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Objective Asthma prevalence and morbidity are disproportionately higher among youth with lower socioeconomic status (SES). Examination of subjective social status (SSS) may improve understanding of associations between SES and health outcomes in pediatric asthma. Method Fifty adolescents with asthma (Mage = 13.2 years, SD = 1.23; 54% male; 55.1% African American) completed the MacArthur Scale of Subjective Social Status-Youth Version, Daily Life Stressors Scale, Children's Depression Inventory-Short Form, Adolescent Sleep-Wake Scale-short version, and Asthma Control Test during the baseline visit of a study of health behaviors. Body mass index z scores (BMIz) were calculated using height and weight obtained during the visits. Hierarchical linear regressions examined associations between SSS and psychosocial and physical health outcomes, controlling for caregiver-reported objective SES. Results Caregiver-reported objective SES was not associated with adolescent SSS. SSS-society was associated with daily stress (b = -3.14), t(47) = -2.13, p = .033; asthma control (β = .34, p = .045); BMIz (β = .38, p = .013); and sleep quality (β = .49, p = .001). SSS-community was associated with daily stress (b = -3.76), t(46) = -3.07, p = .002, and sleep quality (β = .36, p = .010). SSS was not associated with depressive symptoms. Conclusions Adolescents' SSS may not always reflect caregiver's objective SES. Perceived social status may play a role in the experience of daily stress, asthma control, BMIz, and sleep quality among adolescents with asthma. SSS may offer a novel means of assessing health disparities in pediatric asthma. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Objective Increased rates of pediatric obesity extend into early childhood. There have been increasing calls for intervention programs specifically designed to address obesity in preschool-age youth. A review of the literature is critical to guide intervention and future research. The objective of this study was to conduct a meta-analysis of randomized, controlled trials examining the efficacy of lifestyle modification interventions to address overweight and obesity in preschool-age children. Method Six electronic databases were searched for articles through December 8, 2020. After screening articles for inclusion criteria, 14 articles with 12 randomized, controlled trials (41 effect sizes, 2,525 participants) were included in this meta-analysis. Weighted-standardized mean differences for body mass index-related variables were calculated using random-effects models to estimate effect sizes. Risk of bias assessment was conducted. Results There was a statistically significant impact of the interventions on child weight outcomes. Cohen's d was .32 (95% CI [.09, .55]). The quality of evidence was assigned a "low" GRADE rating. Conclusions Lifestyle modification interventions for overweight and obesity in preschool-age children produce small but significant changes in child weight status. However, few new trials have been published in the last 5 years and the quality of evidence in this area is low, limiting confidence in the estimates and the power to examine potential moderator effects. Additional quality, randomized, control trials that report study information consistent with consort guidelines, use intent-to-treatment procedures, assess and report health behaviors and treatment adherence to explore mechanisms of change, and examine sustained effects of interventions are needed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Previous research has shown that food parenting practices, which vary within the context of sociocultural factors, are associated with child weight, eating behaviors, and body dissatisfaction. While parents typically engage in multiple food parenting practices, few studies have examined what subgroups or combinations of food parenting practices are associated with child health outcomes and sociocultural factors. The current study examined profiles of food parenting practices among school-age children with overweight/obesity (OW/OB) from rural communities and examined how they may be associated with sociocultural factors, child-eating habits, and health outcomes. The study included 270 children with OW/OB aged 8-12 (M

Background Childhood acute lymphoblastic leukemia (ALL) survivors' increased risk for adverse health outcomes could be mitigated through consuming a balanced diet. Nonetheless, >70% of adult survivors do not meet survivorship dietary recommendations. ALL treatment may amplify risk for restricted dietary preferences (picky eating) and poor self-regulation of food intake that could contribute to suboptimal diets in survivorship. This study aims to: (a) characterize differences in picky eating and self-regulation of food intake between survivors and peer controls; and (b) examine the associations between these eating behaviors and dietary quality in ALL survivors relative to peer controls. Methods Participants were children (5-13 years) with (n = 32) and without (n = 32) a history of ALL and their caregivers. Children's dietary quality (Healthy Eating Index-2015) was calculated from 24-h dietary recalls. Caregivers completed the Child Eating Behavior Questionnaire-Food Fussiness subscale and the Child Self-Regulation in Eating Questionnaire. Results Independent samples t-tests revealed survivors exhibited greater picky eating than peer controls but comparable self-regulation of food intake. Bootstrapped grouped multivariate regression results showed that for ALL survivors, greater picky eating was associated with worse dietary quality (controlling for age and self-regulation of food intake). For peer controls, worse self-regulation of food intake was associated with poorer dietary quality (controlling for picky eating and age). Conclusions Results provide preliminary support that different eating behaviors contribute to poor dietary quality in children with and without an ALL history. These findings suggest that interventions to improve ALL survivors' dietary quality may benefit targeting picky eating.

During the last century, soils have been over-exploited by humans through agriculture and industrial development. The need to assess different aspects of soil degradation has become a priority in the soil protection management. Among several indices developed in the last years, QBS-ar (Soil Biological Quality-arthropod) index joins the biodiversity of soil microarthropods community with the degree of soil vulnerability. Up to now, numerous publications have reported the results of the QBS-ar application. This paper starts a review process for QBS-ar assessment by taking into account its potential in highlighting the relationship between soil quality and different land uses. In order to clarify the relationship between QBS-ar values and land use, we collected 41 published papers that reported of QBS-ar applications. In this framework, another aim of this paper is to make a critical review of the QBS-ar in respect to applications in different environmental contexts, and to obtain critical indication about problem and potential of QBS-ar for monitoring activities. We collected published data on QBS-ar and we individualized eight groupages in relation to soil uses: 1) Agriculture lands (A, several crops, till and no-tillage, organic, conventional), 2) Woods (W, forests, maquis and bushes), 3) Restored (R, plant remediation, restored pit mine, peri -urban uncultivated areas), 4) Natural degradation (ND, soils in natural degraded conditions, e.g. serpentine soils, soil in the brUle), 5) Permanent grasslands, pastures and meadows (G), 6) Orchards (O), 7) Urban parks, residual urban woods, public gardens, botanical gardens, home gardens (UP), 8) Soils involved in human degradation (D). The results confirmed that land use significantly affects QBS-ar values. The overall mean of QBS-ar = 93.7 can be considered a tentative threshold that separates high quality soils and values which are typical for poor soils. In the end, we would like to affirm the validity of this index, which, allows to evaluate the suffering state of soils and its potentiality for an expeditious use to evaluate soil biological quality in recovery areas.

Litter decomposition is an ecosystem process that is regulated by a multitude of factors and by their complex interactions. Current decomposition paradigms do not always offer a coherent view of the process because it can be hardly understood without a thorough analysis of interacting factors. Thus, there is a need to further understand the mechanics of litter decay with a comprehensive approach, especially in temperate forest ecosystems where decomposition plays a crucial role in regulating them as source or sink of CO2. Therefore, the aim of this work was to identify the interactions between chemical, biological and soil fauna variables in order to discern driving variables and the changes in their interactions during long-time (1300 days) beech leaf litter decomposition. In order to investigate patterns of variation and co-variation within and between datasets, we used Two-block Partial Least Squares, helping us to interpret the decomposition process with a systemic approach. Our key findings showed that the decomposition process of beech litter in two Mediterranean forests was driven by litter quality at the beginning and in the later stages of decomposition, while edaphic and climatic factors were implied in the central steps, with a dramatic change of scenario around 2.5 years. Simultaneous and interacting changes in chemical variables, extracellular enzyme activities, and soil fauna were shown, with a significant role of lignocellulosic components and enzymes involved in their degradation, Mn residual weight, and abundance of Collembola.

Objective: Despite long-standing participation of youth with T1D in research, clinical trials often fail to meet recruitment goals. The current study examined youth, young adult, and caregiver barriers and facilitators of participation in clinical research. Methods: Participants were recruited online nationally and in-clinic from two diabetes clinics in the U.S. Self-report surveys of research participation, barriers, and interests were obtained; HbA1c was collected via chart review. Results: Young adults (N=83; Mage=22.2±2.1; MA1c=7.6±1.5) and caregivers (N=81; Mage=45.3±7.8) via online surveys; and, adolescents (N=16; Mage=14.8±1.7; MA1c=9.1±2.2), young adults (N=10; Mage=20.9±2.2; MA1c=8.7±2.4), and caregivers (N=26; Mage=43.4±9.2) via routine diabetes clinic visits participated. Barriers to enrollment in included: missing school or work, potential unwanted side effects, location, time, and limited information. Over half of online participants (54%) reported lack of discussion with their physician about clinical trials, while 46.9% of in-clinic participants indicated their provider never or almost never discussed clinical research. Highest-rated research interests included: finding a cure, new technology, and closed-loop research. Among caregivers (online cohort), preference for the youth’s provider to discuss clinical trials during clinic visits was correlated with HbA1c% (r=0.302, p Conclusions: Youth, young adults, and caregivers expressed interest in learning more about research, yet identified logistical barriers to participation. Education and outreach are needed. Tailored multi-modal recruitment strategies (e.g., online for young adults; via events/provider for caregivers) may help overcome barriers to participation. Disclosure S.C. Westen: None. L.M. Anderson: None. S.A. Barry: None. S. Look: None. S. Pinto: None. A. Albanese-O'Neill: None. C.A. Kemp: None. M.J. Haller: Advisory Panel; Self; Pancreum, SAB Biotherapeutics. J.L. Papadakis: None. D. Schatz: None. B.T. Olsen: None. D.M. Janicke: None. J. Weissberg-Benchell: Consultant; Self; Roche Diabetes Care. N. Johnson: None. Funding JDRF

Truffles contribute both directly and indirectly to important dynamics in the soil web, being involved in a large number of ecological functions that are crucial for terrestrial ecosystems. Despite this, the interrelationships between true truffles, i.e. hypogeous ectomycorrhizal fungi producing valuable fruiting bodies, and other elements of the soil system are largely unknown. In this study, we aimed to shed new light on whether and how much Tuber aestivum affects soil microbial activities (evaluated as enzyme activities), abundance (assayed as soil DNA content) and bacterial genetic diversity along with soil chemical properties. We compared chemical and biological variables inside and outside brules (i.e. areas inhabited by truffles with scarce vegetation cover around host plants) in two seasons, namely spring and summer, using both a linear mixed model and a multivariate two-block partial least squares approach. The areas with truffle presence had higher pH but lower organic carbon and nitrogen content. Similarly, all enzyme activities were lower inside the brule than outside, with the exception of peroxidase. A soil quality index (i.e. AI3) based on three enzyme activities (β-glucosidase, acid phosphomonoesterase and urease) indicated a reduction in soil quality inside the brule. Overall, soil DNA content responded to an interaction of truffle presence/absence and season, while bacterial genetic diversity indexes were higher in spring. Despite the observational nature of this study, results point out that T. aestivum can be considered a key species in the soil where it is present as it was associated with changes in chemistry as well as microbial activity that were generally more conspicuous than mere seasonal effects, although the causative nature of these associations still needs to be confirmed.

Mining causes significant damage to the environment: the removal of top layers of soil causes loss of structure and functionality, with a subsequent reduction in biodiversity. Soil communities are important for soil formation, they contribute to the improvement of several characteristics of soils and they play key roles in many processes that enhance the success of restoration. Unfortunately, soil fauna are poorly monitored even though they represent a good tool for assessing soil quality. The “La Speranza” quarry in northern Italy was studied from the start of the restoration process in 2008 until 2012. Six sites were selected and monitored annually. Microarthropods were extracted from three replicates of soil drawn from each site, identified to order level and then counted. Both the abundances of taxa and the soil biological indices applied (Shannon diversity index (H’), Pielou's evenness index (J), the Acari to Collembola ratio (A/C) and the QBS-ar index) revealed a good level of soil recovery over the years studied. Furthermore, the edaphic organisms that are generally associated with stable conditions in the soil (e.g. Symphyla, Protura, Chilopoda), appeared in the most recent of the years.

Agriculture and forestry traditionally focus on improving plant growth traits based on an anthropocentric point of view. This paradigm has led to global problems associated to soil overexploitation such as soil losses, reductions of the C stock in soils, and the generalized use of fertilizers, which particularly increases the costs of production and pollution treatment. This view may also have limited our understanding of mutualistic symbioses of plants and microorganisms assuming that the main role of non-photosynthetic symbionts is to mobilize the nutrients that are necessary for plant growth and development, and being plants the dominant agents of the symbiotic relationship. In response to these issues, this chapter offers an alternative approach taking advantage of the “rhizo-centric” point of view, where non-photosynthetic partners are the main protagonists in play; and secondly, it builds a multidisciplinary body of knowledge that could be called “rhizoculture”, which includes techniques focussing on the intensification of the development and activity of roots, mycorrhizae, and other symbiotic and free living rhizosphere organisms. In short, rhizoculture may lead to decrease plant production dependence on fertilization and provides other benefits to agriculture, forestry, and the environment. Within this conceptual framework, the first objective of this book chapter is to explore whether there is a “paradox of calcium salts” (i.e., Ca2+ and its salts are simultaneously nutrients, promoters, and stressors for the host plants) that would explain a dominance of mycorrhizal fungi over plants based on inducing a Ca(pH)–mediated chlorosis to the host plants. If this paradigm shifting hypothesis were finally fully verified, it would provide conceptual bases to reconsider our current technologies in agriculture and forestry by introducing the “rhizocultural” approach, based on the management of roots (introducing alternative cultural practices), Ca2+ salts (using liming and other techniques), rock-eating mycorrhizae, organic matter, and the soil microbiome (increasing the presence of symbiotic microorganisms against saprophytes), N and P contents (by aquaculture and smart recycling of organic waste), and the physical properties of the soil (by the activity of soil symbiotic microorganisms and soil fauna, such as ants, termites and earthworms). The development of such new technological approaches in rhizoculture would significantly decrease the high cost and associated pollution of the application of fertilizers and phytochemicals; as well as it would increase soil C stocks, improve the resilience of agricultural and forest systems to environmental disturbances, such as climate change, and enhance food production and security.

There are numerous aspects related to Tuber species, which have not been explored to date. Tuber aestivum Vitt. is an ectomycorrhizal fungus, that produces an area (called brule) around the host plant trunk, where the germination of other plants is inhibited. What happens inside this particular environment is still not sufficiently understood, especially in terms of soil fauna. A previous work showed that there were higher microarthropod abundances outside during the period of maximum activity of the mycelium. The genus Folsomia (Isotomidae Family; Order Collembola) showed higher abundance inside. The aim of this paper is to investigate the effects of brule, on soil parameters and soil fauna, during the annual biological cycle of T. aestivum. This study was carried out in nine spontaneous brules situated in Northern Italy (Emilia Romagna Region – Piacenza Province). Soil cores were collected in order to perform soil chemical and biological analysis. Moisture content, pH, organic matter content, total organic carbon were analyzed. Biodiversity and soil quality indices were applied. We found higher pH, lower carbon and organic matter content within the brule. Soil fauna community also showed some differences, seasonal and inside vs outside the brule. Some groups seem to be negatively affected by Tuber while Folsomia genus recorded almost always higher values inside. These results suggest that some organisms, such as some Collembola, might find a favorable environment inside the brule, while others - a negative one. However, these results should be compared by other analysis either on other Tuber species and on other soil organisms, such as nematodes and earthworms.

The interactions between fungi and soil fauna are still not well known, but these complex relationships are worthy of attention because both groups are really important as trophic and functional groups in the soil food web. Some studies suggested that soil fauna play an important role in the ecology of fungi and fungi represent an important food resource for some soil animals such as earthworms, nematodes, springtails, beetles and others. Soil fauna can act positively or negatively on fungal growth, dispersion and fruit body production. Grazing on fungal mycelium, many animals may alter fungal morphology and physiology. These effects can alter the fungal fitness and then their combativeness in interaction with other soil microorganisms, including fungi. Various aspects related to the relationships between true truffles (Tuber sp.) and soil fauna and the role that soil animals may play in the ecology of truffles are taken into account in this chapter.

Leaf litter decomposition is one of the key phenomena in forest ecology. The patterns and trends of decomposition are related to the complex interaction of climate, soil biota and litter quality. The decay dynamics for the European beech are well-known for middle Europe, but lesser investigated in the Mediterranean area. In this study, we investigated mass loss and nutrient dynamics, especially nitrogen and manganese, in two Mediterranean beech forest located in northern and southern Italy. We used a litterbag experiment with leaves of each forest incubated in their own area of origin and vice versa. Moreover, we also used microcosms to follow early stages of decomposition under controlled conditions. The aims of this study were to investigate the role of climate and soil/litter quality at the different stages of decomposition and assess the response of diverse soils to changes in temperature and humidity. The results showed a faster field decomposition for the southern (warmer) site compared to the northern (colder) site, whereas under stable conditions in microcosms this trend reversed, implying different microbial adaptations to climate. Moreover, changes in temperature and humidity triggered complex microbial response during litter decay. Additionally, whereas our results showed trends of nitrogen concentration comparable to previous studies, the role of manganese in decomposition was very relevant even from the early stages. Noticeably, manganese was generally lower in both sites compared to middle Europe, but it was higher in the northern site than in the southern one. Manganese concentration, however, strongly increased for those leaves that had a lower initial content in all conditions, giving evidence of a strong mobilization of this nutrient and its essential role for decomposition in Mediterranean beech forests. Leaf litter decomposition is one of the key phenomena in forest ecology. The patterns and trends of decomposition are related to the complex interaction of climate, soil biota and litter quality. The decay dynamics for the European beech are well-known for middle Europe, but lesser investigated in the Mediterranean area. In this study, we investigated mass loss and nutrient dynamics, especially nitrogen and manganese, in two Mediterranean beech forest located in northern and southern Italy. We used a litterbag experiment with leaves of each forest incubated in their own area of origin and vice versa. Moreover, we also used microcosms to follow early stages of decomposition under controlled conditions. The aims of this study were to investigate the role of climate and soil/litter quality at the different stages of decomposition and assess the response of diverse soils to changes in temperature and humidity. The results showed a faster field decomposition for the southern (warmer) site compared to the northern (colder) site, whereas under stable conditions in microcosms this trend reversed, implying different microbial adaptations to climate. Moreover, changes in temperature and humidity triggered complex microbial response during litter decay. Additionally, whereas our results showed trends of nitrogen concentration comparable to previous studies, the role of manganese in decomposition was very relevant even from the early stages. Noticeably, manganese was generally lower in both sites compared to middle Europe, but it was higher in the northern site than in the southern one. Manganese concentration, however, strongly increased for those leaves that had a lower initial content in all conditions, giving evidence of a strong mobilization of this nutrient and its essential role for decomposition in Mediterranean beech forests. (C) 2015 Elsevier B.V. All rights reserved.

Background The present study evaluated the predictive value of renal resistive index (RI) for renal function and blood pressure (BP) outcome in hypertensive patients with unilateral atherosclerotic renal artery stenosis submitted to successful revascularization. Methods In 158 hypertensive patients with atherosclerotic renal artery stenosis RI was acquired. Twelve months after revascularization, they were classified on the basis of renal function and BP outcome as benefit (BP 15 mmHg with the same of reduced drugs; decrease in glomerular filtration rate > 20%), or failure. Results Regarding renal function outcome, RI in the stenotic and in the contralateral kidney were significantly higher in patients with failure (n = 20) than in those with benefit (0.72 ± 0.11 vs 0.61 ± 0.11 and 0.76 ± 0.08 vs 0.66 ± 0.09, p 0.73 provided the largest area under the curve (0.77), and the highest sensitivity (80%) and specificity (72%). In the multivariate logistic regression analysis, RI in the contralateral kidney >0.73 was an independent predictor of a failure in renal function outcome. Regarding BP outcome, patients with no benefit from revascularization (n = 60) had similar RI in the stenotic and contralateral kidney (p = ns), but presented higher pulse pressure, albuminuria and hypertension duration in comparison to patients with improved BP control. Conclusions RI in the contralateral kidney is an independent predictor of renal function outcome after successful revascularization in hypertensive patients with unilateral atherosclerotic renal artery stenosis, whereas it is not able to predict blood pressure outcome.

The aim of our study was to evaluate feasibility and accuracy of colour-coded duplex US in the detection of renal artery stenosis before and after stenting. Eighty-four patients (23 women, 61 men; mean age 64 years) with significant renal artery stenosis were studied with Doppler US, before and after stenting. A combined anterior and translumbar approach was used to visualise the renal arteries. Renal artery stenosis and in-stent restenosis were proved by the increase of renal peak systolic velocity (PSV) and reno-aortic ratio (RAR). Laboratory-specific threshold values of PSV and RAR were used to assess sensitivity and specificity of Doppler US. The renal arteries were visualised in all patients (feasibility 100%). A statistically significant difference of PSV and RAR was demonstrated between patent and stenotic renal arteries, before stenting, and between stenotic and stented renal arteries. No difference was demonstrated in cases of in-stent restenosis ( n=21). Before stenting, sensitivity of PSV and RAR was 93%, whereas specificity rates were 92 and 96%, respectively. After stenting sensitivity and specificity rates were, respectively, 90 and 93% for PSV, and 95 and 95% for RAR. Doppler US represents a feasible and reliable technique in the detection of renal artery stenosis and in-stent restenosis, although laboratory-specific threshold values are required to improve its accuracy.

Background —The goal of this study was to evaluate whether endothelial dysfunction associated with acute estrogen deprivation is caused by an alteration in the l -arginine–nitric oxide (NO) pathway and oxidative stress. Methods and Results —In 26 healthy women (age, 45.7±5.4 years) and 18 fertile women with leiomyoma (age, 44.5±5.1 years), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, or 15 μg · 100 mL −1 · min −1 ) or sodium nitroprusside (1, 2, or 4 μg · 100 mL −1 · min −1 ), an endothelium-dependent or -independent vasodilator, respectively. The NO pathway was evaluated by repeating acetylcholine during l -arginine (200 μg · 100 mL −1 · min −1 ; 13 control subjects and 9 patients) or N G -monomethyl- l -arginine (L-NMMA; 100 μg · 100 mL −1 · min −1 ; 13 control subjects and 9 patients); production of cyclooxygenase-derived vasoconstrictors was assessed by repeating acetylcholine during indomethacin (50 μg · 100 mL −1 · min −1 ; 13 control subjects and 9 patients) or vitamin C (8 mg · 100 mL −1 · min −1 ; 13 control subjects and 9 patients). Patients repeated the study within 1 month after ovariectomy and again after 3 months of estrogen replacement therapy (ERT; 17 β-estradiol TTS, 50 μg/d). Basally, vasodilation to acetylcholine was potentiated and inhibited by l -arginine and L-NMMA, respectively ( P l -arginine and L-NMMA disappeared, whereas indomethacin and vitamin C potentiated the response to acetylcholine ( P l -arginine and L-NMMA effects on vasodilation to acetylcholine but prevented the potentiation caused by indomethacin or vitamin C. Response to sodium nitroprusside was unaffected by either ovariectomy or ERT. Conclusions —Endothelial dysfunction secondary to acute endogenous estrogen deprivation is caused by reduced NO availability. Cyclooxygenase-dependent production of oxidative stress could be responsible for this alteration.

Over the past few years, there has been extensive research for a reliable, noninvasive, and nonionizing imaging method to screen for renal artery stenosis (RAS). Doppler ultrasound (US) is one of many modalities that have been evaluated for the detection of RAS. The lack of standardization in examination protocols and diagnostic criteria, as well as the wide differences in reported accuracy among different laboratories, however, have prevented universal acceptance of this technique as a reliable screening test for RAS. Recently, the introduction of US contrast agents has substantially expanded the potentials of color Doppler US. The use of microbubble echo enhancers in combination with harmonic Doppler imaging has been shown to improve diagnostic confidence by improving the operator's ability to visualize the renal arteries, and to significantly reduce the number of equivocal examinations. In addition, contrast-enhanced harmonic Doppler US can currently provide objective functional assessment of RAS through analysis of time-intensity renal enhancement curve. State-of-the-art contrast-enhanced Doppler US seems to have the potential to become a useful screening test for patients at risk from renovascular hypertension and a tool for follow-up of patients who undergo revascularization procedures.

To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 μg/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly ( P r =−.88, P r =−.87, P r =−.46, P r =−.48, P

BACKGROUND: Rearrangements of the CRLF2 gene, present in 7-15% of childhood BCP-ALL, are responsible of the overexpression of Thymic Stromal Lymphopoietin Receptor (TSLPR) and they are correlated with poor prognosis (Chen IM Blood 2012). TSLPR overexpression can be associated with JAK2 mutations, which leads to aberrant activation of JAK/STAT and PI3K/AKT pathways. Although the cross talk of the signaling pathways is still under investigation, there is a rationale for the use of targeted tyrosine kinase inhibitors (TKIs) to treat this subgroup of patients (Maude SL Blood 2012). We focused on the dissection of CRLF2-driven signaling in primary CRLF2 rearranged(r) BCP-ALL samples by using single cell mass cytometry (CyTOF) analysis. We leveraged the high dimensional single cell capability of the CyTOF to understand, with previously unattainable resolution, the activation of these pathways simultaneously in single cells and their response to inhibition with TKIs and anti-TSLPR monoclonal antibodies (mAbs). This revealed heterogeneity in signaling response, identifying subpopulations which differentially activate intracellular signals through TSLPR and differentially respond to ex vivo treatment. METHODS: Twelve BCP-ALL primary samples, 6 CRLF2r and 6 CRLF2 wild type (wt), were investigated and the expression of 24 phenotypic and 15 functional proteins were measured at single cell level using CyTOF as previous described (Bendall SC Science 2011). To assess the response to ex-vivo TSLP stimulation (10ng/mL) and TKIs/mAbs treatment, data were normalized to the basal levels of each phosphoprotein and significance was calculated using student`s t-test. One million cells per condition were treated with different TKIs, Dasatinib, Ruxolitinib and BEZ-235, and two different clones of anti-TSLPR mAbs (130A10 and 130H3) from MRC Technology. RESULTS: As expected, we observed an aberrant TSLP-induced activation of pSTAT5 and prpS6 in CRLF2r patients as compared with CRLF2wt, used as control group (p=0.0055, p= 0.0007). Of note, we also observed a previously not described TSLP-dependent activation of pERK and pCREB (p=0.0313, p=0.0261) suggesting a cross-talk of the TSLPR-driven signaling also with the RAS/MEK pathway. Treatment with TKIs revealed strong inhibitory activity of Dasatinib, which completely inhibited the TSLP-mediated phosphorylation of STAT5, rpS6, CREB and ERK in CRLF2r treated blasts compared to CRLF2r not treated cells (p= 0.0040, 0.0017, 0.0007, 0.0114 respectively). Ruxolitinib, JAK1/2 inhibitor, also reduced rpS6, CREB and ERK phosphorylation (p=0.0025, 0.037, 0.0132). Interestingly one of the two anti-TSLPR tested mAbs (130A10) was also able to significantly inhibit the TSLP-mediated activation of STAT5, rpS6, and ERK (p= 0.0071, 0.0006, 0.0323). Finally, the PI3K/TORk inhibitor, BEZ-235, did not show any statistically significant reductions. Single cell analysis revealed a population of TSLPR overexpressing blasts (range 20-50%) in which the TSLP stimulation resulted in activation of prpS6 but not pSTAT5, present in all the CRLF2r patients. This rpS6 activation could be inhibited by anti-TSLPR mAb, Dasatinib, Ruxolitinib and BEZ-235, except for one patient in which the activation was blunted only by anti-TSLPR mAb and Dasatinib suggesting an activation of prpS6 through a non canonical pathway. This data reveals heterogeneous signaling populations present within this subtype of leukemia driven by TSLPR overexpression. Finally in 3 additional CRLF2r primary samples, we investigated signaling profile of residual blasts (MRD) at Day8 and Day15 post induction initiation. TSLPR expression was consistently maintained in all patients at both time points. Furthermore, residual blasts were still able to respond to TSLP and the induced pSTAT5 could be effectively inhibited by 130A10 anti-TSLPR clone and Ruxolitinib. CONCLUSION: In summary, these data suggest heterogeneity of TSLPR-related signaling with activation of the expected JAK/STAT and PI3K pathways but also RAS/MEK and CREB activation. Further, TSLPR+ blasts exhibit heterogeneous responses to both treatment with TSLP in combination with TKIs or mAb. Finally, the MRD detection by CyTOF allowed the study of the functional activity of the TSLPR positive resistant cells suggesting a role of CRLF2r in the persistence of the leukemic cells and its targeting to treat late and refractory stages of the disease. Disclosures Davis: Fluidigm, Inc: Honoraria. Dyer:Roche Pharmaceuticals: Speakers Bureau; Gilead: Research Funding; ONO Pharmaceuticals: Research Funding. Nolan:Fluidigm, Inc: Equity Ownership.

Although observational studies have shown that estrogen can protect women against cardiovascular diseases (CVD), the underlying mechanisms are not fully clarified. Endothelium plays a pivotal role in the control of vascular function and structure; endothelial dysfunction, characterized by reduced or absent nitric oxide (NO) bioavailability linked and/or due to the production of cyclooxygenase-dependent endothelial-derived contracting factors (EDCFs), mainly represented by oxygen free radicals, is now viewed as an important mechanism causing atherothrombosis. Data in humans indicate that endogenous estrogen plays a protective role on endothelial function. Thus premenopausal women are protected against the adverse effect of hypercholesterolemia, with age-related impairment of endothelial function occurring only after the menopause in normotensive women and mainly after the menopause in hypertensive women. Moreover endogenous estrogen deprivation selectively impairs endothelial function in normotensive women. There is also evidence that exogenous estrogen can improve endothelial function in postmenopausal women. Thus acute intraarterial or intravenous infusion of estrogen potentiates endothelium-dependent vasodilation both in coronary circulation and the forearm. Estrogen replacement therapy (ERT) seems to improve endothelial function both in coronary arteries of postmenopausal women with coronary atherosclerosis and in brachial arteries of postmenopausal women with mild hypercholesterolemia. Although short-term ERT did not improve endothelial function in the forearm of perimenopausal women and in postmenopausal women with various cardiovascular risk factors, 3-month ERT restored endothelial function in ovariectomized women.

To retrospectively evaluate the role of clinical and procedural factors in predicting in-stent restenosis in patients with renovascular disease treated by renal artery stenting.From 1995 to 2002, 147 patients underwent renal artery stenting for the treatment of significant ostial atherosclerotic stenosis. Patients underwent strict clinical and color-coded duplex ultrasound follow-up. Ninety-nine patients (111 stents), with over 6 months of continuous follow-up (mean 22+/-12 months, range 6-60 months), were selected and classified according to the presence (group A, 30 patients, 32 lesions) or absence (group B, 69 patients, 79 lesions) of significant in-stent restenosis. A statistical analysis was performed to identify possible preprocedural and procedural predictors of restenosis considering the following data: sex, age, smoking habit, diabetes mellitus, hypertension, serum creatinine, cholesterol and triglyceride levels, renal artery stenosis grade, and stent type, length and diameter.Comparing group A and B patients (chi(2) test), a statistically significant relation was demonstrated between stent diameter and length and restenosis: the risk of in-stent restenosis decreased when the stent was/=6 mm in diameter and between 15 and 20 mm in length. This finding was confirmed by multiple logistic regression analysis. Stent diameter and length were proved to be significantly related to in-stent restenosis also when evaluating only patients treated by Palmaz stent (71 stents).Although it is based on a retrospective analysis, the present study confirms the importance of correct stent selection in increasing long-term patency, using stents of at least 6 mm in diameter and with a length of approximately 15-20 mm.

We investigated whether cyclooxygenase (COX) isoforms (COX-1 and COX-2) and decreased NO availability contribute to endothelial dysfunction in endotoxemic rats. The involvement of reactive oxygen species (ROS) was also evaluated. Rats were injected with Salmonella-derived lipopolysaccharide or saline. After 6 h, endothelial function of mesenteric resistance arteries was evaluated. In controls, acetylcholine (ACh)-induced relaxation was inhibited by the nitric-oxide synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) and unaffected by 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)-phenyl-2(5H)-furanone (DFU) (COX-2 inhibitor). In lipopolysaccharide (LPS)-treated rats, the response to ACh was blunted compared with controls, less sensitive to l-NMMA, and enhanced by DFU. COX-2 blockade also improved the inhibitory effect of l-NMMA on cholinergic relaxation. SC-560 [5-(4-clorophenyl)-1-(4-metoxyphenyl)-3-trifluoromethylpirazole] (COX-1 inhibitor) did not modify the response to ACh in both groups. LPS-induced endothelial dysfunction was unaffected by the thromboxane A(2) (TxA(2)) receptor antagonist SQ-29548 (7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1] hept-2-yl]-[1S(1alpha,2alpha(Z),3alpha,4alpha)]-5-heptenoic acid). In vivo inducible nitric-oxide synthase (iNOS) inhibition by S-methylisothiourea partly attenuated LPS-induced endothelial dysfunction. The antioxidants ascorbic acid and superoxide dismutase normalized endothelium-dependent relaxation and restored the inhibitory action of l-NMMA on ACh. Responses to sodium nitroprusside were similar in both groups. In LPS-treated rats, reverse transcription-polymerase chain reaction showed a marked increase in mesenteric iNOS and COX-2 expressions, whereas endothelial nitric-oxide synthase and COX-1 were unchanged. LPS-induced COX-2 overexpression was reduced but not abrogated by S-methylisothiourea. LPS-induced COX-2 up-regulation was also documented by immunohistochemistry. In conclusion, mesenteric resistance vessels from endotoxemic rats show impaired endothelial function due to reduced NO availability, a condition that is partly ascribable to an iNOS-dependent enhanced COX-2 expression, whereas TxA(2) does not seem to be involved. Oxidative stress is the main mechanism responsible for reduced NO availability, and COX-2 might act as a source of ROS.

OBJECTIVES We assessed whether third-generation oral contraceptive (OC) treatment (30 microg ethinylestradiol + 75 microg gestodene daily) could affect the endothelial function of healthy women. METHODS In 20 young healthy women (HW) and 10 hypercholesterolemic women (CW) we assessed forearm blood flow (strain-gauge plethysmography) changes induced by the intrabrachial infusion of acetylcholine (ACH) (0.15-15 microg/100 ml forearm tissue/min) and sodium nitroprusside (SNP) (1-4 microg/100 ml forearm tissue/min). ACH was repeated during the nitric oxide synthase inhibitor intra-arterial NG-monomethyl-L-arginine (L-NMMA) (100 microg/100 ml forearm tissue/min) or the antioxidant vitamin C (8 mg/100 ml forearm tissue/min). HW repeated the protocol after 6-month OC (n = 10) or placebo (n = 10) treatment. RESULTS In HW the maximal vasodilation to ACH, similar between placebo and OC subgroups, was significantly reduced in CW (P < 0.01). Vasodilation to ACH was blunted (P < 0.01) by L-NMMA and unaffected by vitamin C, in both OC and placebo groups. In CW the vasodilation to ACH, not modified by L-NMMA, was improved by vitamin C (P < 0.01). OC treatment raised (P < 0.01) plasma total and low-density lipoprotein cholesterol, and values were similar to those shown by CW. Both OC and placebo intake did not change the response to ACH and the modulation induced by L-NMMA or vitamin C. Vasodilation to SNP was similar in all groups. CONCLUSIONS In HW 6-month treatment with third-generation OC, although associated with an abnormal lipid profile, does not adversely affect endothelium-dependent vasodilation. This neutral effect could be the balance between a deleterious effect of hypercholesterolemia and a protective effect of OC on endothelial function.

To retrospectively evaluate the results of renal artery stenting in patients with renovascular disease and a solitary functioning kidney.Palmaz stents were placed in 16 patients with a solitary functioning kidney, renal artery stenosis, hypertension and renal failure. Stenoses were evaluated with color Doppler ultrasound, MR angiography and digital subtraction angiography (DSA). Indications for stenting were: recoil after percutaneous transluminal renal angioplasty (PTRA) (63%), arterial dissection after PTRA (13%) and primary stenting (25%). Immediate results were evaluated by DSA. On follow-up (6-36 months), patients underwent periodical evaluation of clinical conditions (blood pressure and serum creatinine level) and stent patency, by means of color Doppler ultrasound.Stent placement was successful in all patients (100%). Cumulative primary patency rate was: 100% at 1 day, 93.75% at 6 months, 81.25% at 12 months and 75% at 24 months. A significant reduction in diastolic blood pressure occurred (mean +/- SD 104 +/- 6 vs 92 +/- 3; p0.05); renal function improved or stabilized in over 80% of patients. However, there was no significant difference in the creatinine values before and after treatment (mean +/- SD 200 +/- 142 micromol/l vs 197 +/- 182 micromol/l; p0.05).Renal artery stenting, both after PTRA and as primary stenting, represents a safe procedure, able to preserve renal function in patients with a solitary functioning kidney.

Doppler ultrasound is one of many modalities that have been evaluated for the detection of renal artery stenosis. The lack of standardization in examination protocols and diagnostic criteria, as well as the wide differences in reported accuracy among different laboratories have, however, prevented universal acceptance of this technique as a reliable screening test for renal artery stenosis. The recent introduction of ultrasound contrast agents has substantially expanded the potential of color Doppler ultrasound. The use of microbubble echoenhancers in combination with harmonic Doppler imaging has been shown to improve diagnostic confidence by improving the operator's ability to visualize the renal arteries, and to significantly reduce the number of equivocal examinations. Moreover, contrast-enhanced Doppler ultrasound can provide functional information through analysis of renal time-intensity wash in/wash out curves. State-of-the-art contrast-enhanced Doppler ultrasound seems to have the potential to become a useful screening test for patients at risk from renovascular hypertension.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 15 μg·100 mL −1 ·min −1 ), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 μg·100 mL −1 ·min −1 ), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6±31.3 to P P =NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17β-estradiol, 50 μg/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9±43.1%; P P =NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.