To disclose or not? Children’s tendency to disclose peer victimisation in elementary school

This study aimed to shed light on the prevalence of chronic peer victimisation among Dutch elementary school children and factors associated with (non-)disclosure of such experiences by victims. 5,961 students from 73 schools participated (51.5% male; Mage 9.96; 77.7% native Dutch). Results showed that 12.3% of all children were victimised chronically, of which 29.4% did not disclose. Multilevel logistic regressions indicated that girls, older and native Dutch children were more likely to disclose. Moreover, experiencing depressive symptoms prompts disclosing victimisation. Anxiety, high emotion regulation skills, and perceptions of cohesion in the classroom were negatively associated with disclosure. The disclosure was not related to frequency or duration of victimisation, self-perceived social acceptance, self-worth, impulse control, or perceived classroom climate. Our study reveals information on the prevalence of peer victimisation and its disclosure, based on a nationwide study conducted in 2016–2017. It gives important insights into factors associated with disclosing victimisation experiences

The longitudinal link between popularity, likeability, fear of negative evaluation and social avoidance across adolescence

This study investigated the longitudinal bidirectional associations between likeability, popularity, fear of negative evaluation, and social avoidance, to aid in preventing the negative consequences and persistent trajectories of low social status and heightened social anxiety. In total, 1741 adolescents in grades 7–9 participated at 3 yearly waves. A self-report questionnaire measured fear of negative evaluation. Peer nominations assessed likeability, popularity, and social avoidance. Lower popularity predicted more avoidance, and vice versa. More avoidance was related to lower likeability over time. Being less popular and/or more liked by peers, increased fear of negative evaluation. Support for a transactional model between social anxiety and social status was found, but distinguishing different social status and social anxiety components is necessary

Does Being Defended Relate to Decreases in Victimization and Improved Psychosocial Adjustment Among Victims?

School bullying is a clear violation of children’s rights to a safe education and is a major concern among school professionals and parents. Many antibullying interventions focus on enhancing peer defending of victims to combat bullying and to promote victims’ psychosocial functioning. However, longitudinal studies on the effects of being defended on (a) diminishing victimization and (b) enhancing victims’ psychosocial adjustment are lacking, and the role of the broader peer context has been largely unexplored. Therefore, this study examined whether being defended decreases victimization and improves victims’ psychosocial adjustment, and whether defending peer norms moderate these effects. Data were derived from a nationwide Dutch study on the effectiveness of antibullying interventions, with N = 5,415 students (Mage = 9.93; 48.3% girls) from 238 classrooms (54.2% control classrooms) in 68 elementary schools. Findings indicate that victims with at least one defender at the start of the school year (Time 1) experienced higher feelings of belonging at the end of the school year (Time 2) compared with nondefended victims, but experienced lower feelings of belonging compared with nonvictims. Defended victims did not differ from nondefended victims in self-esteem, depressive symptoms, and severity of victimization at Time 2. Nonvictims were significantly better adjusted than defended and nondefended victims regarding these outcomes. Descriptive and popularity norms for defending did not moderate the links between being defended and victims’ adjustment and severity of victimization at Time 2. Thus, being defended only partly relieves victims’ plight, irrespective of how normative defending behaviors are in classrooms. </p

Functional investigation of two simultaneous or separately segregating DSP variants within a single family support the theory of a dose-dependent disease severity

Desmoplakin (DP) is an important component of desmosomes, essential in cell-cell connecting structures in stress-bearing tissues. Over many hundreds of pathogenic variants in DSP have been associated with different cutaneous and cardiac phenotypes or a combination, known as a cardiocutaneous syndrome. Of less than 5% of the reported DSP variants, the effect on the protein has been investigated. Here, we describe and have performed RNA, protein and tissue analysis in a large family where DSPc.273+5G>A/c.6687delA segregated with palmoplantar keratoderma (PPK), woolly hair and lethal cardiomyopathy, while DSPWT/c.6687delA segregated with PPK and milder cardiomyopathy. hiPSC-derived cardiomyocytes and primary keratinocytes from carriers were obtained for analysis. Unlike the previously reported nonsense variants in the last exon of DSP that bypassed the nonsense-mediated mRNA surveillance system leading to protein truncation, variant c.6687delA was shown to cause loss of protein expression. Patients carrying both variants and having a considerably more severe phenotype were shown to have 70% DP protein reduction, while patients carrying only c.6687delA had 50% protein reduction and a milder phenotype. Analysis of RNA from patient cells did not show any splicing effect of the c.273+5G>A variant. However, a minigene splicing assay clearly showed alternative spliced transcripts originating from this variant. This study shows the importance of RNA and protein analyses to pinpoint the exact effect of DSP variants instead of solely relying on predictions. In addition, the particular pattern of inheritance, with simultaneous or separately segregating DSP variants within the same family, strongly supports the theory of a dose-dependent disease severity

Three female patients with Danon disease presenting with predominant cardiac phenotype:a case series

Background: Danon disease is a rare X-linked multisystemic disorder that has primarily been described in male patients. Case summary: We present three female patients with Danon disease with a predominantly cardiac phenotype in whom disease onset and expression was very different from that of male patients. Case 1 was first admitted for acute heart failure and then readmitted a few months later for cardiac shock, necessitating mechanical support, and heart transplantation. Case 2 had complex arrhythmias for which many antiarrhythmic drugs were tried with only limited success. Her disease accelerated after her first pregnancy, and she showed reduced left ventricular function and dilated cardiomyopathy. Case 3 was referred for near syncope and ablated for an accessory pathway; she had extensive left ventricular hypertrophy. In all three cases, a final diagnosis of Danon disease was only made after genetic testing that identified a causal variant in the lysosome-associated membrane protein 2 gene. Discussion: Danon disease in female patients is a challenging diagnosis that may not be identified until genetic testing has been performed

Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution

Ex situ dual hypothermic oxygenated machine perfusion (DHOPE) and normothermic machine perfusion (NMP) of donor livers may have a complementary effect when applied sequentially. While DHOPE resuscitates the mitochondria and increases hepatic adenosine triphosphate (ATP) content, NMP enables hepatobiliary viability assessment prior to transplantation. In contrast to DHOPE, NMP requires a perfusion solution with an oxygen carrier, for which red blood cells (RBC) have been used in most series. RBC, however, have limitations and cannot be used cold. We, therefore, established a protocol of sequential DHOPE, controlled oxygenated rewarming (COR), and NMP using a new hemoglobin-based oxygen carrier (HBOC)-based perfusion fluid (DHOPE-COR-NMP trial, NTR5972). Seven livers from donation after circulatory death (DCD) donors, which were initially declined for transplantation nationwide, underwent DHOPE-COR-NMP. Livers were considered transplantable if perfusate pH and lactate normalized, bile production was >= 10 mL and biliary pH > 7.45 within 150 minutes of NMP. Based on these criteria five livers were transplanted. The primary endpoint, 3-month graft survival, was a 100%. In conclusion, sequential DHOPE-COR-NMP using an HBOC-based perfusion fluid offers a novel method of liver machine perfusion for combined resuscitation and viability testing of suboptimal livers prior to transplantation

Pesticide Exposure of Residents Living Close to Agricultural Fields in the Netherlands:Protocol for an Observational Study

Background: Application of pesticides in the vicinity of homes has caused concern regarding possible health effects in residents living nearby. However, the high spatiotemporal variation of pesticide levels and lack of knowledge regarding the contribution of exposure routes greatly complicates exposure assessment approaches. Objective: The objective of this paper was to describe the study protocol of a large exposure survey in the Netherlands assessing pesticide exposure of residents living close ( Methods: We performed an observational study involving residents living in the vicinity of agricultural fields and residents living more than 500 m away from any agricultural fields (control subjects). Residential exposures were measured both during a pesticide use period after a specific application and during the nonuse period for 7 and 2 days, respectively. We collected environmental samples (outdoor and indoor air, dust, and garden and field soils) and personal samples (urine and hand wipes). We also collected data on spraying applications as well as on home characteristics, participants' demographics, and food habits via questionnaires and diaries. Environmental samples were analyzed for 46 prioritized pesticides. Urine samples were analyzed for biomarkers of a subset of 5 pesticides. Alongside the field study, and by taking spray events and environmental data into account, we developed a modeling framework to estimate environmental exposure of residents to pesticides. Results: Our study was conducted between 2016 and 2019. We assessed 96 homes and 192 participants, including 7 growers and 28 control subjects. We followed 14 pesticide applications, applying 20 active ingredients. We collected 4416 samples: 1018 air, 445 dust (224 vacuumed floor, 221 doormat), 265 soil (238 garden, 27 fields), 2485 urine, 112 hand wipes, and 91 tank mixtures. Conclusions: To our knowledge, this is the first study on residents' exposure to pesticides addressing all major nondietary exposure sources and routes (air, soil, dust). Our protocol provides insights on used sampling techniques, the wealth of data collected, developed methods, modeling framework, and lessons learned. Resources and data are open for future collaborations on this important topic

Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-beta and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-beta were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8x10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients