Treating individuals with a number of persistent problems: a relentless problem.
 Promoter-anchored chromatin interactions (PAIs) play a pivotal role in transcriptional regulation. Current high-throughput technologies for detecting PAIs, such as promoter capture Hi-C, are not scalable to large cohorts. Here, we present an analytical approach that uses summary-level data from cohort-based DNA methylation (DNAm) quantitative trait locus (mQTL) studies to predict PAIs. Using mQTL data from human peripheral blood ([Formula see text]), we predict 34,797 PAIs which show strong overlap with the chromatin contacts identified by previous experimental assays. The promoter-interacting DNAm sites are enriched in enhancers or near expression QTLs. Genes whose promoters are involved in PAIs are more actively expressed, and gene pairs with promoter-promoter interactions are enriched for co-expression.  https://www.selleckchem.com/products/usp22i-s02.html  Integration of the predicted PAIs with GWAS data highlight interactions among 601 DNAm sites associated with 15 complex traits. This study demonstrates the use of mQTL data to predict PAIs and provides insights into the role of PAIs in complex trait variation.INTRODUCTION For war-injured refugees, spinal cord injury (SCI) is a leading cause of catastrophic neurologic injury and literature focused on the care of this vulnerable population is sparse. This case series describes the unique challenges presented to an outpatient interdisciplinary rehabilitation team in providing SCI care in the USA for refugees who suffered their SCI in their home countries. CASE PRESENTATION Our interdisciplinary rehabilitation team faced challenges related to language, cultural and educational barriers which impacted the typical standard rehabilitation care offered to these individuals. Many of the individuals were focused on curative treatments. As such, managing expectations and educating individuals to rehabilitation practices for chronic SCI and lack of curative treatments for associated medical complications affected the provision of care across all disciplines of the rehabilitation team. DISCUSSION This case series showcases the challenges of caring for international refugees with SCI. The care offered to these individuals highlights the benefits that an interdisciplinary SCI rehabilitation approach can provide to comprehensively care for this vulnerable population.INTRODUCTION Ecstasy is a commonly used party drug and is the second most popular drug after marijuana among youngsters. Serious health hazards have been described including cardiac diseases, neurological complications, multi-organ failure, and even death. Spinal cord injury/dysfunction (SCI/D) is rarely described as a result of ecstasy ingestion. CASE PRESENTATION We present a case of a 19-year-old male patient who was admitted to our rehabilitation center, after developing a T11 AIS B SCI/D following recreational use of ecstasy. DISCUSSION In our case magnetic resonance imaging was inconclusive due to artifacts caused by metallic rods used for surgical scoliosis treatment in the past. This individual received no surgical or pharmacological treatments; however, it is questionable whether any specific treatments would have been beneficial. Ecstasy ingestion leads to a serotonin surge and induces microvascular changes. Neurovascular hemorrhage, subarachnoid hemorrhage, de novo aneurysm formation, and subsequent rupture can occur. 5-hydroxytryptamine, which comes from serotonergic terminals, is a very potent vasoconstrictive amine and can thus lead to prolonged vasoconstriction and ischemia. It is most likely that the SCI/D in our case is the result of an ischemic event following the vasoconstrictive effects of ecstasy ingestion. It is important to stress the possible consequences of recreational ecstasy usage and in unexplained SCI/D, one should consider the possibility of drug-related causes.Genome-wide association studies on bipolar disorders (BD) have revealed an additive polygenic contribution of common single-nucleotide polymorphisms (SNPs). However, these SNPs explain only 25% of the overall genetic variance and suggest a role of rare variants in BD vulnerability. Here, we combined high-throughput genotyping data and whole-exome sequencing in cohorts of individuals with BD as well as in multiplex families with a high density of affected individuals in order to determine the contribution of both common and rare variants to BD genetic vulnerability. Using polygenic risk scores (PRS), we showed a strong contribution of common polymorphisms previously associated with BD and schizophrenia (SZ) and noticed that those specifically associated with SZ contributed more in familial forms of BD than in non-familial ones. The analysis of rare damaging variants shared by affected individuals in multiplex families with BD revealed a single interaction network enriched in neuronal and developmental biological pathways, as well as in the regulation of gene expression. We identified four genes with a higher mutation rate in individuals with BD than in the general population and showed that mutations in two of them were associated with specific clinical manifestations. In addition, we showed a significant negative correlation between PRS and the number of rare damaging variants specifically in unaffected individuals of multiplex families. Altogether, our results suggest that common and rare genetic variants both contribute to the familial aggregation of BD and this genetic architecture may explain the heterogeneity of clinical manifestations in multiplex families.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Goal-directed behavior requires the representation of a task-set that defines the task-relevance of stimuli and guides stimulus-action mappings.  https://www.selleckchem.com/products/usp22i-s02.html  Past experience provides one source of knowledge about likely task demands in the present, with learning enabling future predictions about anticipated demands. We examine whether spatial contexts serve to cue retrieval of associated task demands (e.g., context A and B probabilistically cue retrieval of task demands X and Y, respectively), and the role of the hippocampus and dorsolateral prefrontal cortex (dlPFC) in mediating such retrieval. Using 3D virtual environments, we induce context-task demand probabilistic associations and find that learned associations affect goal-directed behavior. Concurrent fMRI data reveal that, upon entering a context, differences between hippocampal representations of contexts (i.e., neural pattern separability) predict proactive retrieval of the probabilistically dominant associated task demand, which is reinstated in dlPFC. These findings reveal how hippocampal-prefrontal interactions support memory-guided cognitive control and adaptive behavior.