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Family-centered care, in terms of parental involvement and family-centered staff attitude and behavior during placement in secure residential youth care, is increasingly being combined with systemic interventions. Little is known, however, about this combination of family-centered residential care and systemic interventions. This study assessed whether levels of parental involvement or family-centered staff attitude and behavior during placement predicted outcomes of systemic interventions. We first assessed the outcomes in the full sample of families receiving systemic interventions and thereafter in families receiving systemic interventions with a strong evidence base (Multidimensional Family Therapy, Multisystemic Therapy [specializing in treatment of individuals with an intellectual disability/with problem sexual behavior], Relational Family Therapy [MDFT, MST(-ID/-PSB), RGT]) and systemic interventions with a less strong evidence base (Attachment Based Family Therapy, Flexible Assertive Community Treatment [FACT], FamilyFACT, Forensic Ambulant Systemic Therapy, Systemic Therapy [ABFT, (Family)FACT, FAST, ST]). Results revealed that higher levels of parental involvement predicted less family empowerment and a longer duration of the systemic intervention. Higher levels of family-centered staff attitude and behavior predicted more parental distress, a shorter duration of the residential placement and a shorter duration of the systemic intervention. Combinations of secure residential youth care with different systemic interventions of different evidence bases resulted in different outcomes. Future research is needed to establish which components of family-centered care or systemic interventions contribute to adolescent outcomes. [ABSTRACT FROM AUTHOR]

The key to a curative treatment of hepatitis B virus (HBV) infection is the eradication of the intranuclear episomal covalently closed circular DNA (cccDNA), the stable persistence reservoir of HBV. Currently, established therapies can only limit HBV replication but fail to tackle the cccDNA. Thus, novel therapeutic approaches toward curative treatment are urgently needed. Recent publications indicated a strong association between the HBV core protein SUMOylation and the association with promyelocytic leukemia nuclear bodies (PML-NBs) on relaxed circular DNA to cccDNA conversion. We propose that interference with the cellular SUMOylation system and PML-NB integrity using arsenic trioxide provides a useful tool in the treatment of HBV infection. Our study showed a significant reduction in HBV-infected cells, core protein levels, HBV mRNA, and total DNA. Additionally, a reduction, albeit to a limited extent, of HBV cccDNA could be observed. Furthermore, this interference was also applied for the treatment of an established HBV infection, characterized by a stably present nuclear pool of cccDNA. Arsenic trioxide (ATO) treatment not only changed the amount of expressed HBV core protein but also induced a distinct relocalization to an extranuclear phenotype during infection. Moreover, ATO treatment resulted in the redistribution of transfected HBV core protein away from PML-NBs, a phenotype similar to that previously observed with SUMOylation-deficient HBV core. Taken together, these findings revealed the inhibition of HBV replication by ATO treatment during several steps of the viral replication cycle, including viral entry into the nucleus as well as cccDNA formation and maintenance. We propose ATO as a novel prospective treatment option for further pre-clinical and clinical studies against HBV infection., Importance: The main challenge for the achievement of a functional cure for hepatitis B virus (HBV) is the covalently closed circular DNA (cccDNA), the highly stable persistence reservoir of HBV, which is maintained by further rounds of infection with newly generated progeny viruses or by intracellular recycling of mature nucleocapsids. Eradication of the cccDNA is considered to be the holy grail for HBV curative treatment; however, current therapeutic approaches fail to directly tackle this HBV persistence reservoir. The molecular effect of arsenic trioxide (ATO) on HBV infection, protein expression, and cccDNA formation and maintenance, however, has not been characterized and understood until now. In this study, we reveal ATO treatment as a novel and innovative therapeutic approach against HBV infections, repressing viral gene expression and replication as well as the stable cccDNA pool at low micromolar concentrations by affecting the cellular function of promyelocytic leukemia nuclear bodies., Competing Interests: U.P. is a co-founder and shareholder of SCG Cell Therapy and received personal fees as a speaker or an ad hoc scientific advisor from AbbVie, Aligos, Arbutus, Biontech, Gilead, GSK, Leukocare, J&J, Roche, Sanofi, Sobi, Vaccitech, and VIR Biotechnology. The other authors declare no competing interests.

To promote the return of juveniles to a home-like environment (e.g. living with (foster)parents) after secure residential treatment (SRT), it is important to know which factors are related to this outcome. The current study examined which characteristics of the juvenile, family, and SRT, including family centeredness and use of systemic interventions, are related to the living situation after discharge. For 259 juveniles (mean age 15.82 years, 127 girls) in SRT and their parents, questionnaires were administered at admission, discharge, and 6-months follow-up. Furthermore, information about the living situation before and after SRT was gathered. Higher likelihood of living in a home-like setting after SRT correlated with more furlough moments with parents, receiving a systemic intervention, and a shorter duration of the SRT. Systemic interventions during SRT and spending furlough moments with parents may have a positive impact on returning to a home-like situation after SRT for juveniles., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Prevention of fatal side effects during cancer therapy of cancer patients with high-dosed pharmacological inhibitors is to date a major challenge. Moreover, the development of drug resistance poses severe problems for the treatment of patients with leukemia or solid tumors. Particularly drug-mediated dimerization of RAF kinases can be the cause of acquired resistance, also called "paradoxical activation." In the present work we re-analyzed the effects of different tyrosine kinase inhibitors (TKIs) on the proliferation, metabolic activity, and survival of the Imatinib-resistant, KIT V560G, D816V-expressing human mast cell (MC) leukemia (MCL) cell line HMC-1.2. We observed that low concentrations of the TKIs Nilotinib and Ponatinib resulted in enhanced proliferation, suggesting paradoxical activation of the MAPK pathway. Indeed, these TKIs caused BRAF-CRAF dimerization, resulting in ERK1/2 activation. The combination of Ponatinib with the MEK inhibitor Trametinib, at nanomolar concentrations, effectively suppressed HMC-1.2 proliferation, metabolic activity, and induced apoptotic cell death. Effectiveness of this drug combination was recapitulated in the human KIT D816V MC line ROSA KIT D816V and in KIT D816V hematopoietic progenitors obtained from patient-derived induced pluripotent stem cells (iPS cells) and systemic mastocytosis patient samples. In conclusion, mutated KIT-driven Imatinib resistance and possible TKI-induced paradoxical activation can be efficiently overcome by a low concentration Ponatinib and Trametinib co-treatment, potentially reducing the negative side effects associated with MCL therapy., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Objectives: Maximizing quality of life (QoL) is the ultimate goal of long-term dementia care. However, routine QoL measurement is rare in nursing home (NH) and assisted living (AL) facilities. Routine QoL measurement might lead to improvements in resident QoL. Our objective was to assess the feasibility of using DEMQOL-CH, completed by long-term care staff in video calls with researchers, to assess health-related quality of life (HrQoL) of NH and AL residents with dementia or other cognitive impairment., Design: Cross-sectional study., Setting and Participants: We included a convenience sample of 5 NHs and 5 AL facilities in the Canadian province of Alberta. Forty-two care staff who had worked in the facility for ≥3 months completed DEMQOL-CH assessments of 183 residents who had lived in the facility for 3 months or more and were aged ≥65 years. Sixteen residents were assessed independently by 2 care staff to assess inter-rater reliability., Methods: We assessed HrQoL in people with dementia or other cognitive impairment using DEMQOL-CH, and assessed time to complete, inter-rater reliability, internal consistency reliability, and care staff ratings of feasibility of completing the DEMQOL-CH., Results: Average time to complete DEMQOL-CH was <5 minutes. Staff characteristics were not associated with time to complete or DEMQOL-CH scores. Inter-rater reliability [0.735, 95% confidence interval (CI): 0.712-0.780] and internal consistency reliability (0.834, 95% CI: 0.779-0.864) were high. The DEMQOL-CH score varied across residents (mean = 84.8, standard deviation = 11.20, 95% CI: 83.2-86.4). Care aides and managers rated use of the DEMQOL-CH as highly feasible, acceptable, and valuable., Conclusions and Implications: This study provides a proof of concept that DEMQOL-CH can be used to assess HrQoL in NH and AL residents and provides initial indications of feasibility and resources required. DEMQOL-CH may be used to support actions to improve the QoL of residents., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To provide successful treatment to detained adolescents, staff in juvenile justice institutions need to work in family-centered ways. As juvenile justice institutions struggled to involve parents in their child's treatment, we developed a program for family-centered care., Methods: The program was developed in close collaboration with staff from the two juvenile justice institutions participating in the Dutch Academic Workplace Forensic Care for Youth. To achieve an attainable program, we chose a bottom-up approach in which ideas for family-centered care were detailed and discussed by workgroups consisting of group leaders, family therapists, psychologists, other staff, researchers, and a parent., Results: The family-centered care program distinguishes four categories of parental participation: (a) informing parents, (b) parents meeting their child, (c) parents meeting staff, and (d) parents taking part in the treatment program. Additionally, the family-centered care program includes the option to start family therapy during detention of the youths, to be continued after discharge from the juvenile justice institutions. Training and coaching of staff are core components of the family-centered care program., Conclusions: The combination of training and the identification of attainable ways for staff to promote parental involvement makes the family-centered care program valuable for practice. Because the program builds on suggestions from previous research and on the theoretical background of evidence-based family therapies, it has potential to improve care for detained adolescents and their parents. Further research is required to confirm if this assumption is correct.

Background: Treatment and rehabilitation interventions in juvenile justice institutions aim to prevent criminal reoffending by adolescents and to enhance their prospects of successful social reintegration. There is evidence that these goals are best achieved when the institution adopts a family-centered approach, involving the parents of the adolescents. The Academic Workplace Forensic Care for Youth has developed two programs for family-centered care for youth detained in groups for short-term and long-term stay, respectively., Objective: The overall aim of our study is to evaluate the family-centered care program in the first two years after the first steps of its implementation in short-term stay groups of two juvenile justice institutions in the Netherlands. The current paper discusses our study design., Methods: Based on a quantitative pilot study, we opted for a study with an explanatory sequential mixed methods design. This pilot is considered the first stage of our study. The second stage of our study includes concurrent quantitative and qualitative approaches. The quantitative part of our study is a pre-post quasi-experimental comparison of family-centered care with usual care in short-term stay groups. The qualitative part of our study involves in-depth interviews with adolescents, parents, and group workers to elaborate on the preceding quantitative pilot study and to help interpret the outcomes of the quasi-experimental quantitative part of the study., Results: We believe that our study will result in the following findings. In the quantitative comparison of usual care with family-centered care, we assume that in the latter group, parents will be more involved with their child and with the institution, and that parents and adolescents will be more motivated to take part in therapy. In addition, we expect family-centered care to improve family interactions, to decrease parenting stress, and to reduce problem behavior among the adolescents. Finally, we assume that adolescents, parents, and the staff of the institutions will be more satisfied with family-centered care than with usual care. In the qualitative part of our study, we will identify the needs and expectations in family-centered care as well as factors influencing parental participation. Insight in these factors will help to further improve our program of family-centered care and its implementation in practice. Our study results will be published over the coming years., Conclusions: A juvenile justice institution is a difficult setting to evaluate care programs. A combination of practice-based research methods is needed to address all major implementation issues. The study described here takes on the challenge by means of practice-based research. We expect the results of our study to contribute to the improvement of care for adolescents detained in juvenile justice institutions, and for their families., Competing Interests: The managements of the JJIs assigned RB and IS to the AWFZJ. RB works as a consulting psychiatrist in one of the JJIs and IS works as a licensed psychologist in the other JJI, both one day a week. Other than that, the authors declare that they have no competing interests. In order to minimize possible bias occurring from the two authors working in the JJIs, we will reassure staff, adolescents, and parents that all data is handled confidentially and anonymously. Additionally, RB will not be involved in the process of data collection and analyses. IS will not be involved in her clinical work as part of the present study. Data collection will be carried out by trained research assistants or by trained students, under supervision of IS.