Substance use among HIV-infected adolescents in Uganda: rates and association with potential risks and outcome factors.

This article sets out to investigate alcohol and substance use (ASU) among adolescents living with HIV (ALWH) in the sub-Saharan African setting of Uganda. A cross-sectional analysis of the records of 479 adolescents (aged between 12and 17 years) attending the study, "Mental health among HIV infected CHildren and Adolescents in KAmpala and Masaka, Uganda (the CHAKA study)" was undertaken. ASU was assessed through both youth self-report and caregiver report using the Diagnostic and Statistical Manual of Mental Disorders-5 referenced instruments, the Youth Inventory-4R and the Child and Adolescent Symptom Inventory-5 (CASI-5). Rates and association with potential risk and outcome factors were investigated using logistic regression models. The rate of ASU was 29/484 (5.9%) with the most frequently reported ASU being alcohol 22/484 (4.3%) and marijuana 10/484 (2.1%). Functional impairment secondary to ASU was reported by 10/484 (2.1%) of the youth. ASU was significantly associated with urban residence, caregiver psychological distress and the psychiatric diagnosis of post-traumatic stress disorder. On associations with negative outcomes, ASU was significantly associated with only "ever had sex". Health care for ALWH in sub-Saharan Africa should include ASU prevention and management strategies.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

[Characterization of Salmonella Heidelberg strains isolated in Chile]. / Caracterización de cepas clínicas y ambientales de Salmonella enterica subsp. enterica serovar Heidelberg aisladas en Chile.

BACKGROUND: Salmonella Heidelberg (S. Heidelberg) causes gastroenteritis and sometimes bacteremia and endocarditis. In other countries, this serovar has multidrug resistance including extended-spectrum ß-lactamases (ESBLs) and AmpC (ß-lactamases (AmpC), associated with the blaCMY-2 gene. In Chile, an outbreak by S. Heidelberg occurred in 2011, the phenotypic and genetic characteristics of Chilean strains are unknown. AIM: To determine the antimicrobial susceptibility, presence of plasmids and virulence factor genes in S. Heidelberg strains isolated in Chile over the period 2006-2011. MATERIAL AND METHODS: In sixty-one S. Heidelberg clinical and environmental strains collected by the Public Health Institute in Chile during 2006-2011, antimicrobial susceptibility, plasmids and virulence factor genes (invA, sifA, pefA, agfA, lpfA and, stkD) were studied. RESULTS: S. Heidelberg had a high susceptibility to sulfamethoxazole-trimethoprim, gentamicin, ceftriaxone, ceftiofur, chloramphenicol, amoxicillin-clavulanic acid and ampicillin. However, 52% had decreased susceptibility to ciprofloxacin and 33% resistance to tetracycline. ESBLs were detected in three strains isolated from blood cultures, environment and human feces. The latter strain was positive for AmpC and blaCMY-2 gene. Fifty three of 61 strains showed one to seven plasmids of 0.8 to approximately 30 kb. Most plasmids were small with sizes between 0.8 and 2 kb. All isolates were positive for all genes except pefA. CONCLUSIONS: S. Heidelberg isolated from Chilean samples was susceptible to first-line antimicrobials, except tetracycline and ciprofloxacin. The emergence of strains with ESBLs and AmpC should be a warning. The strains were homogeneous for virulence genes, but heterogeneous in their plasmids.

The methods and outcomes of cultural adaptations of psychological treatments for depressive disorders: a systematic review.

BACKGROUND: Cultural adaptations of evidence-based psychological treatments (PTs) are important to enhance their universal applicability. The aim of this study was to review systematically the literature on adaptations of PTs for depressive disorders for ethnic minorities in Western countries and for any population in non-Western countries to describe the process, extent and nature of the adaptations and the effectiveness of the adapted treatments. METHOD: Controlled trials were identified using database searches, key informants, previous reviews and reference lists. Data on the process and details of the adaptations were analyzed using qualitative methods and meta-analysis was used to assess treatment effectiveness. RESULTS: Twenty studies were included in this review, of which 16 were included in the meta-analysis. The process of adaptation was reported in two-thirds of the studies. Most adaptations were found in the dimensions of language, context and therapist delivering the treatment. The meta-analysis revealed a statistically significant benefit in favor of the adapted treatment [standardized mean difference (SMD) -0.72, 95% confidence interval (CI) -0.94 to -0.49]. CONCLUSIONS: Cultural adaptations of PTs follow a systematic procedure and lead primarily to adaptations in the implementation of the treatments rather than their content. Such PTs are effective in the treatment of depressive disorders in populations other than those for whom they were originally developed.

Sleep disturbances and depressive symptoms: an investigation of their longitudinal association in a representative sample of the UK general population.

BACKGROUND: It has been argued that sleep disturbances are a risk factor for depression but previous longitudinal studies have had limitations and not addressed alternative explanations. The aim of this study was to examine the longitudinal association between sleep disturbances and depressive symptoms in a nationally representative sample. METHOD: Data from the 18-month follow-up of the UK National Psychiatric Morbidity survey were used (n = 2406). Sleep disturbances, depressive and other psychiatric symptoms (fatigue, concentration problems, irritability, anxiety and pain symptoms) were assessed using the Revised Clinical Interview Schedule (CIS-R). The bidirectional association between symptoms was investigated with logistic regression analyses and path analysis. RESULTS: Sleep disturbances and depressive symptoms were correlated with each other cross-sectionally (r = 0.52, p < 0.001). In the longitudinal analysis, sleep disturbances at baseline did not predict depressive symptoms at follow-up [odds ratio (OR) 1.27, 95% confidence interval (CI) 0.51-3.19] and the same was observed for the reciprocal association (OR 0.87, 95% CI 0.56-1.35). In the path analysis, the reciprocal model did not have a better fit compared to the simpler first-order model without cross-lagged paths. The path from sleep disturbances at baseline to depressive symptoms at follow-up had a minimal contribution to the explained variance of the latter (<1%). CONCLUSIONS: Previous studies may have overestimated the importance of sleep disturbances as an independent risk factor of depression. The strong cross-sectional association is compatible with sleep disturbances being either a prodromal or a residual symptom of depression and this may have implications for recognition and treatment of depression.

Father absence and depressive symptoms in adolescence: findings from a UK cohort.

BACKGROUND: Previous studies suggest a link between parental separation or divorce and risk of depression in adolescence. There are, however, few studies that have prospectively examined the effects of timing of biological father absence on risk for depressive symptoms in adolescence while controlling for a range of confounding factors. METHOD: We examine the association between father absence occurring in early (the first 5 years) and middle childhood (5-10 years) and adolescent depressive symptoms in a sample comprising 5631 children from the UK-based Avon Longitudinal Study of Parents and Children (ALSPAC). Self-reported depressive symptoms at 14 years were assessed using the Short Mood and Feelings Questionnaire (SMFQ). Father absence was assessed from maternal questionnaires completed at regular intervals from the birth of the study child up to 10 years. RESULTS: There was evidence for an association between father absence in early childhood and increased odds of depressive symptoms at 14 years. This association was stronger in girls than in boys and remained after adjusting for a range of socio-economic, maternal and familial confounders assessed prior to the father's departure. Conversely, there was no evidence for an association between father absence in middle childhood and depressive symptoms at 14 years. CONCLUSIONS: Father absence in early childhood increases risk for adolescent depressive symptoms, particularly in girls. Future research should be aimed at identifying possible biological and psychosocial mechanisms linking father absence to depressive symptomatology to enable the development of family-based early prevention and intervention programmes targeting young children at risk.

Association between pubertal development and depressive symptoms in girls from a UK cohort.

BACKGROUND: It is unclear whether pubertal status or timing of puberty explains the increase in depressive symptoms in girls during adolescence. METHOD: This is a longitudinal study based on 2506 girls from the Avon Longitudinal Study of Parents and Children (ALSPAC). Self-reported depressive symptoms at 10.5, 13 and 14 years were assessed using the Short Mood and Feelings Questionnaire (SMFQ). Pubertal status (Tanner breast and pubic hair stage) and timing of menarche were derived from questionnaires administered from age 8 to 14 years. We used multivariable regression models to examine the relative contributions of pubertal status and timing in accounting for increases in level of depressive symptoms at 14 years. RESULTS: With increasing age, the association between breast development and depressive symptoms strengthened. Pubertal status (breast stage), rather than timing of menarche, was independently associated with depressive symptoms at 14 years. There was strong evidence for a linear relationship between breast stage and depressive symptoms at 14 years [increase in 0.17 S.D. (range 0.10-0.24) of depressive symptoms for advancement of each breast stage]. CONCLUSIONS: Depressive symptoms in mid-adolescence were more strongly influenced by breast stage than timing of menarche. This could imply that the female rise in depression during adolescence is due to increasing estrogen levels, and might explain why the gender difference in rates of depression emerges at this stage. Future research should be aimed at identifying the mechanism of action of pubertal change, including direct effects of pubertal hormones and indirect effects mediated by psychosocial factors.

Understanding the complex relationship between multidimensional poverty and depressive symptoms among young South Africans: A cross-sectional study.

BACKGROUND: We use the Global Multidimensional Poverty Index (MPI) to explore how different dimensions of poverty more directly linked to young people are associated with depressive symptoms among South African youth. METHODS: Data came from the 2017 wave of the nationally-representative National Income Dynamics Study (NIDS) in South Africa. We focused on a sample of 15-24-year-olds whose depressive symptoms were assessed using an adapted version of the 10-item Centre for Epidemiological Studies Depression Scale. We examine how individual dimensions and indicators of the MPI relate to depression, in comparison to more conventional measures, including household income, subjective social standing, overcrowding and personal assets. Cross-sectional analyses were adjusted for clustering to account for sampling design. RESULTS: The MPI index was not associated with probable depression (OR = 1.02, 95 % CI 0.81-1.29). Only lack of access to the labour market emerged as a key individual dimension associated with probable depression (OR = 5.29, 95 % CI 1.70-16.47), a relationship driven by an increased odds for those not in employment, education or training. Lack of household assets, living in an informal dwelling and lower perceived social standing were also associated with increased odds for depression. No gender differences were noted. LIMITATIONS: The study is cross-sectional and not suitable to examine the causal nature of the association between multidimensional poverty and depression. CONCLUSIONS: Poverty dimensions that measure youth's access to employment or training have a strong association with depression. Further research is needed to assess whether improved access to employment or training contributes to improving mental health among young South Africans.

Implementation and scalability of a digital intervention to reduce depressive symptoms in people with diabetes, hypertension or both in Brazil and Peru: a qualitative study of health system's stakeholders' perspectives.

Two randomized controlled trials (RCTs) in Brazil and Peru demonstrated the effectiveness of CONEMO, a digital intervention supported by trained nurses or nurse assistants (NAs), to reduce depressive symptoms in people with diabetes and/or hypertension. This paper extends the RCTs findings by reflecting on the conditions needed for its wider implementation in routine care services. A qualitative study using semi-structured interviews and content analysis was conducted with nurses/NAs, clinicians, healthcare administrators, and policymakers. Informants reported that CONEMO would be feasible to implement in their health services, but some conditions could be improved before its scale-up: reducing workloads of healthcare workers; raising mental health awareness among clinicians and administrators; being able to inform, deliver and accompany the intervention; assuring appropriate training and supervision of nurses/NAs; and supporting the use of technology in public health services and by patients, especially older ones. We discuss some suggestions on how to overcome these challenges.

A pilot study of a stepped-care brief intervention to help psychologically-distressed women displaced by conflict in Bogotá, Colombia.

BACKGROUND: Colombia's 6.5 million internally displaced persons (IDPs) have been exposed to trauma, loss, and hardships. Common mental disorders (CMDs) are prevalent in this group, yet there are few evidence-based psychosocial interventions for this population. We assessed the feasibility and acceptability of a stepped-care intervention for women IDPs in Bogota, Colombia. METHODS: Feasibility to recruit participants for an intervention trial, to screen for CMDs and displacement-related traumas, to refer high-risk cases to professional consultation, to implement evidence-based interpersonal counseling (IPC) for women with diagnosed CMDs, to retain participants in the intervention, and to conduct follow-up assessments was assessed. Assessment instruments were validated. The intervention was delivered by trained outreach personnel. Intervention acceptability was assessed by monitoring session attendance, dropout rates, and satisfaction. Potential efficacy was evaluated with pre- and post-intervention measures of CMDs. RESULTS: We recruited 279 women IDPs into the intervention. On screening, 177 (63.4%) had symptom levels suggesting a CMD. Participants endorsed a wide range of displacement-related exposures. Most participants receiving IPC decreased their symptom levels at follow-up. Many participants did not complete the recommended number of IPC sessions; loss to follow-up was 30%. The performance of the outreach personnel improved after the initial intervention team was replaced with community members trained to deliver the intervention. The Bogotá health system was unable to reliably accommodate emergency psychiatric referrals. CONCLUSIONS: The IPC intervention shows promise, but significant challenges remain for improving reach, adherence, and participant retention. We identified strategies and partnerships to redress some of the main study limitations.

Caracterización epidemiológica: descripción de mortalidad para hemorragia subdural aguda no traumática en el período 2017-2021, en Chile / Epidemiological characterization: description of mortality for non-traumatic acute subdural hemorrhage in the 2017-2021 period, in Chile

Introducción: La hemorragia subdural aguda no traumática (HSDNT) es una patología relacionada a factores de riesgo cardiovascular (RCV). Por falta de estudios epidemiológicos nacionales, se plantea estudiar la tasa de mortalidad (TM) y defunciones por HSDNT entre los años 2017-2021 en Chile. Metodología: Estudio descriptivo, transversal, sobre defunciones por HSDNT entre los años 2017-2021 en Chile (N=878), según grupo etario, sexo y lugar de defunción, usando datos obtenidos del departamento de estadística e información en salud. Se utilizó estadística descriptiva y cálculo de TM. No requirió aprobación por comité de ética. Resultados: Se calculó una TM de 0,99/100.000 habitantes entre los años 2017-2021, siendo la mayor los años 2017-2019 y 2020 con TM de 1/100.000. El sexo masculino presentó TM de 1,27/100.000, el grupo etario mayor a 80 años presentó una TM de 19,28/100.000 habitantes. Según lugar de defunción, el año 2020 un 83% (148) de las defunciones fue en hospital o clínica. Discusión: La prevalencia del RCV hace relevante el estudio de mortalidad por HSDNT, donde la principal hipótesis de su mortalidad en Chile estaría basada en estos factores riesgo latentes. Según lugar de defunción, se podría suponer dadas mayores complicaciones en aquellos pacientes hospitalizados por HSDNT. Conclusión: Dada la nula existencia de datos sobre esta patología en Chile, se realizó una caracterización epidemiológica en conjunto a un análisis de defunciones según el lugar, aportando una perspectiva nacional de mortalidad sobre este cuadro en particular.

Introduction: Non-traumatic acute subdural hemorrhage (NTSDH) is related to cardiovascular risk factors (CVR). Due to lack of national epidemiological studies, it is proposed to study mortality rate (MR) and deaths from HSD between the years 2017-2021 in Chile. Methodology: Descriptive, observational, cross-sectional study on deaths due to SDH between the years 2017-2021 in Chile (N=878), in a population older than 15 years, according to age group, sex and place of death, using data obtained from Departamento de estadísticas e información en salud. Descriptive statistics and MR calculation were used. It did not require approval by an ethics committee. Results: A MR of 0.99/100,000 inhabitants was calculated between the years 2017-2021, the year being the highest in the years 2017-2019 and 2020 with MR of 1/100,000. Male sex presented a MR of 1.27/100,000, the age group over 80 years presented a MR of 19.28/100,000 inhabitants. By place of death, in 2020 there were 148 deaths in hospitals or clinics. Discussion: The prevalence of CVR makes the study of mortality from NTSDH relevant, where the hypothesis of its mortality in Chile would be based on these risk factors. Depending on the place of death, it could be assumed that there are greater complications in those patients hospitalized for NTSDH. Conclusion: Given the null existence of data on this pathology in Chile, an epidemiological characterization was carried out together with an analysis of deaths according to the place, providing a national perspective of mortality about this disease.

Molecular epidemiology and antimicrobial resistance of Clostridium difficile in a national geriatric hospital in Costa Rica.

BACKGROUND: The epidemiology of Clostridium difficile infections (CDI) is changing rapidly worldwide; knowledge on the genotypes of C. difficile circulating in specialized geriatric hospitals and their resistance to antibiotics is scarce or non-existent. METHODS: Prospective study of the molecular epidemiology of CDI, conducted in a national geriatric hospital in Costa Rica for a period of 11 months. RESULTS: The study patients exhibited a diverse range of comorbidities, but none were associated with CDI. Polyclonality, including three new ribotypes, and a high level of resistance to antibiotics were determined by analysing the 32 isolates obtained in these cases. Despite the diversity in strains observed, the most frequent types were NAP6/RT002 and NAP2/RT001. NAP9/RT017 was associated with community acquisition. Nineteen types of antimicrobials were used before the onset of diarrhoea in the patients; no particular genotype was associated with the onset of infection or severity. CONCLUSION: Based on the abundance of strain types observed and their resistance to antibiotics in this geriatric hospital, these results contribute to a better overall understanding of the epidemiology of CDI worldwide, and to surveillance programmes targeting geriatric populations.

LATIN-MH: a model for building research capacity within Latin America.

BACKGROUND: Latin America Treatment and Innovation Network in Mental Health (LATIN-MH) is a research hub located in Brazil and Peru that conducts a research project to help reduce the treatment gap in mental health in Latin America (LA). Besides its research core, LATIN-MH has a Capacity Building (CB) component that aims to help young researchers receive the specific training to contribute to the growing scientific production in mental health in LA. METHODS: LATIN-MH proposal in CB includes a series of actions to prepare professionals in the research area. The main proposals are described here, which include online study groups, promotion of scientific meetings, hands-on training in different levels and sharing of information. RESULTS: LATIN-MH CB activities are at its initial stages but the proposed activities were well evaluated by the participants. The first participating fellows who finished their fellowships are contributing elsewhere in the mental treatment and human resources formation area. CONCLUSION: The repercussion of LATIN-MH actions in CB and its evaluation, particularly on the formation of human resources and dissemination of information, show that the hub is contributing to the critic formation of young researchers and the circulation of important information.

How to reduce the number of rating scale items without predictability loss?

Rating scales are used to elicit data about qualitative entities (e.g., research collaboration). This study presents an innovative method for reducing the number of rating scale items without the predictability loss. The "area under the receiver operator curve method" (AUC ROC) is used. The presented method has reduced the number of rating scale items (variables) to 28.57% (from 21 to 6) making over 70% of collected data unnecessary. Results have been verified by two methods of analysis: Graded Response Model (GRM) and Confirmatory Factor Analysis (CFA). GRM revealed that the new method differentiates observations of high and middle scores. CFA proved that the reliability of the rating scale has not deteriorated by the scale item reduction. Both statistical analysis evidenced usefulness of the AUC ROC reduction method.

Caracterización epidemiológica: análisis de tasa de mortalidad e índice de swaroop para peritonitis en el periodo 2017- 2021, en Chile / Epidemiological characterization: peritonitis mortality rate and swaroop Index in the period 2017 - 2021, in Chile

Introducción: La peritonitis alcanza una mortalidad global de hasta un 60%. Dada la falta de estudios epidemiológicos nacionales, se plantea calcular la tasa de mortalidad (TM) por peritonitis entre los años 2017-2021 en Chile. Metodología: Estudio descriptivo, ecológico, sobre defunciones por peritonitis entre los años 2017-2021 en Chile (N=1.741), en población mayor de 15 años según grupo etario, sexo y región con datos obtenidos del departamento de estadística e información en salud. Se utilizó estadística descriptiva, cálculo de TM e índice de Swaroop (IS). No requirió aprobación por comité de ética. Resultados: Se calculó una TM de 2,47/100.000 habitantes entre los años 2017 y 2021, siendo el año 2020 la mayor con 3,07. El sexo femenino presentó una tasa de 2,65. El grupo etario con mayor TM es el de 80 y más con 141,7/100.000 habitantes. Para el IS por región, lideran las regiones XV y XII con 100%, siendo la más baja la XI con 83,3%. Discusión: El pico de TM para el año 2020 coincide con la pandemia por Covid-19, donde se reporta mayor mortalidad postoperatoria en pacientes infectados. El IS se mantiene mayor al 90% en el país, excepto en las Regiones X y XI, probablemente debido a la menor disponibilidad de centros de alta complejidad. Conclusión: Dada la ausencia de datos recientes de mortalidad para peritonitis, se realizó una actualización epidemiológica local, con perspectiva comparativa regional respecto a las TM de la población general y en mayores de 50 años.

Introduction: Peritonitis reaches an overall mortality of up to 60%. Given the lack of national epidemiological studies, it is proposed to calculate the mortality rate (MR) due to peritonitis between the years 2017-2021 in Chile. Methodology: Descriptive, ecological study about deaths by peritonitis between 2017 and 2021 in Chile (N=1,741), in a population older than 15 years old according to age group, sex, and region with data obtained from Departamento de Estadística e Información en Salud. Descriptive statistics were used, MR calculation, and Swaroop Index (SI). It did not require approval by an ethics committee. Results: A MR of 2.47/100,000 was calculated between the years 2017 and 2021, with 2020 being the highest with 3.07. The female sex presented a rate of 2.65. The age group with the highest MR is 80 and over with 141.7/100,000. For the SI by region, the XV and XII regions lead with 100%, the lowest being XI region with 83.3%. Discussion: The peak of MR for the year 2020 coincides with the Covid-19 pandemic and the highest postoperative mortality in infected patients. The SI remains above 90% in the country, except in X and XI regions, probably due to the lower availability of high complexity centers. Conclusion: Given the lack of recent mortality data for peritonitis, a local epidemiological update was carried out, with a regional comparative perspective regarding MR in the general population and in those over 50 years old.

Monitoring and evaluating capacity building activities in low and middle income countries: challenges and opportunities.

BACKGROUND: Lower and middle income countries (LMICs) are home to >80% of the global population, but mental health researchers and LMIC investigator led publications are concentrated in 10% of LMICs. Increasing research and research outputs, such as in the form of peer reviewed publications, require increased capacity building (CB) opportunities in LMICs. The National Institute of Mental Health (NIMH) initiative, Collaborative Hubs for International Research on Mental Health reaches across five regional 'hubs' established in LMICs, to provide training and support for emerging researchers through hub-specific CB activities. This paper describes the range of CB activities, the process of monitoring, and the early outcomes of CB activities conducted by the five research hubs. METHODS: The indicators used to describe the nature, the monitoring, and the early outcomes of CB activities were developed collectively by the members of an inter-hub CB workgroup representing all five hubs. These indicators included but were not limited to courses, publications, and grants. RESULTS: Results for all indicators demonstrate a wide range of feasible CB activities. The five hubs were successful in providing at least one and the majority several courses; 13 CB recipient-led articles were accepted for publication; and nine grant applications were successful. CONCLUSIONS: The hubs were successful in providing CB recipients with a wide range of CB activities. The challenge remains to ensure ongoing CB of mental health researchers in LMICs, and in particular, to sustain the CB efforts of the five hubs after the termination of NIMH funding.

Yeast two-hybrid screening using constitutive-active caspase-7 as bait in the identification of PA28gamma as an effector caspase substrate.

Caspase-3 and -7 represent executioner/effector caspases that directly cause apoptotic morphological changes by cleaving various death substrates. The substrates for caspases generally interact with active caspases, but not with inactive zymogens of caspase or procaspases. Here, to isolate proteins that interact with caspase-7, we established a yeast two-hybrid screening system using reversed-caspase-7, a constitutive active mutant of caspase-7 as a bait plasmid. Screening of an adult brain cDNA library led to isolation of proteasome activator 28 subunit, PA28gamma. In vitro translates of PA28gamma were cleaved by both recombinant caspase-3 and -7. Mutagenesis of potential cleavage site DGLD80 to EGLE80 completely abolished caspase-mediated cleavage. Moreover, endogenous PA28gamma was cleaved during not only Fas-induced apoptosis of HeLa cells, but also cisplatin-induced cell death of MCF7 cells, which are devoid of caspase-3. These findings indicate that PA28gamma is an endogenous substrate for caspase-3 and -7 and that yeast two-hybrid screening using reversed-caspase is a novel and useful approach to clone substrates for effector caspases.