Background
Antibodies to blood-stage Plasmodium falciparum antigens have been associated with protection against clinical malaria in some studies but not others. Many of these studies have not assessed whether high-titer antibodies are associated with protection and have not adjusted for differences in malaria exposure.
Methods
The presence of high-titer antibodies to apical membrane antigen-1 (AMA-1), erythrocyte binding antigen-175 (EBA-175) and merozoite surface protein-119 (MSP-119) was assessed in 87 children living in a malaria holoendemic area of Kenya. The children were prospectively assessed during one year for clinical malaria.
Results
In unadjusted analyses, high-titer antibodies to MSP-119, but not EBA-175 or AMA-1, were associated with protection from clinical malaria. However, after adjustment for exposure, only high-titer antibodies to EBA-175 were associated with protection from clinical malaria (hazard ratio (HR), 0.48, 95% confidence interval (CI) 0.24, 0.95, P=0.03), and with reduced episodes of clinical malaria (incidence rate ratio, 0.50, 95 % CI, 0.31, 0.81, P=0.005). A trend toward increased protection from clinical malaria in children was seen with antibodies to both EBA-175 and MSP-119 (HR, 0.26, 95% CI 0.03, 1.94, P=0.18)
Conclusions
High-titer antibodies to EBA-175 are associated with protection from clinical malaria in children in a malaria holoendemic area of Kenya. Accurate estimates of antibody-associated protection from clinical malaria require adjustment for malaria exposure.
Purpose: Previous studies of connexin-related hearing loss have typically reported on mixed age groups or adults.To further address epidemiology and natural history of connexin-related hearing loss, we conducted a longitudinal study in an ethnically diverse cohort of infants and toddlers under 3 years of age. Our study compares infants with and without connexin-related hearing loss to examine differences in the prevalence of connexin and non-connexinrelated hearing loss by ethnic origin, detection by newborn hearing screening, phenotype, neonatal risk factors, and family history. This is the first study to differentiate infants with and without connexin-related hearing loss.
Methods:We enrolled 95 infants with hearing loss from whom both exons of Cx26 were sequenced and the Cx30 deletion was assayed. Demographic, family history, newborn hearing screening data, perinatal, and audiologic records were analyzed. Results: Genetic testing identified biallelic Cx26/30 hearing loss-associated variants in 24.7% of infants with a significantly lower prevalence in Hispanic infants (9.1%). Eighty-two infants underwent newborn hearing screening; 12 infants passed, 3 had connexin-related hearing loss. No differences in newborn hearing screening pass rate, neonatal complications, or hearing loss severity were detected between infants with and without connexin-related hearing loss. Family history correlates with connexin-related hearing loss.Conclusions: Connexin-related hearing loss occurs in one quarter of infants in an ethnically diverse hearing loss population but with a lower prevalence in Hispanic infants. Not all infants with connexin-related hearing loss fail newborn hearing screening. Family history correlates significantly with connexin-related hearing loss. Genetic testing should not be deferred because of newborn complications. These results will have an impact on genetic testing for infant hearing loss. Genet Med 2008:10(7):517-524.
Abstract. In highland areas of unstable, low malaria transmission, the extent to which immunity to uncomplicated malaria develops with age and intermittent parasite exposure has not been well characterized. We conducted active surveillance for clinical malaria during
As the world responds to the global crisis of the COVID-19 pandemic an increasing number of patients are experiencing increased morbidity as a result of multi-organ involvement. Of these, a small proportion will progress to end-stage lung disease, become dialysis dependent, or both. Herein, we describe the first reported case of a successful combined lung and kidney transplantation in a patient with COVID-19. Lung transplantation, isolated or combined with other organs, is feasible and should be considered for select patients impacted by this deadly disease.
IntroductionPulmonary arterial hypertension (PAH) is characterized by loss of microvessels. The Wnt pathways control pulmonary angiogenesis, but their role in PAH is incompletely understood. We hypothesized that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis, and its loss contributes to PAH.MethodsLung tissue and PMVECs from healthy and PAH patients were screened for Wnt production. Global and endothelial-specific Wnt7a−/–mice were generated and exposed to chronic hypoxia and Sugen-hypoxia (SuHx).ResultsHealthy PMVECs demonstrated >6-fold Wnt7a expression during angiogenesis that was absent in PAH PMVECs and lungs. Wnt7a expression correlated with formation of tip cells, a migratory endothelial phenotype critical for angiogenesis. PAH PMVECs demonstrated reduced VEGF-induced tip cell formation as evidenced by reduced filopodia formation and motility, which was partially rescued by recombinant Wnt7a. We discovered that Wnt7a promotes VEGF signaling by facilitating Y1175 tyrosine phosphorylation in VEGFR2 through ROR2, a Wnt-specific receptor. We found that ROR2 knockdown mimics Wnt7a insufficiency and prevents recovery of tip cell formation with Wnt7a stimulation. While there was no difference between wild-type and endothelial-specific Wnt7a−/–mice under either chronic hypoxia and SuHx, global Wnt7a+/–mice in hypoxia demonstrated higher pulmonary pressures and severe right ventricular and lung vascular remodeling. Similar to PAH, Wnt7a+/–PMVECs exhibited insufficient angiogenic response to VEGF-A that improved with Wnt7a.ConclusionsWnt7a promotes VEGF signaling in lung PMVECs and its loss is associated with insufficient VEGF-A angiogenic response. We propose that Wnt7a deficiency contributes to progressive small vessel loss in PAH.
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