Biochemical comparison of venoms from young Colombian Crotalus durissus cumanensis and their parents

Crotalus durissus cumanensis, a rattlesnake endemic to Colombia and Venezuela, is considered one of the most lethal snake species in Latin America. The aim of the present study was to compare the protein content and biological activity of the venom obtained from eight specimens of C. durissus cumanensis, namely two adults from different localities of Colombia and six offspring born in captivity. Protein profiles of crude venoms were analyzed by SDS-PAGE and RP-HPLC, and biological activities were evaluated for lethality, edema, defibrination, hemolytic and coagulant activities to assess individual venoms of adults and a pool of young snake venoms. Transient edema appeared rapidly after venom inoculation, whereas hemorrhagic effect was not observed. Differences in protein profiles, lethality, hemolytic, coagulant and defibrinating activities between both adult snake venoms were observed; those from the mother snake exhibited higher activities. Venoms from young snakes were similar to the one obtained from the mother, but the coagulant effect was stronger in offspring venoms. Notably, biological effects of the father snake venom were not comparable to those previously described for C. durissus cumanensis from Venezuela and C. durissus terrificus from Brazil, confirming the high variability of the venom from Crotalus species

Diabetes y enfermedad cardiovascular, aspectos actuales de su manejo: la visión del cardiólogo

La diabetes es una enfermedad prevalente, con casos en aumento en todo el mundo, y se relaciona de forma directa con otras condiciones entre ellas la obesidad. Así, la diabetes supone un riesgo cardiovascular mayor en aquellos pacientes que la padecen y una vez se manifiesta es la causa más importante de morbimortalidad. A lo largo de los últimos años, hemos tenido un cambio en el paradigma del manejo de esta condición, razón por la cual se ha soslayado el enfoque glucocéntrico para hacer una aproximación integral al riesgo global y los demás factores asociados. Los estudios recientes han aportado una valiosa información de seguridad cardiovascular, pero lo más interesante es que han demostrado que algunos grupos farmacológicos generan un beneficio adicional en la población con condición cardiovascular. Es tan fuerte el impacto de estos medicamentos que se están posesionando como la estrategia de manejo inicial para la diabetes

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Protective Efficacy of <i>Plasmodium vivax</i> Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial

<div><p>Background</p><p>Immunizing human volunteers by mosquito bite with radiation-attenuated <i>Plasmodium falciparum</i> sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with <i>P</i>. <i>vivax (Pv)</i> RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of <i>Pv</i>RAS immunization.</p><p>Methodology/Principal Findings</p><p>A randomized, single-blinded trial was conducted. Duffy positive (Fy+; <i>Pv</i> susceptible) individuals were enrolled: 14 received bites from irradiated (150 ± 10 cGy) <i>Pv</i>-infected <i>Anopheles</i> mosquitoes (RAS) and 7 from non-irradiated non-infected mosquitoes (Ctl). An additional group of seven Fy- (<i>Pv</i> refractory) volunteers was immunized with bites from non-irradiated <i>Pv</i>-infected mosquitoes. A total of seven immunizations were carried out at mean intervals of nine weeks. Eight weeks after last immunization, a controlled human malaria infection (CHMI) with non-irradiated <i>Pv</i>-infected mosquitoes was performed. Nineteen volunteers completed seven immunizations (12 RAS, 2 Ctl, and 5 Fy-) and received a CHMI. Five of 12 (42%) RAS volunteers were protected (receiving a median of 434 infective bites) compared with 0/2 Ctl. None of the Fy- volunteers developed infection by the seventh immunization or after CHMI. All non-protected volunteers developed symptoms 8–13 days after CHMI with a mean pre-patent period of 12.8 days. No serious adverse events related to the immunizations were observed. Specific IgG1 anti-<i>Pv</i>CS response was associated with protection.</p><p>Conclusion</p><p>Immunization with <i>Pv</i>RAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to <i>Pv</i> malaria.</p><p>Trial registration</p><p>Identifier: <a href="https://clinicaltrials.gov/ct2/show/NCT01082341" target="_blank">NCT01082341</a>.</p></div

IgG isotype response against <i>Pv</i>CS<i>-</i>NRC peptide.

<p>Antibody IgG isotype levels determined by ELISA in the RAS group (n = 12; <b>A</b>), Fy- group (n = 5; <b>B</b>) and Ctl group (n = 2; <b>B</b>) at seventh immunization are shown. Values are expressed as reactivity index (RI) defined as sample OD divided by the cut-off value. Horizontal bars indicate median values. p value using the Mann-Whitney U test between protected and non-protected are shown.</p

Parasitemia determined by qPCR.

<p><b>A</b>. Number of parasite DNA copies per μL determined during the immunization phase in the Fy- group. <b>B</b>. Parasitemia after the CHMI in Ctl and RAS groups. Ctl* corresponds to the parasitemia dynamics determined by qPCR during a previous CHMI experiment that included naïve Fy+ individuals using the same procedures for comparison. Each point represents mean ± SEM of parasites/μL (Log₁₀).</p

Frequency and intensity of adverse events after the CHMI.

<p>The adverse events graded according to FDA recommendations [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005070#pntd.0005070.ref022" target="_blank">22</a>] and grouped as fever-related symptoms; gastric symptoms; and, others in RAS (n = 12; <b>A</b>) and Ctl group (n = 2; <b>B</b>) are shown. No AE after the CHMI were observed in the Fy- group (n = 5). Abbreviations: Abd, abdominal pain; rash, generalized rash; aphthous, aphthous stomatitis.</p

Antibody response against <i>Pv</i>CS<i>-</i>NRC peptide.

<p>Total IgG response determined by ELISA in the RAS group (n = 12; <b>A</b>), Fy- group (n = 5; <b>B</b>) and Ctl group (n = 2; red line in <b>A</b> and <b>B</b>). Values are expressed as reactivity index (RI) defined as sample OD at 1:200 serum dilutions divided by the cut-off value. Mean ± SEM are shown. <b>C</b>. Correlations between total received dose of infective bites and RI at seventh immunization for RAS and Fy- volunteers. Spearman’s rank correlation (r_s) and p values are shown. <b>D</b>. Mean ± SEM of RI for protected and non-protected volunteers after every immunization. * p < 0.05; ** p < 0.01; *** p < 0.001.</p

Naïve Fy+ volunteers participating in previous CHMI carried out at the MVDC.

<p>Naïve Fy+ volunteers participating in previous CHMI carried out at the MVDC.</p