Violence Exposure, Self-Reported Mental Health Concerns and Use of Alcohol and Drugs for Coping among Youth in the Slums of Kampala, Uganda.

This study aimed to a) compute the prevalence of violence exposure types, polyvictimization, and self-reported depression, anxiety, and using substances to cope among youth ages 12 to 18 years living on the streets or in the slums of Kampala, Uganda, (b) examine the independent associations among orphan status, violence exposure types, and self-reported mental health concerns, and c) explore the association between polyvictimization and mental health concerns. Data are from a 2014 cross-sectional survey of service-seeking youth ages 12 to 18 years (N = 1134) in Kampala, Uganda. Violence exposure types explored in this study were: witnessing family physical violence, direct physical abuse by a parent, any rape history, and physical dating violence. We used descriptive statistics and multivariable logistic regression to test study objectives. Over half of the sample (60.5%) reported experiencing at least one type of violence exposure; many youth endorsed self-reported depression (57.8%), anxiety (76.8%), and substance use to cope (37.0%). Exposure to violence was associated with higher odds for self-reported depression, anxiety, and using substances to cope. These findings underscore the urgent need to implement evidence-based interventions among this young, underserved population and their families to prevent violence, improve mental health outcomes, and promote resilience.

Orphanhood vulnerabilities for violence and HIV by education, sex, and orphan type among 18-24-year-old youth: findings from the 2018 Lesotho violence against children and youth survey.

HIV and violence among orphans are key measures of vulnerability in low-resource settings. Although Lesotho has the second highest HIV adult prevalence rate (21.1%) in the world, and the prevalence of orphanhood (44.2%) and violence exposure (67.0%) is high, little research exist on orphanhood vulnerabilities for violence and HIV in Lesotho. Using data from 4,408 youth (18-24 years old) from Lesotho's 2018 Violence Against Children and Youth survey, a nationally representative cross-sectional household survey, the study examined associations among orphan status, violence, and HIV and assessed how associations differed by education, sex, and orphan type, using logistic regression. Orphans had higher odds of violence (aOR, 1.21; 95% CI, 1.01-1.46) and HIV (aOR, 1.69; 95% CI, 1.24-2.29). Having primary education or less (aOR, 1.43; 95% CI, 1.02-2.02), male sex (aOR, 1.74; 95% CI, 1.27-2.36), and being a paternal orphan (aOR, 1.43; 95% CI, 1.14-1.80) were significant interaction terms for violence. Orphans who completed primary school or less (aOR, 1.61; 95% CI, 1.09-2.39), female (aOR, 3.08; 95% CI, 2.14-4.42) and double orphans (aOR, 2.54; 95% CI, 1.56-4.13) had higher odds of HIV. These relationships highlight the importance of comprehensive strategies to support education and family strengthening for orphans as core violence and HIV prevention efforts.

Systematic braiding of Smoke-Free Home SafeCare to address child maltreatment risk and secondhand smoke exposure: findings from a pilot study.

BACKGROUND: Exposure to secondhand tobacco smoke (SHS) and child maltreatment are preventable threats to child health. Few evidence-based interventions target both SHS and child maltreatment risk. The purpose of this paper is to describe the systematic braiding process of two evidence-based programs to address child SHS in the home and maltreatment perpetration risk, and present results from the formative work and pilot study. METHODS: The first 4 steps of the systematic braiding process were completed, including the following: (1) the identification of core elements of both programs, (2) the development of an initial draft of the braided curriculum (Smoke-Free Home SafeCare - SFH-SC), (3) an acceptability and feasibility pilot of SFH-SC with caregivers of young children who reported a smoker living in the home (N = 8), and (4) feedback collection on the braided curriculum from SafeCare Providers (N = 9). RESULTS: Experts identified common pedagogical and theoretical underpinnings for the two programs and braided Smoke-Free Homes: Some Things Are Better Outside into two SafeCare modules. Caregiver feedback from the pilot demonstrated that participants were engaged with SFH-SC and felt supported and comfortable discussing SHS intervention content with the SFH-SC Provider. Caregiver self-reports indicated a slight increase in smoke-free home rules from baseline to follow-up and a notable reduction in parent stress on the Parent Stress Index of 5.9 points (SD = 10.2). SafeCare Provider feedback following intensive review of the curriculum indicated high feasibility for SFH-SC delivery. CONCLUSIONS: Parent and Provider findings suggest SFH-SC is a viable intervention that has potential to reduce the public health impact of SHS and child maltreatment for at-risk families. PROTOCOL: The protocol for the pilot is not published elsewhere; however, the full protocol for the hybrid trial can be found here: https://clinicaltrials.gov/ct2/show/NCT05000632 . TRIAL REGISTRATION: NCT, NCT05000632. Registered 14 July 2021, there is not a separate registration number for the pilot.

The PTSD Symptom Presentation and the Effect of Polytrauma on PTSD Symptom Clusters Among Young People Who Have Experienced Commercial Sexual Exploitation and Trafficking.

Purpose: The purpose of this study was to describe the PTSD symptom presentation (including dissociative symptoms) of PTSD using the Diagnostic and Statistical Manual of Mental Disorders 5 th Edition diagnostic criteria and explore associations between the symptom severity for each of the four PTSD symptom clusters and polytrauma, defined as multiple exposures to different categories of potentially traumatic events. Methods: This is a secondary analysis of cross-sectional program evaluation data among 95 young people (aged 11-19) at therapy initiation in a southeastern state in the U.S. We used descriptive statistics and multivariable linear regression to test study objectives. Results: Eighty-one respondents (90.0%) experienced a potentially traumatic event in ≥ 2 trauma categories, in addition to experiencing CSE/T. Approximately two-thirds of respondents experienced clinically significant PTSD symptoms for each symptom cluster. Of the 31 young people who met full criteria for PTSD, 9 met criteria for the standard PTSD diagnosis, while 22 met criteria for the dissociative subtype of PTSD. On average, experiencing additional trauma categories was associated with substantively higher PTSD symptom cluster scores for each cluster. Conclusions: These findings support the need for a comprehensive assessment of trauma symptoms that includes cluster-specific PTSD symptoms. They also underscore the need to assess the full breadth and chronicity of trauma experiences to guide treatment planning and delivery, targeting specific domains of trauma impact. These findings can also inform the tailoring and adaptation of evidence-based interventions and strategies to better meet the needs of young people who have experienced CSE/T.

Posttraumatic Cognitions and Posttraumatic Stress Symptoms Among Young People Who Have Experienced Commercial Sexual Exploitation and Trafficking.

OBJECTIVES: The impact of posttraumatic cognitions on the development and maintenance of posttraumatic stress symptoms (PTSS) is understudied among children and adolescents who have experienced commercial sexual exploitation/trafficking (CSE/T). The objectives of this study were to (1) explore posttraumatic cognitions among help-seeking young people aged 11-19 who have experienced CSE/T; (2) determine whether experiencing direct violence, witnessing violence, polyvictimization (ie, multiple exposures to different categories of potentially traumatic events), or demographic characteristics differentially affect whether these young people meet clinical criteria for posttraumatic cognitions using established cutoffs; and (3) explore associations between posttraumatic cognitions and PTSS among young people who have experienced CSE/T. METHODS: This study is a secondary analysis of a baseline cross-sectional survey of 110 young people with substantiated CSE/T experiences who started trauma-focused cognitive behavioral therapy (mean [SD] age = 15.8 [1.5]) from August 1, 2013, through March 31, 2020, in a southeastern US state. We used descriptive statistics, adjusted modified Poisson regression, and adjusted linear regression to test study objectives. RESULTS: Fifty-seven of 110 (51.8%) young people aged 11-19 met clinical criteria for posttraumatic cognitions. Increased age and a greater number of trauma categories experienced were significantly associated with meeting clinical criteria for posttraumatic cognitions. On average, higher posttraumatic cognition scores were associated with higher PTSS scores, controlling for demographic characteristics (ß = 0.95; 95% CI, 0.64-1.26). CONCLUSIONS: These findings underscore the importance of assessing comprehensive trauma history and PTSS of young people who have experienced CSE/T, with added usefulness of measuring cognitive appraisals to inform a therapeutic treatment plan. Measuring cognitive appraisals that may influence PTSS and therapeutic success can ensure an effective public health response for this population.

The Impact of COVID-19 on the Delivery of an Evidence-Based Child Maltreatment Prevention Program: Understanding the Perspectives of SafeCare® Providers.

Child maltreatment (CM) is a global public health problem. Evidence-based home visiting programs, such as SafeCare®, reduce CM risk, and enhance parent-child relationships and other protective factors. As the result of the COVID-19 pandemic and resulting restrictions, SafeCare Providers transitioned from home to virtual delivery for the SafeCare curriculum. The purpose of this study is to 1) examine active SafeCare Providers' opinions on the feasibility and effectiveness of SafeCare via remote delivery, and 2) better understand workforce concerns for human service professionals within the context of COVID-19 mitigation efforts. Data are from a cross-sectional survey of SafeCare Providers (N = 303) in the United States, Canada, and Australia. The majority of Providers reported they were actively delivering SafeCare virtually and were comfortable with the delivery format. Providers indicated that the majority of SafeCare families are making progress on target skills, and that engagement is high among many families. Some service delivery challenges were reported, ranging from family data plan limitations to difficulty with delivery of specific components of the SafeCare curriculum related to modeling and assessment. The impact of COVID-19 on Providers' daily routines, stress level, and work-life balance has been significant. Remote, virtual delivery of CM prevention programming offers the opportunity to continue serving vulnerable families in the midst of a pandemic. Barriers related to family technology and data access must be addressed to ensure reach and the effective delivery of prevention programming during the pandemic and beyond.

Exploring the Impact of Trauma History on the Mental Health Presentations of Youth who have Experienced Commercial Sexual Exploitation and Trafficking.

This study explores the types and extent of potentially traumatic events that youth who have experienced commercial sexual exploitation and trafficking (CSE/T) report, and how these experiences influence mental health. CSE/T youth (N = 110, 11-19 years old) referred to Trauma-Focused Cognitive Behavioral therapists affiliated with Project Intersect provided self-report data between August 2013 and March 2020 at the start (baseline), mid-point, and completion of therapeutic services. This study focuses on the baseline data collected. Bivariate relationships were analyzed, and where bivariate associations were statistically significant, associations were assessed in adjusted regression models. Two logistic regressions were performed: one for the adjusted associations between types of potentially traumatic events reported by CSE/T youth and the outcome PTSD, and a second for the outcome emotional distress. Results indicated that polytrauma was significantly associated with PTSD diagnosis among CSE/T youth. Direct violence victimization and polytrauma were significantly associated with CSE/T youth emotional distress. Results inform behavioral medicine practitioner considerations for how to appropriately assess the potentially traumatic experiences of CSE/T youth, and how these experiences may differentially impact the mental health presentations of youth in clinical treatment. Effective treatment may include precision-based customization of evidence-based practices to ensure that the diverse traumatic experiences and related symptomatology of CSE/T youth are effectively addressed.

Adverse Childhood Experiences and Associated Mental Distress and Suicide Risk: Results From the Zambia Violence Against Children Survey.

Purpose: Adverse childhood experiences (ACEs) are a global public health concern. Little research exists on the prevalence and health consequences of ACEs in Zambia. The current study examined associations between individual and cumulative ACEs, mental distress, and suicide risk among Zambian youth. Methods: Data from Zambia Violence Against Children and Youth Survey were used (18-24 years old, n=1034). Bivariate and adjusted logistic models were performed with independent variables (i.e., experienced physical violence (PV), sexual violence (SV), and emotional violence (EV); witnessed intimate partner violence (IPV) and community violence (CV); orphan status; cumulative ACE exposure) and dependent variables (i.e., mental distress and suicide risk). Adjusted models controlled for demographic and social characteristics. Results: 76.8% of Zambian youth experienced one or more ACEs, and more than 30% witnessed CV (38.4%) or IPV (30.2%), or experienced PV (35.1%), prior to age 18. 27.5% were orphans, and less than 20% experienced EV (17.3%) or SV (15.4%) in childhood. 42.4% experienced mental distress in the past 30 days, and 12.5% reported lifetime suicidal thoughts or suicide attempts. PV, EV, cumulative ACE exposure, older age, being single, and stronger friendships were significantly related to experiencing mental distress. Cumulative ACEs exposure was associated with significantly higher suicide risk. Conclusions: Preventing ACEs can reduce mental distress and suicide risk among Zambian youth. Youth with cumulative ACE exposure can be prioritized for mental health intervention. More research is warranted to investigate the broad-based prevention of ACEs, especially PV and EV, and protective factors that can promote resilience among youth who have experienced ACEs.

Regulation of Estradiol Synthesis by Aromatase Interacting Partner in Breast (AIPB).

Estradiol is essential for the development of female sex characteristics and fertility. Postmenopausal women and breast cancer patients have high levels of estradiol. Aromatase catalyzes estradiol synthesis; however, the factors regulating aromatase activity are unknown. We identified a new 22-kDa protein, aromatase interacting partner in breast (AIPB), from the endoplasmic reticulum of human breast tissue. AIPB expression is reduced in tumorigenic breast and further reduced in triple-negative tumors. Like that of aromatase, AIPB expression is induced by nonsteroidal estrogen. We found that AIPB and aromatase interact in nontumorigenic and tumorigenic breast tissues and cells. In tumorigenic cells, conditional AIPB overexpression decreased estradiol, and blocking AIPB availability with an AIPB-binding antibody increased estradiol. Estradiol synthesis is highly increased in AIPB knockdown cells, suggesting that the newly identified AIPB protein is important for aromatase activity and a key modulator of estradiol synthesis. Thus, a change in AIPB protein expression may represent an early event in tumorigenesis and be predictive of an increased risk of developing breast cancer.

A Novel Mitochondrial Complex of Aldosterone Synthase, Steroidogenic Acute Regulatory Protein, and Tom22 Synthesizes Aldosterone in the Rat Heart.

Aldosterone, which regulates renal salt retention, is synthesized in adrenocortical mitochondria in response to angiotensin II. Excess aldosterone causes myocardial injury and heart failure, but potential intracardiac aldosterone synthesis has been controversial. We hypothesized that the stressed heart might produce aldosterone. We used blue native gel electrophoresis, immunoblotting, protein crosslinking, coimmunoprecipitations, and mass spectrometry to assess rat cardiac aldosterone synthesis. Chronic infusion of angiotensin II increased circulating corticosterone levels 350-fold and induced cardiac fibrosis. Angiotensin II doubled and telmisartan inhibited aldosterone synthesis by heart mitochondria and cardiac production of aldosterone synthase (P450c11AS). Heart aldosterone synthesis required P450c11AS, Tom22 (a mitochondrial translocase receptor), and the intramitochondrial form of the steroidogenic acute regulatory protein (StAR); protein crosslinking and coimmunoprecipitation studies showed that these three proteins form a 110-kDa complex. In steroidogenic cells, extramitochondrial (37-kDa) StAR promotes cholesterol movement from the outer to inner mitochondrial membrane where cholesterol side-chain cleavage enzyme (P450scc) converts cholesterol to pregnenolone, thus initiating steroidogenesis, but no function has previously been ascribed to intramitochondrial (30-kDa) StAR; our data indicate that intramitochondrial 30-kDa StAR is required for aldosterone synthesis in the heart, forming a trimolecular complex with Tom22 and P450c11AS. This is the first activity ascribed to intramitochondrial StAR, but how this promotes P450c11AS activity is unclear. The stressed heart did not express P450scc, suggesting that circulating corticosterone (rather than intracellular cholesterol) is the substrate for cardiac aldosterone synthesis. Thus, the stressed heart produced aldosterone using a previously undescribed intramitochondrial mechanism that involves P450c11AS, Tom22, and 30-kDa StAR. SIGNIFICANCE STATEMENT: Prior studies of potential cardiac aldosterone synthesis have been inconsistent. This study shows that the stressed rat heart produces aldosterone by a novel mechanism involving aldosterone synthase, Tom22, and intramitochondrial steroidogenic acute regulatory protein (StAR) apparently using circulating corticosterone as substrate. This study establishes that the stressed rat heart produces aldosterone and for the first time identifies a biological role for intramitochondrial 30-kDa StAR.

Psychological Distress Among Orphaned Youth and Youth Reporting Sexual Exploitation in Kampala, Uganda.

Psychological distress is a priority health issue in low- and middle-income countries; however, it is inadequately addressed among vulnerable youth living in extremely underserved communities (i.e., on the streets and in the slums) who are at a high risk of experiencing adversity. The purpose of this study was to compute the prevalence of self-reported psychological distress among youth living in the slums of Kampala, Uganda, and examine how orphan status and commercial sexual exploitation (CSE) are related to youth psychological distress. Analyses are based on a 2014 cross-sectional survey of service-seeking youth (N = 1134) in Kampala, Uganda. Bivariate and multivariable multinomial regression analyses were used to determine associations between orphan status, sexual exploitation, and psychological distress (defined as experiencing the following proxy variables for more complex psychopathology: hopelessness and/or worry). Among all youth participants, 83.2% (n = 937) reported at least one type of psychological distress; 51.3% (n = 578) reported experiencing both types. The reported prevalence of any type of psychological distress was highest among youth who reported experiencing sexual exploitation (91.2%), double orphans (90.0%), and single orphans (83.8%); however, a high prevalence (76.7%) of any type of distress was also found among youth who reported both parents alive. Experiencing both types of distress was associated with being a double orphan (adjusted odds ratio [AOR] = 2.92, 95% confidence interval [CI] = [1.77, 4.81]), reporting CSE (AOR = 2.71, 95% CI = [1.67, 4.41]), and increased age (AOR = 1.31, 95% CI = [1.20, 1.44]). Psychological distress is prevalent among all youth living in the slums of Kampala and is independently associated with being a double orphan and experiencing CSE. These findings underscore the urgent need to intervene with all youth who reside in this particular underserved community, especially those who have lost both parents, and to prevent CSE among this vulnerable, underserved population.

Electron Transport Chain Complex II Regulates Steroid Metabolism.

The first steroidogenic enzyme, cytochrome P450-side-chain-cleavage (SCC), requires electron transport chain (ETC) complexes III and IV to initiate steroid metabolic processes for mammalian survival. ETC complex II, containing succinate dehydrogenase (quinone), acts with the TCA cycle and has no proton pumping capacity. We show that complex II is required for SCC activation through the proton pump, generating an intermediate state for addition of phosphate by succinate. Phosphate anions in the presence of succinate form a stable mitochondrial complex with higher enthalpy (-ΔH) and enhanced activity. Inhibition of succinate action prevents SCC processing at the intermediate state and ablates activity and mitochondrial protein network. This is the first report directly showing that a protein intermediate state is activated by succinate, facilitating the ETC complex II to interact with complexes III and IV for continued mitochondrial metabolic process, suggesting complex II is essential for steroid metabolism regulation.

Deficient pregnenolone synthesis associated with congenital adrenal hyperplasia and organelle dysfunction.

Steroid hormones are essential for the survival of all mammals. In adrenal glands and gonads, cytochrome P450 side chain cleavage enzyme (SCC or CYP11A1), catalyzes conversion of cholesterol to pregnenolone. We studied a patient with ambiguous genitalia by the absence of Müllerian ducts and the presence of an incompletely formed vagina, who had extremely high adrenocorticotropic hormone (ACTH) and reduced pregnenolone levels with enlarged adrenal glands. The testes revealed seminiferous tubules, stroma, rete testis with interstitial fibrosis and reduced number of germ cells. Electron microscopy showed that the patient's testicular mitochondrial size was small with little SCC expression within the mitochondria. The mitochondria were not close to the mitochondria-associated ER membrane (MAM), and cells were filled with the microfilaments. Our result revealed that absence of pregnenolone is associated with organelle stress, leading to altered protein organization that likely created steric hindrance in testicular cells. Learning points: Testes revealed seminiferous tubules, stroma, rete testis with interstitial fibrosis and reduced number of germ cells; Testicular mitochondrial size was small with little SCC expression within the mitochondria; Absence of pregnenolone is associated with organelle stress.

Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis.

Adrenal and gonadal mitochondrial metabolic activity requires electrons from cofactors, cholesterol, and a substrate for rapid steroid synthesis, an essential requirement for mammalian survival. Substrate activity depends on its environment, which is regulated by chaperones and mitochondrial translocases. Cytochrome P450 side-chain cleavage enzyme (SCC or CYP11A1) catalyzes cholesterol to pregnenolone conversion, although its mechanism of action is not well understood. We find that SCC is directly imported into the mitochondrial matrix, where its N-terminal sequence is cleaved sequentially, after which it becomes activated following the second cleavage, which is dependent on the folding of the protein. Following integration of the SCC C terminus into the TIM23 complex, amino acids 141 to 146 interact with the intermembrane-exposed Tim50 protein, forming a large complex. The absence of Tim50 or its mutation reduced enzymatic activity. For the first time, we report that a protein activated at the matrix remains mostly unfolded and is transported back to the IMS to integrate with the TIM23 translocase complex and align with the Tim50 protein. Amino acid changes that suppress the association of Tim50 with SCC ablate metabolic activity. Thus, the TIM23 complex is the central regulator of metabolism guided by Tim50.

An Outer Mitochondrial Translocase, Tom22, Is Crucial for Inner Mitochondrial Steroidogenic Regulation in Adrenal and Gonadal Tissues.

After cholesterol is transported into the mitochondria of steroidogenic tissues, the first steroid, pregnenolone, is synthesized in adrenal and gonadal tissues to initiate steroid synthesis by catalyzing the conversion of pregnenolone to progesterone, which is mediated by the inner mitochondrial enzyme 3ß-hydroxysteroid dehydrogenase 2 (3ßHSD2). We report that the mitochondrial translocase Tom22 is essential for metabolic conversion, as its knockdown by small interfering RNA (siRNA) completely ablated progesterone conversion in both steroidogenic mouse Leydig MA-10 and human adrenal NCI cells. Tom22 forms a 500-kDa complex with mitochondrial proteins associated with 3ßHSD2. Although the absence of Tom22 did not inhibit mitochondrial import of cytochrome P450scc (cytochrome P450 side chain cleavage enzyme) and aldosterone synthase, it did inhibit 3ßHSD2 expression. Electron microscopy showed that Tom22 is localized at the outer mitochondrial membrane (OMM), while 3ßHSD2 is localized at the inner mitochondrial space (IMS), where it interacts through a specific region with Tom22 with its C-terminal amino acids and a small amino acid segment of Tom22 exposed to the IMS. Therefore, Tom22 is a critical regulator of steroidogenesis, and thus, it is essential for mammalian survival.