Altered inflammatory mucosal signatures within their spatial and cellular context during active ileal Crohn's disease.

Crohn's disease (CD) involves a complex intestinal microenvironment driven by chronic inflammation. While single-cell RNA sequencing has provided valuable insights into this biology, the spatial context is lost during single-cell preparation of mucosal biopsies. To deepen our understanding of the distinct inflammatory signatures of CD and overcome the limitations of single-cell RNA sequencing, we combined spatial transcriptomics of frozen CD surgical tissue sections with single-cell transcriptomics of ileal CD mucosa.

PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells.

Background: The prostaglandin receptor PTGER4 facilitates homeostasis in the gut. Previous reports indicate that goblet cells, marked by SPINK4 expression, might be affected by PTGER4 activity. Current evidence suggests that prostaglandin E2 (PGE2) produced by mesenchymal stromal cells (MSC) stimulates PTGER4 in epithelial cells during inflammatory conditions.

Exploring Funeral Directors' Experience and Perceived Impact of Providing Funeral Services During COVID-19 Restrictions.

The importance of ritual/ceremony following bereavement is well documented, however restrictions during the COVID-19 pandemic impacted the freedom to bury loved ones according to beliefs/traditions. This study explores the experiences of staff providing funeral services during COVID-19 and considers the implications for supporting bereaved families. Fifty-eight staff (male, 72.

Concordant B and T Cell Heterogeneity Inferred from the Multiomic Landscape of Peripheral Blood Mononuclear Cells in a Crohn's Disease Cohort.

Background And Aims: Crohn's disease is characterized by inflammation in the gastrointestinal tract due to a combination of genetic, immune, and environmental factors. Transcriptomic and epigenomic profiling of intestinal tissue of Crohn's disease patients have revealed valuable insights into pathology, however have not been conducted jointly on less invasive peripheral blood mononuclear cells (PBMCs). Furthermore, the heterogeneous responses to treatments among individuals with Crohn's disease imply hidden diversity of pathological mechanisms.

Assessing Cellular and Transcriptional Diversity of Ileal Mucosa Among Treatment-Naïve and Treated Crohn's Disease.

Background: Crohn's disease is a lifelong disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn's.

Methods: Ileal biopsies were obtained from (1) control subjects (n = 6), (2) treatment-naïve patients (n = 7), and (3) established (n = 14) Crohn's patients along with remission (n = 3) and refractory (n = 11) treatment groups.

How can we know what we don't know? An exploration of professionals' engagement with complicated grief.

Objective: Research has shown that complicated grief has the potential to adversely affect bereaved individuals, and in this context, understanding how mental health professionals engage with it in practice is of relevance. Gaining an understanding of professionals' knowledge, attitudes, skills and training in relation to complicated grief could provide insights that will inform their training and professional development. The aim of this study was to consider professionals' engagement with complicated grief, as represented by self-reported knowledge, attitudes, skills and training.

Ileal Derived Organoids From Crohn's Disease Patients Show Unique Transcriptomic and Secretomic Signatures.

Background & Aims: We used patient-derived organoids (PDOs) to study the epithelial-specific transcriptional and secretome signatures of the ileum during Crohn's disease (CD) with varying phenotypes to screen for disease profiles and potential druggable targets.

Methods: RNA sequencing was performed on isolated intestinal crypts and 3-week-old PDOs derived from ileal biopsies of CD patients (n = 8 B1, inflammatory; n = 8 B2, stricturing disease) and non-inflammatory bowel disease (IBD) controls (n = 13). Differentially expressed (DE) genes were identified by comparing CD vs control, B1 vs B2, and inflamed vs non-inflamed.

Site- and Taxa-Specific Disease-Associated Oral Microbial Structures Distinguish Inflammatory Bowel Diseases.

Background: The gut and oral microbiome have independently been shown to be associated with inflammatory bowel disease (IBD). However, it is not known to what extent gut and oral microbial disease markers converge in terms of their composition in IBD. Further, the spatial and temporal variation within the oral microenvironments of IBD remain to be elucidated.

Complicated grief knowledge and practice: a qualitative study of general practitioners in Ireland.

Objective: Complicated grief is a debilitating condition that individuals may experience after losing a loved one. General practitioners (GPs) are well positioned to provide patients with support for grief-related issues. Traditionally, Irish GPs play an important role in providing patients with emotional support regarding bereavement.

Complicated grief knowledge, attitudes, skills, and training among mental health professionals: A qualitative exploration.

The knowledge, attitudes, skills, and training of professionals regarding complicated grief influence their practice. We conducted 30 semi-structured interviews with psychiatrists, psychologists, and counselor/psychotherapists; the preliminary findings were contextualized via interviews with three experts in complicated grief research/practice. Findings suggest that professionals did not substantially rely on research evidence, favoring instead personal and professional knowledge.

Neutrophil GM-CSF signaling in inflammatory bowel disease patients is influenced by non-coding genetic variants.

Neutrophil dysfunction and GM-CSF auto-antibodies are observed in pediatric and adult patients with Crohn's disease (CD). We associated damaging coding variants with low GM-CSF induced STAT5 stimulation index (GMSI) in pediatric CD patients and implicated variation of neutrophil GM-CSF signaling in cell function and disease complications. Because many CD patients with low GMSI do not carry damaging coding mutations, we sought to test the hypothesis that non-coding variants contribute to this phenotype.

Psychiatrists', psychologists' and counselors' attitudes regarding complicated grief.

Background: Complicated grief encompasses various presentations where aspects of grief do not become integrated into the bereaved person's life. Professionals' attitudes to complicated grief may impact how they engage with bereaved patients/clients. The aim of this study was to empirically examine the attitudes of mental health professionals, specifically psychologists, psychiatrists and counselor/psychotherapists, regarding complicated grief and to investigate any between profession-differences.

Genetic and Transcriptomic Variation Linked to Neutrophil Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Pediatric Crohn's Disease.

Background: Granulocyte-macrophage colony-stimulating factor auto-antibodies (GMAbs) suppress neutrophil-extrinsic GM-CSF signaling and increase risk for stricturing behavior in Crohn's disease (CD). We aimed to define clinical, genomic, and functional associations with neutrophil-intrinsic GM-CSF signaling.

Methods: Missense mutations in CSF2RA, CSF2RB, JAK2, STAT5A, and STAT5B were identified using whole-exome sequencing in 543 pediatric inflammatory bowel disease (IBD) patients.

Genetic variants and pathways implicated in a pediatric inflammatory bowel disease cohort.

In the United States, approximately 5% of individuals with inflammatory bowel disease (IBD) are younger than 20 years old. Studies of pediatric cohorts can provide unique insights into genetic architecture of IBD, which includes Crohn's disease (CD) and ulcerative colitis (UC). Large genome-wide association studies have found more than 200 IBD-associated loci but explain a minority of disease variance for CD and UC.

Clinical and Genomic Correlates of Neutrophil Reactive Oxygen Species Production in Pediatric Patients With Crohn's Disease.

Background & Aims: Individuals with monogenic disorders of phagocyte function develop chronic colitis that resembles Crohn's disease (CD). We tested for associations between mutations in genes encoding reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, neutrophil function, and phenotypes of CD in pediatric patients.

Methods: We performed whole-exome sequence analysis to identify mutations in genes encoding NADPH oxidases (such as CYBA, CYBB, NCF1, NCF2, NCF4, RAC1, and RAC2) using DNA from 543 pediatric patients with inflammatory bowel diseases.

Complicated grief: Knowledge, attitudes, skills and training of mental health professionals: A systematic review.

Objective: A systematic review and qualitative synthesis was undertaken to deduce the knowledge, attitudes, skills and training of mental health professionals regarding complicated grief (CG).

Methods: PsychInfo, Embase, Medline, CINAHL, PBSC, Web of Science and ERIC databases were used to identify relevant literature. Searches were executed from inception to September 2014.

Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome 7q11.23 is associated with schizophrenia.

Background: Several copy number variants (CNVs) have been implicated as susceptibility factors for schizophrenia (SZ). Some of these same CNVs also increase risk for autism spectrum disorders, suggesting an etiologic overlap between these conditions. Recently, de novo duplications of a region on chromosome 7q11.

Diverse mutational mechanisms cause pathogenic subtelomeric rearrangements.

Chromosome rearrangements are a significant cause of intellectual disability and birth defects. Subtelomeric rearrangements, including deletions, duplications and translocations of chromosome ends, were first discovered over 40 years ago and are now recognized as being responsible for several genetic syndromes. Unlike the deletions and duplications that cause some genomic disorders, subtelomeric rearrangements do not typically have recurrent breakpoints and involve many different chromosome ends.

Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population.

The Ashkenazi Jewish (AJ) population has long been viewed as a genetic isolate, yet it is still unclear how population bottlenecks, admixture, or positive selection contribute to its genetic structure. Here we analyzed a large AJ cohort and found higher linkage disequilibrium (LD) and identity-by-descent relative to Europeans, as expected for an isolate. However, paradoxically we also found higher genetic diversity, a sign of an older or more admixed population but not of a long-term isolate.

Microdeletions of 3q29 confer high risk for schizophrenia.

Schizophrenia (SZ) is a severe psychiatric illness that affects approximately 1% of the population and has a strong genetic underpinning. Recently, genome-wide analysis of copy-number variation (CNV) has implicated rare and de novo events as important in SZ. Here, we report a genome-wide analysis of 245 SZ cases and 490 controls, all of Ashkenazi Jewish descent.