Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

A single dose of heroin can reduce stress responses in heroin-dependent patients. Schmidt et al. report that increased amygdala-related functional connectivity during fearful face processing in heroin-dependent patients transiently normalises after a single dose of heroin. This measure may help to assess the efficacy of maintenance treatments in drug addictio

Impaired high-density lipoprotein function in patients with heart failure

Background: We recently showed that, in patients with heart failure, lower high‐density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow‐up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed. Methods and Results: We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti‐inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT‐CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti‐inflammatory capacity declined (both P<0.001). In contrast, antioxidative capacity increased (P<0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT‐CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71–0.92; P=0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures. Conclusions: Better HDL cholesterol efflux at baseline was associated with lower mortality during follow‐up, independent of HDL cholesterol. HDL cholesterol efflux and anti‐inflammatory capacity declined during follow‐up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure

Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of amygdala-related connectivity during fear processing may provide a prognostic tool to assess stress levels in heroin-dependent patients and to quantify the efficacy of maintenance treatments in drug addiction

Distinct pathophysiological pathways in women and men with heart failure

Aims: Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and Results: In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuroinflammatory response in men (all p < 0.0001). Conclusion: In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies

Distinct pathophysiological pathways in women and men with heart failure

Aims Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and results In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro-inflammatory response in men (all p &lt; 0.0001). Conclusion In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies.</p

The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure

In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR)

Understanding Flood Regime Changes in Europe: a state-of-the-art assessment

There is growing concern that flooding is becoming more frequent and severe in Europe. A better understanding of flood regime changes and their drivers is therefore needed. The paper reviews the current knowledge on flood regime changes in European rivers that has traditionally been obtained through two alternative research approaches. The first approach is the data-based detection of changes in observed flood events. Current methods are reviewed together with their challenges and opportunities. For example, observation biases, the merging of different data sources and accounting for nonlinear drivers and responses. The second approach consists of modelled scenarios of future floods. Challenges and opportunities associated with flood change scenarios are discussed such as fully accounting for uncertainties in the modelling cascade and feedbacks. To make progress in flood change research, we suggest that a synthesis of these two approaches is needed. This can be achieved by focusing on long duration records and flood-rich and flood-poor periods rather than on short duration flood trends only, by formally attributing causes of observed flood changes, by validating scenarios against observed flood regime dynamics, and by developing low-dimensional models of flood changes and feedbacks. The paper finishes with a call for a joint European flood change research network

Common Data Elements to Facilitate Sharing and Re-use of Participant-Level Data: Assessment of Psychiatric Comorbidity Across Brain Disorders

The Ontario Brain Institute\u27s “Brain-CODE” is a large-scale informatics platform designed to support the collection, storage and integration of diverse types of data across several brain disorders as a means to understand underlying causes of brain dysfunction and developing novel approaches to treatment. By providing access to aggregated datasets on participants with and without different brain disorders, Brain-CODE will facilitate analyses both within and across diseases and cover multiple brain disorders and a wide array of data, including clinical, neuroimaging, and molecular. To help achieve these goals, consensus methodology was used to identify a set of core demographic and clinical variables that should be routinely collected across all participating programs. Establishment of Common Data Elements within Brain-CODE is critical to enable a high degree of consistency in data collection across studies and thus optimize the ability of investigators to analyze pooled participant-level data within and across brain disorders. Results are also presented using selected common data elements pooled across three studies to better understand psychiatric comorbidity in neurological disease (Alzheimer\u27s disease/amnesic mild cognitive impairment, amyotrophic lateral sclerosis, cerebrovascular disease, frontotemporal dementia, and Parkinson\u27s disease)