Global Mental Health: Where We Are and Where We Are Going.

PURPOSE OF REVIEW: To summarize recent findings in global mental health along several domains including socioeconomic determinants, inequities, funding, and inclusion in global mental health research and practice. RECENT FINDINGS: Mental illness continues to disproportionately impact vulnerable populations and treatment coverage continues to be low globally. Advances in integrating mental health care and adopting task-shifting are accompanied by implementation challenges. The mental health impact of recent global events such as the COVID-19 pandemic, geo-political events, and environmental change is likely to persist and require coordinated care approaches for those in need of psychosocial support. Inequities also exist in funding for global mental health and there has been gradual progress in terms of building local capacity for mental health care programs and research. Lastly, there is an increasing effort to include people with lived experiences of mental health in research and policy shaping efforts. The field of global mental health will likely continue to be informed by evidence and perspectives originating increasingly from low- and middle-income countries along with ongoing global events and centering of relevant stakeholders.

Brief Report: Time to Repeat Viral Load Testing Among Unsuppressed Adolescents and Young Adults Living With HIV in Kenya.

BACKGROUND: Repeat HIV viral load (VL) testing is required after unsuppressed VL to confirm treatment failure. We assessed proportion of adolescents and young adults living with HIV (AYALHIV) in Kenya with a confirmatory VL test and time to repeat testing. DESIGN: A retrospective analysis of longitudinal data abstracted from Kenya's national VL database. METHODS: VL data for AYALHIV who were 10-24 year old between April 2017 and May 2019 were abstracted from 117 HIV care clinics. Records were eligible if at least one VL test was performed ≥6 months after antiretroviral therapy (ART) initiation. The proportion of unsuppressed AYALHIV (≥1000 copies/mL) and time in months between first unsuppressed VL and repeat VL was determined. RESULTS: We abstracted 40,928 VL records for 23,969 AYALHIV; of whom, 17,092 (71%) were eligible for this analysis. Of these, 12,122 (71%) were women, median age of 19 years [interquartile range (IQR): 13-23], and median ART duration of 38 months (IQR: 16-76). Among eligible AYALHIV, 4010 (23%) had an unsuppressed VL at first eligible measurement. Only 316 (8%) of the unsuppressed AYALHIV had a repeat VL within 3 months and 1176 (29%) within 6 months. Among 2311 virally unsuppressed AYALHIV with a repeat VL, the median time between the first and the repeat VL was 6 months (IQR: 4-8), with 1330 (58%) having confirmed treatment failure. CONCLUSIONS: One-quarter of AYALHIV on ART had unsuppressed VL, with less than a third receiving a repeat VL within 6 months. Strategies to improve VL testing practices are needed to improve AYALHIV's outcomes.

A lifetime of violence: results from an exploratory survey of Mexican women with HIV.

Despite recognition that traditional Mexican gender norms can contribute to the twin epidemics of violence against women and HIV, there is an absence of published literature on experiences of violence among Mexican women with HIV. We conducted a cross-sectional survey with 77 HIV-infected women from 21 of Mexico's 32 states to describe experiences of violence before and after HIV-diagnosis. We measured lifetime physical, sexual, and psychological violence; physical violence from a male partner in the previous 12 months; and physical and psychological violence related to disclosing an HIV diagnosis. Respondents reported ever experiencing physical violence (37.3%) and sexual violence (29.2%). Disclosure of HIV status resulted in physical violence for 7.2% and psychological violence for 26.5% of the respondents. This study underlines the need to identify and address past and current gender-based violence during pre- and post-HIV test counseling and as a systematic and integral part of HIV care.

Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases.

A consistent feature of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is the constitutive activation of NF-kappaB transcription factors. In Epstein-Barr virus (EBV)-associated cases of cHL, expression of viral antigens most probably leads to NF-kappaB activation but for non-EBV-associated cases, the mechanism is not clear. Previous small studies have demonstrated deleterious mutations of NFKBIA, the gene encoding IkappaB alpha, in HRS cells. In the present study, we aimed to establish the frequency of NFKBIA mutation in cHL by investigating a larger series of cases and to determine whether these mutations are a characteristic feature of non-EBV-associated cHL. Single HRS cells from 20 cases of cHL were analysed by PCRs covering all 6 exons of the gene. Clonal deleterious mutations were detected in 3 cases and in 1 case both alleles of the gene were shown to harbour mutations. NFKBIA mutations were detected only in non-EBV-associated cases but the majority of these cases had wild-type NFKBIA. It remains possible that defects in genes encoding other inhibitors of NF-kappaB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series.

Assessing the efficacy of a voluntary HIV counseling and testing intervention for pregnant women and male partners in Urumqi City, China.

This study investigated the efficacy of voluntary counseling and testing (VCT) in an educated cohort of pregnant women attending antenatal clinics in Urumqi, China. VCT was given to women and their partners (experimental group) or women alone (control group). Both groups were given pre- and post-intervention questionnaires to assess HIV knowledge and willingness to get HIV testing. Multivariate analysis showed that all women improved significantly in HIV knowledge between baseline and follow-up. Moreover, HIV knowledge was significantly associated with HIV testing willingness. At follow-up, women in the control and experimental groups were 6.8 and 7.9 times more willing to receive HIV testing than at baseline, respectively. VCT seems effective in this cohort of educated pregnant women.

Viruses and Hodgkin lymphoma: no evidence of polyomavirus genomes in tumor biopsies.

The epidemiology of young adult Hodgkin lymphoma (HL) suggests that delayed exposure to a common childhood pathogen may be involved in disease pathogenesis. The Epstein-Barr virus (EBV) is associated with a proportion of cases but cases of young adult HL in westernized countries are less frequently EBV-associated than cases in other age groups and geographical locales. This study investigated the possibility that polyomaviruses might be involved in the etiology of HL by analysing a series of 35 cases of classical HL using both specific and degenerate PCR assays for polyomavirus genomes. No positive results were obtained, indicating that it is highly unlikely that this virus family is directly involved in the pathogenesis of HL.

The putative role of transforming viruses in childhood acute lymphoblastic leukemia.

Epidemiological evidence suggests that infection is involved in the etiology of common acute lymphoblastic leukemia, either by stimulating an inappropriate immune response or in the form of a classical transforming agent. In an attempt to elucidate the role that infection is playing in this disease, we used representational difference analysis (RDA) to examine tumor samples for the presence of exogenous genomes. Twenty RDA experiments were carried out, using four different restriction enzymes, but no exogenous sequences were identified within leukemic cells. These results suggest that it is unlikely that a single, direct transforming agent is involved in the pathogenesis of common acute lymphoblastic leukemia.

Association between simian virus 40 DNA and lymphoma in the United kingdom.

Recent studies have reported the presence of simian virus 40 (SV40) DNA sequences in approximately 40% of tumor samples from non-Hodgkin's lymphoma (NHL) patients from the United States. We examined a series of 259 tumor and blood samples, including 152 NHL samples, from patients in the U.K. with lymphadenopathy and lymphoid leukemia for the presence of SV40 DNA using a highly sensitive quantitative polymerase chain reaction (PCR) assay and a consensus PCR assay capable of detecting the polyomaviruses SV40, BK, and JC. SV40 DNA sequences were not detected in any sample using either assay. Because the incidence of NHL is similar in the U.K. and the United States, this finding suggests that SV40 is unlikely to have an etiologic role in NHL.

Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues.

Overexpression of the oncogene HER2/neu (c-erbB-2) occurs in up to 30% of breast cancers and is correlated with reduced survival, especially in node-positive disease. The aim of this study was to identify genes associated with the aggressive phenotype of HER2/neu-positive breast cancer cells using cDNA microarrays. RNA was extracted from three HER2/neu-positive and three HER2/neu-negative breast cancer cell lines. Pooled RNA was hybridized in duplicate to the breast specific microarray filters from Research Genetics containing 5184 unique cDNAs. Subsequently, a similar comparison was performed for pooled RNAs from 10 node-positive, ER-positive invasive ductal carcinomas, half of which were HER2/neu overexpressers. In HER2/neu overexpressing breast cancer cell lines, 90 (1.7%) genes were up-regulated and 46 (0.9%) were down-regulated, compared to cell lines with low HER2/neu protein levels. In contrast, in HER2/neu overexpressing primary breast cancers, more genes were down-regulated (N = 132, 2.5%) than up-regulated (N = 19, 0.4%). Many of the differentially expressed genes have previously not been known to play a role in human neoplasia, and some of them may represent novel tumor suppressor or oncogenes. No genes were up-regulated, and only a small number of genes were down-regulated both in cell lines and in carcinomas with high HER2/neu protein levels. These included transforming acidic coiled-coil containing protein 1, glycogen phosphorylase BB, complement 1q and one EST. The differential expression of select genes was confirmed by Northern blotting (trefoil factor 3) or by immunocytochemistry (glycogen phosphorylase BB, vimentin, KAI1). In an extended validation study, 18 of 41 ER-negative, but none of 46 ER-positive, breast carcinomas were found to express vimentin, and all but one of the vimentin-positive tumors were confined to the HER2/neu-negative subgroup (P = 0.0019). Our findings support an important role of the mammary stroma in determining the clinical breast cancer phenotype.