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

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.

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

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.

Congenital transmission of Chagas disease in a non-endemic area, is an early diagnosis possible?

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.

Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2.

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.

Recomendaciones para el diagnóstico, seguimiento y tratamiento de la embarazada y del niño con enfermedad de Chagas / Recommendations for the diagnosis, treatment and follow-up of the pregnant woman and child with Chagas disease

La enfermedad de Chagas en zonas no endémicas, como nuestro país, se adquiere fundamentalmente por transmisión vertical. La prevalencia de la enfermedad en embarazadas latinoamericanas oscila entre el 0,7 y el 54% en función del país de origen, la procedencia rural o la edad de la madre, situándose la tasa de transmisión vertical entre el 5 y el 6%. Se sabe que el tratamiento en fases precoces y en concreto en el niño < 15 años tiene altas tasas de curación y parece que el tratamiento de la embarazada tras el parto podría prevenir la transmisión en otros embarazos. Todo ello justificaría el diagnóstico y tratamiento precoz de esta entidad en ambos grupos. En este documento se exponen las recomendaciones actuales de diagnóstico y tratamiento de la enfermedad en el niño y la embarazada. Estas recomendaciones han sido elaboradas por un grupo de trabajo formado por especialistas en Enfermedades Infecciosas, Microbiología Clínica, Ginecología y Pediatría (AU)

Congenital transmission of Chagas disease now occurs in areas where the disease is non-endemic, and also from one generation to another. According to epidemiological data from Latin America, the prevalence of the disease in pregnant women is 0.7%-54%, and the prevalence of vertical transmission is around 5%-6%.Congenital T. cruzi infection is an acute infection in newborns that should be treated with anti-parasitic therapy. The treatment of pregnant women could also have an impact on the control of the disease. This article has been prepared following the recommendations suggested by a group of experts in Infectious Diseases, Microbiology, Gynaecology and Paediatrics (AU)

Pandemic H1N1 influenza-associated hospitalizations in children in Madrid, Spain.

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.

La eliminación urinaria de productos de lipoperoxidación depende de un ritmo biológico anual / Annual rhythm of urinary excretion of lipoperoxidation products

Introducción: existen numerosos rasgos biológicos ligados a ritmos diarios, anuales o estacionales. Uno de estos rasgos podría ser la producción y eliminación urinaria de productos de lipoperoxidación (sustancias reactivas al ácido tiobarbitúrico [TBARS]) eliminados por orina que son modificados por la crenoterapia con diferentes aguas mineromedicinales. El objetivo del presente artículo es analizar si la eliminación urinaria de TBARS depende de la época del año en que se determina. Material y métodos: se han obtenido muestras de orina de 230 voluntarios del Programa de Termalismo Social del IMSERSO (edad 52-81 años), 115 varones y 115 mujeres que se adscribieron a 2 balnearios diferentes en 6 épocas distintas del año: 110 al primero y 120 al segundo. A la llegada al balneario se determinó la concentración de TBARS mediante espectrofotometría; paralelamente se realizó a los pacientes historia clínica que incluyó registros de la presión arterial. Resultados: la media de eliminación total de TBARS a la llegada al balneario en la población del primero fue de 0,418 ± 0,025 nmol/mg de creatinina; en la segunda fue de 0,368 ± 0,01 nmol/mg de creatinina. Una de las posibles razones de los diferentes valores de ambas poblaciones, con un máximo de excreción urinaria en julio y un mínimo en noviembre, fue el hecho de que las determinaciones se realizaron en diferentes meses del año en ambas poblaciones. Conclusión: este estudio muestra que las tasas de eliminación de productos de lipoperoxidación siguen un ritmo anual

Introduction: many biological features are linked to daily, annual, or seasonal rhythms. One of these features could be the production and urinary excretion of lipoperoxidation products (TBARS), which are modified by crenotherapy with different mineromedicinal waters. The objective of the present article was to analyse whether urinary excretion of TBARS depends on the time of the year in which it is determined. Material and methods: urinary samples were obtained from 230 volunteers from the Social Thermalism Program of the Institute for the Elderly and Social Services (Instituto de Mayores y Servicios Sociales [IMSERSO]). There were 115 men and 115 women (aged 52-81years) who where assigned to two different spas at six different times of the year: 110 were assigned to the first spa and 120 to the second. TBARS concentration was determined on arrival at the spa by means of spectrophotometry; a clinical history was also taken, including blood pressure measurement. Results: the mean total TBARS excretion on arrival was 0.418 ± 0.025 nmol/mg of creatinine for the population from the first spa and 0.368 ± 0.01 nmol/mg of creatinine for the second. One of the reasons why these values differed between the two populations was that they were determined in different months of the year, showing a maximum excretion in July and a minimum in November. Conclusion: this study shows that excretion rates of lipid peroxidation products follows an annual rhythm