Publications by authors named "Rafael Delgado"

129 Publications

Newborn Auditory Brainstem Responses in Children with Developmental Disabilities.

J Autism Dev Disord 2021 Jun 28. Epub 2021 Jun 28.

Department of Health Systems Management, Ben-Gurion University of the Negev, Beer Sheva, Israel.

We integrated data from a newborn hearing screening database and a preschool disability database to examine the relationship between newborn click evoked auditory brainstem responses (ABRs) and developmental disabilities. This sample included children with developmental delay (n = 2992), speech impairment (SI, n = 905), language impairment (n = 566), autism spectrum disorder (ASD, n = 370), and comparison children (n = 128,181). We compared the phase of the ABR waveform, a measure of sound processing latency, across groups. Children with SI and children with ASD had greater newborn ABR phase values than both the comparison group and the developmental delay group. Newborns later diagnosed with SI or ASD have slower neurological responses to auditory stimuli, suggesting sensory differences at birth.
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http://dx.doi.org/10.1007/s10803-021-05126-1DOI Listing
June 2021

Potential pharmacological strategies targeting the Niemann-Pick C1 receptor and Ebola virus glycoprotein interaction.

Eur J Med Chem 2021 Jun 19;223:113654. Epub 2021 Jun 19.

Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain. Electronic address:

Niemann-Pick C1 (NPC1) receptor is an intracellular protein located in late endosomes and lysosomes whose main function is to regulate intracellular cholesterol trafficking. Besides being postulated as necessary for the infection of highly pathogenic viruses in which the integrity of cholesterol transport is required, this protein also allows the entry of the Ebola virus (EBOV) into the host cells acting as an intracellular receptor. EBOV glycoprotein (EBOV-GP) interaction with NPC1 at the endosomal membrane triggers the release of the viral material into the host cell, starting the infective cycle. Disruption of the NPC1/EBOV-GP interaction could represent an attractive strategy for the development of drugs aimed at inhibiting viral entry and thus infection. Some of the today available EBOV inhibitors were proposed to interrupt this interaction, but molecular and structural details about their mode of action are still preliminary thus more efforts are needed to properly address these points. Here, we provide a critical discussion of the potential of NPC1 and its interaction with EBOV-GP as a therapeutic target for viral infections.
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http://dx.doi.org/10.1016/j.ejmech.2021.113654DOI Listing
June 2021

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist.

PLoS Pathog 2021 05 20;17(5):e1009576. Epub 2021 May 20.

Univ. Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, France.

The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.
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http://dx.doi.org/10.1371/journal.ppat.1009576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136665PMC
May 2021

First confirmation of importation and transmission in Spain of the newly identified SARS-CoV-2 B.1.1.7 variant.

Enferm Infecc Microbiol Clin (Engl Ed) 2021 Feb 19. Epub 2021 Feb 19.

Servicio de Microbiología Clínica y Enfermedades Infecciosas, Gregorio Marañón General University Hospital, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; CIBER Enfermedades Respiratorias (CIBERES), Spain. Electronic address:

Introduction: A newly identified SARS-CoV-2 variant, VOC202012/01 originating lineage B.1.1.7, recently emerged in the United Kingdom. The rapid spread in the UK of this new variant has caused other countries to be vigilant.

Material And Methods: We based our initial screening of B.1.1.7 on the dropout of the S gene signal in the TaqPath assay, caused by the 69/70 deletion. Subsequently, we confirmed the B.1.1.7 candidates by whole genome sequencing.

Results: We describe the first three imported cases of this variant from London to Madrid, subsequent post-arrival household transmission to three relatives, and the two first cases without epidemiological links to UK. One case required hospitalization. In all cases, drop-out of gene S was correctly associated to the B.1.1.7 variant, as all the corresponding sequences carried the 17 lineage-marker mutations.

Conclusion: The first identifications of the SARS-CoV-2 B.1.1.7 variant in Spain indicate the role of independent introductions from the UK coexisting with post-arrival transmission in the community, since the early steps of this new variant in our country.
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http://dx.doi.org/10.1016/j.eimc.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894114PMC
February 2021

Genomic Epidemiology of SARS-CoV-2 in Madrid, Spain, during the First Wave of the Pandemic: Fast Spread and Early Dominance by D614G Variants.

Microorganisms 2021 Feb 22;9(2). Epub 2021 Feb 22.

Servicio de Microbiología, Hospital Universitario La Paz and Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28046 Madrid, Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Madrid, Spain, on 25 February 2020. It increased in frequency very fast and by the end of May more than 70,000 cases had been confirmed by reverse transcription-polymerase chain reaction (RT-PCR). To study the lineages and the diversity of the viral population during this first epidemic wave in Madrid we sequenced 224 SARS-CoV-2 viral genomes collected from three hospitals from February to May 2020. All the known major lineages were found in this set of samples, though B.1 and B.1.5 were the most frequent ones, accounting for more than 60% of the sequences. In parallel with the B lineages and sublineages, the D614G mutation in the Spike protein sequence was detected soon after the detection of the first coronavirus disease 19 (COVID-19) case in Madrid and in two weeks became dominant, being found in 80% of the samples and remaining at this level during all the study periods. The lineage composition of the viral population found in Madrid was more similar to the European population than to the publicly available Spanish data, underlining the role of Madrid as a national and international transport hub. In agreement with this, phylodynamic analysis suggested multiple independent entries before the national lockdown and air transportation restrictions.
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http://dx.doi.org/10.3390/microorganisms9020454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926973PMC
February 2021

Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19.

Clin Microbiol Infect 2021 Jun 22;27(6):886-891. Epub 2021 Feb 22.

Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain; Research Institute Hospital 12 de Octubre, imas12, Madrid, Spain; Department of Medicine, Complutense University of Madrid, School of Medicine, Madrid, Spain.

Objectives: This study compares the infectivity of SARS-CoV-2 in respiratory samples from patients with mild COVID-19 with those from hospitalized patients with severe bilateral pneumonia. In severe COVID-19, we also analysed the presence of neutralizing activity in paired sera.

Methods: We performed cell cultures on 193 real-time reverse transcription polymerase chain reaction respiratory samples, positive for SARS-CoV-2, obtained from 189 patients at various times, from clinical diagnosis to follow-up. Eleven samples were obtained from asymptomatic individuals, 91 samples from 91 outpatients with mild forms of COVID-19 and 91 samples from 87 inpatients with severe pneumonia. In these patients, neutralizing activity was analysed in 30 paired sera collected after symptom onset >10 days.

Results: We detected a cytopathic effect (CPE) in 91/193 (47%) samples. Viral viability was maintained for up to 10 days in patients with mild COVID-19. In patients with severe COVID-19, the virus remained viable for up to 32 days after the onset of symptoms. Patients with severe COVID-19 presented infectious virus at a significantly higher rate in the samples with moderate to low viral load (cycle threshold value ≥ 26): 32/75 (43%) versus 14/63 (22%) for mild cases (p < 0.01). We observed a positive CPE despite the presence of clear neutralizing activity (NT50 > 1:1024 in 10% (3/30) of samples.

Discussion: Patients with severe COVID-19 might shed viable virus during prolonged periods of up to 4 weeks after symptom onset, even when presenting high cycle threshold values in their respiratory samples and despite having developed high neutralizing antibody titres.
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http://dx.doi.org/10.1016/j.cmi.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898982PMC
June 2021

Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

Eur J Pediatr 2021 Jul 19;180(7):2099-2106. Epub 2021 Feb 19.

Red de Investigación Translacional en Infectología Pediátrica (RITIP), Madrid, Spain.

Fever without source (FWS) in infants is a frequent cause of consultation at the emergency department, and the emergence of SARS-CoV-2 could affect the approach to those infants. The aim of this study is to define the clinical characteristics and rates of bacterial coinfections of infants < 90 days with FWS as the first manifestation of SARS-CoV-2 infection. This is a cross-sectional study of infants under 90 days of age with FWS and positive SARS-CoV2 PCR in nasopharyngeal swab/aspirate, attended at the emergency departments of 49 Spanish hospitals (EPICO-AEP cohort) from March 1 to June 26, 2020. Three hundred and thirty-three children with COVID-19 were included in EPICO-AEP. A total of 67/336 (20%) were infants less than 90 days old, and 27/67(40%) presented with FWS. Blood cultures were performed in 24/27(89%) and were negative in all but one (4%) who presented a Streptococcus mitis bacteremia. Urine culture was performed in 26/27(97%) children and was negative in all, except in two (7%) patients. Lumbar puncture was performed in 6/27(22%) cases, with no growth of bacteria. Two children had bacterial coinfections: 1 had UTI and bacteremia, and 1 had UTI. C-reactive was protein over 20 mg/L in two children (one with bacterial coinfection), and procalcitonin was normal in all. One child was admitted to the pediatric intensive care unit because of apnea episodes. No patients died.Conclusion: FWS was frequent in infants under 90 days of age with SARS-CoV-2 infection. Standardized markers to rule out bacterial infections remain useful in this population, and the outcome is generally good. What is Known: • Fever without source (FWS) in infants is a common cause of consultation at the emergency department, and young infants have a higher risk of serious bacterial infections (SBI). • The emergence of the new coronavirus SARS-CoV-2 could affect the approach to young infants with FWS in the emergency department. management of those children is a challenge because information about bacterial coinfection and prognosis is scarce. What is New: • SARS-CoV-2 infection should be ruled out in young infants (< 90 days of age) with FWS in areas with community transmission. • Bacterial coinfection rarely coexists in those infants. • Inflammatory markers were not increased in children without bacterial coinfection. • Outcome is good in most patients.
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http://dx.doi.org/10.1007/s00431-021-03973-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893843PMC
July 2021

Identification of potential inhibitors of protein-protein interaction useful to fight against Ebola and other highly pathogenic viruses.

Antiviral Res 2021 02 8;186:105011. Epub 2021 Jan 8.

Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040, Madrid, Spain. Electronic address:

Despite the efforts to develop new treatments against Ebola virus (EBOV) there is currently no antiviral drug licensed to treat patients with Ebola virus disease (EVD). Therefore, there is still an urgent need to find new drugs to fight against EBOV. In order to do this, a virtual screening was done on the druggable interaction between the EBOV glycoprotein (GP) and the host receptor NPC1 with a subsequent selection of compounds for further validation. This screening led to the identification of new small organic molecules with potent inhibitory action against EBOV infection using lentiviral EBOV-GP-pseudotype viruses. Moreover, some of these compounds have shown their ability to interfere with the intracellular cholesterol transport receptor NPC1 using an ELISA-based assay. These preliminary results pave the way to hit to lead optimization programs that lead to successful candidates.
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http://dx.doi.org/10.1016/j.antiviral.2021.105011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833471PMC
February 2021

Evaluation of the MOD11A2 product for canopy temperature monitoring in the Brazilian Atlantic Forest.

Environ Monit Assess 2021 Jan 7;193(1):45. Epub 2021 Jan 7.

Department of Soils, Federal Rural University of Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro, 23897-000, Brazil.

Forest canopies have an important influence on the global climate balance. Through the analysis of the temperature of the canopy, it is possible to infer about the physiological aspects of the plants, helping to understand the behavior of the vegetation and, consequently, in the environmental monitoring and management of green areas. This study aims to validate the MOD11A2 V006 product from canopy surface temperature data obtained by an infrared radiation sensor. For the validation of the MOD11A2 product, a comparative analysis was performed between the land surface temperature (LST) data, obtained by the MODIS sensor, and the canopy temperature data, obtained by the SI-111 infrared radiation sensor coupled to the Itatiaia National Park (PNI) micrometeorological tower. Meteorological variables and land surface temperature collected from January to December 2018 in the PNI were also analyzed. The results reveal that the MOD11A2 product overestimates the canopy temperature in the daytime (MB ranging from 1.56 to 3.57 °C) and underestimates in the night time (MB ranging from - 0.18 to - 4.22 °C). During daytime, the months corresponding to the dry season presented a very high correlation (r = 0.74 and 0.86) and the highest values for the Willmott index (d = 0.70 and 0.64). At nighttime, the MOD11A2 product did not present a good performance for the LST estimation, especially in the rainy season. Therefore, we observed that the MOD11A2 product has limitations to estimate the land surface temperature and that possible changes in the algorithm of this product can be performed for high atmospheric humidity conditions.
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http://dx.doi.org/10.1007/s10661-020-08788-zDOI Listing
January 2021

Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound.

Sci Rep 2020 12 18;10(1):22286. Epub 2020 Dec 18.

Servicio de Enfermedades Infecciosas, Instituto Ramón Y Cajal de Investigación Sanitaria (IRYCIS) - Hospital Universitario Ramón Y Cajal, Carretera de Colmenar, Km 9.100, 28034, Madrid, Spain.

Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently infected cells, commonly known as latency reversing agents (LRAs). Some drugs have been shown to reactivate latent HIV but do not cause a reduction in reservoir size. Therefore, finding new LRAs or new combinations or increasing the round of stimulations is needed to cure HIV. However, the effects of these drugs on viral rebound after prolonged treatment have not been evaluated. In a previous clinical trial, antiretroviral therapy intensification with maraviroc for 48 weeks caused an increase in residual viremia and episomal two LTR-DNA circles suggesting that maraviroc could reactivate latent HIV. We amended the initial clinical trial to explore additional virologic parameters in stored samples and to evaluate the time to viral rebound during analytical treatment interruption in three patients. Maraviroc induced an increase in cell-associated HIV RNA during the administration of the drug. However, there was a rapid rebound of viremia after antiretroviral therapy discontinuation. HIV-specific T cell response was slightly enhanced. These results show that maraviroc can reactivate latent HIV in vivo but further studies are required to efficiently reduce the reservoir size.
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http://dx.doi.org/10.1038/s41598-020-79002-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749169PMC
December 2020

Seroprevalence analysis of SARS-CoV-2 in pregnant women along the first pandemic outbreak and perinatal outcome.

PLoS One 2020 30;15(11):e0243029. Epub 2020 Nov 30.

Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.

Objectives: To evaluate the progression of the seroprevalence of SARS-CoV-2 in the pregnant population of the south of Madrid during the first wave of the COVID-19 pandemic. Secondarily we aimed to evaluate maternal and perinatal outcomes.

Study Design: Retrospective cohort study conducted at Hospital Universitario 12 de Octubre during weeks 10 to 19 of 2020, coinciding with the Spanish lockdown. We tested 769 serum samples obtained from routine serological testing during the first and third trimesters of pregnancy for specific IgG anti SARS-CoV-2 RBD and S proteins. RT-PCR tests were performed in suspected cases according to clinical practice. We compared maternal and perinatal outcomes in those with delivered pregnancies (n = 578) according to the presence or absence of specific IgG antibodies. Those with positive IgG were subdivided by the presence or absence of Covid-19 related symptoms at any time and the results of RT-PCR testing if performed. Therefore, we had 4 study groups: G1 (IgG negative), G2 (IgG positive, asymptomatic, RT-PCR testing negative or not done), G3 (IgG positive, symptomatic, RT-PCR testing negative or not done), and G4 (IgG positive, symptomatic, RT-PCR positive).

Results: Seropositivity increased from 0% to 21.4% (95% CI 11.8-31.0) during the study period, of which 27.9% had an asymptomatic course. Overall outcomes were favorable with a significant increased rate of preterm birth in G4 vs G1 (21.4% vs 6.7%) and cesarean/operative delivery (50% vs 26.9%). Asymptomatic and mild cases did not have differences regarding pregnancy course when compared to seronegative women. There were no documented cases of vertical or horizontal transmission.

Conclusion: Seroprevalence in pregnant women in southern Madrid went up to 21.4% of which 27.9% had an asymptomatic course. Overall perinatal results were favorable, especially in those asymptomatic.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243029PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703887PMC
December 2020

Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.

J Antimicrob Chemother 2021 02;76(3):738-742

Hospital Universitario La Paz - IdiPAZ, Paseo de la Castellana 261 28046, Madrid, Spain.

Background: In the ART-PRO pilot trial there were no virological failures through 48 weeks of treatment with dolutegravir plus lamivudine in suppressed individuals with and without archived lamivudine resistance-associated mutations (RAMs) detected through next-generation sequencing (NGS) but without evidence of lamivudine RAMs in baseline proviral DNA population sequencing.

Objectives: To present 96 week results from ART-PRO.

Methods: Open-label, single-arm pilot trial. At baseline, all participants switched to dolutegravir plus lamivudine. Participants were excluded if proviral DNA population genotyping detected lamivudine RAMs. To detect resistance minority variants, proviral DNA NGS was retrospectively performed from baseline samples. For this analysis the efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 96. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations.

Results: Forty-one participants were included, 21 with lamivudine RAMs in historical plasma RNA genotypes. Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively. At 96 weeks, 90.2% of participants achieved the efficacy endpoint. Between week 48 and 96 there was one discontinuation due to consent withdrawal and no discontinuations related to adverse events. Two participants had a transient viral rebound, both re-suppressed on dolutegravir plus lamivudine. Through week 96, there were no virological failures.

Conclusions: In this pilot trial, dolutegravir plus lamivudine maintained virological suppression at 96 weeks despite historical lamivudine resistance and persisting archived minority lamivudine RAMs.
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http://dx.doi.org/10.1093/jac/dkaa479DOI Listing
February 2021

Prolonged Auditory Brainstem Response in Universal Hearing Screening of Newborns with Autism Spectrum Disorder.

Autism Res 2021 01 2;14(1):46-52. Epub 2020 Nov 2.

Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.

Previous studies report prolonged auditory brainstem response (ABR) in children and adults with autism spectrum disorder (ASD). Despite its promise as a biomarker, it is unclear whether healthy newborns who later develop ASD also show ABR abnormalities. In the current study, we extracted ABR data on 139,154 newborns from their Universal Newborn Hearing Screening, including 321 newborns who were later diagnosed with ASD. We found that the ASD newborns had significant prolongations of their ABR phase and V-negative latency compared with the non-ASD newborns. Newborns in the ASD group also exhibited greater variance in their latencies compared to previous studies in older ASD samples, likely due in part to the low intensity of the ABR stimulus. These findings suggest that newborns display neurophysiological variation associated with ASD at birth. Future studies with higher-intensity stimulus ABRs may allow more accurate predictions of ASD risk, which could augment the universal ABR test that currently screens millions of newborns worldwide. LAY SUMMARY: Children with autism spectrum disorder (ASD) have slow brain responses to sounds. We examined these brain responses from newborns' hearing tests and found that newborns who were later diagnosed with autism also had slower brain responses to sounds. Future studies might use these findings to better predict autism risk, with a hearing test that is already used on millions of newborns worldwide.
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http://dx.doi.org/10.1002/aur.2422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894135PMC
January 2021

Persistent fire foci in all biomes undermine the Paris Agreement in Brazil.

Sci Rep 2020 10 1;10(1):16246. Epub 2020 Oct 1.

Postgraduate Program in Management and Regulation of Water Resources - ProfÁgua, State University of Mato Grosso (UNEMAT), Cuiabá, Mato Grosso, Brazil.

Brazil is one of the world's biggest emitters of greenhouse gases (GHGs). Fire foci across the country contributes to these emissions and compromises emission reduction targets pledged by Brazil under the Paris Agreement. In this paper, we quantify fire foci, burned areas, and carbon emissions in all Brazilian biomes (i.e., Amazon, Cerrado, Caatinga, Atlantic Forest, Pantanal and Pampa). We analyzed these variables using cluster analysis and non-parametric statistics to predict carbon and CO emissions for the next decade. Our results showed no increase in the number of fire foci and carbon emissions for the evaluated time series, whereby the highest emissions occur and will persist in the Amazon and Cerrado biomes. The Atlantic Forest, Pantanal, Caatinga and Pampa biomes had low emissions compared to the Amazon and Cerrado. Based on 2030 projections, the sum of emissions from fire foci in the six Brazilian biomes will exceed 5.7 Gt CO2, compromising the national GHG reduction targets. To reduce GHG emissions, Brazil will need to control deforestation induced by the expansion of the agricultural frontier in the Amazon and Cerrado biomes. This can only be achieved through significant political effort involving the government, entrepreneurs and society as a collective.
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http://dx.doi.org/10.1038/s41598-020-72571-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529887PMC
October 2020

Prevalence and Clinical Manifestations of Congenital Cytomegalovirus Infection in a Screening Program in Madrid (PICCSA Study).

Pediatr Infect Dis J 2020 11;39(11):1050-1056

Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain.

Background: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Up to 15%-20% of infected newborns will develop long-term sequelae such as hearing loss and neurologic abnormalities. The aim of this study was to investigate the prevalence of congenital CMV infection (cCMV) and associated clinical abnormalities in Spain.

Methods: A prospective screening for cCMV by viral load in saliva was performed. Saliva samples were obtained within the first 72 hours of life in a maternity ward in Madrid (Spain), during a 1-year period. All positive screening tests were confirmed with viral load in urine. Clinical, laboratory, auditory, visual and cerebral imaging assessments were performed in all children with cCMV.

Results: Of the 4097 neonates born during the study period, 3190 (78%) were included. CMV viral load in saliva was detectable in 24/3190 (0.75%) children, and congenital infection was confirmed in 15/3190 (0.47%, CI 95%: 0.29%-0.77%). Positive predictive value was 62.5% (CI 95%: 46.5%-76.1%). Two infants presented symptoms at birth. Eight (53.3%) children showed abnormalities in magnetic resonance imaging; most of them isolated white matter abnormalities. Newborns with abnormalities in magnetic resonance imaging showed higher viral loads in blood and saliva (P = 0.04).

Conclusions: One in 200 neonates born in our hospital presented a cCMV infection. CMV viral load in saliva has been shown to be a simple and highly accepted screening method but should be confirmed by CMV detection in urine. In spite of the fact that half of infected children had abnormalities in cerebral imaging, diagnosis during the neonatal period would have been impossible without a screening program in most cases.
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http://dx.doi.org/10.1097/INF.0000000000002808DOI Listing
November 2020

Clinical course and risk factors for mortality from COVID-19 in patients with haematological malignancies.

Eur J Haematol 2020 Nov 11;105(5):597-607. Epub 2020 Aug 11.

Department of Hematology, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Complutense University, CNIO, CIBERONC, Madrid, Spain.

Background: The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported.

Methods: We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer patients with COVID-19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome.

Results: The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty-seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non-cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID-19 therapy were not predictors of outcome.

Conclusion: Mortality of COVID-19 is significantly higher in patients with haematological malignancies compared to non-cancer patients. The impact of persistent viral shedding must be considered in order to re-start therapies and maintain infectious control measures.
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http://dx.doi.org/10.1111/ejh.13493DOI Listing
November 2020

Universal screening for SARS-CoV-2 before labor admission during Covid-19 pandemic in Madrid.

J Perinat Med 2020 Nov;48(9):981-984

Fetal Medicine Unit - Maternal and Child Health and Development Network (Red SAMID-RD12/0026/0016), Department of Obstetrics and Gynecology, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain.

Objectives Asymptomatic women admitted to labor may act as silent spreaders of COVID-19. Therefore, universal screening at admission has been proposed. The objective of the study was to evaluate the performance of universal screening for SARS-CoV-2 using quantitative reverse transcription polymerase-chain-reaction (qRT-PCR) tests in women admitted to labor. Methods Observational retrospective study of a cohort of pregnant women admitted to labor and delivery between April 8 and May 2, 2020 in a large maternity in Madrid. SARS-CoV-2 screening with qRT-PCR from combined nasopharyngeal and oropharyngeal swabs was carried out systematically. Screening performance was described. Results We attended 212 deliveries. Nine cases with COVID-19 diagnosis before admission were excluded. In the remaining 203 women, seven referred COVID-19-related symptoms but only one had a positive qRT-PCR. Among the 194 asymptomatic women, only one case (0.5%) was positive. Conclusions The percentage of positive tests in asymptomatic women admitted to delivery was only 0.5% during the post-peak period.
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http://dx.doi.org/10.1515/jpm-2020-0236DOI Listing
November 2020

HBV-RNA Co-amplification May Influence HBV DNA Viral Load Determination.

Hepatol Commun 2020 Jul 26;4(7):983-997. Epub 2020 May 26.

Department of Gastroenterology, Hepatology and Endocrinology Hannover Medical School Hannover Germany.

Despite effective hepatitis B virus (HBV)-DNA suppression, HBV RNA can circulate in patients receiving nucleoside/nucleotide analogues (NAs). Current assays quantify HBV DNA by either real-time polymerase chain reaction (PCR), which uses DNA polymerase, or transcription-mediated amplification, which uses reverse-transcriptase (RT) and RNA polymerase. We assessed the effect of RT capability on HBV-DNA quantification in samples from three cohorts, including patients with quantified HBV RNA. We compared the HBV-DNA levels by real-time PCR (cobas HBV, Roche 6800/8800; Xpert HBV, Cepheid), transcription-mediated amplification (Aptima HBV, Hologic), and real-time PCR with added RT capability (cobas HBV+RT). In the first cohort (n = 45) followed over 192 weeks of NA therapy, on-treatment HBV-DNA levels were higher with cobas HBV+RT than cobas HBV (mean difference: 0.14 log IU/mL). In a second cohort (n = 50) followed over 96 weeks of NA therapy, HBV-DNA viral load was significantly higher with the cobas HBV+RT and Aptima HBV compared with the cobas HBV test at all time points after initiation of NA therapy (mean difference: 0.65-1.16 log IU/mL). A clinically significant difference was not detected between the assays at baseline. In a third cohort (n = 53), after a median of 2.2 years of NA therapy, we detected HBV RNA (median 5.6 log copies/mL) in 23 patients (43.4%). Median HBV-DNA levels by Aptima HBV were 2.4 versus less than 1 log IU/mL in samples with HBV RNA and without HBV RNA, respectively ( = 0.0006). In treated patients with HBV RNA, Aptima HBV measured higher HBV-DNA levels than Xpert HBV and cobas HBV. Tests including an RT step may overestimate HBV DNA, particularly in samples with low viral loads as a result of NA therapy. This overestimation is likely due to amplification of HBV RNA and may have an impact on clinical decisions.
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http://dx.doi.org/10.1002/hep4.1520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327219PMC
July 2020

Assessment of evapotranspiration estimates based on surface and satellite data and its relationship with El Niño-Southern Oscillation in the Rio de Janeiro State.

Environ Monit Assess 2020 Jun 23;192(7):449. Epub 2020 Jun 23.

Department of Environmental Sciences, Forest Institute, Federal Rural University of Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro, 23890-000, Brazil.

The need to validate the quality of evapotranspiration estimates is essential for this parameter which has extended its use. For this, it is necessary to evaluate both new remote sensing products that expand the areas of estimated evapotranspiration and empirical equations that provide estimates with different data requirements. In order to examine this problem, the present study compared the estimates of evapotranspiration obtained by remote sensing of the MOD16A2 product and seven empirical equations with the estimates obtained through the FAO-56 reference method, with data obtained from six meteorological stations in the State of Rio de Janeiro, Brazil. Data cover the period from 2007 to 2013, which contains different phases of the El Niño-Southern Oscillation phenomenon. The methods proposed by Valiantzas were those that obtained the best performances when compared with FAO-56 with R over 90%. The non-parametric analysis of Mann-Kendall for the six seasons was mostly not significant; only the station of Resende showed a tendency of significant growth during the El Niño episode (Z = 0.283 and p value = 0.050). The mangrove and forest classes were the ones that obtained the highest averages (3.75 mm d and 3.62 mm d), where the gradient of evapotranspiration can be observed in the South-Northeast portions. The MOD16A2 orbital product was inferior to the methods that used surface meteorological station data.
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http://dx.doi.org/10.1007/s10661-020-08421-zDOI Listing
June 2020

Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children.

N Engl J Med 2020 06;382(23):2207-2219

From the Departments of Pediatric and Adolescent Oncology (V.M.-C., C.P.) and Clinical Research (G.V.), INSERM Unité 1015 (V.M.-C.), and the Unit of Biostatistics and Epidemiology and INSERM Unité 1018 (A.A.), Gustave Roussy, Université Paris-Saclay, Villejuif, France; the Department of Pediatric Hematology and Oncology, University of Padua, Padua, Italy (M.P.); the Department of Paediatric Haematology, Oncology, and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge (G.A.A.B.), Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham (K.W.), and the Department of Histopathology, Royal Marsden NHS Foundation Trust, London (A.W.) - all in the United Kingdom; the Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (D.A.B.); the Department of Pediatric Hematology and Oncology, University of Valencia, Valencia, Spain (R.F.D.); the Division of Haematology-Oncology, Hospital for Sick Children, Toronto (S.A.); the Department of Pediatric Hematology and Oncology, University Hospitals Leuven, Leuven, Belgium (A.U.); the Center for Cancer and Immunology Research, Children's National Health System and George Washington University, Washington, DC (C.M.B.); Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands (J.Z.); the Department of Pediatric Hematology and Oncology, Semmelweis University, Budapest, Hungary (M.C.); the Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland (B.K.); the Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong (A.K.C.); the Department of Pathology, University of Utah, Salt Lake City (R.R.M.); Children's Hospital of Philadelphia, Philadelphia (P.C.A.); and the National Cancer Institute, Center for Global Health, Rockville, MD (T.G.G.).

Background: Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited.

Methods: We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin's lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed.

Results: Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt's lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab-chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P = 0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab-chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group (P = 0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab-chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion.

Conclusions: Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin's lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; ClinicalTrials.gov number, NCT01516580.).
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http://dx.doi.org/10.1056/NEJMoa1915315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720281PMC
June 2020

Improved blood culture workflow in the time to detection of microorganisms placing incubators systems outside of microbiology laboratory.

Braz J Microbiol 2020 Sep 18;51(3):1103-1108. Epub 2020 May 18.

Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain.

Purpose: We analyzed the workflow of the blood culture procedure with one blood culture incubator in the microbiology laboratory, in comparison with the workflow with the incubators systems placing outside, and in a microbiology laboratory without 24-h staffing.

Methods: We assessed the elapsed time (ET) and time-to-result (TTR) in the two laboratory workflows during 1 month period in consecutive years. First period with one BACT/ALERT 3D module located in the microbiology laboratory (ML) (access 8 a.m. to 10 p.m.) and second period with three BACT/ALERT VIRTUO modules (one located in ML and two in the core sample laboratory, access 24 h).

Results: The mean ET with BACT/ALERT 3D was 7.09 ± 6.15 h and 1.32 ± 3.14 h with BACT/ALERT VIRTUO. During the 8:00 a.m. to 10:00 p.m. shift, the average ETs were 3.54 ± 5.06 vs 1.59 ± 1.29 h for the two time periods, respectively. Since the automated loading of bottles on the BACT/ALERT VIRTUO allows processing of blood cultures during the night shift, there was a significant reduction of time during the 10:00 p.m. to 8:00 a.m. shift, where the average ET was 10.52 ± 5.23 vs 1.00 ± 4.40 h, respectively. The percentage of positivity in the first period was 9.03% and 11.18% in the second (p = 0.0003). The average TTR in the first period was 24.78 ± 15.9 h and 16.85 ± 14.13 h in the second (p < 0.0001).

Conclusions: Easy 24-h access to blood culture incubators resulted in significant improvement in the workflow of blood culture, decreasing ET, and therefore decreasing the time to positivity and the efficiency of recovery.
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http://dx.doi.org/10.1007/s42770-020-00298-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455611PMC
September 2020

Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO).

EBioMedicine 2020 May 11;55:102779. Epub 2020 May 11.

Hospital Universitario La Paz - IdiPAZ. Paseo de la Castellana 261, 28046, Madrid, Spain. Electronic address:

Background: We investigated the efficacy of a switch to dolutegravir plus lamivudine in aviremic individuals without evidence of persistent lamivudine resistance-associated mutations in baseline proviral DNA population sequencing.

Methods: Open-label, single-arm, 48-week pilot trial. HIV-1 infected adults, naïve to integrase inhibitors, with CD4+ above 350 cell/μL and fewer than 50 HIV-1 RNA copies per mL the year prior to study entry switched to dolutegravir plus lamivudine. Participants were excluded if baseline proviral DNA population genotyping detected lamivudine resistance-associated mutations. To detect resistance minority variants, proviral DNA next-generation sequencing was retrospectively performed from baseline samples. Primary efficacy endpoint was proportion of participants with fewer than 50 HIV-1 RNA copies per mL at week 48. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations. ART-PRO is registered with ClinicalTrials.gov, NCT03539224.

Findings: 41 participants switched to dolutegravir plus lamivudine, 21 with lamivudine resistance mutations in historical plasma genotypes. Baseline next-generation sequencing detected lamivudine resistance mutations (M184V/I and/or K65R/E/N) over a 5% threshold in 15/21 (71·4%) and 3/20 (15%) of participants with and without history of lamivudine resistance, respectively. At week 48, 92·7% of participants (38/41) had fewer than 50 HIV-1 RNA copies per mL. There were no cases of virologic failure. Three participants with historical lamivudine resistance were prematurely discontinued from the study (2 protocol violations, one adverse event). Ten participants (4 in the group with historical lamivudine resistance) had a transient viral rebound, all resuppressed on dolutegravir plus lamivudine. There were 28 drug-related adverse events, only one leading to discontinuation.

Interpretation: In this pilot trial, dolutegravir plus lamivudine was effective in maintaining virologic control despite past historical lamivudine resistance and presence of archived lamivudine resistance-associated mutations detected by next generation sequencing. Further studies are needed to confirm our results.

Funding: Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III PI16/00837-PI16/00678.
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http://dx.doi.org/10.1016/j.ebiom.2020.102779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225620PMC
May 2020

Anthropogenic and climatic influences in the swamp environment of the Pandeiros River basin, Minas Gerais-Brazil.

Environ Monit Assess 2020 Mar 7;192(4):219. Epub 2020 Mar 7.

Federal University of Mato Grosso do Sul (UFMS), Chapadão do Sul, Mato Grosso do Sul, 79560-000, Brazil.

Several environmental impacts are resulting from the process of anthropization and climate variability that have caused degradation of biomes and humid environments. Thus, the objective of this study was to evaluate the effect of the anthropic process and the variation of climatic conditions on the dynamics of the marsh vegetation in the Pandeiros River preservation area in the north of Minas Gerais, Brazil. The Enhanced Vegetation Index (EVI) of product MOD13Q1 and the gross primary productivity (GPP) of product MOD17A2 of the Moderate Resolution Imaging Spectroradiometer (MODIS) were used for the period from 2001 to 2017 were used in this process. Rain and air temperature data were obtained from the Conventional Weather Station of Januária-MG. The time series were submitted to the nonparametric statistical test of Mann-Kendall. The process of anthropization of the swamp area in the environmental protection area of the Pandeiros River/MG (EPA) showed a pattern of expansion of vegetation cover associated with the reduction of the water table, a phenomenon resulting from the silting process and reduction of the incidence of rain in this region, which contributes to the reduction of ecosystem services. Thus, understanding the influence of climatic variables on the dynamics of vegetation in humid environments, such as the EPA swamp area on the Pandeiros River, is essential for the preservation and recovery of these ecosystems and for the implementation of public policies for preservation and conservation.
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http://dx.doi.org/10.1007/s10661-020-8192-7DOI Listing
March 2020

Comparison of the Panther Fusion and Allplex assays for the detection of respiratory viruses in clinical samples.

PLoS One 2019 27;14(12):e0226403. Epub 2019 Dec 27.

Microbiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.

Respiratory viral infections are the most frequent clinical syndrome affecting both children and adults, and early detection is fundamental to avoid infection-related risks and reduce the healthcare costs incurred by unnecessary antibiotic treatments. In this study, performance characteristics of two commercial methods, the Panther Fusion® assay (Hologic Inc., San Diego, CA, USA) were compared to Allplex™ respiratory panels (Seegene, Seoul, South Korea) for the detection of influenza A (Flu A), influenza B (Flu B), respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus (hMPV), rhinovirus (RV) and adenovirus (AdV) targets. A total of 865 specimens collected prospectively and retrospectively were included, and discordant results were further examined using another commercial product, R-GENE™ respiratory kits (bioMérieux, Marcy l'Etoile, France). There was high agreement between both methods, with 98.6% concordance and a kappa (k) value of 0.9 (95% CI: 0.89-0.92). A specific analysis of both methods for each viral agent demonstrated comparable sensitivity and specificity, both ranging from 0.83 to 1 with good predictive values for the prospective part of the study. Good agreement between both methods was also found for the κ values obtained (ranging from 97.55% to 98.9%), with the lowest for hMPV (k = 0.83, 95% CI: 0.75-0.91) and RV (k = 0.73, 95% CI: 0.65-0.81). Amplification efficiency, measured according to the value of the cycle threshold (Ct) obtained in each of the amplifications in both tests, was significantly better with Panther Fusion for Flu A, Flu B, hMPV and RV. Regarding discordant results, R-GENE showed higher agreement with Panther Fusion-positive specimens (negative for Allplex; n = 28/71, 34.9%) than with Allplex-positive samples (negative for Panther Fusion; n = 7/49, 14.3%). In summary, Panther Fusion proved to be a more efficient fully-automated methodology, requiring shorter hands-on and turnaround times than Allplex.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226403PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934309PMC
March 2020

Tandem Ion Mobility Spectrometry for the Detection of Traces of Explosives in Cargo at Concentrations of Parts Per Quadrillion.

Anal Chem 2019 11 9;91(21):14009-14018. Epub 2019 Oct 9.

SEADM , Parque Tecnológico de Boecillo 205 , Valladolid , Spain.

A tandem ion mobility spectrometer (IMS) built from two differential mobility analyzers (DMAs) is coupled at ambient pressure with a thermal fragmenter placed in between, such that the precursor ions selected in the first DMA are thermally decomposed at ambient pressure in the fragmenter and the product ions generated are filtered in the second DMA. A thermal desorber and a multicapillary gas chromatography (GC) column are coupled to a secondary electrospray (SESI) ion source, so the adsorption sampling filters are thermally desorbed and the liberated vapors are separated in the GC column, prior to their ionization and mobility/mobility classification. The new fragmenter allows the fragmentation of the five explosives studied: RDX, PETN, NG, EGDN, and TNT. The background of the analyzer is evaluated for the five explosives using air samples of 500 L volume. An atmospheric background of only 2.5 pg (5 ppq) is found for TNT, being somewhat higher for the rest of explosives studied. The architecture GC-IMS is compared with GC-IMS obtaining a 100-fold increase of sensitivity in the first configuration, confirming the high selectivity provided by the fragmentation cell and the second IMS stage for the product ion mobility analysis. The analyzer is tested also with real explosives hidden in cargo pallets achieving successful detection of four (EGDN, NG, TNT, and PETN) out of five explosives.
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http://dx.doi.org/10.1021/acs.analchem.9b03589DOI Listing
November 2019

Synthesis of Highly Efficient Multivalent Disaccharide/[60]Fullerene Nanoballs for Emergent Viruses.

J Am Chem Soc 2019 09 11;141(38):15403-15412. Epub 2019 Sep 11.

Departamento de Química Orgánica, Facultad de Química , Universidad Complutense , 28040 Madrid , Spain.

After the last epidemic of the Zika virus (ZIKV) in Brazil that peaked in 2016, growing evidence has been demonstrated of the link between this teratogenic flavivirus and microcephaly cases. However, no vaccine or antiviral drug has been approved yet. ZIKV and Dengue viruses (DENV) entry to the host cell takes place through several receptors, including dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), so that the blockade of this receptor through multivalent glycoconjugates supposes a promising biological target to inhibit the infection process. In order to get enhanced multivalency in biocompatible systems, tridecafullerenes appended with up to 360 1,2-mannobiosides have been synthesized using a strain-promoted cycloaddition of azides to alkynes (SPAAC) strategy. These systems have been tested against ZIKV and DENV infection, showing an outstanding activity in the picomolar range.
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http://dx.doi.org/10.1021/jacs.9b08003DOI Listing
September 2019

Analytical performance of four molecular platforms used for HIV-1, HBV and HCV viral load determinations.

Expert Rev Mol Diagn 2019 10 19;19(10):941-949. Epub 2019 Jun 19.

Department of Molecular Diagnostics, Labor Stein , Monchengladbach , Germany.

: Viral load (VL) quantification is important for the management of HBV, HCV, and HIV-1-infected patients. Several semi- or fully automated systems and assays are available that can be used to measure VL for these and other targets. : We assessed the accuracy, genotype/subtype inclusivity, and precision of four VL assays for three viral targets: cobas 4800 (Roche), cobas 6800 (Roche), Aptima (Hologic) and VERIS (Beckman), using WHO standards, cell culture supernatants and clinical samples. : Most results were close to expected values, except for significant under-quantification of HIV-1 group O, HBV genotype C, and D at high VL, and HCV genotype 3 by Aptima, and of HIV-1 CRF01_AE and group N and HCV genotype 3 by VERIS. Precision was comparable between tests except for VERIS HCV, which showed more variability. Aptima and cobas 6800 results agreed well with each other except HBV VL at lower VL (<10,000 IU/mL) where Aptima results tended to be higher. : Results from different VL assays may not always agree in certain subsets of patients. Clinicians should we aware of these findings when making treatment decisions.
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http://dx.doi.org/10.1080/14737159.2019.1624162DOI Listing
October 2019

Unprecedented Thiacalixarene Fucoclusters as Strong Inhibitors of Ebola cis-Cell Infection and HCMV-gB Glycoprotein/DC-SIGN C-type Lectin Interaction.

Bioconjug Chem 2019 04 4;30(4):1114-1126. Epub 2019 Apr 4.

Laboratoire de Glycochimie des Antimicrobiens et des Agroressources (LG2A-UMR7378-CNRS) , Université de Picardie Jules Verne , 10 Rue Baudelocque , 80039 , Amiens , France.

Glycan-protein interactions control numerous biological events from cell-cell recognition and signaling to pathogen host cell attachment for infections. To infect cells, some viruses bind to immune cells with the help of DC-SIGN (dendritic cell [DC]-specific ICAM3-grabbing nonintegrin) C-type lectin expressed on dendritic and macrophage cell membranes, via their envelope protein. Prevention of this infectious interaction is a serious therapeutic option. Here, we describe the synthesis of the first water-soluble tetravalent fucocluster pseudopeptide-based 1,3-alternate thiacalixarenes as viral antigen mimics designed for the inhibition of DC-SIGN, to prevent viral particle uptake. Their preparation exploits straightforward convergent strategies involving one-pot Ugi four-component (Ugi-4CR) and azido-alkyne click chemistry reactions as key steps. Surface plasmon resonance showed strong inhibition of DC-SIGN interaction properties by tetravalent ligands designed with high relative potencies and β avidity factors. All ligands block DC-SIGN active sites at nanomolar IC preventing cis-cell infection by Ebola viral particles pseudotyped with EBOV glycoprotein (Zaire species of Ebola virus) on Jurkat cells that express DC-SIGN. In addition, we observed strong inhibition of DC-SIGN/human cytomegalovirus (HCMV)-gB recombinant glycoprotein interaction. This finding opens the way to the simple development of new models of water-soluble glycocluster-based thia-calixarenes with wide-ranging antimicrobial activities.
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00066DOI Listing
April 2019
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