Successful Retention Strategies for Research Targeting Hispanic/Latinx (Including Recent Immigrants) in the Midwest Region of the United States.

Recruiting and retaining Hispanic/Latinx (H/L) participants, specifically undocumented immigrants, is challenging in part because of the mistrust and fear in participating in research studies. Additionally, only a few longitudinal studies describe the recruit and retention strategies among Mexican and Central American immigrants aiming to expand the knowledge base about those underprivileged groups; this was the objective of the 6-year longitudinal VidaSana study. In the present methods report, we specifically omit the presentation of results from the empirical data findings of the VidaSana study: the present report describes the process and offers a subjective appraisal of multiple and complementary approaches in the recruitment and retention strategies for Hispanics living in the Midwest region of the United States, including very recently arrived immigrants. This study was able to effectively recruit and retain (81.7%) a cohort of Mexican and Central American immigrants within a period of 36 months. Our recruitment and retention performance were successful in the context of the hostile environment against immigration that dominated the national landscape at the time of our study. The present methods report of the VidaSana study provides an insightful understanding in recruiting and, in particular, retaining H/Ls and H/L recent immigrants into longitudinal studies.

Transmission of malaria from donors to solid organ transplant recipients: A case report and literature review.

Malaria is a febrile and potentially fatal infection. It is typically transmitted to humans through the bite of Anopheles mosquitoes and less frequently can be contracted through blood transfusions, sharing contaminated needles and syringes, mother-to-child transmission, or after solid organ transplantation. Posttransplant malaria has rarely been reported in the literature, even in endemic areas. We report the cases of three solid organ recipients in which Plasmodium vivax infection was documented during postsurgical evaluation 30 days after transplant surgery. The diagnosis of donor-derived malaria was confirmed in all patients by demonstrating Plasmodium in a peripheral blood smear and by polymerase chain reaction (PCR). All recipients had symptoms. The liver transplant recipient had myalgia, arthralgia, and thrombocytopenia; the kidney transplant recipient developed acute renal failure; and the heart transplant recipient had fever, cephalalgia, and tonic-clonic seizures. Pre-transplant screening of donors and recipients from endemic regions may not be sufficient to safely rule out persistent malaria. In Colombia, according to legislation, no mandatory testing is required for the diagnosis of malaria in organ donors in nonendemic areas. Therefore, donor screening by questionnaire is the only tool for preventing transplant-borne malaria. The migratory trend from Venezuela to Colombia has increased the number of imported cases of malaria, and the infection may be present in endemic and nonendemic regions. Although donor evaluation is not standardized in current guidelines, we suggest that donors be tested for malaria with a peripheral blood smear, detection of specific IgG antibodies against Plasmodium, and techniques such as PCR, if possible.

Diabetic Kidney Disease, Endothelial Damage, and Podocyte-Endothelial Crosstalk.

Diabetes-related complications are a significant source of morbidity and mortality worldwide. Diabetic kidney disease is a frequent microvascular complication and a primary cause of kidney failure in patients with diabetes. The glomerular filtration barrier is composed of 3 layers: the endothelium, glomerular basement membrane, and podocytes. Podocytes and the endothelium communicate through molecular crosstalk to maintain filtration at the glomerular filtration barrier. Chronic hyperglycemia affects all 3 layers of the glomerular filtration barrier, as well as the molecular crosstalk that occurs between the 2 cellular layers. One of the earliest events following chronic hyperglycemia is endothelial cell dysfunction. Early endothelial damage is associated with progression of diabetic kidney disease. However, current therapies are based in controlling glycemia and arterial blood pressure without targeting endothelial dysfunction. Disruption of the endothelial cell layer also alters the molecular crosstalk that occurs between the endothelium and podocytes. This review discusses both the physiologic and pathologic communication that occurs at the glomerular filtration barrier. It examines how these signaling components contribute to podocyte foot effacement, podocyte detachment, and the progression of diabetic kidney disease.

Alk1 haploinsufficiency causes glomerular dysfunction and microalbuminuria in diabetic mice.

Endothelial dysfunction has been shown to play an important role in the pathogenesis of glomerular damage during diabetic kidney disease (DKD). As such, a better understanding of the molecular mechanisms involved in glomerular endothelial dysfunctions could provide novel therapeutic strategies for the prevention of DKD. We have previously shown that Alk1/BMP9 signaling plays an important function to maintain vascular integrity in diabetic animals. As such, we evaluated the effects of Alk1 suppression on glomerular endothelial function in diabetic mice. In the present study, we used mice with conditional heterozygote deletion of Alk1 in the endothelium (Alk1ΔEC) to evaluate the role of Alk1 on kidney function during STZ-induced diabetes. DKD was investigated in diabetic control and Alk1ΔEC mice euthanized eight weeks after the onset of diabetes. We showed that Alk1 expression is reduced in the glomeruli of human DKD patients. While renal function was not altered in Alk1ΔEC non-diabetic mice, we showed that Alk1 haploinsufficiency in the glomerular endothelium leads to microalbuminuria, thickening of the glomerular basement membrane, glomerular apoptosis and podocyte loss in diabetic mice. These data suggest that Alk1 is important for the proper function of glomerular endothelial cells and that decreased Alk1 combined with chronic hyperglycemia can impair renal function.

The VidaSana Study: Recruitment Strategies for Longitudinal Assessment of Egocentric Hispanic Immigrant Networks.

We disseminate the recruitment strategies used in the five-year VidaSana study (started in 2017) in the Midwest region of the United States, targeting recently arrived Hispanic immigrants. VidaSana aims to follow immigrants within six months of arrival for 24 months to (1) characterize features of networks (personal and community) that improve or undermine dental health; and (2) further refine methods to quantify the evolution of egocentric networks, using social network methodology. We implemented several strategies to promote and recruit potential participants into the study. We collaborate with agents serving Indiana's Hispanic communities using three levels of visibility. The broad level includes radio advertisements, TV interviews, newspaper advertisements, and targeted Facebook advertisements. Intermediate level visibility includes posting flyers in schools, employment agencies, immigrant welcome centers, and Hispanic businesses; making announcements at church/temple and school events; tabling at community, church and school events; and a pervasive adaptation of our strategies to the requirements of our partners. Lastly, the individualized level includes direct referrals by partners through word of mouth. From the initial 13 months of recruitment (494 screened contacts and 202 recruited participants), the most successful recruitment strategies appear to be a combination of intermediate- and individual-level strategies; specifically, face-to-face recruitment at school events, direct referrals from our community partners, and tabling at community/school/church events. The current interim findings and future final findings will help guide recruitment and retention strategies for studies focused on immigrants in the current climate of heightened immigration regulations and enforcement.

BMP9 (Bone Morphogenetic Protein-9)/Alk1 (Activin-Like Kinase Receptor Type I) Signaling Prevents Hyperglycemia-Induced Vascular Permeability.

Objective- Diabetic macular edema is a major cause of visual impairment. It is caused by blood-retinal barrier breakdown that leads to vascular hyperpermeability. Current therapeutic approaches consist of retinal photocoagulation or targeting VEGF (vascular endothelial growth factor) to limit vascular leakage. However, long-term intravitreal use of anti-VEGFs is associated with potential safety issues, and the identification of alternative regulators of vascular permeability may provide safer therapeutic options. The vascular specific BMP (bone morphogenetic protein) receptor ALK1 (activin-like kinase receptor type I) and its circulating ligand BMP9 have been shown to be potent vascular quiescence factors, but their role in the context of microvascular permeability associated with hyperglycemia has not been evaluated. Approach and Results- We investigated Alk1 signaling in hyperglycemic endothelial cells and assessed whether BMP9/Alk1 signaling could modulate vascular permeability. We show that high glucose concentrations impair Alk1 signaling, both in cultured endothelial cells and in a streptozotocin model of mouse diabetes mellitus. We observed that Alk1 signaling participates in the maintenance of vascular barrier function, as Alk1 haploinsufficiency worsens the vascular leakage observed in diabetic mice. Conversely, sustained delivery of BMP9 by adenoviral vectors significantly decreased the loss of retinal barrier function in diabetic mice. Mechanistically, we demonstrate that Alk1 signaling prevents VEGF-induced phosphorylation of VE-cadherin and induces the expression of occludin, thus strengthening vascular barrier functions. Conclusions- From these data, we suggest that by preventing retinal vascular permeability, BMP9 could serve as a novel therapeutic agent for diabetic macular edema.

Divergent macrophage responses to Mycobacterium bovis among naturally exposed uninfected and infected cattle.

Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), is a successful pathogen that remains an important global threat to livestock. Cattle naturally exposed to M. bovis normally become reactive to the M. bovis-purified protein derivative (tuberculin) skin test; however, some individuals remain negative, suggesting that they may be resistant to infection. To better understand host innate resistance to infection, 26 cattle from herds with a long history of high TB prevalence were included in this study. We investigated the bactericidal activity, the production of reactive oxygen and nitrogen species and the TB-related gene expression profile after in vitro M. bovis challenge of monocyte-derived macrophages from cattle with TB (n=17) and from non-infected, exposed cattle (in-contacts, n=9). The disease status was established based on the tuberculin skin test and blood interferon-gamma test responses, the presence of visible lesions at inspection on abattoirs and the histopathology and culture of M. bovis. Although macrophages from TB-infected cattle enabled M. bovis replication, macrophages from healthy, exposed cattle had twofold lower bacterial loads, overproduced nitric oxide and had lower interleukin (IL)-10 gene expression (P⩽0.05). Higher mRNA expression levels of inducible nitric oxide synthase, C-C motif chemokine ligand 2 and IL-12 were observed in macrophages from all in-contact cattle than in macrophages from their TB-infected counterparts, which expressed more tumour necrosis factor-α; however, the differences were not statistically significant owing to individual variation. These results confirm that macrophage bactericidal responses have a crucial role in innate resistance to M. bovis infection in cattle.