Can understanding reward help illuminate anhedonia?

Purpose of review: The goal of this paper is to examine how reward processing might help us understand the symptom of anhedonia. Recent findings: There are extensive reviews exploring the relationship between responses to rewarding stimuli and depression. These often include a discussion on anhedonia and how this might be underpinned in particular by dysfunctional reward processing. However, there is no specific consensus on whether studies to date have adequately examined the various sub-components of reward processing or how these might relate in turn to various aspects of anhedonia symptoms. Summary: The approach to understanding the symptom of anhedonia should be to examine all the sub-components of reward processing at the subjective and objective behavioural and neural level, with well validated tasks that can be replicated. Investigating real life experiences of anhedonia and how theses might be predicted by objective lab measures is also needed in future research

Anti-infectives in Drug Delivery-Overcoming the Gram-Negative Bacterial Cell Envelope.

Infectious diseases are becoming a major menace to the state of health worldwide, with difficulties in effective treatment especially of nosocomial infections caused by Gram-negative bacteria being increasingly reported. Inadequate permeation of anti-infectives into or across the Gram-negative bacterial cell envelope, due to its intrinsic barrier function as well as barrier enhancement mediated by resistance mechanisms, can be identified as one of the major reasons for insufficient therapeutic effects. Several in vitro, in silico, and in cellulo models are currently employed to increase the knowledge of anti-infective transport processes into or across the bacterial cell envelope; however, all such models exhibit drawbacks or have limitations with respect to the information they are able to provide. Thus, new approaches which allow for more comprehensive characterization of anti-infective permeation processes (and as such, would be usable as screening methods in early drug discovery and development) are desperately needed. Furthermore, delivery methods or technologies capable of enhancing anti-infective permeation into or across the bacterial cell envelope are required. In this respect, particle-based carrier systems have already been shown to provide the opportunity to overcome compound-related difficulties and allow for targeted delivery. In addition, formulations combining efflux pump inhibitors or antimicrobial peptides with anti-infectives show promise in the restoration of antibiotic activity in resistant bacterial strains. Despite considerable progress in this field however, the design of carriers to specifically enhance transport across the bacterial envelope or to target difficult-to-treat (e.g., intracellular) infections remains an urgently needed area of improvement. What follows is a summary and evaluation of the state of the art of both bacterial permeation models and advanced anti-infective formulation strategies, together with an outlook for future directions in these fields

Multimodal neuroimaging of suicidal thoughts and behaviors in a U.S. population-based sample of school-age children

Objective: Suicide deaths and suicidal thoughts and behaviors are considered a public health emergency, yet their underpinnings in the brain remain elusive. The authors examined the classification accuracy of individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates, of suicidal thoughts and behaviors in a U.S. population-based sample of school-age children. Methods: Children ages 9-10 years (N=7,994) from a population-based sample from the Adolescent Brain Cognitive Development study were assessed for lifetime suicidal thoughts and behaviors. After quality control procedures, structural MRI (N=6,238), resting-state functional MRI (N=4,134), and task-based functional MRI (range, N=4,075-4,608) were examined. Differences with Welch's t test and equivalence tests, with observed effect sizes (Cohen's d) and their 90% confidence intervals,|0.15|, were examined. Classification accuracy was examined with area under precision-recall curves (AUPRCs). Results: Among the 7,994 unrelated children (females, N53,757, 47.0%), those with lifetime suicidal thoughts and behaviors based on child (N5684, 8.6%), caregiver (N5654, 8.2%), and concordant (N5198, 2.5%) reports had higher levels of social adversity and psychopathology, among themselves and their caregivers, compared with never-suicidal children (N56,854, 85.7%). Only one imaging test survived statistical correction: caregiver-reported suicidal thoughts and behaviors were associated with a thinner left bank of the superior temporal sulcus. On the basis of the prespecified bounds of |0.15|, approximately 48% of the group mean differences for child-reported suicidal thoughts and behaviors comparisons and approximately 22% for caregiver-reported suicidal thoughts and behaviors comparisons were considered equivalent. All observed effect sizes were relatively small (d#|0.30|), and both non-imaging and imaging correlates had low classification accuracy (AUPRC #0.10). Conclusions: Commonly applied neuroimaging measures did not reveal a discrete brain signature related to suicidal thoughts and behaviors in youths. Improved approaches to the neurobiology of suicide are critically needed