AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro , in vivo , and in human prostate cancer (PCa) tumors ex vivo . Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.

An agricultural livelihood intervention is associated with reduced HIV stigma among people living with HIV.

OBJECTIVE: HIV stigma undermines antiretroviral treatment (ART) adherence and viral suppression. Livelihood interventions may target drivers of negative attitudes towards people living with HIV (PLHIV) by improving their health and strengthening their economic contributions. We examined the effects of a multisectoral agricultural livelihood intervention on HIV stigma among PLHIV in western Kenya. DESIGN: Sixteen health facilities were randomly allocated (1:1) to intervention or control arms in Shamba Maisha, a cluster randomized controlled trial that aimed to improve HIV-related health through behavioral, mental health, and nutritional pathways. METHODS: The intervention included a farming loan and agricultural and financial training. Participants had access to farmland and surface water and were ≥18 years old, on ART >six months, and moderately-to-severely food insecure. We measured internalized, anticipated, and enacted HIV stigma semiannually over two years using validated scales. In blinded intent-to-treat analyses, we compared changes in scores over 24 months, by study arm, using longitudinal multi-level difference-in-differences linear regression models that accounted for clustering. RESULTS: Of 720 enrolled participants (354 intervention), 55% were female, and the median age was 40 years (interquartile range 34-47 years). Two-year retention was 94%. Compared to the control arm, the intervention resulted in significant decreases (p < 0.001) of 0.42 points (95% confidence interval (CI) -0.52, -0.31) in internalized stigma, 0.43 points (95% CI -0.51, -0.34) in anticipated stigma, and 0.13 points (95% CI -0.16, -0.09) in enacted stigma over 24 months. CONCLUSIONS: The agricultural livelihood intervention reduced HIV stigma among PLHIV. Poverty-reduction approaches may be a novel strategy for reducing HIV stigma.

ACSM1 and ACSM3 regulate fatty acid metabolism to support prostate cancer growth and constrain ferroptosis.

Solid tumors are highly reliant on lipids for energy, growth, and survival. In prostate cancer, the activity of the androgen receptor (AR) is associated with reprogramming of lipid metabolic processes. Here, we identified acyl-CoA synthetase medium chain family members 1 and 3 (ACSM1 and ACSM3) as AR-regulated mediators of prostate cancer metabolism and growth. ACSM1 and ACSM3 were upregulated in prostate tumors compared to non-malignant tissues and other cancer types. Both enzymes enhanced proliferation and protected prostate cancer cells from death in vitro, while silencing ACSM3 led to reduced tumor growth in an orthotopic xenograft model. ACSM1 and ACSM3 were major regulators of the prostate cancer lipidome and enhanced energy production via fatty acid oxidation. Metabolic dysregulation caused by loss of ACSM1/3 led to mitochondrial oxidative stress, lipid peroxidation and cell death by ferroptosis. Conversely, elevated ACSM1/3 activity enabled prostate cancer cells to survive toxic levels of medium chain fatty acids and promoted resistance to ferroptosis-inducing drugs and AR antagonists. Collectively, this study reveals a tumor-promoting function for medium chain acyl-CoA synthetases and positions ACSM1 and ACSM3 as key players in prostate cancer progression and therapy resistance.

Disclosure Events and Psychosocial Well-Being Among Young South African Adults Living with HIV.

BACKGROUND: Poor psychological well-being is both prevalent among South Africans living with HIV and has been associated with poor HIV clinical outcomes. However, the relationship between disclosure and psychological well-being remains unclear. This analysis sought to examine the relationship between two disclosure-related variables, disclosure status and reaction received, and psychosocial well-being among a sample of young adults living with HIV (YALWH) in urban South Africa. METHOD: This was a secondary analysis using observational data from Standing Tall, a randomized controlled trial that recruited 100 participants ages 18-24 who tested positive for HIV after initially presenting to two well-established mobile clinics for HIV testing. Interviews investigating primary and secondary outcomes of interest were done at baseline and 6 months following recruitment. RESULTS: About half (51%) of participants disclosed their HIV status within 6 months after recruitment. Simple linear regression analyses revealed that disclosure of HIV status within 6 months after study enrollment predicted significantly lower levels of disclosure concerns and internalized stigma (p < 0.05). Reactions to disclosure were not significantly associated with any of the measures of psychosocial well-being considered in this analysis (p > 0.05). CONCLUSION: The results suggest that the act of disclosure among newly diagnosed YALWH may be associated with reductions in internalized stigma. In addition, the finding that the act of disclosure may be a more important determinant of psychosocial well-being than the reaction to disclosure has important implications for interventions designed to promote disclosure and psychosocial well-being in YALWH.

FixNCut: single-cell genomics through reversible tissue fixation and dissociation.

The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We applied FixNCut to human and mouse tissues to demonstrate the preservation of RNA integrity, sequencing library complexity, and cellular composition, while diminishing stress-related artifacts. Besides single-cell RNA sequencing, FixNCut is compatible with multiple single-cell and spatial technologies, making it a versatile tool for robust and flexible study designs.

Defining the challenges and opportunities for using patient-derived models in prostate cancer research.

BACKGROUND: There are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants. METHODS: In May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research. RESULTS: An increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups. CONCLUSIONS: There are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future.

Spatial MS multiomics on clinical prostate cancer tissues.

Mass spectrometry (MS) and MS imaging (MSI) are used extensively for both the spatial and bulk characterization of samples in lipidomics and proteomics workflows. These datasets are typically generated independently due to different requirements for sample preparation. However, modern omics technologies now provide higher sample throughput and deeper molecular coverage, which, in combination with more sophisticated bioinformatic and statistical pipelines, make generating multiomics data from a single sample a reality. In this workflow, we use spatial lipidomics data generated by matrix-assisted laser desorption/ionization MSI (MALDI-MSI) on prostate cancer (PCa) radical prostatectomy cores to guide the definition of tumor and benign tissue regions for laser capture microdissection (LCM) and bottom-up proteomics all on the same sample and using the same mass spectrometer. Accurate region of interest (ROI) mapping was facilitated by the SCiLS region mapper software and dissected regions were analyzed using a dia-PASEF workflow. A total of 5525 unique protein groups were identified from all dissected regions. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), a lipid remodelling enzyme, was significantly enriched in the dissected regions of cancerous epithelium (CE) compared to benign epithelium (BE). The increased abundance of this protein was reflected in the lipidomics data with an increased ion intensity ratio for pairs of phosphatidylcholines (PC) and lysophosphatidylcholines (LPC) in CE compared to BE.

Peroxisomal ß-oxidation enzyme, DECR2, regulates lipid metabolism and promotes treatment resistance in advanced prostate cancer.

BACKGROUND: Peroxisomes are central metabolic organelles that have key roles in fatty acid homoeostasis. As prostate cancer (PCa) is particularly reliant on fatty acid metabolism, we explored the contribution of peroxisomal ß-oxidation (perFAO) to PCa viability and therapy response. METHODS: Bioinformatic analysis was performed on clinical transcriptomic datasets to identify the perFAO enzyme, 2,4-dienoyl CoA reductase 2 (DECR2) as a target gene of interest. Impact of DECR2 and perFAO inhibition via thioridazine was examined in vitro, in vivo, and in clinical prostate tumours cultured ex vivo. Transcriptomic and lipidomic profiling was used to determine the functional consequences of DECR2 inhibition in PCa. RESULTS: DECR2 is upregulated in clinical PCa, most notably in metastatic castrate-resistant PCa (CRPC). Depletion of DECR2 significantly suppressed proliferation, migration, and 3D growth of a range of CRPC and therapy-resistant PCa cell lines, and inhibited LNCaP tumour growth and proliferation in vivo. DECR2 influences cell cycle progression and lipid metabolism to support tumour cell proliferation. Further, co-targeting of perFAO and standard-of-care androgen receptor inhibition enhanced suppression of PCa cell proliferation. CONCLUSION: Our findings support a focus on perFAO, specifically DECR2, as a promising therapeutic target for CRPC and as a novel strategy to overcome lethal treatment resistance.

Emotional Betrayal From Child Sexual Abuse Measure (EBSCAM): A psychometric analysis.

OBJECTIVE: This study examined the psychometric properties of a new scale, the Emotional Betrayal from Child Sexual Abuse Measure (EBCSAM), which assesses feelings of betrayal in adult survivors of child sexual abuse (CSA). Emotional betrayal is examined with respect to the perpetrator as well as others in the survivor's immediate environment (i.e., family, friends, etc.) during the time of the abuse. METHOD: A sample of 342 CSA survivors were anonymously surveyed online in order to examine the psychometric properties of the EBCSAM. RESULTS: The original 16-item measure did not produce a good-fitting model, nor was it considered reliable or valid. Instead, a shortened six-item measure produced a successful model, was reliable (overall Cronbach's α = .85), and exploratory/confirmatory factor analyses suggested two valid latent subscales (Perpetrator Betrayal and Environmental Betrayal). CONCLUSION: This measure could be useful to clinicians treating survivors of child sexual abuse, as well as researchers, to reveal and evaluate aspects of emotional betrayal that impacted survivors.CSA). Emotional betrayal is examined with respect to the perpetrator as well as others in the survivor's immediate environment (i.e., family, friends, etc.) during the time of the abuse. METHOD: A sample of 342 CSA survivors were anonymously surveyed online in order to examine the psychometric properties of the (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Fatty acid elongation regulates mitochondrial ß-oxidation and cell viability in prostate cancer by controlling malonyl-CoA levels.

Recently, the fatty acid elongation enzyme ELOVL5 was identified as a critical pro-metastatic factor in prostate cancer, required for cell growth and mitochondrial homeostasis. The fatty acid elongation reaction catalyzed by ELOVL5 utilizes malonyl-CoA as the carbon donor. Here, we demonstrate that ELOVL5 knockdown causes malonyl-CoA accumulation. Malonyl-CoA is a cellular substrate that can inhibit fatty acid ß-oxidation in the mitochondria through allosteric inhibition of carnitine palmitoyltransferase 1A (CPT1A), the enzyme that controls the rate-limiting step of the long chain fatty acid ß-oxidation cycle. We hypothesized that changes in malonyl-CoA abundance following ELOVL5 knockdown could influence mitochondrial ß-oxidation rates in prostate cancer cells, and regulate cell viability. Accordingly, we find that ELOVL5 knockdown is associated with decreased mitochondrial ß-oxidation in prostate cancer cells. Combining ELOVL5 knockdown with FASN inhibition to increase malonyl-CoA abundance endogenously enhances the effect of ELOVL5 knockdown on prostate cancer cell viability, while preventing malonyl-CoA production rescues the cells from the effect of ELOVL5 knockdown. Our findings indicate an additional role for fatty acid elongation, in the control of malonyl-CoA homeostasis, alongside its established role in the production of long-chain fatty acid species, to explain the importance of fatty acid elongation for cell viability.

Targeting hyaluronan-mediated motility receptor (HMMR) enhances response to androgen receptor signalling inhibitors in prostate cancer.

BACKGROUND: Resistance to androgen receptor signalling inhibitors (ARSIs) represents a major clinical challenge in prostate cancer. We previously demonstrated that the ARSI enzalutamide inhibits only a subset of all AR-regulated genes, and hypothesise that the unaffected gene networks represent potential targets for therapeutic intervention. This study identified the hyaluronan-mediated motility receptor (HMMR) as a survival factor in prostate cancer and investigated its potential as a co-target for overcoming resistance to ARSIs. METHODS: RNA-seq, RT-qPCR and Western Blot were used to evaluate the regulation of HMMR by AR and ARSIs. HMMR inhibition was achieved via siRNA knockdown or pharmacological inhibition using 4-methylumbelliferone (4-MU) in prostate cancer cell lines, a mouse xenograft model and patient-derived explants (PDEs). RESULTS: HMMR was an AR-regulated factor that was unaffected by ARSIs. Genetic (siRNA) or pharmacological (4-MU) inhibition of HMMR significantly suppressed growth and induced apoptosis in hormone-sensitive and enzalutamide-resistant models of prostate cancer. Mechanistically, 4-MU inhibited AR nuclear translocation, AR protein expression and subsequent downstream AR signalling. 4-MU enhanced the growth-suppressive effects of 3 different ARSIs in vitro and, in combination with enzalutamide, restricted proliferation of prostate cancer cells in vivo and in PDEs. CONCLUSION: Co-targeting HMMR and AR represents an effective strategy for improving response to ARSIs.

Ultrastructural analysis of prostate cancer tissue provides insights into androgen-dependent adaptations to membrane contact site establishment.

Membrane trafficking and organelle contact sites are important for regulating cell metabolism and survival; processes often deregulated in cancer. Prostate cancer is the second leading cause of cancer-related death in men in the developed world. While early-stage disease is curable by surgery or radiotherapy there is an unmet need to identify prognostic biomarkers, markers to treatment response and new therapeutic targets in intermediate-late stage disease. This study explored the morphology of organelles and membrane contact sites in tumor tissue from normal, low and intermediate histological grade groups. The morphology of organelles in secretory prostate epithelial cells; including Golgi apparatus, ER, lysosomes; was similar in prostate tissue samples across a range of Gleason scores. Mitochondrial morphology was not dramatically altered, but the number of membrane contacts with the ER notably increased with disease progression. A three-fold increase of tight mitochondria-ER membrane contact sites was observed in the intermediate Gleason score group compared to normal tissue. To investigate whether these changes were concurrent with an increased androgen signaling in the tissue, we investigated whether an anti-androgen used in the clinic to treat advanced prostate cancer (enzalutamide) could reverse the phenotype. Patient-derived explant tissues with an intermediate Gleason score were cultured ex vivo in the presence or absence of enzalutamide and the number of ER-mitochondria contacts were quantified for each matched pair of tissues. Enzalutamide treated tissue showed a significant reduction in the number and length of mitochondria-ER contact sites, suggesting a novel androgen-dependent regulation of these membrane contact sites. This study provides evidence for the first time that prostate epithelial cells undergo adaptations in membrane contact sites between mitochondria and the ER during prostate cancer progression. These adaptations are androgen-dependent and provide evidence for a novel hormone-regulated mechanism that support establishment and extension of MAMs. Future studies will determine whether these changes are required to maintain pro-proliferative signaling and metabolic changes that support prostate cancer cell viability.

Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression.

Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with ß3 integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly ß3 integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa.

Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome.

Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and vernix caseosa. The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene-interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.

Development of "Yima Nkqo," a community-based, peer group intervention to support treatment initiation for young adults with HIV in South Africa.

AIMS: Half of young adults diagnosed with HIV in South Africa start antiretroviral therapy (ART). We developed and field tested a facilitator-guided peer support group called Yima Nkqo ("Standing Tall" in isiXhosa) to promote treatment initiation for young adults newly diagnosed with HIV in communities around Cape Town. METHODS: Following an adapted version of the UK Medical Research Council's framework for developing complex interventions, we 1) identified evidence on previous interventions to improve ART uptake in sub-Saharan Africa; 2) collected and analyzed qualitative data on the acceptability of our proposed intervention; 3) proposed a theoretical understanding of the process of behavior change; and 4) developed an intervention manual and feedback tools. During field-testing, participant feedback on intervention acceptability, and team feedback on consistency of content delivery and facilitation quality, were analyzed using an iterative, rapid-feedback evaluation approach. In-depth written and verbal summaries were shared in weekly team meetings. Team members interpreted feedback, identified areas for improvement, and proposed suggestions for intervention modifications. RESULTS: Based on our formative research, we developed three, 90-minute sessions with content including HIV and ART education, reflection on personal resources and strengths, practice disclosing one's status, strategies to overcome stressors, and goal setting to start treatment. A lay facilitator was trained to deliver intervention content. Two field testing groups (five and four participants, respectively) completed the intervention. Participants highlighted that strengths of Yima Nkqo included peer support, motivation, and education about HIV and ART. Team feedback to the facilitator ensured optimal consistency of intervention content delivery. CONCLUSIONS: Iteratively developed in collaboration with youth and healthcare providers, Yima Nkqo is a promising new intervention to improve treatment uptake among young adults with HIV in South Africa. The next phase will be a pilot randomized controlled trial of Yima Nkqo (ClinicalTrials.gov Identifier: NCT04568460).

Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1.

Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.

Incidence of HIV disclosure among HIV affected heterosexual partners using a community health worker led mechanism in rural Uganda; a quasi-experimental study.

BACKGROUND: HIV disclosure is vital in HIV management. Community Health Workers (CHW) were reported to support partner disclosure among HIV affected heterosexual partners with disclosure difficulties. However, time to disclosure attributed to use of CHW led disclosure support mechanism was not documented. This study compared the incidence of sexual partner disclosure among adults living with HIV (ALHIV) with CHW support and those without in the greater Luwero region, Uganda. METHODS: We conducted a quasi-experimental study with two arms allocated by geographically determined clusters and adjusted for between-group differences; among ALHIV in the greater Luwero region of Uganda who had never disclosed to their current primary sexual partners. We allocated study clusters to either a CHW-led intervention or control arm. In both arms, we consecutively recruited participants; those in the intervention arm received CHW disclosure support in addition to routine care. The overall follow-up was six months, and the primary outcome was disclosure to the partner. We used survival analysis with proportional hazard ratios to determine the time to partner disclosure in both arms. RESULTS: A total of 245 participants were enrolled, and 230 (93.9%) completed the study; of these, 112 (48.7%) were in the intervention and 118 (51.3%) in the control arm. The mean age was 31 ± 8 years with a range of 18 to 55 years; the majority were females, 176 (76.5%). The cumulative incidence of disclosure was higher in the intervention arm, 8.76 [95% CI: 7.20-10.67] per 1,000 person-days versus 5.15 [95%CI: 4.85-6.48] per 1,000 person-days in the control arm, log-rank test, X2 = 12.93, P < 0.001. Male gender, aHR = 1.82, tertiary education, aHR = 1.51, and relationship duration of > six months, aHR = 1.19 predicted disclosure. Prior disclosure to a relative, aHR = 0.55, and having more than one sexual partner in the past three months, aHR = 0.74, predicted non-disclosure. CONCLUSION: CHW-led support mechanism increased the rate of sexual partner disclosure among ALHIV with disclosure difficulties. Therefore, to achieve the global targets of ending HIV, near location CHW-led disclosure support mechanism may be used to hasten HIV disclosure in rural settings.

Burden of adult atopic dermatitis and unmet needs with existing therapies.

OBJECTIVE: Patients with atopic dermatitis (AD) have low treatment satisfaction. In this study, we evaluated the humanistic burden, treatment satisfaction, and treatment expectations in patients with AD in the United States. METHODS: Adults with AD recruited through the National Eczema Association and clinical sites completed a web-based survey comprising the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Dermatology Life Quality Index; Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis; Treatment Satisfaction Questionnaire for Medication (TSQM); and answered questions on healthcare provider (HCP) visits, treatment history, and treatment goals. Descriptive analyses were performed to compare participants by severity. RESULTS: Among 186 participants (mean [standard deviation] age 39.7 [15.3] years, 79.6% female), 26.9%, 44.6%, and 26.3% of the participants had mild, moderate, or severe AD, respectively, based on PO-SCORAD. Greater disease severity was associated with a greater impact on work and daily life, decreased TSQM scores, and increased HCP visits. Corticosteroid topical cream or ointment (53.8%) and oral antihistamines (31.2%) were most commonly used for the treatment of AD. Participants reported declining/stopping/changing AD treatment due to the potential for side effects or lack of efficacy. 'Leading normal lives' (28.0%) and 'being itch-free' (33.9%) were important treatment goals. CONCLUSIONS: Individuals with AD, especially severe disease, face a considerable humanistic burden even while using treatment.

Experiences and challenges of using community health worker-led mechanism in supporting HIV disclosure among adults living with HIV in heterosexual relationships in the rural Uganda.

BACKGROUND: HIV status disclosure among sexual partners is vital in HIV management. Community health workers (CHW) support HIV disclosure among adults living with HIV (ALHIV) in sexual relationships with disclosure difficulties. However, experiences and challenges of using CHW-led disclosure support mechanism were not documented. This study explored experiences and challenges involved in using CHW-led disclosure support mechanism among ALHIV in heterosexual relationships in the rural Uganda. METHODS: This was a phenomenological qualitative study involving in-depth interviews among CHWs and ALHIV with HIV disclosure difficulties to sexual partners in greater Luwero region, Uganda. We conducted 27 interviews among purposively selected CHWs and participants who had participated in the CHW-led disclosure support mechanism. Interviews were conducted until saturation was reached; and analysis was done using inductive and deductive content analysis in Atlas. RESULTS: All respondents viewed HIV disclosure as an important strategy in HIV management. Provision of adequate counseling and support to those intending to disclose was instrumental for successful disclosure. However, fear of the negative disclosure outcomes was viewed as a barrier to disclosure. The CHWs were viewed as having an added advantage in supporting disclosure as opposed to the routine disclosure counseling. However, HIV disclosure using CHW-led support mechanism would be limited by possible bleach of client's confidentiality. Therefore, respondents thought that appropriate selection of CHWs would improve their trust in the community. Additionally, providing CHWs with adequate training and facilitation during the disclosure support mechanism was viewed to improve their work. CONCLUSION: Community health workers were viewed as being more supportive in HIV disclosure among ALHIV with disclosure difficulties to sexual partners compared to routine facility based disclosure counseling. Therefore, near location CHW-led disclosure mechanism was acceptable and useful in supporting HIV disclosure among HIV-affected sexual partners in rural settings.