The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional ...brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network's associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN's cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.
The extracellular matrix (ECM) regulates cell behavior by influencing cell proliferation, survival, shape, migration and differentiation. Far from being a static structure, the ECM is constantly ...undergoing remodeling - i.e. assembly and degradation - particularly during the normal processes of development, differentiation and wound repair. When misregulated, this can contribute to disease. ECM assembly is regulated by the 3D environment and the cellular tension that is transmitted through integrins. Degradation is controlled by complex proteolytic cascades, and misregulation of these results in ECM damage that is a common component of many diseases. Tissue engineering strives to replace damaged tissues with stem cells seeded on synthetic structures designed to mimic the ECM and thus restore the normal control of cell function. Stem cell self-renewal and differentiation is influenced by the 3D environment within the stem cell niche. For tissue-engineering strategies to be successful, the intimate dynamic relationship between cells and the ECM must be understood to ensure appropriate cell behavior.
People living in deprived areas are more likely to be overweight or obese, have poorer health outcomes, and tend to benefit less from interventions than those from more affluent backgrounds. One ...approach to address such health inequalities is to tailor existing interventions to low socio-economic populations, yet there is limited evidence to inform their design. This study aims to identify how best to tailor lifestyle interventions to low socio-economic populations to improve outcomes.
Following direct observations of community-run weight loss groups, we interviewed 11 group facilitators and 14 service users from a health improvement service in a low socio-economic area in the North West of England. Audio-recorded interviews were transcribed verbatim and analysed thematically.
We identified two overarching themes within the data. The first theme, managing diversity, included challenges faced in delivering a generic intervention to a diverse population in terms of knowledge, language and literacy skills, and cultural diversity. The second theme incorporated all issues relating to the environment, such as cost, access and availability of food and leisure facilities, and 'life gets in the way'.
Tailoring interventions for this population is necessary, and more attention is needed to develop ways to ensure service providers and users engage with behaviour change techniques such as goal setting, rather than focusing on information provision alone. Interventions should also be mindful of cost, cultural diversity, and language and literacy barriers, as well as potential for disengaging this hard to reach population.
ObjectiveThe aim of this review was to investigate whether e-cigarette use compared with non-use in young non-smokers is associated with subsequent cigarette smoking.Data sourcesPubMed, Embase, Web ...of Science, Wiley Cochrane Library databases, and the 2018 Society for Research on Nicotine and Tobacco and Society for Behavioural Medicine conference abstracts.Study selectionAll studies of young people (up to age 30 years) with a measure of e-cigarette use prior to smoking and an outcome measure of smoking where an OR could be calculated were included (excluding reviews and animal studies).Data extractionIndependent extraction was completed by multiple authors using a preprepared extraction form.Data synthesisOf 9199 results, 17 studies were included in the meta-analysis. There was strong evidence for an association between e-cigarette use among non-smokers and later smoking (OR: 4.59, 95% CI: 3.60 to 5.85) when the results were meta-analysed in a random-effects model. However, there was high heterogeneity (I2 =88%).ConclusionsAlthough the association between e-cigarette use among non-smokers and subsequent smoking appears strong, the available evidence is limited by the reliance on self-report measures of smoking history without biochemical verification. None of the studies included negative controls which would provide stronger evidence for whether the association may be causal. Much of the evidence also failed to consider the nicotine content of e-liquids used by non-smokers meaning it is difficult to make conclusions about whether nicotine is the mechanism driving this association.
Adherence to weight loss interventions is crucial to successful outcomes, yet little is known about how best to improve it. This suggests a need for developing and improving adherence strategies, ...such as formal commitments. This review aims to identify the effect of including a commitment device alongside lifestyle interventions on weight loss, and identify the most appropriate delivery mechanisms and target behaviours.
We searched five databases and hand-searched reference lists for trials of behavioural interventions to achieve weight loss among adults with excess weight or obesity. Interventions incorporating commitment devices were included in a narrative review and meta-analysis where appropriate. Commitment devices with financial incentives were excluded.
Of 2675 unique studies, ten met the inclusion criteria. Data from three randomised trials including 409 participants suggests that commitment interventions increases short-term weight loss by a mean of 1.5 kg (95% CI: 0.7, 2.4). Data from two randomised trials including 302 patients suggests that benefits were sustained at 12 months (mean difference 1.7 kg; 95% CI: 0.0, 3.4). Commitment devices appeared most successful when made publicly, and targeting diet rather than physical activity.
Using commitment devices, such as behavioural contracts, as part of a weight loss intervention may be useful in improving weight loss outcomes and dietary changes, at least in the short-term. However, evidence is limited and of variable quality so results must be interpreted with caution. Poor reporting of intervention details may have limited the number of identified studies. More rigorous methodology and longer term follow-ups are required to determine the effectiveness of behavioural contracts given their potential for use in public health interventions.
•Neural overlap is reported between autobiographical memory and prospective tasks.•It remains unclear if these findings extend to complex personal problem solving.•We report both overlap and ...dissociation between problem solving and memory.•We delineated the neural correlates across multiple phases of retrieval for both tasks.•These findings provide novel insight into the functions of autobiographical memory
Prior research has documented engagement of a common ‘core’ retrieval network during autobiographical memory retrieval and higher-order prospective tasks, such as personal problem solving. This neural overlap has overwhelmingly been documented in the context of the 'elaboration phase' of retrieval, when a single mental event is simulated in detail . However, recollective and prospective tasks are often associated with generic cues, which require the retrieval and consideration of multiple conceptually-related events. This initial ‘generation phase’ of retrieval has received comparably little attention in the literature, leaving open questions as to how and when autobiographical memory and prospective tasks overlap within the brain. Here, we compare and contrast neural activity between autobiographical memory retrieval and personal problem solving with a focus on the initial generation phase of retrieval. In the MRI scanner, young adults completed both an autobiographical memory and a personal problem solving task. Each task consisted of a generation phase, which required participants to generate multiple past personal events or problem solutions to a given cue and a subsequent elaboration phase, where a single memory or solution was simulated in detail. A multivariate Partial Least Squares analysis revealed patterns of neural overlap between memory and problem solving during the generation phase that were distinct from the elaboration phase. Among regions commonly recruited during the generation phase was the anterior hippocampus, a structure involved in initiating mental construction and integrating concepts. Subsequent analyses demonstrated that the anterior hippocampus interacted with distinct cortical regions as a function of task, in particular the ventromedial prefrontal cortex. Together, these data provide novel evidence that neural overlap between autobiographical memory and personal problem solving does not occur solely in the context of detailed simulation but, instead, is driven by common retrieval demands.
Background
Obesity rates are higher among people of lower socioeconomic status. While numerous health behaviour interventions targeting obesity exist, they are more successful at engaging higher ...socioeconomic status populations, leaving those in less affluent circumstances with poorer outcomes. This highlights a need for more tailored interventions. The aim of this study was to enhance an existing weight loss course for adults living in low socioeconomic communities.
Methods
The Behaviour Change Wheel approach was followed to design an add‐on intervention to an existing local authority‐run weight loss group, informed by mixed‐methods research and stakeholder engagement.
Results
The COM‐B analysis of qualitative data revealed that changes were required to psychological capability, physical and social opportunity and reflective motivation to enable dietary goal‐setting behaviours. The resulting SMART‐C booklet included 6 weeks of dietary goal setting, with weekly behavioural contract and review.
Conclusion
This paper details the development of the theory‐ and evidence‐informed SMART‐C intervention. This is the first report of the Behaviour Change Wheel being used to design an add‐on tool to enhance existing weight loss services. The process benefitted from a further checking stage with stakeholders.
Significance Common features have been observed in the genome sequences of bacterial pathogens that infect few hosts. These “host adaptations” include the acquisition of pathogenicity islands of ...multiple genes involved in disease, losses of whole genes, and even single mutations that affect gene function. Within Salmonella enterica is a natural model system of four pathogens that are each other’s closest relatives, including a host-generalist, two host-specialists, and one with strong host associations. With whole-genome sequences, we aimed to improve our understanding of the number, nature, and order of these host adaptation events, shedding light on how human and animal pathogens arose in the past, and potentially allowing us to predict how emerging pathogens will evolve in the future.
Many bacterial pathogens are specialized, infecting one or few hosts, and this is often associated with more acute disease presentation. Specific genomes show markers of this specialization, which often reflect a balance between gene acquisition and functional gene loss. Within Salmonella enterica subspecies enterica , a single lineage exists that includes human and animal pathogens adapted to cause infection in different hosts, including S. enterica serovar Enteritidis (multiple hosts), S. Gallinarum (birds), and S. Dublin (cattle). This provides an excellent evolutionary context in which differences between these pathogen genomes can be related to host range. Genome sequences were obtained from ∼60 isolates selected to represent the known diversity of this lineage. Examination and comparison of the clades within the phylogeny of this lineage revealed signs of host restriction as well as evolutionary events that mark a path to host generalism. We have identified the nature and order of events for both evolutionary trajectories. The impact of functional gene loss was predicted based upon position within metabolic pathways and confirmed with phenotyping assays. The structure of S. Enteritidis is more complex than previously known, as a second clade of S. Enteritidis was revealed that is distinct from those commonly seen to cause disease in humans or animals, and that is more closely related to S. Gallinarum. Isolates from this second clade were tested in a chick model of infection and exhibited a reduced colonization phenotype, which we postulate represents an intermediate stage in pathogen–host adaptation.
Chickens, pigs, and cattle are key reservoirs of Salmonella enterica, a foodborne pathogen of worldwide importance. Though a decade has elapsed since publication of the first Salmonella genome, ...thousands of genes remain of hypothetical or unknown function, and the basis of colonization of reservoir hosts is ill-defined. Moreover, previous surveys of the role of Salmonella genes in vivo have focused on systemic virulence in murine typhoid models, and the genetic basis of intestinal persistence and thus zoonotic transmission have received little study. We therefore screened pools of random insertion mutants of S. enterica serovar Typhimurium in chickens, pigs, and cattle by transposon-directed insertion-site sequencing (TraDIS). The identity and relative fitness in each host of 7,702 mutants was simultaneously assigned by massively parallel sequencing of transposon-flanking regions. Phenotypes were assigned to 2,715 different genes, providing a phenotype-genotype map of unprecedented resolution. The data are self-consistent in that multiple independent mutations in a given gene or pathway were observed to exert a similar fitness cost. Phenotypes were further validated by screening defined null mutants in chickens. Our data indicate that a core set of genes is required for infection of all three host species, and smaller sets of genes may mediate persistence in specific hosts. By assigning roles to thousands of Salmonella genes in key reservoir hosts, our data facilitate systems approaches to understand pathogenesis and the rational design of novel cross-protective vaccines and inhibitors. Moreover, by simultaneously assigning the genotype and phenotype of over 90% of mutants screened in complex pools, our data establish TraDIS as a powerful tool to apply rich functional annotation to microbial genomes with minimal animal use.
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