acid; glucose; insulin resistance

A study explores the short- and long-term efficacy of two distinct weight maintenance approaches versus no continued treatment control following standard family-based behavioral weight loss treatment for childhood overweight, and examines children's social functioning as a moderator of outcome. Results indicate that the addition of maintenance-targeted treatment improves short-term efficacy of weight loss treatment for children relative to no maintenance treatment.

Background. Caloric restriction (CR) increases maximal life span in short-lived organisms, and its effects are being explored in nonhuman primates. The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity. Methods. A randomized, controlled trial was conducted with 48 healthy, nonobese women and men, aged 57 [+ or -] 1 (mean [+ or -] standard error [SE]) years, with body mass index 27.3 [+ or -] 0.3 kg/[m.sup.2]. Participants were randomly assigned to a 20% calorically-restricted diet (CR, n = 19), exercise designed to produce a similar energy deficit (EX, n = 19), or a healthy lifestyle control group (HL, n = 10) for 1 year. Assessments included weight, body composition by dual-energy x-ray absorptiometry, abdominal adipose tissue by magnetic resonance imaging, and energy intake by doubly labeled water. Results. The average level of CR achieved by the CR group was 11.5 [+ or -] 2.1%, and the EX group completed 59 [+ or -] 6.7% of their prescribed exercise. Weight changes were greater (p < .0005) in the CR (-8.0 [+ or -] 0.9 kg) and EX (-45.4 [+ or -] 0.9) groups as compared to the HL group (-1.3 [+ or -] 0.9 kg), corresponding to reductions of 10.7%, 8.4%, and 1.7% of baseline weights, respectively. Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly (p < .005) and comparably in the CR and EX groups, but did not change in the HL group. Conclusions. CR for 1 year was feasible, but the level of CR achieved was less than prescribed. CR and exercise were equally effective in reducing weight and adiposity.

Background. Progressive resistance exercise training (PRT) has been shown to increase muscle strength and fat-free mass (FFM) in elderly persons. Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons. Methods. Ninety-one community-dwelling sedentary men and women, 78 years and older with physical frailty (defined using standardized objective criteria) were enrolled in a 9-month trial of exercise training (ET). Physical frailty was defined as having 2 of the 3 following criteria: modified Physical Performance Test score between 18 and 32, peak aerobic power between 10 and 18 ml/kg/min, or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living. Participants were randomly assigned to either a control (CTL) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT. Results. After completion of PRT, ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension (mean [DELTA] +5.3 [+ or -] 13 ft/lb vs +1.1 [+ or -] 11 ft/lb, p = .05), measured using isokinetic dynamometry. Total body FFM (measured using dual energy x-ray absorptiometry) increased in the ET group, but not in the CTL group (mean [DELTA] +0.84 [+ or -] 1.4 kg vs +0.01 [+ or -] 1.5 kg, p = .005). Total, trunk, intra-abdominal, and subcutaneous fat mass (measured using dual energy x-ray absorptiometry and [sup.1]H-magnetic resonance imaging) did not change in response to PRT. Conclusions. Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail, community-dwelling elderly women and men. This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population.

A study to determine whether the extended outpatient rehabilitation, which includes progressive resistance training, improves physical function and reduces disability compared with low-intensity home exercise among physically frail elderly patients with hip fracture is presented. The results indicate that six months of extended outpatient rehabilitation can improve physical function and quality of life, and reduce disability compared with low intensity home exercise.

Soto, Pablo F., Pilar Herrero, Andrew M. Kates, Carmen S. Dence, Ali A. Ehsani, Victor Davila-Roman, Kenneth B. Schechtman, and Robert J. Gropler. Impact of aging on myocardial metabolic response to dobutamine. Am J Physiol Heart Circ Physiol 285: H2158-H2164, 2003. First published July 24, 2003; 10.1152/ajpheart.00086. 2003.-In humans, under resting conditions there is an age-related decrease in myocardial fatty acid utilization (MFAU) and oxidation (MFAO) and a relative increase in myocardial glucose utilization (MGU). The impact of age on an individual's myocardial metabolic response to catecholamines is not well defined. Sixteen younger (mean age, 26 [+ or -] 5 yr) and 14 older (mean age, 69 [+ or -] 4 yr) volunteers underwent positron emission tomography to measure myocardial blood flow, myocardial oxygen consumption (MV[O.sub.2]), MFAU, MFAO, and MGU both under resting conditions and during dobutamine infusion. In response to dobutamine administration, the rate-pressure product, myocardial blood flow, and MV[O.sub.2] measurements increased by similar amounts in both groups. No age-related differences, were noted in the responses of plasma insulin, glucose, fatty acid, or lactate levels to dobutamine. With dobutamine infusion, MFAU and MFAO increased by a similar extent in both younger and older volunteers (age/ dobutamine interactions, P=0.62 and 0.75 respectively). In contrast, MGU increased with dobutamine adminidtration in the younger (from 149 [+ or -] 71 to 209 [+ or -] 78 [nmol * g.sup.-1] * [min.sup.-1]; P=0.04) but not in the older (from 235 [+ or -] 147 to 176 [+ or -] 84 [nmol * g.sup.-1] * [min.sup.-1]; P=0.23; age/dobutamine interaction, P= 0.03) group. With dobutamine infusion, hearts in both younger and older volunteers responded by increasing their MFAU and MFAO values. Whereas younger hearts also responded with an increase in MGU, older hearts did not. Although the clinical significance of these findings awaits further study, these results may partially explain the impaired contractile reserve and the increased incidence of cardiovascular disease in older individuals. fatty acids; glucose; oxidation; heart; cathecholamine