Patient perspectives on the helpfulness of a community health worker program for HIV care engagement in Tanzania.

Task-shifting is a valuable approach for redistributing clinical tasks to nonprofessional health workers and relieving human resource shortages. The Community-Based HIV Services (CBHS) program is a national cohort of volunteer community health workers (CHWs) who support HIV care engagement at clinics in Tanzania. We recruited 23 patients initiating HIV care at two clinics to understand their experiences with the CBHS program. Participants completed qualitative interviews by telephone discussing the perceived helpfulness of the program, their level of connection with CHWs, and suggestions for improvement. Data were analyzed through an inductive, team-based qualitative approach. Most participants found the program to be helpful and described close, positive connections. CHWs offered education, emotional support to accept one's diagnosis and cope with stigma, and encouragement to remain engaged in HIV care. However, several participants described minimal, shallow contact with CHWs, and felt the program did not benefit their HIV care. Participants recommended increasing CHW efforts to engage people living with HIV (PLWH) in the broader community, and addressing socioeconomic barriers to care engagement. When contacts are consistent, the CBHS program is a strong resource for PLWH. To maximize the potential of the program, administrators should enhance oversight and extend new training opportunities for CHWs.

Biological Assay-Guided Fractionation and Mass Spectrometry-Based Metabolite Profiling of Annona muricata L. Cytotoxic Compounds against Lung Cancer A549 Cell Line.

Annona muricata L. (Guyabano) leaves are reported to exhibit anticancer activity against cancer cells. In this study, the ethyl acetate extract from guyabano leaves was purified through column chromatography, and the cytotoxic effects of the semi-purified fractions were evaluated against A549 lung cancer cells using in vitro MTS cytotoxicity and scratch/wound healing assays. Fractions F15-16C and F15-16D exhibited the highest anticancer activity in the MTS assay, with % cytotoxicity values of 99.6% and 99.4%, respectively. The bioactivity of the fractions was also consistent with the results of the scratch/wound healing assay. Moreover, untargeted metabolomics was employed on the semi-purified fractions to determine the putative compounds responsible for the bioactivity. The active fractions were processed using LC-MS/MS analysis with the integration of the following metabolomic tools: MS-DIAL (for data processing), MetaboAnalyst (for data analysis), GNPS (for metabolite annotation), and Cytoscape (for network visualization). Results revealed that the putative compounds with a significant difference between active and inactive fractions in PCA and OPLS-DA models were pheophorbide A and diphenylcyclopropenone.

Association of JAK/STAT genetic variants with cutaneous melanoma.

Background: The Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway regulates cutaneous melanoma (CM) development and progression. The JAK1, JAK2, and STAT3 proteins are encoded by polymorphic genes. This study aimed to verify whether single-nucleotide variants (SNVs) in JAK1 (c.1648+1272G>A, c.991-27C>T), JAK2 (c.-1132G>T, c.-139G>A), and STAT3 (c.*1671T>C, c.-1937C>G) altered the risk, clinicopathological aspects, and survival of CM patients as well as protein activity. Methods: CM patients (N = 248) and controls (N = 274) were enrolled in this study. Genotyping was performed by real-time polymerase chain reaction (PCR), and JAK1, JAK2, and STAT3 expression was assessed by quantitative PCR (qPCR). STAT3 c.-1937C>G SNV was investigated by luciferase, qPCR, western blot, apoptosis, and cell cycle assays in SKMEL-28 cells with CC or GG genotype. Results: Individuals with STAT3 c.*1671TT and c.-1937CC genotypes and TC haplotype of both SNVs were under about 2.0-fold increased risk of CM. Specific JAK1, JAK2, and STAT3 combined genotypes were associated with up to 4.0-fold increased risk of CM. Higher luciferase activity [4,013.34 vs. 2,463.32 arbitrary units (AU); p = 0.004], STAT3 expression by qPCR (649.20 vs. 0.03 AU; p = 0.003) and western blot (1.69 vs. 1.16 AU; p = 0.01), and percentage of cells in the S phase of the cell cycle (57.54 vs. 30.73%; p = 0.04) were more frequent in SKMEL-28 with STAT3 c.-1937CC than with GG genotype. CM cell line with CC genotype presented higher STAT3 protein levels than the one with GG genotype (1.93 versus 1.27 AU, p = 0.0027). Conclusion: Our data present preliminary evidence that inherited abnormalities in the JAK/STAT pathway can be used to identify individuals at a high risk of CM, who deserve additional attention for tumor prevention and early detection.

Assessing the Influence of Community Health Worker Support on Early Antiretroviral Therapy Adherence, Anticipated Stigma, and Mental Health Among People Living with HIV in Tanzania.

In many low- and middle-income countries, community health workers (CHWs) support multiple aspects of HIV care, including patient education and counseling, adherence support, and re-engaging patients lost to care. In Tanzania, the Community-Based HIV Services program is a nationwide cohort of CHWs supporting HIV care engagement. We enrolled a prospective cohort study of 80 people initiating HIV care at two Tanzanian clinics and conducted baseline and 3-month follow-up assessments to examine the potential influence of CHW support and other factors on patient early self-reported medication adherence, depression, anxiety, attitudes about medication, and HIV stigma. The vast majority of participants reported maintaining strong antiretroviral therapy (ART) adherence during the study and endorsed beliefs that ART is beneficial for them. However, there was high occurrence of likely depression and anxiety disorders in the study sample. Patient contact with CHWs at the clinic was unexpectedly low; fewer than two-thirds of participants were informed about the CHW program and fewer than one-third ever met with a CHW. Among participants who met with a CHW, there was mixed feedback about the helpfulness of the program, and contact with a CHW did not improve medication adherence at 3-month follow-up. Male participants, those with likely depression, and those who lived further from the clinic were significantly more likely to experience adherence challenges. The study findings indicate that CHWs are currently underutilized to provide patient support and may not be producing observable benefits to patients in this setting, representing a missed opportunity to address patient challenges, including depression and anxiety.

The Role of Community Health Workers in HIV Care Engagement: A Qualitative Study of Stakeholder Perspectives in Tanzania.

ABSTRACT: Suboptimal retention in HIV care is a major driver of the global epidemic, including in sub-Saharan Africa. In Tanzania, the national Community-Based HIV Services program integrates volunteer community health workers (CHWs) to support patient care engagement and reduce the burden placed on HIV clinic nurses; however, few studies have assessed the value of CHWs supporting HIV care. Qualitative interviews were conducted with 48 administrators, nurses, CHWs, and patients to explore strengths and limitations of the Community-Based HIV Services program. Stakeholders believed CHWs are uniquely positioned to establish trust and provide patient support. Patients who had frequent contact with CHWs described them as valued sources of education and encouragement, but fewer than half of the patients interviewed had ever met with a CHW. Clinic nurses described feeling disconnected from CHWs, and stakeholders highlighted the need for financial, logistical, and educational support to rejuvenate the program and effectively address care engagement challenges.