Impact of stent overlap on long-term clinical outcomes in patients treated with newer-generation drug-eluting stents

Aims: Early-generation drug-eluting stent (DES) overlap (OL) is associated with impaired long-term clinical outcomes whereas the impact of OL with newer-generation DES is unknown. Our aim was to assess the impact of OL on long-term clinical outcomes among patients treated with newer-generation DES. Methods and results: We analysed the three-year clinical outcomes of 3,133 patients included in a prospective DES registry according to stent type (sirolimus-eluting stents [SES; N=1,532] versus everolimus-eluting stents [EES; N=1,601]), and the presence or absence of OL. The primary outcome was a composite of death, myocardial infarction (MI), and target vessel revascularisation (TVR). The primary endpoint was more common in patients with OL (25.1%) than in those with multiple DES without OL (20.8%, adj HR=1.46, 95% CI: 1.03-2.09) and patients with a single DES (18.8%, adj HR=1.74, 95% CI: 1.34-2.25, p<0.001) at three years. A stratified analysis by stent type showed a higher risk of the primary outcome in SES with OL (28.7%) compared to other SES groups (without OL: 22.6%, p=0.04; single DES: 17.6%, p<0.001), but not between EES with OL (22.3%) and other EES groups (without OL: 18.5%, p=0.30; single DES: 20.4%, p=0.20). Conclusions: DES overlap is associated with impaired clinical outcomes during long-term follow-up. Compared with SES, EES provide similar clinical outcomes irrespective of DES overlap status.

The effect of aerobic exercise on intrahepatocellular and intramyocellular lipids in healthy subjects

BACKGROUND Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass). AIM To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy. METHODS Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO(2max)) using ¹H-MR-spectroscopy. RESULTS Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO(2max), 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (-22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity. CONCLUSIONS IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions. TRIAL REGISTRATION ClinicalTrial.gov NCT00491582.

Impact of environmental estrogens on Yfish considering the diversity of estrogen signaling.

Research on endocrine disruption in fish has been dominated by studies on estrogen-active compounds which act as mimics of the natural estrogen, 17β-estradiol (E2), and generally exert their biological actions by binding to and activation of estrogen receptors (ERs). Estrogens play central roles in reproductive physiology and regulate (female) sexual differentiation. In line with this, most adverse effects reported for fish exposed to environmental estrogens relate to sexual differentiation and reproduction. E2, however, utilizes a variety of signaling mechanisms, has multifaceted functions and targets, and therefore the toxicological and ecological effects of environmental estrogens in fish will extend beyond those associated with the reproduction. This review first describes the diversity of estrogen receptor signaling in fish, including both genomic and non-genomic mechanisms, and receptor crosstalk. It then considers the range of non-reproductive physiological processes in fish that are known to be responsive to estrogens, including sensory systems, the brain, the immune system, growth, specifically through the growth hormone/insulin-like growth factor system, and osmoregulation. The diversity in estrogen responses between fish species is then addressed, framed within evolutionary and ecological contexts, and we make assessments on their relevance for toxicological sensitivity as well as ecological vulnerability. The diversity of estrogen actions raises questions whether current risk assessment strategies, which focus on reproductive endpoints, and a few model fish species only, are protective of the wider potential health effects of estrogens. Available - although limited - evidence nevertheless suggests that quantitative environmental threshold concentrations for environmental protection derived from reproductive tests with model fish species are protective for non-reproductive effects as well. The diversity of actions of estrogens across divergent physiological systems, however, may lead to and underestimation of impacts on fish populations as their effects are generally considered on one functional process only and this may underrepresent the impact on the different physiological processes collectively.

The impact of absolute importance on prospective memory: Instructions matter

Prospective memory (ProM) is the ability to remember and carry out a planned intention in the future. ProM performance can be improved by instructing participants to prioritize the ProM task over the ongoing task. However, the improvement of ProM performance by emphasizing the relative importance typically restricted to situations in which the overlap between processing requirements of the ProM task and the ongoing task is low. Thus, additional processing resources are allocated to the ProM task and consequently, a cost emerges for the ongoing task. The aim of the present study was to further investigate this relationship. Participants were asked to respond to either semantic or perceptual ProM cues, which were embedded in a complex ongoing short term memory task. We manipulated absolute rather than relative importance by emphasizing the importance of the ProM task to half of the participants (i.e., without instructing them to prioritize it over the ongoing task). The results revealed that importance boosted ProM performance independent of the processing overlap between the ProM task and the ongoing task. Moreover, no additional cost was associated with absolute importance. These results challenge the view that importance always enhances the allocation of resources to the ProM task.

The effect of shoulder variation on IMRT and SmartArc for Head and Neck Cancer

Purpose: First, to determine an average and maximum displacement of the shoulder relative to isocenter over the course of treatment. Second, to establish the dosimetric effect of shoulder displacements relative to correct isocenter alignment on the dose delivered to the target and the surrounding structures for head and neck cancer patients. Method and Materials: The frequency of shoulder shifts of various magnitudes relative to isocenter was assessed for 4 patients using image registration software. The location of the center of the right and left humeral head relative to isocenter (usually C2) was found daily from CT on rails scans, and was compared to the location of the humeral heads relative to isocenter on the initial simulation CT. Three Baseline head and neck IMRT and SmartArc plans were generated in Pinnacle based on simulation CTs. The CT datasets (external contour and boney structures) were then modified to represent shifts of the shoulder (relative to isocenter) between 3 mm and 15 mm in the SI, AP, and LR directions. The initial plans were recalculated on the image sets with shifted shoulders. Results: On average, shoulder variation was 2-5 mm in each direction, although displacements of over 1 cm in the inferior and posterior directions occurred. Shoulder shifts induced perturbations in the dose distribution, although generally only for large shifts. Most substantially, large, superior shifts resulted in coverage loss by the 95% isodose line for targets in the lower neck. Inferior shifts elevated the dose to the brachial plexus by 0.6-4.1 Gy. SmartArc plans showed similar loss of target coverage as IMRT plans. Conclusions: The position of the shoulder can have an impact on target coverage and critical structure dose. Shoulder position may need to be considered for setup of head and neck patients depending on target location.

Commentary on "The Impact of Family Stressors on the Social Development of Adolescents in Residential Facilities"

This is a commentary on “The impact of family stressors on the social development of adolescents admitted to a residential treatment facility,” by Cynthia Harr. This article examines the important but relatively understudied relationship of family dynamics in the social development of high risk teens in residential treatment facility (RTF) care. The commentary supports the author’s calls for a continuum of care involving greater cooperation with parents, and critiques and expands on some of the recommendations.

Review: The Batterer as Parent: Addressing the Impact of Domestic Violence on Family Dynamics

A Review of The Batterer as Parent: Addressing the Impact of Domestic Violence on Family Dynamics, 2nd Edition, by Lundy Bancroft, Jay G. Silverman, and D. Ritchie.

The Impact of Family Stressors on the Social Development of Adolescents Admitted to a Residential Treatment Facility

The focus of this research was to determine the impact of family stressors on the social development of adolescents at admission to long-term mental health residential care. The study was conducted at the Waco Center for Youth, the only long-term residential care agency serving emotionally and behaviorally challenged adolescents and their families that functions under the authority of the Texas Department of State Health Services. Data was obtained from social assessment forms (N=457) in case records of clients. The prevalence of problem behaviors exhibited by the youth upon entry to the residential facility was examined and it was found that the youth entering the facility were experiencing severe impairment in their social development across several domains. Results indicated that youth with more family stressors exhibited significantly greater impairment in their social development (b = .19, p = .000) which suggests that the combination of multiple stressors within a family inhibits adolescent social development. The research supports a family systems approach to treatment that focuses on building family strengths and actively involving family in the intervention process.

Acculturation and cultural identity of immigrant youth: The impact of courses in the language and culture of origin

Career choices in the fields of science, technology, engineering, and mathematics (STEM) are favoured by men and often avoided by women; on the other hand, women tend to choose fields such as the social sciences. This not only leads to a shortage of employees with STEM degrees, but also reinforces the prejudice that certain (personality) characteristics are ‘typically female’ or ‘typically male’. Career orientation motives of young women and men can have important implications for gender (a-)typical career choices. However, there is little empirical research on the correlates of career orientation motives in young women in the field of STEM. This study seeks to address this gap by outlining the components of career orientation motives and showing relationships among them. Therefore, our results provide insight into the circumstances and conditions that are associated with academic and career choices.

The impact of social roles on trait judgments: a critical reexamination

Consistent with social role theory's assumption that the role behavior of men and women shapes gender stereotypes, earlier experiments have found that men's and women's occupancy of the same role eliminated gender-stereotypical judgments of greater agency and lower communion in men than women. The shifting standards model raises the question of whether a shift to within-sex standards in judgments of men and women in roles could have masked underlying gender stereotypes. To examine this possibility, two experiments obtained judgments of men and women using measures that do or do not restrain shifts to within-sex standards. This measure variation did not affect the social role pattern of smaller perceived sex differences in the presence of role information. These findings thus support the social role theory claim that designations of identical roles for subgroups of men and women eliminate or reduce perceived sex differences.

Communality sells: The impact of perceivers' sexism on the evaluation of women's portrayals in advertisements

Portrayals of women in advertisements have a significant impact on the maintenance of gender stereotypes in society. Therefore, the present research investigates the effectiveness of communal and agentic female characters in advertisements as well as the question how evaluations of such characters are influenced by perceivers' sexist attitudes toward women. Results show that communal female advertising characters are evaluated more favorably than agentic ones and that these evaluations predict advertising effectiveness. Benevolent sexism predicts more positive evaluations of communal female advertising characters (studies 1 and 2). Moreover, hostile sexism predicts less positive evaluations of agentic female advertising characters when it is assessed under time pressure (Study 2). Implications of these findings for the perpetuation of gender stereotypes in advertisements and in society are discussed.

The mentalizing network orchestrates the impact of parochial altruism on social norm enforcement.

Parochial altruism - a preference for altruistic behavior towards ingroup members and mistrust or hostility towards outgroup members--is a pervasive feature in human society and strongly shapes the enforcement of social norms. Since the uniqueness of human society critically depends on the enforcement of norms, the understanding of the neural circuitry of the impact of parochial altruism on social norm enforcement is key, but unexplored. To fill this gap, we measured brain activity with functional magnetic resonance imaging (fMRI) while subjects had the opportunity to punish ingroup members and outgroup members for violating social norms. Findings revealed that subjects' strong punishment of defecting outgroup members is associated with increased activity in a functionally connected network involved in sanction-related decisions (right orbitofrontal gyrus, right lateral prefrontal cortex, right dorsal caudatus). Moreover, the stronger the connectivity in this network, the more outgroup members are punished. In contrast, the much weaker punishment of ingroup members who committed the very same norm violation is associated with increased activity and connectivity in the mentalizing-network (dorsomedial prefrontal cortex, bilateral temporo-parietal junction), as if subjects tried to understand or justify ingroup members' behavior. Finally, connectivity analyses between the two networks suggest that the mentalizing-network modulates punishment by affecting the activity in the right orbitofrontal gyrus and right lateral prefrontal cortex, notably in the same areas showing enhanced activity and connectivity whenever third-parties strongly punished defecting outgroup members.

Impact of IL28B genotype on first-week response to telaprevir-based therapy in HIV-HCV coinfection

BACKGROUND IL28B genotype predicts response to treatment against hepatitis C virus (HCV) with pegylated interferon/ribavirin (PR) and impacts on the outcome of therapy including telaprevir (TVR). This study aimed to determine the influence of the favorable IL28B genotype on early viral kinetics during therapy with TVR/PR in HIV/HCV-coinfected patients. METHODS All HIV/HCV genotype 1-coinfected subjects who received TVR/PR for at least 4 weeks were included from populations prospectively followed in 22 centers throughout Germany, Switzerland and Spain. RESULTS Of the 129 subjects included, 38 (29.5%) presented with IL28B genotype CC and 94 (72.9%) were treatment-experienced. Ninety-six (73.8%) patients showed undetectable plasma HCV-RNA at treatment week (W) 4: 30 (78.9%) of the IL28B-CC carriers and 65 (71.4%) of the non-CC carriers (p=0.377). Among treatment-naïve patients, proportions of undetectable HCV-RNA among IL28B-CC versus non-CC carriers were 8/9 (88.9%) versus 3/9 (33.3%, p=0.016) and 14/17 (82.4%) versus 11/18 (61.1%, p=0.164) at W2 and W4. The decrease of HCV-RNA at W2 and W4 was similar among the IL28B carriers. CONCLUSIONS IL28B genotype does not predict W4 response to TVR/PR in HIV/HCV-coinfected patients, regardless of their treatment history. However, there is evidence of an impact on response during the first weeks in treatment-naïve patients.

Isotopic constraints on marine and terrestrial N2O emissions during the last deglaciation

Nitrous oxide (N2O) is an important greenhouse gas and ozone-depleting substance that has anthropogenic as well as natural marine and terrestrial sources. The tropospheric N2O concentrations have varied substantially in the past in concert with changing climate on glacial–interglacial and millennial timescales. It is not well understood, however, how N2O emissions from marine and terrestrial sources change in response to varying environmental conditions. The distinct isotopic compositions of marine and terrestrial N2O sources can help disentangle the relative changes in marine and terrestrial N2O emissions during past climate variations. Here we present N2O concentration and isotopic data for the last deglaciation, from 16,000 to 10,000 years before present, retrieved from air bubbles trapped in polar ice at Taylor Glacier, Antarctica. With the help of our data and a box model of the N2O cycle, we find a 30 per cent increase in total N2O emissions from the late glacial to the interglacial, with terrestrial and marine emissions contributing equally to the overall increase and generally evolving in parallel over the last deglaciation, even though there is no a priori connection between the drivers of the two sources. However, we find that terrestrial emissions dominated on centennial timescales, consistent with a state-of-the-art dynamic global vegetation and land surface process model that suggests that during the last deglaciation emission changes were strongly influenced by temperature and precipitation patterns over land surfaces. The results improve our understanding of the drivers of natural N2O emissions and are consistent with the idea that natural N2O emissions will probably increase in response to anthropogenic warming.

Impact of miR-21, miR-126 and miR-221 as prognostic factors of clear cell renal cell carcinoma with tumor thrombus of the inferior vena cava

Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.