The TOPLESS corepressor regulates developmental switches in the bryophyte Physcomitrium patens that were critical for plant terrestrialisation.

The plant-specific TOPLESS (TPL) family of transcriptional corepressors is integral to multiple angiosperm developmental processes. Despite this, we know little about TPL function in other plants. To address this gap, we investigated the roles TPL plays in the bryophyte Physcomitrium patens, which diverged from angiosperms approximately 0.5 billion years ago. Although complete loss of PpTPL function is lethal, transgenic lines with reduced PpTPL activity revealed that PpTPLs are essential for two fundamental developmental switches in this plant: the transitions from basal photosynthetic filaments (chloronemata) to specialised foraging filaments (caulonemata) and from two-dimensional (2D) to three-dimensional (3D) growth. Using a transcriptomics approach, we integrated PpTPL into the regulatory network governing 3D growth and we propose that PpTPLs represent another important class of regulators that are essential for the 2D-to-3D developmental switch. Transcriptomics also revealed a previously unknown role for PpTPL in the regulation of flavonoids. Intriguingly, 3D growth and the formation of caulonemata were crucial innovations that facilitated the colonisation of land by plants, a major transformative event in the history of life on Earth. We conclude that TPL, which existed before the land plants, was co-opted into new developmental pathways, enabling phytoterrestrialisation and the evolution of land plants.

Preliminary Impact of Group-Based Interventions on Stigma, Mental Health, and Treatment Adherence Among Adolescents Living with Human Immunodeficiency Virus in Uganda.

OBJECTIVE: To examine the preliminary impact of group cognitive behavioral therapy and multiple family group-based family strengthening to address HIV stigma and improve the mental health functioning of adolescents living with HIV in Uganda. STUDY DESIGN: We analyzed data from the Suubi4Stigma study, a 2-year pilot randomized clinical trial that recruited adolescents living with HIV (10-14 years) and their caregivers (n = 89 dyads), from 9 health clinics. We fitted separate three-level mixed-effects linear regression models to test the effect of the interventions on adolescent outcomes at 3 and 6 months post intervention initiation. RESULTS: The average age was 12.2 years and 56% of participants were females. Participants in the multiple family group-based family strengthening intervention reported lower levels of internalized stigma (mean difference = -0.008, 95% CI = -0.015, -0.001, P = .025) and depressive symptoms at 3 months (mean difference = -0.34, 95% CI = -0.53, -0.14, P < .001), compared with usual care. On the other hand, participants in the group cognitive behavioral therapy intervention reported lower levels of anticipated stigma at 3 months (mean difference = -0.039, 95% CI = -0.072, -0.006), P = .013) and improved self-concept at 6 months follow-up (mean difference = 0.04, 95% CI = 0.01, 0.01, P = .025). CONCLUSION: Outcome trends from this pilot study provide compelling evidence to support testing the efficacy of these group-based interventions on a larger scale. TRIAL REGISTRATION: The study is registered in the Clinical trials.gov database (Identifier #: NCT04528732).

Feasibility and Acceptability of Group-Based Stigma Reduction Interventions for Adolescents Living with HIV and Their Caregivers: The Suubi4Stigma Randomized Clinical Trial (2020-2022).

This study examined the feasibility and acceptability of two group-based interventions: group-cognitive behavioral therapy (G-CBT) and a family-strengthening intervention delivered via multiple family group (MFG-FS), to address HIV stigma among adolescents living with HIV (ALHIV) and their caregivers. A total of 147 adolescent -caregiver dyads from 9 health clinics situated within 7 political districts in Uganda were screened for eligibility. Of these, 89 dyads met the inclusion criteria and provided consent to participate in the study. Participants were randomized, at the clinic level, to one of three study conditions: Usual care, G-CBT or MFG-FS. The interventions were delivered over a 3-month period. While both adolescents and their caregivers attended the MFG-FS sessions, G-CBT sessions were only attended by adolescents. Data were collected at baseline, 3 and 6-months post intervention initiation. The retention rate was 94% over the study period. Across groups, intervention session attendance ranged between 85 and 92%, for all sessions. Fidelity of the intervention was between 85 and 100%, and both children and caregivers rated highly their satisfaction with the intervention sessions. ALHIV in Uganda, and most of sub-Saharan Africa, are still underrepresented in stigma reduction interventions. The Suubi4Stigma study was feasible and acceptable to adolescents and their caregivers -supporting testing the efficacy of the interventions in a larger trial.

Self-esteem and self-concept as correlates of life satisfaction and attitudes toward school among Ghanaian girls.

During adolescence, youth experience several physical, psychosocial, and cognitive changes. Self-esteem and self-concept are identified as protective factors for adolescents in high-income countries, but studies are limited in sub-Saharan Africa. We examined the associations of self-esteem and self-concept with life satisfaction and attitudes toward school using baseline data from 97 Ghanaian adolescent girls at risk of school dropout. Ordinary Least Squares regression models were fitted to examine the association between self-esteem and self-concept on school attitudes and life satisfaction. Self-esteem was positively associated with life satisfaction. Self-concept was associated with more positive attitudes toward school. Hence, self-esteem and self-concept may be critical protective factors in promoting adolescent girls' life satisfaction and positive attitudes toward school.

Short-term impact of a combination intervention on family cohesion: Results from a pilot cluster-randomized clinical trial in Northern Ghana.

Child labor remains a concern in sub-Saharan Africa. Yet, evidence-based preventive efforts are limited. We analyzed longitudinal data from Ghanaian adolescent girls in a pilot randomized clinical trial testing the preliminary impact of a combination intervention on family cohesion as a protective factor against child labor and school dropout. While there was no statistical difference between the control and intervention groups at 9 months, the results show that family cohesion scores improved significantly from baseline to 9 months for the ANZANSI intervention group. Qualitative results indicated improved family cohesion in the intervention group. Hence, future studies should further examine this promising social work intervention.

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on family cohesion among children in Uganda: Analysis of the cluster randomized SMART Africa-Uganda scale-up study (2016-2022).

Family functioning plays a critical role in childhood disruptive behavior disorders (The Family Journal, 2003, 11(1), 33-41; Research in Nursing and Health, 2016, 39(4), 229-243). Yet, there is limited research on the impact of evidence-based family strengthening interventions on improving family cohesion as a protective factor among children experiencing behavioral challenges. To address this gap, we analyzed data (N = 636) from the SMART Africa-Uganda study (2016-2022), a cluster randomized clinical trial testing an evidence-based family-strengthening intervention called Amaka Amasanyufu (translated as "Happy Families" in the local language). Children aged 8-13 and their caregivers were recruited from 26 public primary schools that were randomized to: (1) control condition receiving generalized psychosocial literature (10 schools), (2) intervention delivered via parent peers (eight schools), and (3) intervention delivered via community healthcare workers (eight schools). Children completed the family cohesion questionnaire at baseline, 8 weeks, 16 weeks, and 6 months post-intervention completion. The intervention effectiveness was evaluated via a three-level logistic mixed effects model with pairwise comparisons across study conditions within each time point. Participants in the parent-peer intervention group had greater odds of being in the higher family cohesion group than participants in the control group at 8 weeks (OR = 3.24), 16 weeks (OR = 1.88) and 6 months (OR = 2.07). At 8 weeks, 16 weeks, and 6 months, participants in the community health worker group had 3.98, 2.08, and 1.79 times greater odds of being in the higher family cohesion group than participants in the control group, respectively. Our findings strengthen the evidence base for Amaka Amansayufu as an effective intervention that can be utilized in SSA to improve family cohesion in families with children experiencing behavioral challenges.

Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.

Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Here we show that activation of complement C5a and C5a receptor 1 (C5aR1) controls GC accumulation and the inflammatory response in experimental and clinical Gaucher disease. Marked local and systemic complement activation occurred in GCase-deficient mice or after pharmacological inhibition of GCase and was associated with GC storage, tissue inflammation and proinflammatory cytokine production. Whereas all GCase-inhibited mice died within 4-5 weeks, mice deficient in both GCase and C5aR1, and wild-type mice in which GCase and C5aR were pharmacologically inhibited, were protected from these adverse effects and consequently survived. In mice and humans, GCase deficiency was associated with strong formation of complement-activating GC-specific IgG autoantibodies, leading to complement activation and C5a generation. Subsequent C5aR1 activation controlled UDP-glucose ceramide glucosyltransferase production, thereby tipping the balance between GC formation and degradation. Thus, extensive GC storage induces complement-activating IgG autoantibodies that drive a pathway of C5a generation and C5aR1 activation that fuels a cycle of cellular GC accumulation, innate and adaptive immune cell recruitment and activation in Gaucher disease. As enzyme replacement and substrate reduction therapies are expensive and still associated with inflammation, increased risk of cancer and Parkinson disease, targeting C5aR1 may serve as a treatment option for patients with Gaucher disease and, possibly, other lysosomal storage diseases.

An Examination of the 4 Rs 2 Ss for Problem Behaviors: A Preventive Approach.

Early treatment of behavioral problems can prevent their progression into intractable disorders. This study examined the impact of a multiple family group (MFG) intervention for children with behavior symptoms and their families. Fifty-four (n = 54) caregiver/child dyads with sub-clinical levels of oppositional defiant disorder (ODD) participated in a 16-week MFG. Child, caregiver, and family outcomes were assessed at baseline, post-treatment, and at 6 months follow-up. Significant decreases in impairment with parents, family members, and peers, and improvements in child self-esteem were found from baseline to follow-up. Caregiver stress increased; no significant changes in depression or perceived social support were found over time. The effectiveness of MFG as a preventive approach and areas of future research are discussed.

Plants utilise ancient conserved peptide upstream open reading frames in stress-responsive translational regulation.

The regulation of protein synthesis plays an important role in the growth and development of all organisms. Upstream open reading frames (uORFs) are commonly found in eukaryotic messenger RNA transcripts and typically attenuate the translation of associated downstream main ORFs (mORFs). Conserved peptide uORFs (CPuORFs) are a rare subset of uORFs, some of which have been shown to conditionally regulate translation by ribosome stalling. Here, we show that Arabidopsis CPuORF19, CPuORF46 and CPuORF47, which are ancient in origin, regulate translation of any downstream ORF, in response to the agriculturally significant environmental signals, heat stress and water limitation. Consequently, these CPuORFs represent a versatile toolkit for inducible gene expression with broad applications. Finally, we note that different classes of CPuORFs may operate during distinct phases of translation, which has implications for the bioengineering of these regulatory factors.

The longitudinal impact of an evidence-based multiple family group intervention (Amaka Amasanyufu) on oppositional defiant disorder and impaired functioning among children in Uganda: analysis of a cluster randomized trial from the SMART Africa-Uganda scale-up study (2016-2022).

BACKGROUND: Oppositional Defiant Disorders (ODDs) and other Disruptive Behavior Disorders (DBDs) are common among children and adolescents in poverty-impacted communities in sub-Saharan Africa. Without early intervention, its progression into adulthood can result in dire consequences. We examined the impact of a manualized family strengthening intervention called Amaka Amasanyufu designed to reduce ODDs and other DBDs among school-going children residing in low-resource communities in Uganda. METHODS: We used longitudinal data from the SMART Africa-Uganda study (2016-2022). Public primary schools were randomized to: (1) Control condition (receiving usual care comprising generalized psychosocial functioning literature), 10 schools; (2) intervention delivered via parent peers (Amaka-parents), 8 schools or; (3) intervention delivered via community healthcare workers (Amaka-community), 8 schools. All the participants were blinded. At baseline, 8- and 16-weeks postintervention initiation, caregivers completed the Iowa Conners Scale, which measured Oppositional Defiant Disorder (ODD) and Impairment Rating Scale to evaluate children's overall impairment and impaired functioning with peers, siblings, and parents; impaired academic progress, self-esteem, and family functioning. Three-level linear mixed-effects models were fitted to each outcome. Pairwise comparisons of postbaseline group means within each time point were performed using Sidak's adjustment for multiple comparisons. Only children positive for ODD and other DBDs were analyzed. RESULTS: Six hundred and thirty-six children screened positive for ODDs and other DBDs (Controls: n = 243; Amaka-parents: n = 194; Amaka-community: n = 199). At 8 weeks, Amaka-parents' children had significantly lower mean scores for overall impairment compared to controls, (mean difference: -0.71, p = .001), while Amaka-community children performed better on ODD (mean difference: -0.84, p = .016). At 16 weeks, children in both groups were performing better on ODD and IRS than controls, and there were no significant differences between the two intervention groups. CONCLUSIONS: The Amaka Amasanyufu intervention was efficacious in reducing ODD and impaired functioning relative to usual care. Hence, the Amaka Amasanyufu intervention delivered either by Amaka-community or Amaka-parents has the potential to reduce negative behavioral health outcomes among young people in resource-limited settings and improve family functioning. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03081195. Registered on 16 March 2017.

The Long-term (5-year) Impact of a Family Economic Empowerment Intervention on Adolescents Living with HIV in Uganda: Analysis of Longitudinal Data from a Cluster Randomized Controlled Trial from the Suubi+Adherence Study (2012-2018).

150/150 words.We examined the 5-year impact of an economic empowerment (EE) intervention on: adherence, viral suppression, sexual risk-taking intentions (primary); and physical health, educational and economic (secondary) outcomes among adolescents living with HIV in Uganda. The Suubi + Adherence study (2012-2018) randomized clinics to: (1) Control group, n = 19 clinics, n = 344 participants; (2) intervention group which received matched savings accounts, mentorship, financial management and, business development training, n = 20 clinics, n = 358 participants. Participants completed post-baseline assessments at 12-, 24-, 36-, and 48-months. No significant differences in viral load, sexual risk-intentions and physical health perception were observed. The intervention group had better adherence (at 24-months) (Contrast=-0.28; 95% CI: -0.55, -0.004), higher school enrolment (OR = 2.18; 95% CI:1.30, 3.66); reported savings OR = 2.03 (1.29, 3.18) and higher savings (Contrast = 0.40; 95% CI:0.10, 0.70) than controls at 48-months. The EE intervention was efficacious in improving adherence, school enrolment, and economic outcomes creating opportunities for improved overall health among adolescents living with HIV.

Interpersonal Psychotherapy's problem areas as an organizing framework to understand depression and sexual and reproductive health needs of Kenyan pregnant and parenting adolescents: a qualitative study.

BACKGROUND: Peripartum adolescents experience significant interpersonal transitions in their lives. Depression and emotional distress are often exacerbated by adolescents' responses to these interpersonal changes. Improved understanding of pregnancy-related social changes and maladaptive responses to these shifts may inform novel approaches to addressing the mental health needs of adolescents during the perinatal period. The paper aims to understand the sources of psychological distress in peripartum adolescents and map these to Interpersonal Psychotherapy's (IPT) problem areas as a framework to understand depression. METHOD: We conducted interviews in two Nairobi primary care clinics with peripartum adolescents ages 16-18 years (n = 23) with experiences of depression, keeping interpersonal psychotherapy framework of problem areas in mind. We explored the nature of their distress, triggers, antecedents of distress associated with an unplanned pregnancy, quality of their relationships with their partner, parents, and other family members, perceived needs, and sources of support. RESULTS: We found that the interpersonal psychotherapy (IPT) framework of interpersonal problems covering grief and loss, role transitions, interpersonal disputes, and social isolation was instrumental in conceptualizing adolescent depression, anxiety, and stress in the perinatal period. CONCLUSION: Our interviews deepened understanding of peripartum adolescent mental health focusing on four IPT problem areas. The interpersonal framework yields meaningful information about adolescent depression and could help in identifying strategies for addressing their distress.

Male Caregivers and Engagement in a Family Strengthening Program for Child Disruptive Behavior Disorders.

Awareness and interest in involving male caregivers in child mental health treatment has grown, especially for youth with disruptive behavior disorders like oppositional defiant disorder (ODD). The purpose of this study was to examine the relationship between male caregiver involvement and treatment engagement for child ODD. Children (n = 122) ages 7-11 and their caregivers participated in the 4 Rs 2 Ss Strengthening Families Program for child-onset ODD. Families were compared based on male caregiver presence. Families with a male caregiver were significantly more resourced with respect to income, educational status, and food security. Additionally, they were over three times less likely to drop out of the program than those without a male caregiver. The presence of a male caregiver was associated with increased resources and higher rates of engagement in services than single, female-headed families. Future research is needed to discern the underlying mechanisms of this association.

Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a-C5aR1-glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a-C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. These results reveal a common involvement of the complement and glycosphingolipid systems driving immune inflammation and tissue damage in COVID-19 and GD, respectively. It is therefore expected that combined targeting of the complement and sphingolipid pathways could ameliorate the tissue destruction, organ failure, and death in patients at high-risk of developing severe cases of COVID-19.

Family-level correlates of disruptive behavior challenges among children in Southwestern Uganda.

Introduction: This exploratory study sought to examine the extent to which family-level factors are associated with disruptive behavioral disorder (DBD) symptoms, including oppositional defiant disorder (ODD) and conduct disorder (CD) among school children in Uganda, a low-resource country in SSA. The examination of key influences within the SSA context is important to guide needed investments in mental health care and family-level support. Importantly, identifying families at higher risk can inform the development of contextualized family interventions that reinforce positive parenting practices. Method: We analyzed baseline data (N = 2110) from the NIH-funded Strengthening Mental health And Research Training in Africa (SMART Africa) scale-up study in Southwestern Uganda. Children aged 8-13 and their caregivers were recruited from 30 public primary schools. DBDs were examined using the DBD rating scale, Iowa Conners, and Impairment scales. Logistic regression analysis using cluster adjusted robust standard errors to adjust for within-school clustering was conducted to assess the association between DBD symptoms and family-level factors, including parenting practices, marital status, and family size. Results: Results indicate that poor parental supervision (OR = 1.17; CI: 1.13, 1.21; P <.001), divorced families (OR = 1.33; CI: 1.03, 1.72; P <.05), and widowed families (OR = 1.48; CI: 1.10, 2.00; P <.01) were associated with higher DBD symptoms among children. On the other hand, caregiver age (OR = 0.99; CI: 0.98, 0.99; P <.01) was associated with lower DBD symptoms among children. Moreover, caregiver employment and parental education were not statistically significant in the model. Conclusion: Findings from the study reveal an association between family-level factors and behavioral difficulties among children in Uganda suggesting that divorced and widowed families may benefit from additional support in caring for children. Moreover, caregivers may also benefit from programs that provide tools for effective parental supervision.

Relationship Between Mental Health and HIV Transmission Knowledge and Prevention Attitudes Among Adolescents Living with HIV: Lessons from Suubi + Adherence Cluster Randomized Study in Southern Uganda.

We assessed the effect of depression, hopelessness, and self-concept on HIV prevention attitudes and knowledge about infection, transmission and sexual risk behavior among adolescents living with HIV in Uganda. Utilizing longitudinal data from 635 adolescents living with HIV, multiple ordinary least square regression was used to evaluate associations between the three indicators of mental health functioning at baseline and HIV knowledge and prevention attitudes at 12-months follow-up. We found that depression (ß = - 0.17; 95% CI - 0.31, - 0.04) and hopelessness (ß = - 0.16; 95% CI - 0.28, - 0.04) scores at baseline were associated with a 0.17 and 0.16 average reduction in HIV prevention attitudes and HIV knowledge scores, respectively at 12-months follow-up. However, self-concept was not significantly associated with HIV knowledge or prevention attitudes. Adolescents living with HIV with greater levels of hopelessness are at increased risk of having limited HIV knowledge while those with greater symptoms of depression had less favorable HIV prevention attitudes.

Suubi+Adherence-Round 2: A study protocol to examine the longitudinal HIV treatment adherence among youth living with HIV transitioning into young adulthood in Southern Uganda.

BACKGROUND: Youth living with HIV (YLHIV) in Sub-Saharan African (SSA) are less likely to adhere to antiretroviral therapy (ART) and other health-related regimens. As a consequence, YLHIV are not only at risk for health problems and mental health comorbidities, but are also at risk for cognitive deficits, including in areas of memory and executive functioning. The Suubi+Adherence study followed 702 adolescents (10-16 years of age) receiving bolstered standard of care and a family economic empowerment intervention comprising an incentivized youth financial savings account (YSA) augmented with financial literacy training (FLT) and peer mentorship. The study findings pointed to superior short-term viral suppression and positive adolescent health and mental health functioning among participants receiving the intervention. The original group of adolescents who received Suubi+Adherence are now transitioning into young adulthood. This paper presents a protocol for the follow-up phase titled Suubi+Adherence Round 2. METHODS: The original cohort in Suubi+Adherence will be tracked for an additional five years (2020-2025). Specifically, the long term follow-up will allow to: 1) ascertain the extent to which the short term outcomes identified in the first 6 years of the intervention are maintained as the same group transitions through young adulthood; and 2) address new scientific questions regarding ART adherence; HIV care engagement; protective health behaviors; and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. Additionally, the team examines the potential mechanisms through which the observed long-term outcomes happen. Moreover, the Suubi+Adherence-Round 2 adds a qualitative component and extends the cost effectiveness component. DISCUSSION: Guided by asset and human development theories, Suubi+Adherence-R2 will build on the recently concluded Suubi+Adherence study to conduct one of the largest and longest running studies of YLHIV in SSA as they transition into young adulthood. The study will address new scientific questions regarding long-term ART adherence, HIV care engagement, protective health behaviors, and the potential of FEE to mitigate the development of HIV-associated neurocognitive disorders in YLHIV. The findings may inform efforts to improve HIV care among Uganda's YLHIV, with potential replicability in other low-resource countries. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT01790373.

Examining Organizational Factors Supporting the Adoption and Use of Evidence-Based Interventions.

The purpose of this study was to develop a greater understanding of the factors influencing the adoption of evidence-based interventions in outpatient mental health clinics serving youth. An improved understanding of these factors can potentially improve efforts to ensure effective adoption, implementation, and sustainment of evidence-based interventions, and thus improve treatment for youth in mental health settings. This explanatory cross-sectional study involves secondary data analysis of a longitudinal randomized control intervention trial. The SEM- based model that was tested supported the primary hypothesis that a more supportive organizational climate with greater readiness for change is more likely to improve the chances for the adoption of evidence-based interventions in outpatient mental health clinics serving youths.

C-X-C Motif Chemokine Ligand 9 and Its CXCR3 Receptor Are the Salt and Pepper for T Cells Trafficking in a Mouse Model of Gaucher Disease.

Gaucher disease is a lysosomal storage disease, which happens due to mutations in GBA1/Gba1 that encodes the enzyme termed as lysosomal acid ß-glucosidase. The major function of this enzyme is to catalyze glucosylceramide (GC) into glucose and ceramide. The deficiency of this enzyme and resultant abnormal accumulation of GC cause altered function of several of the innate and adaptive immune cells. For example, augmented infiltration of T cells contributes to the increased production of pro-inflammatory cytokines, (e.g., IFNγ, TNFα, IL6, IL12p40, IL12p70, IL23, and IL17A/F). This leads to tissue damage in a genetic mouse model (Gba19V/-) of Gaucher disease. The cellular mechanism(s) by which increased tissue infiltration of T cells occurs in this disease is not fully understood. Here, we delineate role of the CXCR3 receptor and its exogenous C-X-C motif chemokine ligand 9 (CXCL9) in induction of increased tissue recruitment of CD4+ T and CD8+ T cells in Gaucher disease. Intracellular FACS staining of macrophages (Mϕs) and dendritic cells (DCs) from Gba19V/- mice showed elevated production of CXCL9. Purified CD4+ T cells and the CD8+ T cells from Gba19V/- mice showed increased expression of CXCR3. Ex vivo and in vivo chemotaxis experiments showed CXCL9 involvement in the recruitment of Gba19V/- T cells. Furthermore, antibody blockade of the CXCL9 receptor (CXCR3) on T cells caused marked reduction in CXCL9- mediated chemotaxis of T cells in Gba19V/- mice. These data implicate abnormalities of the CXCL9-CXCR3 axis leading to enhanced tissue recruitment of T cells in Gaucher disease. Such results provide a rationale for blockade of the CXCL9/CXCR3 axis as potential new therapeutic targets for the treatment of inflammation in Gaucher disease.

From "4Rs and 2Ss" to "Amaka Amasanyufu" (Happy Families): Adapting a U.S.-based Evidence-Based Intervention to the Uganda Context.

In Uganda, one in five children presents mental health challenges, including disruptive behavior disorders (DBDs). DBDs can persist through adulthood and result in negative outcomes. Effective interventions for DBDs have been developed and tested in high-poverty communities in developed countries. Yet, most African countries, such as Uganda, lack such interventions. This paper describes the adaptation process of an evidence-based intervention of U.S. origin to optimize fit to context with intervention fidelity, as part of a randomized trial conducted with youth that exhibit behavioral challenges and their caregivers in 30 schools in Uganda. The process involved: initial meetings with headteachers and teachers to introduce the study and the main concepts of the intervention; initial manual review focusing on 4Rs and 2Ss content by the Uganda team; engagement of community stakeholders for additional feedback on content and cultural relevance; final revision of the manual; and collection of children's drawings for the illustration of the manual. This paper describes both similarities and differences between the original and adapted intervention content and methods of delivery. The findings also highlight the importance of involving community stakeholders in the adaptation process.

En Uganda, uno de cada cinco niños presenta problemas de salud mental, incluidos los trastornos del comportamiento disruptivo (TCD). Los TCD pueden continuar hasta la adultez y tener consecuencias negativas. Se han desarrollado intervenciones eficaces para los TCD, las cuales se han evaluado en comunidades con altos índices de pobreza en países desarrollados. Sin embargo, la mayoría de los países africanos, como Uganda, carecen de dichas intervenciones. Este artículo describe el proceso de adaptación de una intervención factual de origen estadounidense para optimizar su adaptación al contexto con la fidelidad de la intervención como parte de un ensayo aleatorizado realizado con jóvenes que presentan problemas conductuales y sus cuidadores en 30 escuelas de Uganda. El proceso consistió en reuniones iniciales con directores y maestros para presentar el estudio y los conceptos principales de la intervención; una revisión inicial del manual centrada en el contenido de la intervención "4Rs and 2 Ss" por parte del equipo de Uganda; la participación de partes interesadas de la comunidad para obtener comentarios adicionales sobre el contenido y la relevancia cultural; la revisión final del manual; y la recopilación de dibujos de los niños para la ilustración del manual. Este artículo describe tanto las similitudes como las diferencias entre el contenido de la intervención original y la adaptada y los métodos de implementación. Los resultados también destacan la importancia de hacer participar a las partes interesadas en el proceso de adaptación.