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  1. Article ; Online: Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.

    Jiménez de Ory, Santiago / Beltrán-Pavez, Carolina / Gutiérrez-López, Miguel / Santos, María Del Mar / Prieto, Luis / Sainz, Talía / Guillen, Sara / Aguilera-Alonso, David / Díez, Cristina / Bernardino, Jose Ignacio / Mellado, María José / Ramos, José Tomás / Holguín, África / Navarro, Marisa

    The Journal of antimicrobial chemotherapy

    2021  Volume 76, Issue 7, Page(s) 1886–1892

    Abstract: Objectives: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples.: Methods: ... ...

    Abstract Objectives: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples.
    Methods: We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool.
    Results: Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs sampling of 21.3 years (IQR: 15.6-23.1) with 4 years (IQR 2.1-6.5) of suppressed viral load (VL). Nine (75%) youths did not present M184V/I in pDNA after at least 1 year of viral suppression. In December 2019, the remaining three subjects carrying M184V/I in pDNA maintained suppressed viraemia, and two still used emtricitabine in ART.
    Conclusions: The prevalence of resistance mutations to lamivudine and emtricitabine in pDNA in a cohort of youths perinatally infected with HIV who remain with undetectable VL, previously lamivudine and/or emtricitabine experienced, was infrequent. Our results indicate that ART including lamivudine or emtricitabine may also be safe and successful in youths with perinatal HIV with previous experience of and resistances to these drugs detected in plasma.
    MeSH term(s) Adolescent ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Child ; DNA ; Drug Resistance, Viral ; Emtricitabine/therapeutic use ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Humans ; Lamivudine/therapeutic use ; Prevalence ; Proviruses/genetics ; Viral Load
    Chemical Substances Anti-HIV Agents ; Lamivudine (2T8Q726O95) ; DNA (9007-49-2) ; Emtricitabine (G70B4ETF4S)
    Language English
    Publishing date 2021-03-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkab080
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1197: Show issues Location:
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    Zs.MO 124: Show issues

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  2. Article ; Online: Congenital transmission of Chagas disease in a non-endemic area, is an early diagnosis possible?

    Francisco-González, Laura / Rubio-San-Simón, Alba / González-Tomé, María Isabel / Manzanares, Ángela / Epalza, Cristina / Santos, María Del Mar / Gastañaga, Teresa / Merino, Paloma / Ramos-Amador, José Tomás

    PloS one

    2019  Volume 14, Issue 7, Page(s) e0218491

    Abstract: Background: Chagas disease (CD) is an emergent disease in Europe, due to immigration. The aims of this study are to describe the epidemiological characteristics of a cohort of Chagas infected pregnant women in Spain, to assess the vertical transmission ( ...

    Abstract Background: Chagas disease (CD) is an emergent disease in Europe, due to immigration. The aims of this study are to describe the epidemiological characteristics of a cohort of Chagas infected pregnant women in Spain, to assess the vertical transmission (VT) rate and evaluate the usefulness of the PCR in the diagnosis of congenital infection in the first months of life.
    Methods: A descriptive, retrospective study including Chagas seropositive pregnant women who were attended at three tertiary hospitals in Madrid, from January 2012 to September 2016. Infants were examined by PCR at birth and 1 month later and serologically studied at 9 months or later. Children were considered infected when the parasite was detected by PCR at any age or when serology remained positive without decline over the age of 9 months.
    Results: We included 122 seropositive-infected pregnant women, 81% were from Bolivia and only 8.2% had been treated before. 125 newborns were studied and finally 109 were included (12.8% lost the follow-up before performing the last serology). The VT rate was 2.75% (95% CI: 0,57-8,8%). Infected infants had positive PCR at birth and 1 month later. All of them were treated successfully with benznidazole (PCR and serology became negative later on). All non-infected children presented negative PCR. The mean age at which uninfected patients had negative serology was 10.5 months.
    Conclusions: The VT rate is in keeping with literature and confirms the need to carry out a screening in pregnant women coming from endemic areas. PCR seems to be a useful tool to provide early diagnosis of congenital CD.
    MeSH term(s) Adult ; Bolivia/epidemiology ; Chagas Disease/diagnosis ; Chagas Disease/epidemiology ; Chagas Disease/transmission ; Early Diagnosis ; Emigration and Immigration ; Female ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Pregnancy ; Pregnancy Complications, Parasitic/diagnosis ; Pregnancy Complications, Parasitic/epidemiology ; Retrospective Studies ; Spain/epidemiology ; Trypanosoma cruzi/isolation & purification ; Young Adult
    Language English
    Publishing date 2019-07-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0218491
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  3. Article ; Online: Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2.

    Mora-Santos, Maria Del Mar / Hervas-Aguilar, America / Sewart, Katharina / Lancaster, Theresa C / Meadows, John C / Millar, Jonathan B A

    Current biology : CB

    2016  Volume 26, Issue 19, Page(s) 2642–2650

    Abstract: The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), ...

    Abstract The spindle assembly checkpoint (SAC) ensures that sister chromatids do not separate until all chromosomes are attached to spindle microtubules and bi-oriented. Spindle checkpoint proteins, including Mad1, Mad2, Mad3 (BubR1), Bub1, Bub3, and Mph1 (Mps1), are recruited to unattached and/or tensionless kinetochores. SAC activation catalyzes the conversion of soluble Mad2 (O-Mad2) into a form (C-Mad2) that binds Cdc20, BubR1, and Bub3 to form the mitotic checkpoint complex (MCC), a potent inhibitor of the anaphase-promoting complex (APC/C). SAC silencing de-represses Cdc20-APC/C activity allowing poly-ubiquitination of Securin and Cyclin B, leading to the dissolution of sister chromatids and anaphase onset [1]. Understanding how microtubule interaction at kinetochores influences the timing of anaphase requires an understanding of how spindle checkpoint protein interaction with the kinetochore influences spindle checkpoint signaling. We, and others, recently showed that Mph1 (Mps1) phosphorylates multiple conserved MELT motifs in the Spc7 (Spc105/KNL1) protein to recruit Bub1, Bub3, and Mad3 (BubR1) to kinetochores [2-4]. In budding yeast, Mps1 phosphorylation of a central non-catalytic region of Bub1 promotes its association with the Mad1-Mad2 complex, although this association has not yet been detected in other organisms [5]. Here we report that multisite binding of Bub3 to the Spc7 MELT array toggles the spindle checkpoint switch by permitting Mph1 (Mps1)-dependent interaction of Bub1 with Mad1-Mad2.
    MeSH term(s) Cell Cycle Checkpoints/physiology ; Phosphorylation ; Schizosaccharomyces/genetics ; Schizosaccharomyces/physiology ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism ; Signal Transduction ; Spindle Apparatus/metabolism
    Chemical Substances Schizosaccharomyces pombe Proteins
    Language English
    Publishing date 2016-09-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2016.07.040
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    Zs.A 3208: Show issues Location:
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  4. Article ; Online: Fever without source as the first manifestation of SARS-CoV-2 infection in infants less than 90 days old.

    Blázquez-Gamero, Daniel / Epalza, Cristina / Cadenas, José Antonio Alonso / Gero, Lourdes Calleja / Calvo, Cristina / Rodríguez-Molino, Paula / Méndez, María / Santos, Maria Del Mar / Fumadó, Victoria / Guzmán, María Fernanda / Soriano-Arandes, Antoni / Jiménez, Ana B / Penin, Maria / Cobo-Vazquez, Elvira / Pareja, Marta / Lobato, Zulema / Serna, Miquel / Delgado, Rafael / Moraleda, Cinta /
    Tagarro, Alfredo

    European journal of pediatrics

    2021  Volume 180, Issue 7, Page(s) 2099–2106

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) COVID-19 ; Child ; Cross-Sectional Studies ; Fever/epidemiology ; Fever/etiology ; Humans ; Infant ; RNA, Viral ; SARS-CoV-2
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2021-02-19
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 194196-3
    ISSN 1432-1076 ; 0340-6199 ; 0943-9676
    ISSN (online) 1432-1076
    ISSN 0340-6199 ; 0943-9676
    DOI 10.1007/s00431-021-03973-9
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  5. Article ; Online: Pandemic H1N1 influenza-associated hospitalizations in children in Madrid, Spain.

    del Rosal, Teresa / Baquero-Artigao, Fernando / Calvo, Cristina / Mellado, María J / Molina, Juan C / Santos, María del Mar / Cilleruelo, María J / Bueno, Mercedes / Storch de Gracia, Pilar / Terol, Covadonga / Roa, Miguel Á / Piñeiro, Roi / García López-Hortelano, Milagros / García-García, María L / Rodríguez, Sonia / Penín, María / Zarauza, Alejandro / Alvarado, Francisco / de Blas, Ana /
    Otheo, Enrique / Rodríguez, Alfonso / Herreros, María L / Tagarro, Alfredo / Grande, Luis / Ramos, José T / Maté, Irene / Muñoz, Cristina / Zafra, Miguel Á / Romero-Gómez, María P / Pérez-Fernández, Elia / Delgado, Alberto / Casas, Inmaculada / Cabezas, María E

    Influenza and other respiratory viruses

    2011  Volume 5, Issue 6, Page(s) e544–51

    Abstract: Objective: To describe the epidemiological and clinical characteristics of children hospitalized with 2009 pandemic influenza (pH1N1) in Madrid, Spain.: Patients/methods: We included patients less than 14 years of age admitted to one of 18 hospitals ... ...

    Abstract Objective: To describe the epidemiological and clinical characteristics of children hospitalized with 2009 pandemic influenza (pH1N1) in Madrid, Spain.
    Patients/methods: We included patients less than 14 years of age admitted to one of 18 hospitals in Madrid, Spain, between May 1 and November 30, 2009 and diagnosed with pH1N1 by polymerase chain reaction. A retrospective chart review was conducted and data were compared by age, presence of high-risk medical conditions, and pediatric intensive care unit (PICU) admission.
    Results: A total of 517 pH1N1 cases were included for final analysis. One hundred and forty-two patients (27·5%) had predisposing underlying illnesses, with immunosuppression (36 children, 7%) and moderate persistent asthma (34, 6·6%) being the most common ones. Patients with underlying medical conditions had longer hospital stays [median 5, interquartile range (IQR) 3-8 days, versus median 4, IQR 3-6, P < 0·001] and required intensive care (20·4% versus 5·9%, P < 0·001) and mechanical ventilation more frequently than previously healthy children. Globally, intensive care was required for 51 patients (10%) and invasive mechanical ventilation for 12 (2%). Pediatric intensive care unit admission was significantly associated with abnormal initial chest X-ray [Odds Ratio (OR) 3·5, 95% confidence interval (CI) 1·5-8·5], underlying neurological condition (OR 3·1, CI 1·2-7·5) and immunosuppression (OR 2·9, 1·2-6·8). Five patients (0·9%) died; two with severe neurological disease, two with leukemia, and one with a malignant solid tumor.
    Conclusions: Children with underlying medical conditions experienced more severe pH1N1 disease. Risk factors for admission to the PICU included underlying neurological conditions, immunosuppression and abnormal initial chest X-ray.
    MeSH term(s) Adolescent ; Child ; Child, Preschool ; Female ; Hospitalization/statistics & numerical data ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A Virus, H1N1 Subtype/isolation & purification ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza, Human/complications ; Influenza, Human/epidemiology ; Influenza, Human/virology ; Intensive Care Units, Pediatric/statistics & numerical data ; Male ; Pandemics ; Retrospective Studies ; Spain/epidemiology
    Language English
    Publishing date 2011-07-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2274538-5
    ISSN 1750-2659 ; 1750-2640
    ISSN (online) 1750-2659
    ISSN 1750-2640
    DOI 10.1111/j.1750-2659.2011.00272.x
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