Personal Recovery in People With a Psychotic Disorder:A Systematic Review and Meta-Analysis of Associated Factors

Background: Personal recovery (PR) is a subjective, multidimensional concept, and quantitative research using PR as an outcome is rapidly increasing. This systematic review is intended to support the design of interventions that contribute to PR in psychotic disorders, by providing an overview of associated factors and their weighted importance to PR: clinical factors, social factors, and socio-demographic characteristics are included, and factors related to the concept of PR (organized into CHIME dimensions). Methods: A systematic literature search was conducted from inception to March 2020. Quantitative studies that had used a validated questionnaire assessing the concept of PR were included. Mean effect sizes for the relationship between PR-scale total scores and related factors were calculated using meta-analyses. Sources of heterogeneity were examined using meta-regression tests. Results: Forty-six studies, that used (a total of) eight PR measures, showed that in clinical factors, affective symptoms had a medium negative association with PR-scale total scores (r = −0.44, 95%CI −0.50 to −0.37), while positive, negative and general symptoms had small negative correlations. No association was found with neuro-cognition. Social factors (support, work and housing, and functioning) showed small positive correlations. Gender and age differences had barely been researched. Large associations were found for PR-scale total scores with the CHIME dimensions hope (r = 0.56, 95%CI 0.48–0.63), meaning in life (r = 0.48, 95%CI 0.38–0.58) and empowerment (r = 0.53, 95%CI 0.42–0.63); while medium associations were found with connectedness (r = 0.34, 95%CI 0.43–0.65) and identity (r = 0.43, 95%CI 0.35–0.50). Levels of heterogeneity were high, sources included: the variety of PR measures, variations in sample characteristics, publication bias, variations in outcome measures, and cultural differences. Discussion: Most interventions in mental healthcare aim to reduce symptoms and improve functioning. With regard to stimulating PR, these interventions may benefit from also focusing on enhancing hope, empowerment, and meaning in life. The strength of these findings is limited by the challenges of comparing separate CHIME dimensions with questionnaires assessing the concept of PR, and by the high levels of heterogeneity observed. Future research should focus on the interaction between elements of PR and clinical and social factors over time

Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic

Introduction Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes. Research design and methods We performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes >= 18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown. Results In total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: -0.39% (-4.3 mmol/mol) (p<0.0001 and type 2 diabetes: -0.62% (-6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001). Conclusions An increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.Diabetes mellitus: pathophysiological changes and therap

Genetically Programmed Differences in Epidermal Host Defense between Psoriasis and Atopic Dermatitis Patients

In the past decades, chronic inflammatory diseases such as psoriasis, atopic dermatitis, asthma, Crohn’s disease and celiac disease were generally regarded as immune-mediated conditions involving activated T-cells and proinflammatory cytokines produced by these cells. This paradigm has recently been challenged by the finding that mutations and polymorphisms in epithelium-expressed genes involved in physical barrier function or innate immunity, are risk factors of these conditions. We used a functional genomics approach to analyze cultured keratinocytes from patients with psoriasis or atopic dermatitis and healthy controls. First passage primary cells derived from non-lesional skin were stimulated with pro-inflammatory cytokines, and expression of a panel of 55 genes associated with epidermal differentiation and cutaneous inflammation was measured by quantitative PCR. A subset of these genes was analyzed at the protein level. Using cluster analysis and multivariate analysis of variance we identified groups of genes that were differentially expressed, and could, depending on the stimulus, provide a disease-specific gene expression signature. We found particularly large differences in expression levels of innate immunity genes between keratinocytes from psoriasis patients and atopic dermatitis patients. Our findings indicate that cell-autonomous differences exist between cultured keratinocytes of psoriasis and atopic dermatitis patients, which we interpret to be genetically determined. We hypothesize that polymorphisms of innate immunity genes both with signaling and effector functions are coadapted, each with balancing advantages and disadvantages. In the case of psoriasis, high expression levels of antimicrobial proteins genes putatively confer increased protection against microbial infection, but the biological cost could be a beneficial system gone awry, leading to overt inflammatory disease

Apilimod Inhibits the Production of IL-12 and IL-23 and Reduces Dendritic Cell Infiltration in Psoriasis

Psoriasis is characterized by hyperplasia of the epidermis and infiltration of leukocytes into both the dermis and epidermis. IL-23, a key cytokine that induces TH17 cells, has been found to play a critical role in the pathogenesis of psoriasis. Apilimod is a small-molecule compound that selectively suppresses synthesis of IL-12 and IL-23. An open-label clinical study of oral administration of apilimod was conducted in patients with psoriasis. Substantial improvements in histology and clinical measurements were observed in patients receiving 70mg QD. The expression of IL-23p19 and IL-12/IL-23p40 in skin lesions was significantly reduced in this dose group, with a simultaneous increase in IL-10 observed. A decrease in the levels of TH1 and TH17 cytokines/chemokines in skin lesions followed these p19 and p40 changes. In parallel, a reduction in skin-infiltrating CD11c+ dendritic cells and CD3+ T cells was seen, with a greater decrease in the CD11c+ population. This was accompanied by increases in T and B cells, and decreases in neutrophils and eosinophils in the periphery. This study demonstrates the immunomodulatory activity of apilimod and provides clinical evidence supporting the inhibition of IL-12/IL-23 synthesis for the treatment of TH1- and TH17-mediated inflammatory diseases

Msb2 Shedding Protects Candida albicans against Antimicrobial Peptides

Msb2 is a sensor protein in the plasma membrane of fungi. In the human fungal pathogen C. albicans Msb2 signals via the Cek1 MAP kinase pathway to maintain cell wall integrity and allow filamentous growth. Msb2 doubly epitope-tagged in its large extracellular and small cytoplasmic domain was efficiently cleaved during liquid and surface growth and the extracellular domain was almost quantitatively released into the growth medium. Msb2 cleavage was independent of proteases Sap9, Sap10 and Kex2. Secreted Msb2 was highly O-glycosylated by protein mannosyltransferases including Pmt1 resulting in an apparent molecular mass of >400 kDa. Deletion analyses revealed that the transmembrane region is required for Msb2 function, while the large N-terminal and the small cytoplasmic region function to downregulate Msb2 signaling or, respectively, allow its induction by tunicamycin. Purified extracellular Msb2 domain protected fungal and bacterial cells effectively from antimicrobial peptides (AMPs) histatin-5 and LL-37. AMP inactivation was not due to degradation but depended on the quantity and length of the Msb2 glycofragment. C. albicans msb2 mutants were supersensitive to LL-37 but not histatin-5, suggesting that secreted rather than cell-associated Msb2 determines AMP protection. Thus, in addition to its sensor function Msb2 has a second activity because shedding of its glycofragment generates AMP quorum resistance

UP's: A cohort study on recovery in psychotic disorder patients : Design protocol

Recovery is a multidimensional concept, including symptomatic, functional, social, as well as personal recovery. The present study aims at exploring psychosocial and biological determinants of personal recovery, and disentangling time-dependent relationships between personal recovery and the other domains of recovery in a sample of people with a psychotic disorder. A cohort study is conducted with a 10-year follow-up. Personal recovery is assessed using the Recovering Quality of Life Questionnaire (ReQoL) and the Individual Recovery Outcomes Counter (I.ROC). Other domains of recovery are assessed by the Positive and Negative Symptom Scale Remission (PANSS-R), the BRIEF-A and the Social Role Participation Questionnaire—Short version (SRPQ) to assess symptomatic, functional and societal recovery, respectively. In addition, multiple biological, psychological, and social determinants are assessed. This study aims to assess the course of personal recovery, and to find determinants and time-dependent relationships with symptomatic, functional and societal recovery in people with a psychotic disorder. Strengths of the study are the large number of participants, long duration of follow-up, multiple assessments over time, extending beyond the treatment trajectory, and the use of a broad range of biological, psychological, and social determinants

Establishment of the epithelial-specific transcriptome of normal and malignant human breast cells based on MPSS and array expression data

INTRODUCTION: Diverse microarray and sequencing technologies have been widely used to characterise the molecular changes in malignant epithelial cells in breast cancers. Such gene expression studies to identify markers and targets in tumour cells are, however, compromised by the cellular heterogeneity of solid breast tumours and by the lack of appropriate counterparts representing normal breast epithelial cells. METHODS: Malignant neoplastic epithelial cells from primary breast cancers and luminal and myoepithelial cells isolated from normal human breast tissue were isolated by immunomagnetic separation methods. Pools of RNA from highly enriched preparations of these cell types were subjected to expression profiling using massively parallel signature sequencing (MPSS) and four different genome wide microarray platforms. Functional related transcripts of the differential tumour epithelial transcriptome were used for gene set enrichment analysis to identify enrichment of luminal and myoepithelial type genes. Clinical pathological validation of a small number of genes was performed on tissue microarrays. RESULTS: MPSS identified 6,553 differentially expressed genes between the pool of normal luminal cells and that of primary tumours substantially enriched for epithelial cells, of which 98% were represented and 60% were confirmed by microarray profiling. Significant expression level changes between these two samples detected only by microarray technology were shown by 4,149 transcripts, resulting in a combined differential tumour epithelial transcriptome of 8,051 genes. Microarray gene signatures identified a comprehensive list of 907 and 955 transcripts whose expression differed between luminal epithelial cells and myoepithelial cells, respectively. Functional annotation and gene set enrichment analysis highlighted a group of genes related to skeletal development that were associated with the myoepithelial/basal cells and upregulated in the tumour sample. One of the most highly overexpressed genes in this category, that encoding periostin, was analysed immunohistochemically on breast cancer tissue microarrays and its expression in neoplastic cells correlated with poor outcome in a cohort of poor prognosis estrogen receptor-positive tumours. CONCLUSION: Using highly enriched cell populations in combination with multiplatform gene expression profiling studies, a comprehensive analysis of molecular changes between the normal and malignant breast tissue was established. This study provides a basis for the identification of novel and potentially important targets for diagnosis, prognosis and therapy in breast cancer