Histories of Social Functioning and Mental Healthcare in Severely Dysfunctional Dual-Diagnosis Psychiatric Patients

Abstract Disengagement from mental health services is a major obstacle to the treatment of homeless dual-diagnosis patients (i.e., those with severe mental illness and substance-use disorder). A subgroup of these patients is considered to be treatment resistant and we aim to explore whether patients’ reasons for disengagement may stem from negative experiences in their lives and treatment histories. This retrospective, explorative study examined the medical files of 183 severely dysfunctional dual-diagnosis patients who had been admitted involuntarily to a new specialized clinic for long-term treatment. Most patients shared common negative experiences with respect to childhood adversities, low school achievement, high levels of unemployment, discontinuity of care, and problems with the judicial system. The lifetime histories of treatment-resistant, severely dysfunctional dual-diagnosis patients showed a common pattern of difficulties that may have contributed to treatment resistance and disengagement from services. If these adversities are targeted, disengagement may be prevented and outcome improved

Health and Its Relationship with Residential Relocations of Older People to Institutions versus to Independent Dwellings

Research into older people's relocations to independent dwellings has largely remained separate from research into moves to institutions. Yet, both types of moves could be a response to health problems and to a certain extent they could be substitutes for each other. Using Litwak and Longino's model of moves of older people, this study assesses the extent to which three commonly used health measures (limitations in activities of daily living [ADL], self-rated health, and the prevalence of [limiting] chronic conditions) predict older people's moves to subsidized care institutions and elsewhere, in one multinomial logistic regression model. The data were derived from the POLS survey for the Netherlands (N=8306) enriched with administrative data on subsequent moves. In line with Litwak and Longino's model, the findings indicate that older people's moves to institutions were more likely among those with more severe health problems, whereas moves elsewhere were more likely among those with moderate health problems. Among the three investigated health measures, limitations in ADL had the strongest predictive value, and was the only one for which the difference in effect between relocations to care institutions and relocations elsewhere was statistically significant

A randomized controlled study of a social skills training for preadolescent children with autism spectrum disorders:generalization of skills by training parents and teachers?

Background: Social skills training (SST) is a common intervention for children with autism spectrum disorders (ASDs) to improve their social and communication skills. Despite the fact that SSTs are often applied in clinical practice, the evidence for the effectiveness of these trainings for children with ASD is inconclusive. Moreover, long term outcome and generalization of learned skills are little evaluated. Additionally, there is no research on the influence of involvement of parents and teachers on effectiveness of SST and on the generalization of learned social skills to daily life. We expect parent and teacher involvement in SST to enhance treatment efficacy and to facilitate generalization of learned skills to daily life. Method/Design: In a randomized controlled trial (RCT) with three conditions, 120 participants with ASD at the end of primary school (10-12 years of calendar age) have been randomized to SST, SST-PTI SST with Parent & Teacher Involvement), or care-as-usual. The SST consists of 18 group sessions of 1.5 hours for the children. In the SST-PTI condition, parents additionally participate in 8 parent sessions and parents and teachers are actively involved in homework assignments. Assessment takes place at three moments: before and immediately after the intervention period and at 6 months follow-up. Primary outcome is socialization, as an aspect of adaptive functioning. Secondary outcomes focus on specific social skills children learn during SST and on more general social skills pertaining to home and community settings from a multi informant perspective. Additionally, possible predictors of treatment outcome will be assessed. Discussion: The current study is an RCT study evaluating SST in a large sample of Dutch children with ASD in a specific age range (10-12 years). Strengths of the study are the use of one manualized protocol, application of standardized and internationally used rating instruments, use of multiple raters, investigation of generalization of learned skills to daily life, and the evaluation of efficacy in the longer term by follow-up measures at 6 months after the end of training

The interobserver and test-retest variability of the dysphonia severity index

Objective: The purpose of this study was to investigate the interobserver variability and the test-retest variability of the Dysphonia Severity Index (DSI), a multiparametric instrument to assess voice quality. Methods: The DSI was measured in 30 nonsmoking volunteers without voice complaints or voice disorders by two speech pathologists. The subjects were measured on 3 different days, with an interval of 1 week. Results: The difference in DSI between two observers (interobserver difference) was not significant. The intraclass correlation coefficient for the DSI was 0.79. The standard deviation of the difference between two duplicate measurements by different observers was 1.27. Conclusion: Differences in measurements between different observers were not significant. The intraclass correlation coefficient of the DSI was 0.79, which is to be considered good. Differences in DSI within one patient need to be larger than 2.49 to be significant. Copyrigh

Clinical and genetic aspects of bicuspid aortic valve:a proposed model for family screening based on a review of literature

Bicuspid aortic valve (BAV) is the most common congenital cardiac defect causing serious morbidity including valvular dysfunction and thoracic aortic aneurysms (TAA) in around 30% of BAV patients. Cardiological screening of first-degree relatives is advised in recent guidelines given the observed familial clustering of BAV. However, guidelines regarding screening of family members and DNA testing are not unequivocal. The aim of this review is to provide an overview of the literature on echocardiographic screening in first-degree relatives of BAV patients and to propose a model for family screening. In addition, we provide a flowchart for DNA testing. We performed a PubMed search and included studies providing data on echocardiographic screening in asymptomatic relatives of BAV patients. Nine studies were included. In 5.8-47.4% of the families BAV was shown to be familial. Of the screened first-degree relatives 1.8-11% was found to be affected with BAV. Results regarding a potential risk of TAA in first-degree relatives with a tricuspid aortic valve (TAV) were conflicting. The reported familial clustering of BAV underlines the importance of cardiological screening in relatives. After reviewing the available family history, patient characteristics and the results of cardiological screening in relatives, follow-up in relatives with a TAV and/or DNA testing may be advised in a subset of families. In this study we propose a model for the clinical and genetic work-up in BAV families, based on the most extensive literature review on family screening performed until now

Liver Monocytes and Kupffer Cells Remain Transcriptionally Distinct during Chronic Viral Infection

Due to the scarcity of immunocompetent animal models for chronic viral hepatitis, little is known about the role of the innate intrahepatic immune system during viral replication in the liver. These insights are however fundamental for the understanding of the inappropriate adaptive immune responses during the chronic phase of the infection. We apply the Lymphocytic Choriomenigitis Virus (LCMV) clone 13 mouse model to examine chronic virus-host interactions of Kupffer cells (KC) and infiltrating monocytes (IM) in an infected liver. LCMV infection induced overt clinical hepatitis, with rise in ALT and serum cytokines, and increased intrahepatic F4/80 expression. Despite ongoing viral replication, whole liver transcriptome showed baseline expression levels of inflammatory cytokines, interferons, and interferon induced genes during the chronic infection phase. Transcriptome analyses of sorted KC and IMs using NanoString technology revealed two unique phenotypes with only minimal overlap. At the chronic viral infection phase, KC showed no increased transcription of activation markers Cd80 and Cd86, but an increased expression of genes related to antigen presentation, whereas monocytes were more activated and expressed higher levels of Tnf transcripts. Although both KCs and intrahepatic IM share the surface markers F4/80 and CD11b, their transcriptomes point towards distinctive roles during virus-induced chronic hepatitis

A Polymorphism in the Splice Donor Site of ZNF419 Results in the Novel Renal Cell Carcinoma-Associated Minor Histocompatibility Antigen ZAPHIR

Nonmyeloablative allogeneic stem cell transplantation (SCT) can induce remission in patients with renal cell carcinoma (RCC), but this graft-versus-tumor (GVT) effect is often accompanied by graft-versus-host disease (GVHD). Here, we evaluated minor histocompatibility antigen (MiHA)-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI). One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT

Appetite-regulating hormone trajectories and relationships with fat mass development in term-born infants during the first 6 months of life

BACKGROUND: The first 6 months of life are a critical window for adiposity programming. Appetite-regulating hormones (ARH) are involved in food intake regulation and might, therefore, play a role in adiposity programming. Studies examining ARH in early life are limited. PURPOSE: To investigate ghrelin, peptide YY (PYY) and leptin until 6 months and associations with fat mass percentage (FM%), infant feeding and human milk macronutrients. PROCEDURES: In 297 term-born infants (Sophia Pluto Cohort), ghrelin (acylated), PYY and leptin were determined at 3 and 6 months, with FM% measurement by PEAPOD. Exclusive breastfeeding (BF) was classified as BF ≥ 3 months. Human milk macronutrients were analyzed (MIRIS Human Milk Analyzer). MAIN FINDINGS: Ghrelin increased from 3 to 6 months (p < 0.001), while PYY decreased (p < 0.001), resulting in increasing ghrelin/PYY ratio. Leptin decreased. Leptin at 3 months was higher in girls, other ARH were similar between sexes. Leptin at 3 and 6 months correlated with FM% at both ages(R ≥ 0.321, p ≤ 0.001) and gain in FM% from 1 to 6 months(R ≥ 0.204, p = 0.001). In BF infants, also ghrelin and ghrelin/PYY ratio correlated with this gain in FM%. Exclusively BF infants had lower ghrelin and higher PYY compared to formula fed infants at 3 months (p ≤ 0.039). ARH did not correlate with macronutrients. CONCLUSIONS: Increasing ghrelin and decreasing PYY, thus increasing ghrelin/PYY ratio, suggests an increasing orexigenic drive until 6 months. ARH were different between BF and FF infants at 3 months, but did not correlate with human milk macronutrients. Ghrelin and leptin, but not PYY, correlated with more FM development during the first 6 months, suggesting that they might be involved in adiposity programming. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02533-z

Mucosal-associated invariant T-cell frequency and function in blood and liver of HCV mono- and HCV/HIV co-infected patients with advanced fibrosis

__Background & Aims:__ Mucosal-associated invariant T (MAIT) cells are important innate T cells with antimicrobial and immunoregulatory activity, recently found to be depleted in blood of patients with HIV and HCV mono-infections. In this study, we assessed the impact of HIV, HCV and HCV/HIV co-infection on circulating and intrahepatic MAIT-cells and correlations with liver fibrosis. __Methods:__ In this cross-sectional study, nine healthy subjects, nine HIV, 20 HCV and 22 HCV/HIV co-infected patients were included. Blood and liver fine needle aspirate biopsies were studied using flowcytometry for CD3+CD161+Vα7.2+ MAIT-cell frequency, phenotype and function in HCV mono-infected and HCV/HIV co-infected patients without or with mild fibrosis (Metavir-score F0-F1) or severe fibrosis to cirrhosis (Metavir-score F3-F4). __Results:__ Circulating MAIT-cells were decreased in blood of HCV, HIV and HCV/HIV patients with F0-F1. In HCV/HIV co-infected individuals with severe fibrosis to cirrhosis, the frequency of circulating MAIT-cells was even further depleted, whereas their function was comparable to HCV/HIV co-infected patients with low or absent fibrosis. In contrast, in HCV mono-infected patients, MAIT-cell frequencies were not related to fibrosis severity; however, MAIT-cell function was impaired in mono-infected patients with more fibrosis. More advanced liver fibrosis in HCV or HCV/HIV-infected patients was not reflected by increased accumulation of MAIT-cells in the affected liver. __Conclusions:__ Severe liver fibrosis is associated with dysfunctional MAIT-cells in blood of HCV mono-infected patients, and lower MAIT frequencies in blood of HCV/HIV co-infected patients, without evidence for accumulation in the liver