Trust links citizens to the institutions intended to represent them and to one another. By reducing trust, crime has the potential to grind down social capital and become an obstacle to development. ...This paper analyzes the relationship between individual victimization and trust in Latin America using an empirical strategy that reduces both overt and hidden biases. Victimization significantly reduces vertical trust (in the local police) but has no robust effect on measures of horizontal trust. Governments need to reduce actual victimization but also rebuild trust in local public institutions to enhance the effectiveness of crime prevention efforts.
Our purpose was to elucidate the genotype and ophthalmological and audiological phenotype in TUBB4B-associated inherited retinal dystrophy (IRD) and sensorineural hearing loss (SNHL), and to model ...the effects of all possible amino acid substitutions at the hotspot codons Arg390 and Arg391. Six patients from five families with heterozygous missense variants in TUBB4B were included in this observational study. Ophthalmological testing included best-corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Audiological examination included pure-tone and speech audiometry in adult patients and auditory brainstem response testing in a child. Genetic testing was performed by disease gene panel analysis based on genome sequencing. The molecular consequences of the substitutions of residues 390 and 391 on TUBB4B and its interaction with α-tubulin were predicted in silico on its three-dimensional structure obtained by homology modelling. Two independent patients had amino acid exchanges at position 391 (p.(Arg391His) or p.(Arg391Cys)) of the TUBB4B protein. Both had a distinct IRD phenotype with peripheral round yellowish lesions with pigmented spots and mild or moderate SNHL, respectively. Yet the phenotype was milder with a sectorial pattern of bone spicules in one patient, likely due to a genetically confirmed mosaicism for p.(Arg391His). Three patients were heterozygous for an amino acid exchange at position 390 (p.(Arg390Gln) or p.(Arg390Trp)) and presented with another distinct retinal phenotype with well demarcated pericentral retinitis pigmentosa. All showed SNHL ranging from mild to severe. One additional patient showed a variant distinct from codon 390 or 391 (p.(Tyr310His)), and presented with congenital profound hearing loss and reduced responses in ERG. Variants at codon positions 390 and 391 were predicted to decrease the structural stability of TUBB4B and its complex with α-tubulin, as well as the complex affinity. In conclusion, the twofold larger reduction in heterodimer affinity exhibited by Arg391 substitutions suggested an association with the more severe retinal phenotype, compared to the substitution at Arg390.
Pancreatic ductal adenocarcinoma (PDAC) lethality is due to metastatic dissemination. Characterization of rare, heterogeneous circulating tumor cells (CTCs) can provide insight into metastasis and ...guide development of novel therapies. Using the CTC-iChip to purify CTCs from PDAC patients for RNA-seq characterization, we identify three major correlated gene sets, with stemness genes LIN28B/KLF4, WNT5A, and LGALS3 enriched in each correlated gene set; only LIN28B CTC expression was prognostic. CRISPR knockout of LIN28B-an oncofetal RNA-binding protein exerting diverse effects via negative regulation of let-7 miRNAs and other RNA targets-in cell and animal models confers a less aggressive/metastatic phenotype. This correlates with de-repression of let-7 miRNAs and is mimicked by silencing of downstream let-7 target HMGA2 or chemical inhibition of LIN28B/let-7 binding. Molecular characterization of CTCs provides a unique opportunity to correlated gene set metastatic profiles, identify drivers of dissemination, and develop therapies targeting the "seeds" of metastasis.
Background
Headache disorders are highly prevalent worldwide, but not so well investigated in children and adolescents as in adults: few studies have included representative nationwide samples. No ...data exist for Austria until now. In a representative sample of children and adolescents in Austria, we estimated the prevalence and attributable burden of headache disorders, including the new diagnostic category of “undifferentiated headache” (UdH) defined as mild headache lasting less than 1 hour.
Methods
Within the context of a broader national mental health survey, children and adolescents aged 10–18 years were recruited from purposively selected schools. Mediated self-completed questionnaires included sociodemographic enquiry (gender, age, socioeconomic status, family constellation, residence urban or rural and migration background). Prevalence and attributable burden of all headache, UdH, migraine (definite plus probable), tension-type headache (TTH: definite plus probable) and headache on ≥15 days/month (H15+) were assessed using the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire for children and adolescents. Health-related quality of life (HrQoL) was assessed using the KIDSCREEN questionnaire.
Results
Of 7643 selected pupils, 3386 (44.3%) completed the questionnaires. The 1-year prevalence of headache was 75.7%, increasing with age and higher in girls (82.1%) than in boys (67.7%;
p
< 0.001). UdH, migraine, TTH and H15+ were reported by 26.1%, 24.2%, 21.6% and 3.0% of participants. Attributable burden was high, with 42% of those with headache experiencing restrictions in daily activities. Medication use (50% overall) was highest in H15+ (67%) and still considerable in UdH (29%). HrQoL was reduced for all headache types except UdH. Participants in single parent or patchwork families had a higher probability of migraine (respectively, OR 1.5,
p
< 0.001; OR 1.5,
p
< 0.01). Participants with a migration background had a lower probability of TTH (OR 0.7,
p
< 0.01).
Conclusions
Headache disorders are both very common and highly burdensome in children and adolescents in Austria. This study contributes to the global atlas of headache disorders in these age groups, and corroborates and adds knowledge of the new yet common and important diagnostic category of UdH. The findings call for action in national and international health policies, and for further epidemiological research.
Overweight and underweight adolescents have an increased risk of psychological problems and reduced quality of life. We used a network analysis approach on a variety of psychopathology and well-being ...variables to identify central factors in these populations. The network analysis was conducted on data of 344 overweight adolescents (>90th BMI-percentile) and 423 underweight adolescents (<10th BMI-percentile) drawn from a large community sample (10-19 years) including behavioral and emotional problems (Youth Self-Report), eating disorder risk (SCOFF) and well-being variables (KIDSCREEN). Additionally, psychopathology and well-being scores of overweight and underweight individuals were compared with 1.560 normal weight adolescents. Compared to their normal weight peers, overweight adolescents showed elevated psychopathology and eating disorder risk as well as reduced well-being. Underweight adolescents reported increased levels of internalizing problems but no increased eating disorder risk or reduced well-being. The network analysis revealed that anxious/depressed mood and attention problems were the most central and interconnected nodes for both overweight and underweight subsamples. Among underweight individuals, social problems and socially withdrawn behavior additionally functioned as a bridge between other nodes in the network. The results support psychological interventions focusing on improving mood, coping with negative emotions and tackling inner tension.
Despite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes. Here, we find that the RNA-binding protein IGF2BP3, which is overexpressed in ...MLL-translocated leukemia, strongly amplifies MLL-Af4-mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4-driven leukemia and greatly attenuates disease, with a minimal impact on baseline hematopoiesis. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. At the molecular level, IGF2BP3 regulates a complex posttranscriptional operon governing leukemia cell survival and proliferation. IGF2BP3-targeted mRNA transcripts include important MLL-Af4-induced genes, such as those in the Hoxa locus, and the Ras signaling pathway. Targeting of transcripts by IGF2BP3 regulates both steady-state mRNA levels and, unexpectedly, pre-mRNA splicing. Together, our findings show that IGF2BP3 represents an attractive therapeutic target in this disease, providing important insights into mechanisms of posttranscriptional regulation in leukemia.
In this paper, I study the role of gender-typical parental occupation for young adults’ gender-typical university major choice using data on a recent cohort of university students in Germany. Results ...show significant intergenerational associations between the gender typicality in parental occupation and young adults’ majors. As to why these effects occur, findings suggest that the transfer of occupation-specific resources from parents to their children plays an important role and that a transmission of gender roles explains at least some of the father-son associations. The paper contributes to existing literature by introducing a novel measure that operationalises the extent to which majors and occupations are ‘typically female’ or ‘typically male’ and by studying different transmission channels.
BMP4/7-dependent expression of inhibitor of differentiation/DNA binding (Id) proteins 1 and 3 has been implicated in tumor progression and poor prognosis of malignant melanoma patients. Hyaluronic ...acid (HA), a pericellular matrix component, supports BMP7 signalling in murine chondrocytes through its receptor CD44. However, its role in regulating BMP signalling in melanoma is not clear. In this study we found that depletion of endogenously-produced HA by hyaluronidase treatment or by inhibition of HA synthesis by 4-methylumbelliferone (4-MU) resulted in reduced BMP4/7-dependent Id1/3 protein expression in mouse melanoma B16-F10 and Ret cells. Conversely, exogenous HA treatment increased BMP4/7-dependent Id1/3 protein expression. Knockdown of CD44 reduced BMP4/7-dependent Id1/3 protein expression, and attenuated the ability of exogenous HA to stimulate Id1 and Id3 expression in response to BMP. Co-IP experiments demonstrated that CD44 can physically associate with the BMP type II receptor (BMPR) ACVR2B. Importantly, we found that coordinate expression of Id1 or Id3 with HA synthases HAS2, HAS3, and CD44 is associated with reduced overall survival of cutaneous melanoma patients. Our results suggest that HA-CD44 interactions with BMPR promote BMP4/7-dependent Id1/3 protein expression in melanoma, contributing to reduced survival in melanoma patients.
Purpose
Research on the engagement of fathers in the treatment of childhood psychiatric disorders is scarce. This study aims to investigate differences between mothers and fathers of adolescents with ...anorexia nervosa regarding parental burden and effectiveness of a parental skills training.
Methods
Ninety-one mother–father dyads caring for a child with anorexia nervosa participated in an 8-week parental skills training and completed a set of questionnaires assessing parental psychopathology, eating disorder related burden, caregiver skills and expressed emotion at baseline and post-intervention.
Results
Fathers showed lower levels of general psychological distress, depression, anxiety and eating disorder related burden as well as lower emotional overinvolvement compared to mothers. The skills training was effective in reducing parental psychopathology, eating disorder-related burden and emotional overinvolvement as well as in increasing caregiver skills with no differences between mothers and fathers. However, session adherence and the willingness to practice skills between the sessions were slightly lower in fathers.
Conclusions
These findings show that fathers are a great resource for the child’s eating disorder treatment as they may counterbalance maternal emotional overinvolvement and over-protection. Furthermore, this is the first study demonstrating that fathers can profit from a parental skills training for anorexia nervosa in a similar way as mothers.
Level III
Evidence obtained from well-designed cohort or case–control analytic studies.
Chronic physical health conditions (CPHC) are on the rise in younger age groups and might have a negative impact on children and adolescents. In a representative sample of Austrian adolescents aged ...10-18 years, internalizing, externalizing, and behavioral problems were assessed cross-sectionally using the Youth Self-Report and health-related quality of life (HrQoL) using the KIDSCREEN questionnaire. Sociodemographic variables, life events, and chronic illness specific parameters were considered as associated variables with mental health problems in individuals with CPHC. Of 3469 adolescents, 9.4% of girls and 7.1% of boys suffered from a chronic pediatric illness. Of these individuals, 31.7% and 11.9% had clinically relevant levels of internalizing and externalizing mental health problems, respectively, compared to 16.3% and 7.1% adolescents without a CPHC. Anxiety, depression, and social problems were twice as high in this population. Medication intake due to CPHC and any traumatic life-event were related to mental health problems. All HrQoL domains were deteriorated in adolescents with a double burden of mental and CPHC, whereas adolescents with a CPHC without mental health problems did not differ significantly from adolescents without a chronic illness. Targeted prevention programs for adolescents with a CPHC are urgently needed to prevent mental health problems in the long term.
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