Global health reciprocal innovation to address mental health and well-being: strategies used and lessons learnt.

Over the past two decades there have been major advances in the development of interventions promoting mental health and well-being in low- and middle-income countries (LMIC), including delivery of care by non-specialist providers, incorporation of mobile technologies and development of multilevel community-based interventions. Growing inequities in mental health have led to calls to adopt similar strategies in high-income countries (HIC), learning from LMIC. To overcome shared challenges, it is crucial for projects implementing these strategies in different global settings to learn from one another. Our objective was to examine cases in which mental health and well-being interventions originating in or conceived for LMIC were implemented in the USA. The cases included delivery of psychological interventions by non-specialists, HIV-related stigma reduction programmes, substance use mitigation strategies and interventions to promote parenting skills and family functioning. We summarise commonly used strategies, barriers, benefits and lessons learnt for the transfer of these innovative practices among LMIC and HIC. Common strategies included intervention delivery by non-specialists and use of digital modalities to facilitate training and increase reach. Common barriers included lack of reimbursement mechanisms for care delivered by non-specialists and resistance from professional societies. Despite US investigators' involvement in most of the original research in LMIC, only a few cases directly involved LMIC researchers in US implementation. In order to achieve greater equity in global mental health and well-being, more efforts and targeted funding are needed to develop best practices for global health reciprocal innovation and iterative learning in HIC and LMIC.

Barriers and Facilitators to Integrating Depression Treatment Within a TB Program and Primary Care in Brazil.

Tuberculosis (TB) and depression is common and is associated with poor TB outcomes. The World Health Organization End TB Strategy explicitly calls for the integration of TB and mental health services. Interpersonal Counseling (IPC) is a brief evidence-based treatment for depression that can be delivered by non-mental health specialists with expert supervision. The goal of this study was to explore potential barriers and facilitators to training non-specialist providers to deliver IPC within the TB Control Program and primary care in Itaboraí, Rio de Janeiro state. Data collection consisted of six focus groups (n = 42) with health professionals (n = 29), program coordinators (n = 7), and persons with TB (n = 6). We used open coding to analyze the data, followed by deductive coding using the Chaudoir multi-level framework for implementation outcomes. The main structural barriers identified were poverty, limited access to treatment, political instability, violence, and social stigma. Organizational barriers included an overburdened and under-resourced health system with high staff turnover. Despite high levels of stress and burnout among health professionals, several provider-level facilitators emerged including a high receptivity to, and demand for, mental health training; strong community relationships through the community health workers; and overall acceptance of IPC delivered by any type of health provider. Patients were also receptive to IPC being delivered by any type of professional. No intervention-specific barriers or facilitators were identified. Despite many challenges, integrating depression treatment into primary care in Itaboraí using IPC was perceived as acceptable, feasible, and desirable.

The impact of COVID-19 on self-reported burnout and health and mental health services in Nampula, Mozambique.

Background: The purpose of this study was to examine the impact of the COVID-19 pandemic on self-reported burnout of health workers, quality of care, and perceptions of COVID-19-related stigma in Mozambique. Method: We conducted a cross-sectional quantitative assessment of 170 frontline health workers in Nampula District, Mozambique, including 149 (87.6%) primary care providers and 21 (12.4%) mental health specialists. Results: Of the 170 frontline workers, only 10.1% of frontline workers were experiencing more professional burnout, whereas 33.3% felt it had lessened. The perceived impact on quality of care also varied, without any significant differences by sex, education level, or mental health training background. Compared to the beginning of the COVID-19 pandemic in March 2020, 42.3 and 38.1% providers felt that their ability to provide mental health and general health care, respectively, had worsened, compared to 57.7 and 61.9% who believed that either there was no change, or that the work had become easier. Likewise, 26.8% of providers felt that their ability to meet patients' needs had gotten more difficult, whereas 43.4% reported no change and 29.8% reported that it was easier. Twenty-two percent of providers reported an overall increase in caseloads since before the pandemic whereas the majority (67.9%) reported a decrease. Providers believed that 57.1% of people in general were afraid of people with COVID-19, 27.5% were afraid of a person recovered from COVID-19, and 39.9% were afraid of a person with family members with COVID-19. The perceived stigma about healthcare professionals was also low; only 27.4% believed that people in general were afraid of healthcare providers who deliver care to people with COVID-19. Conclusion: In contrast with other global studies, many healthcare workers in our sample reported a reduction in burnout, which may be associated with the lower overall caseloads seen during this period. Similarly, the quality of care was minimally impacted. More research is needed to determine whether the experience in Mozambique is unique, or similarly observed in other low-resource settings.

Impact of sex, race and socioeconomic status on survival after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

OBJECTIVES: Pulmonary thromboendarterectomy (PTE) is a definitive treatment for chronic thromboembolic pulmonary hypertension. Demographic-based disparities in PTE outcomes have not been well-studied. METHODS: We reviewed all patients who underwent PTE for chronic thromboembolic pulmonary hypertension between 2009 and 2019 at our institution, tracking demographic information including self-identified race, preoperative characteristics and 2-year survival. Socioeconomic status was assessed using the zip code-linked Distressed Communities Index, a validated holistic measure of community well-being. Survival was estimated using Kaplan-Meier method and factors associated with mortality were estimated using Cox regression. RESULTS: Of 235 PTE patients, 101 (42.9%) were white and 87 (37.0%) were black. White patients had a higher median age at surgery (57 vs 51 years, P = 0.035) and a lower degree of economic distress (33.6 vs 61.2 percentile, P < 0.001). Regarding sex, 106 (45.1%) patients were male and 129 (53.6%) were female. Male patients had a higher median age (59 vs 50 years, P = 0.004), greater rates of dyslipidaemia (34% vs 20.2%, P = 0.025), a lower ejection fraction (55% vs 57%, P = 0.046) and longer cross-clamp (77 vs 67.50 min, P = 0.004) and circulatory arrest times (42 vs 37.50 min, P = 0.007). No difference was observed in unadjusted 2-year survival after PTE between patients stratified by race and sex (P = 0.35). After adjustment for clinically relevant variables, neither socioeconomic status, sex nor race were associated with mortality in Cox proportional hazard analysis. CONCLUSIONS: Sex, socioeconomic status and race were not associated with adverse outcomes after PTE in our single-centre experience.

Production of 10-methyl branched fatty acids in yeast.

BACKGROUND: Despite the environmental value of biobased lubricants, they account for less than 2% of global lubricant use due to poor thermo-oxidative stability arising from the presence of unsaturated double bonds. Methyl branched fatty acids (BFAs), particularly those with branching near the acyl-chain mid-point, are a high-performance alternative to existing vegetable oils because of their low melting temperature and full saturation. RESULTS: We cloned and characterized two pathways to produce 10-methyl BFAs isolated from actinomycetes and γ-proteobacteria. In the two-step bfa pathway of actinomycetes, BfaB methylates Δ9 unsaturated fatty acids to form 10-methylene BFAs, and subsequently, BfaA reduces the double bond to produce a fully saturated 10-methyl branched fatty acid. A BfaA-B fusion enzyme increased the conversion efficiency of 10-methyl BFAs. The ten-methyl palmitate production (tmp) pathway of γ-proteobacteria produces a 10-methylene intermediate, but the TmpA putative reductase was not active in E. coli or yeast. Comparison of BfaB and TmpB activities revealed a range of substrate specificities from C14-C20 fatty acids unsaturated at the Δ9, Δ10 or Δ11 position. We demonstrated efficient production of 10-methylene and 10-methyl BFAs in S. cerevisiae by secretion of free fatty acids and in Y. lipolytica as triacylglycerides, which accumulated to levels more than 35% of total cellular fatty acids. CONCLUSIONS: We report here the characterization of a set of enzymes that can produce position-specific methylene and methyl branched fatty acids. Yeast expression of bfa enzymes can provide a platform for the large-scale production of branched fatty acids suitable for industrial and consumer applications.

Loss of Notch1 Activity Inhibits Prostate Cancer Growth and Metastasis and Sensitizes Prostate Cancer Cells to Antiandrogen Therapies.

Prostate cancer remains among the leading causes of cancer-related deaths in men. Patients with aggressive disease typically undergo hormone deprivation therapy. Although treatment is initially very successful, these men commonly progress to lethal, castration-resistant prostate cancer (CRPC) in 2 to 3 years. Standard therapies for CRPC include second-generation antiandrogens, which prolong patient lifespan by only several months. It is imperative to advance our understanding of the mechanisms leading to resistance to identify new therapies for aggressive prostate cancer. This study identifies Notch1 as a therapeutic target in prostate cancer. Loss of NOTCH1 in aggressive prostate cancer cells decreases proliferation, invasion, and tumorsphere formation. Therapeutic inhibition of Notch1 activity with gamma secretase inhibitors RO4929097 or DAPT in prostate cancer cells further results in decreased proliferative abilities. Loss of NOTCH1 and treatment of immunocompromised mice bearing prostate cancer xenografts with RO4929097 display significantly impaired tumor growth. Loss of NOTCH1 additionally decreased metastatic potential of prostate cancer cells in invasion assays in vitro as well as in vivo experiments. Moreover, treatment with gamma secretase inhibitors or NOTCH1 gene deletion synergized with antiandrogen therapies, enzalutamide or abiraterone, to decrease the growth of prostate cancer cells. Combination of gamma secretase inhibitors with abiraterone significantly inhibited cell migration and invasion, while combination with enzalutamide reversed enzalutamide-induced migration and invasion. These collective findings suggest loss of NOTCH1 delays growth of CRPC and inhibits metastasis, and inhibition of Notch1 activation in conjunction with second-generation antiandrogen therapies could delay growth and progression of prostate cancer.

High-oleate yeast oil without polyunsaturated fatty acids.

BACKGROUND: Oleate-enriched triacylglycerides are well-suited for lubricant applications that require high oxidative stability. Fatty acid carbon chain length and degree of desaturation are key determinants of triacylglyceride properties and the ability to manipulate fatty acid composition in living organisms is critical to developing a source of bio-based oil tailored to meet specific application requirements. RESULTS: We sought to engineer the oleaginous yeast Yarrowia lipolytica for production of high-oleate triacylglyceride oil. We studied the effect of deletions and overexpressions in the fatty acid and triacylglyceride synthesis pathways to identify modifications that increase oleate levels. Oleic acid accumulation in triacylglycerides was promoted by exchanging the native ∆9 fatty acid desaturase and glycerol-3-phosphate acyltransferase with heterologous enzymes, as well as deletion of the Δ12 fatty acid desaturase and expression of a fatty acid elongase. By combining these engineering steps, we eliminated polyunsaturated fatty acids and created a Y. lipolytica strain that accumulates triglycerides with > 90% oleate content. CONCLUSIONS: High-oleate content and lack of polyunsaturates distinguish this triacylglyceride oil from plant and algal derived oils. Its composition renders the oil suitable for applications that require high oxidative stability and further demonstrates the potential of Y. lipolytica as a producer of tailored lipid profiles.