Plasma-Derived Extracellular Vesicles as Potential Biomarkers in Heart Transplant Patient with Chronic Chagas Disease

Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers.Barcelona Institute for Global Health (ISGlobal) receives support from the Spanish Ministry of Science, Innovation and Universities through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S). ISGlobal and Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP) are members of the Centres de Recerca de Catalunya (CERCA Program), Generalitat de Catalunya. Work in the laboratory of C.F.B. is funded by Fundació La Marató de TV3 (reference 566/U/2018) and Fundación Mundo Sano. This project was co-financed by the European Union through the European Regional Development Fund with the support of Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya. N.C., M.G., J.G., and M.J.P. receive funds from the Redes temáticas de investigación cooperativa en salud (RETICS), Spanish Tropical Diseases Network “RD12/0018/0010” and from the Agencia de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya; grant “2017 SGR 00924.” M.G., C.B., J.G., M.J.P., and I.C.A. belong to the Ibero-American Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas network. I.C.A. is partially supported by grants no. 2G12MD007592 and 5U54MD007592 from the National Institute on Minority Health and Health Disparities of the US National Institutes of Health. We are grateful to the Biomolecule Analysis Core Facility at University of Texas at El Paso, Border Biomedical Research Center, funded by National Institute on Minority Health and Health Disparities grants 2G12MD007592 and 5U54MD007592. M.T.M. received a PhD fellowship from the Science Without Borders Program, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil.S

Efficacy of Liposomal Amphotericin B Combined with Gamma Interferon or Granulocyte-Macrophage Colony-Stimulating Factor for Treatment of Systemic Zygomycosis in Mice▿

Granulocyte-macrophage colony-stimulating factor enhanced the efficacy of liposomal amphotericin B (LAMB) in a murine model of disseminated infection by Rhizopus oryzae, significantly prolonging survival and reducing tissue burden. The use of gamma interferon (IFN-γ) alone was ineffective, and IFN-γ combined with LAMB did not improve the results obtained with LAMB alone

Exposure to Folate Receptor Alpha Antibodies during Gestation and Weaning Leads to Severe Behavioral Deficits in Rats: A Pilot Study

<div><p>The central nervous system continues to develop during gestation and after birth, and folate is an essential nutrient in this process. Folate deficiency and folate receptor alpha autoantibodies (FRα-AuAb) have been associated with pregnancy-related complications and neurodevelopmental disorders. In this pilot study, we investigated the effect of exposure to FRα antibodies (Ab) during gestation (GST), the pre-weaning (PRW), and the post weaning (POW) periods on learning and behavior in adulthood in a rat model. In the open field test and novel object recognition task, which examine locomotor activity and anxiety-like behavior, deficits in rats exposed to Ab during gestation and pre-weaning (GST+PRW) included more time spent in the periphery or corner areas, less time in the central area, frequent self-grooming akin to stereotypy, and longer time to explore a novel object compared to a control group; these are all indicative of increased levels of anxiety. In the place avoidance tasks that assess learning and spatial memory formation, only 30% of GST+PRW rats were able to learn the passive place avoidance task. None of these rats learned the active place avoidance task indicating severe learning deficits and cognitive impairment. Similar but less severe deficits were observed in rats exposed to Ab during GST alone or only during the PRW period, suggesting the extreme sensitivity of the fetal as well as the neonatal rat brain to the deleterious effects of exposure to Ab during this period. Behavioral deficits were not seen in rats exposed to antibody post weaning. These observations have implications in the pathology of FRα-AuAb associated with neural tube defect pregnancy, preterm birth and neurodevelopmental disorders including autism.</p></div

Changes in the Epidemiology of Diabetic Retinopathy in Spain: A Systematic Review and Meta-Analysis.

The aim of the present study was to determine the prevalence and incidence of diabetic retinopathy (DR) and its changes in the last 20 years in type 2 diabetes mellitus (T2DM) patients in Spain. A systematic review with a meta-analysis was carried out on the studies published between 2001-2020 on the prevalence and incidence of DR and sight-threatening diabetic retinopathy (STDR) in Spain. The articles included were selected from four databases and publications of the Spanish Ministry of Health and Regional Health Care System (RHCS). The meta-analysis to determine heterogeneity and bias between studies was carried out with the MetaXL 4.0. Since 2001, we have observed an increase in the detection of patients with DM, and at the same time, screening programs for RD have been launched; thus, we can deduce that the increase in the detection of patients with DM, many of them in the initial phases, far exceeds the increased detection of patients with DR. The prevalence of DR was higher between 2001 and 2008 with values of 28.85%. These values decreased over the following period between 2009 and 2020 with a mean of 15.28%. Similarly the STDR prevalence decrease from 3.67% to 1.92% after 2008. The analysis of the longitudinal studies determined that the annual DR incidence was 3.83%, and the STDR annual incidence was 0.41%. In Spain, for T2DM, the current prevalence of DR is 15.28% and 1.92% forSTDR. The annual incidence of DR is 3.83% and is 0.41% for STDR

Maternal Folate Status and the BHMT c.716G&gt;A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy

The effect of the betaine: homocysteine methyltransferase BHMT c.716G&gt;A (G: guanosine; A: adenosine) single nucleotide polymorphism (SNP) on the BHMT pathway is unknown during pregnancy. We hypothesised that it impairs betaine to dimethylglycine conversion and that folate status modifies its effect. We studied 612 women from the Reus Tarragona Birth Cohort from ≤12 gestational weeks (GW) throughout pregnancy. The frequency of the variant BHMT c.716A allele was 30.8% (95% confidence interval (CI): 28.3, 33.5). In participants with normal-high plasma folate status (&gt;13.4 nmol/L), least square geometric mean [95% CI] plasma dimethylglycine (pDMG, µmol/L) was lower in the GA (2.35 [2.23, 2.47]) versus GG (2.58 [2.46, 2.70]) genotype at ≤12 GW (p &lt; 0.05) and in the GA (2.08 [1.97, 2.19]) and AA (1.94 [1.75, 2.16]) versus GG (2.29 [2.18, 2.40]) genotypes at 15 GW (p &lt; 0.05). No differences in pDMG between genotypes were observed in participants with possible folate deficiency (≤13.4 nmol/L) (p for interactions at ≤12 GW: 0.023 and 15 GW: 0.038). PDMG was lower in participants with the AA versus GG genotype at 34 GW (2.01 [1.79, 2.25] versus 2.44 [2.16, 2.76] and at labour, 2.51 [2.39, 2.64] versus 3.00 [2.84, 3.18], (p &lt; 0.01)). Possible deficiency compared to normal-high folate status was associated with higher pDMG in multiple linear regression analysis (β coefficients [SEM] ranging from 0.07 [0.04], p &lt; 0.05 to 0.20 [0.04], p &lt; 0.001 in models from early and mid-late pregnancy) and the AA compared to GG genotype was associated with lower pDMG (β coefficients [SEM] ranging from −0.11 [0.06], p = 0.055 to −0.23 [0.06], p &lt; 0.001). Conclusion: During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele

Tracking the movement of the rat in the place avoidance arena.

<p>Tracings of the rat’s movement in the place avoidance arena for a SC rat (A), a GST+PRW rat able to learn the passive place avoidance task but fails the active place avoidance task (B) and a GST+PRW rat unable to learn both passive and active place avoidance tasks (C). The dots in the triangle represent number of shocks received during that trial.</p

Place avoidance in GST, PRW and SC rats.

<p>Parameters for the place avoidance tasks for GST (-○-, n = 4) and SC (-●-, n = 8) rats (Panels A and B) or PRW (-○-, n = 8) and SC (-●-, n = 4) rats (Panels C and D). Median values for each parameter are reported. *Different from the control group (<i>P</i> < 0.05); ^†different from the first trial (<i>P</i> < 0.05). Note: in Panel C, ^† indicates difference compared to the first trial in the exposed group (<i>P</i> < 0.05). Bonferroni correction for multiple comparisons was applied to the <i>P</i> values.</p

Place avoidance parameters in SC and GST-PRW rats.

<p>Passive and active place avoidance parameters in different trials for normal rabbit IgG exposed rats (-●-; SC group; <i>n</i> = 8) and GST-PRW rats exposed to FRα Ab (-○-; GST-PRW group; <i>n</i> = 6). Inability of the GST-PRW rats to learn the passive place avoidance (Panels A and B) and the active place avoidance (Panels C and D) is evident from the lack of a decrease in number of entrances and the shocks received along with lack of a decrease in time to first entry in subsequent trials. Median values for each parameter are reported. *Different from the SC group (<i>P</i> < 0.05). †The first trial (in the control group) was different from the rest of the trials (<i>P</i> < 0.05). Bonferroni correction was applied to the <i>P</i> values for multiple comparisons.</p

Anti FRα antibody titer.

<p>Binding (A) and blocking (B) titer of rabbit polyclonal antibody to recombinant rat folate receptor alpha.</p

Summary data of the place avoidance tasks for SC, GST+PRW, GST and PRW rats.

<p>While 30% of the GST+PRW rats learned the passive place avoidance task (PA), none were able to learn the active place avoidance task (AA). As per protocol, since all the GST+PRW rats failed the active place avoidance task, they were not tested for the conflict place avoidance task (CA). Similar but less severe effects were seen in GST only and PRW only rats.</p