Highly Potent Antisense Oligonucleotides Locked Nucleic Acid Gapmers Targeting the SARS-CoV-2 RNA Genome.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the current worldwide pandemic and the associated coronavirus disease 2019 with potentially lethal outcome. Although effective vaccines strongly contributed to reduce disease severity, establishing a toolbox to control current and newly emerging coronaviruses of epidemic concern requires the development of novel therapeutic compounds, to treat severely infected individuals and to prevent virus transmission. Here we present a therapeutic strategy targeting the SARS-CoV-2 RNA genome using antisense oligonucleotides (ASOs). We demonstrate that selected locked nucleic acid gapmers have the potency to reduce the in vitro intracellular viral load by up to 96%. Our promising results strongly support the case for further development of our preselected ASOs as therapeutic or prophylactic antiviral agents.

Identifying effective moderators of cognitive behavioural trauma treatment with caregiver involvement for youth with PTSD: a meta-analysis.

Children can develop post-traumatic stress disorder (PTSD) and mental health symptoms after traumatic events. This meta-analysis evaluated the influence of moderators of cognitive behavioural trauma treatment (CBTT) with caregiver involvement in traumatized children. A total of 28 studies were included, with 23 independent samples and 332 effect sizes, representing the data of 1931 children (M age = 11.10 years, SD = 2.36). Results showed a significant medium overall effect (d = 0.55, t = 2.478, p = 0.014), indicating CBTT with caregiver involvement was effective in treating PTSD (d = 0.70), with somewhat smaller effect sizes for internalizing, externalizing, social, cognitive and total problems (0.35 < d > 0.48). The positive treatment effect was robust; we found somewhat smaller effect sizes at follow-up (d = 0.49) compared to post-test (d = 0.57) assessments. Furthermore, several sample (i.e. child's age, gender, and trauma event), programme (i.e. the duration of treatment, number of sessions), study (i.e. control condition, type of instrument, informant, type of sample), and publication (i.e. publication year and impact factor) characteristics moderated the treatment outcomes of the child. In sum, the results of our meta-analysis might help to improve the effectiveness of cognitive behavioural trauma treatment for youth with PTSD, and guide the development of innovative trauma interventions that involve caregivers. Implications for theory and practice are discussed.

Development and validation of the Attachment Relationship Inventory-Caregiver Perception 2-5 years (ARI-CP 2-5): Psychometric structure, external validity, and norms.

There is a lack of instruments assessing child-caregiver attachment relationships in early childhood to be used in attachment-based practice, in particular from a caregiver's perception, which is an important factor of clinical importance to take into account in parenting interventions targeting young children. Therefore, the 48-item Attachment Relationship Inventory-Caregiver Perception 2-5 years (ARI-CP 2-5) was developed. Survey data of 446 caregivers of 2- to 5-year-old children were collected, and a subsample of 83 caregivers participated in an observation study. Confirmatory factor analysis confirmed a four-factor structure of secure, avoidant, ambivalent, and disorganized attachment relationship. Indications of configural, metric, and scalar invariance were found for caregivers' and children's sex, children's age, and population (clinical vs. general population). The four scales showed sufficient internal consistency and significant associations with children's psychopathology, caregivers' general attachment representations, caregivers' mind-mindedness, and population type. Moreover, preliminary evidence for convergent validity with observational attachment measures was found. It is concluded that the ARI-CP 2-5 is a valid instrument that can be used as part of the screening and assessment of insecure attachment relationships.

Hacen falta instrumentos que evalúen las relaciones de afectividad niño-cuidador en la temprana niñez para ser usados en la práctica que se basa en la afectividad, en particular desde la perspectiva del cuidador, lo cual es un factor clave de importancia clínica para tomar en cuenta en las intervenciones de crianza que se enfocan en niños pequeños. Por tanto, se desarrolló el Inventario de la Relación Afectiva - Percepción del Cuidador 2-5 años, que consta de 48 aspectos (ARI-CP 2-5). Se recogió información de encuesta de 446 cuidadores de niños de 2 a 5 años de edad, y un subgrupo muestra de 83 cuidadores participó en un estudio de observación. Los análisis de factores confirmatorios corroboraron una estructura de cuatro factores de la relación de afectividad que es segura, la que evita, la ambivalente y la desorganizada. Se encontraron indicaciones de invariabilidad en el aspecto configuracional, métrico y de escala en cuanto al género sexual de los cuidadores y del niño, la edad del niño, y la población (clínica y general). Las cuatro escalas mostraron una suficiente consistencia interna y asociaciones significativas con la sicopatología de los niños, las representaciones generales de afectividad del cuidador, la conciencia mental de los cuidadores, así como el tipo de población. Es más, se encontró una evidencia preliminar para la validez convergente con las medidas de afectividad de observación. Se concluye con que el ARI-CP 2-5 es un instrumento válido que puede usarse como parte de la detección y evaluación de las relaciones de afectividad inseguras.

Il y a un manque d'instruments évaluant les relations d'attachement enfant-aidant naturel dans la petite enfance pouvant être utilisés dans une pratique basée sur l'attachement, en particulier sur la perception de l'aidant naturel, qui est un facteur important de l'importance clinique à prendre en compte dans les interventions de parentages ciblant les jeunes enfants. Par conséquent l'Inventaire de 48 articles de la Relation d'Attachement - Perception de l'Aidant Naturel 2-5 ans (abrégé en anglais ARI-CP 2-5) a été développé. Les données de sondage de 446 aidants naturels d'enfants de 2 à 5 ans ont été recueillies et un sous-échantillon de 83 aidants naturels ont participé à une étude d'observation. Une analyse factorielle confirmatoire a confirmé une structure à quatre facteurs de la relation d'attachement sécure, évitant, ambivalent et désorganisé. Des indications d'invariance configurale, métrique et scalaire ont été trouvées pour le sexe des aidants naturels et des enfants, l'âge des enfants, et la population (clinique par rapport à population générale). Les quatre échelles ont démontré une cohérence interne suffisante et des associations importantes avec la psychopathologie des enfants, les représentations de l'attachement générale des aidants naturels, l'esprit-qualité mentale et le type de population. De plus une preuve préliminaire de validité convergente ave les mesures observationnelles d'attachement a été trouvée. Nous concluons que l'ARI-CP 205 est un instrument valide qui peut être utilisé pour le dépistage et l'évaluation de relations d'attachement insécures.

Effects of music interventions on stress-related outcomes: a systematic review and two meta-analyses.

Music interventions are used for stress reduction in a variety of settings because of the positive effects of music listening on both physiological arousal (e.g., heart rate, blood pressure, and hormonal levels) and psychological stress experiences (e.g., restlessness, anxiety, and nervousness). To summarize the growing body of empirical research, two multilevel meta-analyses of 104 RCTs, containing 327 effect sizes and 9,617 participants, were performed to assess the strength of the effects of music interventions on both physiological and psychological stress-related outcomes, and to test the potential moderators of the intervention effects. Results showed that music interventions had an overall significant effect on stress reduction in both physiological (d = .380) and psychological (d = .545) outcomes. Further, moderator analyses showed that the type of outcome assessment moderated the effects of music interventions on stress-related outcomes. Larger effects were found on heart rate (d = .456), compared to blood pressure (d = .343) and hormone levels (d = .349). Implications for stress-reducing music interventions are discussed.

The Relation Between Attachment and Depression in Children and Adolescents: A Multilevel Meta-Analysis.

Insecure attachment to primary caregivers is associated with the development of depression symptoms in children and youth. This association has been shown by individual studies testing the relation between attachment and depression and by meta-analyses focusing on broad internalizing problems instead of depression or adult samples only. We therefore meta-analytically examined the associations between attachment security and depression in children and adolescents, using a multilevel approach. In total, 643 effect sizes were extracted from 123 independent samples. A significant moderate overall effect size was found (r = .31), indicating that insecure attachment to primary caregivers is associated with depression. Multivariate analysis of the significant moderators that impacted on the strength of the association between attachment security and depression showed that country of the study, study design, gender, the type of attachment, and the type of instrument to assess attachment uniquely contributed to the explanation of variance. This study suggests that insecure attachment may be a predictor of the development of depression in children and adolescents. When treating depression in children, attachment should therefore be addressed.

The Relationship between Moral Climate of Sports and the Moral Behavior of Young Athletes: A Multilevel Meta-analysis.

Sports are among the most important leisure activities for youth and adolescents. Both positive (i.e., prosocial) and negative (i.e., antisocial) moral behaviors occur on the playing field. To stimulate positive sports experiences, it is important to understand which factors are related to the moral behavior of young athletes; one of these is the moral climate, that is, the socio-moral environment in which sports take place. Little is known about the overall strength of the relationship between moral climate and moral behavior of young athletes, as well as the potential moderating factors of this relationship. A meta-analysis of 27 studies containing 117 effect sizes and N = 7726 young athletes (age < 18 years) was conducted. The results show that there is an overall significant association between these two variables (r= 0.40), indicating that a prosocial moral climate is related to less antisocial and more prosocial behavior, while an antisocial moral climate is associated with more antisocial and less prosocial behavior of young athletes. Two study characteristics significantly moderated this relationship: specifically, stronger associations were found in cross-sectional and in older studies. In addition, the strength of the association between moral climate and moral behavior was stronger for antisocial moral climate compared to prosocial moral climate. Finally, associations for team members were stronger than those of coaches or a broad moral club climate. Implications for further research and sports practice are discussed.

The intergenerational transmission of child maltreatment: A three-level meta-analysis.

A parental history of experiencing child maltreatment is an important risk factor in several etiological theories of child maltreatment. In the past, two reviews have been conducted on the available evidence for intergenerational continuity in child maltreatment, but were only qualitative in nature. Therefore, the present review aimed to provide a quantitative summary of the current knowledge on intergenerational transmission of child maltreatment. In our 3-level random-effects meta-analysis, we included 84 studies reporting on 285 effect sizes and found a medium summary effect of r = 0.289; 95% CI [0.257, 0.337], with significant variation in effect sizes within (level 2) and between (level 3) studies. This implies that in families of parents who experienced maltreatment in their own childhood, the odds of child maltreatment are almost three times the odds of child maltreatment in families of parents without a history of experiencing child maltreatment (OR = 2.990). However, as indications for bias were found, caution is warranted in interpreting this effect. Moderator analyses revealed that the effect of intergenerational transmission was the smallest in children who experienced physical abuse. Further, study quality was negatively associated with effect size magnitude. We highlight the need for an improvement in quality of primary research, and discuss implications of our findings for clinical practice.

Internal structure and reliability of the Attachment Insecurity Screening Inventory (AISI) for children age 6 to 12.

BACKGROUND: The aim of the present study was to examine the internal structure and reliability of the Attachment Insecurity Screening Inventory (AISI) 6-12. The AISI 6-12 years is a parent-report questionnaire for assessing the parents' perspective on the quality of the attachment relationship with their child aged between 6 and 12 years. METHODS: The sample consisted of 681 mothers and fathers reporting on 372 children (72.3% adoption parents, 14.9% non-biological primary care takers including foster parents, and 12.8% biological parents). The internal structure was assessed with multilevel confirmatory factor analyses (CFA) and the reliability of the scores with Cronbach's and ordinal alphas. RESULTS: Multilevel CFA confirmed a three-factor model of avoidant, ambivalent/resistant and disorganized attachment. Multi-group CFA indicated full configural and metric measurement invariance, and partial scalar and strict measurement invariance across mothers and fathers. Reliability coefficients were found to be sufficient. CONCLUSIONS: This study showed the potential of using parental reports in the initial screening of attachment related problems, especially considering the practical approach of parental reports. However, further development of the AISI 6-12 years seems important to increase the validity of the AISI 6-12 years. In addition, future studies are necessary to replicate the current findings, and to strengthen the evidence that the AISI 6-12 years is appropriate for the use in middle childhood and validly assesses the parents' perspective on attachment insecurities in their child.

Predictors of Intervention Success in a Sports-Based Program for Adolescents at Risk of Juvenile Delinquency.

To prevent juvenile delinquency, there is growing interest in the use of sports-based interventions. To date, there is little empirical research that provides insights into for whom, how, and when sports-based crime prevention programs are most effective. Therefore, the current study assessed which youth, coach, and context factors were predictive of change in risk factors and protective factors for delinquency in a sports-based crime prevention program for at-risk adolescents. Participants ( N = 155) and their teachers filled in questionnaires about risk and protective factors for delinquency at the start of the intervention and 13 months later. In addition, the coaches and participants filled in questionnaires about the predictors of intervention success. The youths showed significant improvements over the course of the intervention. Various youth, coach, and context factors (e.g., the type of education of youth and the sociomoral climate at the sports club) were associated to change in the outcome variables.

Treatment Effect on Recidivism for Juveniles Who Have Sexually Offended: a Multilevel Meta-Analysis.

The current study investigated the effect on recidivism of treatment aimed at juveniles who have sexually offended. It also assessed the potential moderating effect of type of recidivism, and several treatment, participant and study characteristics. In total, 14 published and unpublished primary studies, making use of a comparison group and reporting on official recidivism rates, were included in a multilevel meta-analysis. This resulted in the use of 77 effect sizes, and 1726 participants. A three-level meta-analytic model was used to calculate the combined effect sizes (Cohens d) and to perform moderator analyses. Study quality was assessed with the EPHPP Quality Assessment Tool for Quantitative Studies. A moderate effect size was found (d = 0.37), indicating that the treatment groups achieved an estimated relative reduction in recidivism of 20.5% as compared to comparison groups. However, after controlling for publication bias, a significant treatment effect was no longer found. Type of recidivism did not moderate the effect of treatment, indicating that treatment groups were equally effective for all types of recidivism. Also, no moderating effects of participant or treatment characteristics were found. Regarding study characteristics, a shorter follow up time showed a trend for larger effect sizes, and the effect size calculation based on proportions yielded larger effect sizes than calculation via mean frequency of offending. Implications for future research and clinical practice are discussed.

The care of Filipino juvenile offenders in residential facilities evaluated using the risk-need-responsivity model.

According to the risk-need-responsivity model of offender, assessment and rehabilitation treatment should target specific factors that are related to re-offending. This study evaluates the residential care of Filipino juvenile offenders using the risk-need-responsivity model. Risk analyses and criminogenic needs assessments (parenting style, aggression, relationships with peers, empathy, and moral reasoning) have been conducted using data of 55 juvenile offenders in four residential facilities. The psychological care has been assessed using a checklist. Statistical analyses showed that juvenile offenders had a high risk of re-offending, high aggression, difficulties in making pro-social friends, and a delayed socio-moral development. The psychological programs in the residential facilities were evaluated to be poor. The availability of the psychological care in the facilities fitted poorly with the characteristics of the juvenile offenders and did not comply with the risk-need-responsivity model. Implications for research and practice are discussed.

The effects of physical activity interventions on psychosocial outcomes in adolescents: A meta-analytic review.

Physical activity interventions are often implemented in the adolescent mental health care practice to prevent or treat psychosocial problems. To date, no systematic review of the effect of these physical activity interventions in adolescents has been conducted. In the current study, four multilevel meta-analyses were performed to assess the overall effect of physical activity interventions on externalizing problems, internalizing problems, self-concept, and academic achievement in adolescents. In addition, possible moderating factors were examined. In total, 57 studies reporting on 216 effect sizes were included, and the results showed significant small-to-moderate effects of physical activity interventions on externalizing problems (d=0.320), internalizing problems (d=0.316), self-concept (d=0.297), and academic achievement (d=0.367). Further, moderator analyses showed that outcome, study, sample, and intervention characteristics influenced the effects of physical activity interventions on psychosocial outcomes. Implications for theory and practice concerning the use of physical activity interventions in adolescent mental health care practice are discussed.

Sports Participation and Juvenile Delinquency: A Meta-Analytic Review.

Participation in sports activities is very popular among adolescents, and is frequently encouraged among youth. Many psychosocial health benefits in youth are attributed to sports participation, but to what extent this positive influence holds for juvenile delinquency is still not clear on both the theoretical and empirical level. There is much controversy on whether sports participation should be perceived as a protective or a risk factor for the development of juvenile delinquency. A multilevel meta-analysis of 51 published and unpublished studies, with 48 independent samples containing 431 effect sizes and N = 132,366 adolescents, was conducted to examine the relationship between sports participation and juvenile delinquency and possible moderating factors of this association. The results showed that there is no overall significant association between sports participation and juvenile delinquency, indicating that adolescent athletes are neither more nor less delinquent than non-athletes. Some study, sample and sports characteristics significantly moderated the relationship between sports participation and juvenile delinquency. However, this moderating influence was modest. Implications for theory and practice concerning the use of sports to prevent juvenile delinquency are discussed.