Collinsmcneil6387

Angiogenesis is a multistep process requiring endothelial cell activation, migration, proliferation and tube formation. We recently reported that elevated secretion of interlukin 8 (IL8) by myotubes (MT) from subjects with Type-2 Diabetes (T2D) reduced angiogenesis by human umbilical vein endothelial cells (HUVEC) and human skeletal muscle explants. This lower vascularization was mediated through impaired activation of the phosphatidylinositol 3-kinase (PI3K)-pathway. We sought to investigate additional signaling elements that might mediate reduced angiogenesis. HUVEC were exposed to levels of IL8 equal to those secreted by MT from non-diabetic (ND) and T2D subjects and the involvement of components in the angiogenic response pathway examined. Cellular content of reactive oxygen species and Nitrate secretion were similar after treatment with [ND-IL8] and [T2D-IL8]. CXCR1 protein was down-regulated after treatment with [T2D-IL8] (p  less then  0.01 vs [ND-IL8] treatment); CXCR2 expression was unaltered. Addition of neutralizing antibodies against CXCR1 and CXCR2 to HUVEC treated with IL8 confirmed that CXCR1 alone mediated the angiogenic response to IL8. A key modulator of angiogenesis is matrix metalloproteinase-2 (MMP2). MMP2 secretion was higher after treatment with [ND-IL8] vs [T2D-IL8] (p  less then  0.01). Olaparib ic50 MMP2 inhibition reduced tube formation to greater extent with [ND-IL8] than with [T2D-IL8] (p  less then  0.005). The PI3K-pathway inhibitor LY294002 reduced IL8-induced MMP2 release. IL8 regulation of MMP2 release was CXCR1 dependent, as anti-CXCR1 significantly reduced MMP2 release (p  less then  0.05). These results suggest that high levels of IL8 secreted by T2D MT trigger reduced capillarization via lower activation of a CXCR1-PI3K pathway, followed by impaired release and activity of MMP2.The present investigation examined the longitudinal effects of Child-Parent Psychotherapy (CPP) for toddlers and their mothers with depression on a) maternal affective expression, b) child affective expression, and c) mother-child cohesion. Mothers with depression (Mage = 31.7 years; 92.8% White, 3.5% Black, 2.1% Hispanic, 2.3% other) and their toddlers were randomized to receive CPP (DI; n = 66) or to a control group (DC; n = 64). Mothers without depression and their toddlers (NC; n = 68) were recruited as an additional comparison group. Dyads were assessed at baseline (T1; 20 months old), post-intervention (T2; 36 months old), and follow-up (T3; 9 years old). Data from a mother-child conflict task was coded as a measure of observed outcome variables. Change in post-intervention attachment security assessed via the Strange Situation was evaluated as a mediator between intervention condition and maternal and child affective expression and dyadic cohesion at T3. Change to secure attachment post-intervention significantly mediated the association between intervention condition and T3 maternal warmth and child anger/problem behavior. Toddlers of mothers with depression who received CPP showed higher rates of change to secure attachment compared to those in both the DC and NC groups. Dyads who changed to secure attachment at T2 displayed higher levels of maternal warmth at T3 and lower levels of child anger and problem behavior at T3. Implications for the use of CPP as a preventive intervention and the importance of attachment as a mediator of long-term outcomes are discussed.Caregivers play a central role in promoting emotion regulation throughout infancy, childhood, and adolescence. However, there are no existing psychometric measures to assess how parents assist children in employing emotion regulation strategies for negative emotions. We therefore developed the Parental Assistance with Child Emotion Regulation (PACER) Questionnaire to assess the degree to which parents assist their children in their use of ten different regulation strategies. In this paper, we describe the development of the PACER and examine its psychometric properties (N = 407 parents of children ages birth to 17 years). In so doing, we also use the PACER to comprehensively explore the links between parent-assisted emotion regulation and indices of parent and child stress, symptomatology, and attachment. Confirmatory factor analyses of the PACER items supported its intended ten-factor structure (corresponding to ten specific regulation strategies), which was invariant across different child age and sex categories. PACER scale scores had excellent internal consistency and generally acceptable test-retest reliability over a one-week period. Convergent validity was established via correlations between PACER scales and indices of parental emotion sensitivity, expressivity, and regulation, as well as parents' perception of the efficacy of their assistance with children's execution of emotion regulatory strategies. Lower parental facilitation of stereotypically adaptive emotion regulatory strategies was associated with higher child internalizing and externalizing problems and with poorer parent-child relationship quality. Overall, these findings suggest that the PACER may be a useful tool for the assessment of parental assistance with child emotion regulation across development.

Studies on the use of non-vitaminK antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban.

With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), alarge prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban creatinine clearance 15-50 ml/min, weight ≤60 kg, and/or use of strong p‑glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC).

Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age 72.3 vs 73.9 years), and had lower CHA

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-VASc (mean 2.8 vs3.2) and HAS-BLED scores (mean 2.4 vs2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.