Accumulating clinical observations suggest pathogenesis beyond viral pneumonia and its secondary consequences in COVID-19 patients. In particular, many patients develop profound hyperinflammation and hypercoagulopathy with disseminated thrombogenesis and thromboembolism, which we observe also in a Swedish COVID-19 intensive care patient cohort. To understand these vascular manifestations, it is important to establish the potential vascular entry point(s) of the SARS-CoV-2 virus, i.e. which vascular cell types express the SARS-CoV-2 receptor ACE2. We present data that ACE2 is specifically and highly expressed in microvascular pericytes, but absent from endothelial cells, perivascular macrophages and fibroblasts. Mice with pericyte ablation show increased expression and release of Von Willebrand Factor from microvascular endothelial cells, suggesting that pericytes orchestrate thrombogenic responses in neighboring endothelial cells. Identifying pericytes rather than endothelial cells as the ACE2-expressing cells in the vasculature may explain why hypertension, diabetes and obesity are risk factors for severe COVID-19 patients, as these conditions are characterized by an impaired endothelial barrier function, allowing SARS-CoV-2 to reach and infect the pericytes that are normally shielded from the blood behind an intact endothelial barrier. This novel COVID-19-(which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

BackgroundImmigrants and refugees are affected by diabetes-related health disparities, with higher rates of incident diabetes and sub-optimal diabetes outcomes. Digital storytelling interventions for chronic diseases, such as diabetes may be especially powerful among immigrants because often limited English proficiency minimizes access to and affects the applicability of the existing health education opportunities. Community-based participatory research (CBPR), whereby community members and academia partner in an equitable relationship through all phases of the research, is an intuitive approach to develop these interventions. The main objective of this study was to develop a diabetes digital storytelling intervention with and for immigrant and refugee populations.MethodsWe used a CBPR approach to develop a diabetes digital storytelling intervention with and for immigrant and refugee Somali and Latino communities. Building on an established CBPR partnership, we conducted focus groups among community members with type II diabetes for a dual purpose: 1) to inform the intervention as it related to four domains of diabetes self-management (medication management, glucose self-monitoring, physical activity, and nutrition); 2) to identify champion storytellers for the intervention development. Eight participants attended a facilitated workshop for the creation of the digital stories.ResultsEach of the eight storytellers, from the Somali and Latino communities with diabetes (four from each group), created a powerful and compelling story about their struggles and accomplishments related to the four domains of diabetes self-management.ConclusionsThis report is on a systematic, participatory process for the successful development of a diabetes storytelling intervention for Somali and Latino adults. Processes and products from this work may inform the work of other CBPR partnerships.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2628-y) contains supplementary material, which is available to authorized users.

Purpose The purpose of this pilot feasibility project was to examine the potential effectiveness of a digital storytelling intervention designed through a community-based participatory research approach for immigrants and refugees with type 2 diabetes mellitus (T2DM). Methods The intervention was a 12-minute culturally and linguistically tailored video consisting of an introduction, 4 stories, and a concluding educational message. A structured interview was used to assess the intervention for acceptability, interest level, and usefulness among 25 participants with T2DM (15 Latino, 10 Somali) across 5 primary care clinical sites. After watching the video, participants rated their confidence and motivation about managing T2DM as a result of the intervention. Baseline hemoglobin A1c (A1C) and follow-up values (up to 6 months) were abstracted from medical records. Results All participants reported that the intervention got their attention, was interesting, and was useful; 96% reported that they were more confident about managing their T2DM than before they watched the video; and 92% reported that the video motivated them to change a specific behavior related to T2DM self-management. The mean baseline A1C level for the intervention participants was 9.3% (78 mmol/mol). The change from baseline to first follow-up A1C level was −0.8% (−10 mmol/mol) (P<.05). Conclusions Implementation of a digital storytelling intervention for T2DM among immigrant populations in primary care settings is feasible and resulted in self-rated improvement in psychosocial constructs that are associated with healthy T2DM self-management behaviors, and there was some evidence of improvement in glycemic control. A large-scale efficacy trial of the intervention is warranted.

Purpose To evaluate healthy eating and physical activity intervention for immigrant families, derived through community-based participation. Design Healthy Immigrant Families study, randomized controlled trial with delayed-intervention control group, with families as the randomization unit. Setting US Midwest city. Participants Participants recruited by community partners from Hispanic, Somali, and Sudanese immigrant communities. Intervention Family health promoters from participating communities delivered 6 healthy eating modules, 4 physical activity modules, and 2 modules synthesizing information in 12 home visits (60–90 minutes) within first 6 months. Up to 12 follow-up phone calls to each participant occurred within second 6 months. Measures Primary measures were dietary quality measured with weekday 24-hour recall and reported as Healthy Eating Index score (0–100) and physical activity measured with accelerometers (14 wear days) at baseline, 6, 12, and 24 months. Results In total, 151 persons (81 adolescents and 70 adults; 44 families) were randomly assigned. At 12 months, significant improvement occurred in Healthy Eating Index score for adults in intervention compared with controls (change, +8.6 vs −4.4; P<.01) and persisted at 24 months (+7.4 from baseline; P<.01). No differences for adolescents and no significant differences occurred between groups and for physical activity. Conclusions This intervention produced sustained dietary quality improvement among adults but not adolescents. Program outcomes are relevant to communities working to decrease cardiovascular risk among immigrant populations.

Background US immigrants often have escalating cardiovascular risk. Barriers to optimal physical activity and diet have a significant role in this risk accumulation. Methods We developed a physical activity and nutrition intervention with immigrant and refugee families through a community-based participatory research approach. Work groups of community members and health scientists developed an intervention manual with 12 content modules that were based on social-learning theory. Family health promoters from the participating communities (Hispanic, Somali, Sudanese) were trained to deliver the intervention through 12 home visits during the first 6 months and up to 12 phone calls during the second 6 months. The intervention was tested through a randomized community-based trial with a delayed-intervention control group, with measurements at baseline, 6, 12, and 24 months. Primary measurements included accelerometer-based assessment of physical activity and 24-hour dietary recall. Secondary measures included biometrics and theory-based instruments. Results One hundred fifty-one individuals (81 adolescents, 70 adults; 44 families) were randomized. At baseline, mean (SD) time spent in moderate-to-vigorous physical activity was 64.7 (30.2) minutes/day for adolescents and 43.1 (35.4) minutes/day for adults. Moderate dietary quality was observed in both age groups. Biometric measures showed that 45.7% of adolescents and 80.0% of adults were overweight or obese. Moderate levels of self-efficacy and social support were reported for physical activity and nutrition. Discussion Processes and products from this program are relevant to other communities aiming to reduce cardiovascular risk and negative health behaviors among immigrants and refugees. Trial Registration This trial was registered at Clinicaltrials.gov (NCT01952808).

Background Ethnic minorities remain underrepresented in clinical trials despite efforts to increase their enrollment. Although community-based participatory research (CBPR) approaches have been effective for conducting research studies in minority and socially disadvantaged populations, protocols for CBPR recruitment design and implementation among immigrants and refugees have not been well described. Methods We used a community-led and community-implemented CBPR strategy for recruiting 45 Hispanic, Somali, and Sudanese families (160 individuals) to participate in a large, randomized, community-based trial aimed at evaluating a physical activity and nutrition intervention. Results We achieved 97.7% of our recruitment goal for families and 94.4% for individuals. Discussion Use of a CBPR approach is an effective strategy for recruiting immigrant and refugee participants for clinical trials. We believe the lessons we learned during the process of participatory recruitment design and implementation will be helpful for others working with these populations.

BackgroundVisceral leishmaniasis (VL), caused by protozoa of the Leishmania donovani complex, is a widespread parasitic disease of great public health importance; without effective chemotherapy symptomatic VL is usually fatal. Distinction of asymptomatic carriage from progressive disease and the prediction of relapse following treatment are hampered by the lack of prognostic biomarkers for use at point of care.Methodology/Principal FindingsAll IgG subclass and IgG isotype antibody levels were determined using unpaired serum samples from Indian and Sudanese patients with differing clinical status of VL, which included pre-treatment active VL, post-treatment cured, post-treatment relapsed, and post kala-azar dermal leishmaniasis (PKDL), as well as seropositive (DAT and/or rK39) endemic healthy controls (EHCs) and seronegative EHCs. L. donovani antigen-specific IgG1 levels were significantly elevated in relapsed versus cured VL patients (p<0.0001). Using paired Indian VL sera, consistent with the known IgG1 half-life, IgG1 levels had not decreased significantly at day 30 after the start of treatment (p = 0.8304), but were dramatically decreased by 6 months compared to day 0 (p = 0.0032) or day 15 (p<0.0001) after start of treatment. Similarly, Sudanese sera taken soon after treatment did not show a significant change in the IgG1 levels (p = 0.3939). Two prototype lateral flow immunochromatographic rapid diagnostic tests (RDTs) were developed to detect IgG1 levels following VL treatment: more than 80% of the relapsed VL patients were IgG1 positive; at least 80% of the cured VL patients were IgG1 negative (p<0.0001).Conclusions/SignificanceSix months after treatment of active VL, elevated levels of specific IgG1 were associated with treatment failure and relapse, whereas no IgG1 or low levels were detected in cured VL patients. A lateral flow RDT was successfully developed to detect anti-Leishmania IgG1 as a potential biomarker of post-chemotherapeutic relapse.

Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.