COVID-19 Associated Pulmonary Aspergillosis (CAPA): Hospital or Home Environment as a Source of Life-Threatening Aspergillus fumigatus Infection?

Most cases of invasive aspergillosis are caused by Aspergillus fumigatus, whose conidia are ubiquitous in the environment. Additionally, in indoor environments, such as houses or hospitals, conidia are frequently detected too. Hospital-acquired aspergillosis is usually associated with airborne fungal contamination of the hospital air, especially after building construction events. A. fumigatus strain typing can fulfill many needs both in clinical settings and otherwise. The high incidence of aspergillosis in COVID patients from our hospital, made us wonder if they were hospital-acquired aspergillosis. The purpose of this study was to evaluate whether the hospital environment was the source of aspergillosis infection in CAPA patients, admitted to the Hospital Universitario Central de Asturias, during the first and second wave of the COVID-19 pandemic, or whether it was community-acquired aspergillosis before admission. During 2020, sixty-nine A. fumigatus strains were collected for this study: 59 were clinical isolates from 28 COVID-19 patients, and 10 strains were environmentally isolated from seven hospital rooms and intensive care units. A diagnosis of pulmonary aspergillosis was based on the ECCM/ISHAM criteria. Strains were genotyped by PCR amplification and sequencing of a panel of four hypervariable tandem repeats within exons of surface protein coding genes (TRESPERG). A total of seven genotypes among the 10 environmental strains and 28 genotypes among the 59 clinical strains were identified. Genotyping revealed that only one environmental A. fumigatus from UCI 5 (box 54) isolated in October (30 October 2020) and one A. fumigatus isolated from a COVID-19 patient admitted in Pneumology (Room 532-B) in November (24 November 2020) had the same genotype, but there was a significant difference in time and location. There was also no relationship in time and location between similar A. fumigatus genotypes of patients. The global A. fumigatus, environmental and clinical isolates, showed a wide diversity of genotypes. To our knowledge, this is the first study monitoring and genotyping A. fumigatus isolates obtained from hospital air and COVID-19 patients, admitted with aspergillosis, during one year. Our work shows that patients do not acquire A. fumigatus in the hospital. This proves that COVID-associated aspergillosis in our hospital is not a nosocomial infection, but supports the hypothesis of "community aspergillosis" acquisition outside the hospital, having the home environment (pandemic period at home) as the main suspected focus of infection.

Vigilancia del consumo de antibióticos en España: la importancia del indicador DHD / Surveillance of antibiotic consumption in Spain: The importance of the DHD indicator

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Análisis del uso ambulatorio de antibióticos en los hospitales generales de Asturias entre 2006 y 2015 / Analysis on the ambulatory usage of antibiotics at general hospitals in Asturias (2006-2015)

Introducción. La Organización para la Cooperación y el Desarrollo Económicos (OCDE) señala, en su informe sobre políticas de salud de 2017 que, España es uno de los países con mayor consumo en antibióticos, 21,6 DHD (dosis diaria definida por 1000 habitantes y día) en 2014 superior a los 20,5 DHD de media en sus países, situándose según el European Centre for Disease Prevention and Control (ECDC) en el puesto 11 de 30 países europeos en 2016. La prescripción ambulatoria de atención especializada se analiza con menor frecuencia, debido a la mayor contribución en consumo y gasto de la atención primaria. Material y métodos. Estudio descriptivo, observacional, y retrospectivo del consumo y gasto del grupo J01 derivado de la prescripción ambulatoria (consulta externa y urgencias) de los hospitales públicos generales de Asturias, en una década (2006- 2015). Se estudió el consumo a través de la base de datos de facturación de receta del Servicio de Salud del Principado de Asturias, los datos demográficos se obtuvieron del Instituto Nacional de Estadística. El consumo se expresó en DHD y el gasto: en gasto por habitante e importe por dosis diaria definida. Resultados. El consumo medio ambulatorio global del periodo fue de 23,4 DHD, correspondiendo el 11,5% (2,7 DHD) a la receta ambulatoria de atención especializada. En términos de gasto, supuso el 13,6% del gasto global ambulatorio en antibióticos. Conclusiones. Gasto y consumo tuvieron tendencias opuestas, las medidas de control del gasto no tuvieron, o tuvieron poco impacto en consumo, por tanto, se precisan en este ámbito medidas de racionalización independientes y específicas (AU)

Introduction. The Organization for Economic Co-operation and Development (OECD) emphasize, in its report on health policies from 2017 that, Spain is one of the countries with largest consumption of antibiotics, 21.6 DHD (defined daily dose per 1000 inhibitants per day) in 2014 greater than the average 20.5 DHD in their countries, ranking according to the European Center for Disease Prevention and Control (ECDC) in the 11th place out of 30 European countries in 2016. The outpatient prescription of specialized care is analyzed less frequently, due to the greater contribution in consumption and expenditure of primary care. Material and methods. A descriptive, observational, and retrospective study of the consumption and expenditure of the J01 group derived from outpatient prescription (outpatient and urgent care) of public hospitals in Asturias, in a period of ten years (2006-2015). Consumption data were obtained using the database of prescription billing of the Health Service of the Principality of Asturias, demographic data were provided by the National Institute of Statistics. Consumption was expressed in DHD and antibiotics expenditure in: expenditure per capita and expenditure in euros per defined daily dose. Results. The average global ambulatory consumption for the period was 23.4 DHD, corresponding 11.5% (2.7 DHD) to the ambulatory specialty care prescription. In terms of expenditure, it accounted for 13.6% of overall outpatient spending on antibiotics. Conclusions. Outlay and consumption had opposite tendencies, the expenditure control measures did not have or had little impact on consumption, therefore, independent and specific rationalization measures are required in this area (AU)

Fat Intolerance in Apparently Healthy Individuals with Normal Fasting Lipoproteins Is Associated with Markers of Cardiovascular Risk.

BACKGROUND: Postprandial increase of triglyceride-rich lipoproteins augments the risk of atherosclerotic cardiovascular disease and all-cause mortality. We explored the hypothesis that a simplified oral fat tolerance test can uncover differences in postprandial triglyceride response associated with potentially atherogenic lipoprotein characteristics, even in a cohort of apparently healthy 31-year-old [mean (SD), 31 (11)] nonobese individuals with normal fasting lipids and lipoproteins. METHODS: We used a fat tolerance test in 96 females and 62 males with blood sampled at 0, 2, and 4 h after a breakfast containing 26.3 g of fats. The postprandial triglyceride response was used to classify the individuals in apparently fat-tolerant and apparently fat-intolerant participants. RESULTS: The intolerant individuals were found to have at 0 h significantly higher body mass index, plasma triglycerides, remnant cholesterol, VLDL cholesterol, and LDL cholesterol and lower apolipoprotein (apo) AI and HDL cholesterol than the tolerant individuals. More than 70% of the variability (r2) of the postprandial response in tolerant and intolerant individuals measured as area under the curve or, at a single point at 4 h after the oral fat load, was linearly correlated with 0-h triglycerides (P < 0001). Fasting lipoprotein parameters, proposed to be markers of cardiovascular risk, as the ratios apo B/apo AI, total cholesterol/HDL cholesterol, and triglycerides/HDL cholesterol, were increased in the intolerant individuals. CONCLUSIONS: A simplified oral fat tolerance test, even when used in an apparently healthy, nonobese, normolipidemic cohort, detected that an increased postprandial triglycerides response was associated with augmented lipoprotein markers of increased cardiovascular risk.

Regulation of Ace2-dependent genes requires components of the PBF complex in Schizosaccharomyces pombe.

The division cycle of unicellular yeasts is completed with the activation of a cell separation program that results in the dissolution of the septum assembled during cytokinesis between the 2 daughter cells, allowing them to become independent entities. Expression of the eng1(+) and agn1(+) genes, encoding the hydrolytic enzymes responsible for septum degradation, is activated at the end of each cell cycle by the transcription factor Ace2. Periodic ace2(+) expression is regulated by the transcriptional complex PBF (PCB Binding Factor), composed of the forkhead-like proteins Sep1 and Fkh2 and the MADS box-like protein Mbx1. In this report, we show that Ace2-dependent genes contain several combinations of motifs for Ace2 and PBF binding in their promoters. Thus, Ace2, Fkh2 and Sep1 were found to bind in vivo to the eng1(+) promoter. Ace2 binding was coincident with maximum level of eng1(+) expression, whereas Fkh2 binding was maximal when mRNA levels were low, supporting the notion that they play opposing roles. In addition, we found that the expression of eng1(+) and agn1(+) was differentially affected by mutations in PBF components. Interestingly, agn1(+) was a major target of Mbx1, since its ectopic expression resulted in the suppression of Mbx1 deletion phenotypes. Our results reveal a complex regulation system through which the transcription factors Ace2, Fkh2, Sep1 and Mbx1 in combination control the expression of the genes involved in separation at the end of the cell division cycle.

Removal of centrosomal PP1 by NIMA kinase unlocks the MPF feedback loop to promote mitotic commitment in S. pombe.

BACKGROUND: Activation of the Cdk1/cyclin B complex, also known as mitosis-promoting factor (MPF), drives commitment to mitosis. Interphase MPF is inhibited through phosphorylation of Cdk1 by Wee1-related kinases. Because Cdc25 phosphatases remove this phosphate, Cdc25 activity is an essential part of the switch that drives cells into mitosis. The generation of a critical "trigger" of active MPF promotes a positive feedback loop that employs Polo kinase to boost Cdc25 activity and inhibit Wee1, thereby ensuring that mitotic commitment is a bistable switch. Mutations in the spindle pole body (SPB) component Cut12 suppress otherwise lethal deficiencies in Cdc25. RESULTS: Cut12 harbors a bipartite protein phosphatase 1 (PP1) docking domain. Mutation of either element alone suppressed the temperature-dependent lethality of cdc25.22, whereas simultaneous ablation of both allowed cells to divide in the complete absence of Cdc25. Late G2 phase phosphorylation between the two elements by MPF and the NIMA kinase Fin1 blocked PP1(Dis2) recruitment, thereby promoting recruitment of Polo to Cut12 and the SPB and elevating global Polo kinase activity throughout the cell. CONCLUSIONS: PP1 recruitment to Cut12 sets a threshold for Polo's feedback-loop activity that locks the cell in interphase until Cdc25 pushes MPF activity through this barrier to initiate mitosis. We propose that events on the SPB (and, by inference, the centrosome) integrate inputs from diverse signaling networks to generate a coherent decision to divide that is appropriate for the particular environmental context of each cell. PP1 recruitment sets one or more critical thresholds for single or multiple local events within this switch.

Infección asintomática: un seguimiento cuidadoso / Asymptomatic infection: a careful monitoring

La infección asintomática por VIH se inicia genaralmente al sexto mes después de la infección primaria, coincidiendo con la seroconversión. Durante esta fase que dura generalmente entre 7 a 10 años, la actividad proliferativa viral persiste y alcanza un equilibrio dinámico que estaría limitada por factores relacionados con el huésped y/o con el virus. La infección asintomática por VIH, puede ser detectada en diversas circunstancias, las razones que generalmente motivan la realización de la prueba de despistaje no necesariamente están relacionadas con problemas de salud, sino como consecuencia de requisito por viaje, trabajo, estudios, aspirante a donante, control prenatal, prequirúrgico, diagnóstico de VIH o SIDA en la pareja. Cuando existen conducta de riesgo reconocida; por la propia persona o en su pareja, el despistaje se realiza por demanda espontánea o sugerida por el médico tratante. Se consideran Criterios de Sospecha el inicio temprano de la actividad sexual, una alta tasa de recambio de parejas sexuales, hombres que tienen sexo no protegido con otros hombres o con trabajadoras sexuales, uso de alcohol y drogas promueven conductas de alto riesgo (sexo sin protección) y antecedentes de ITS o que consultan por una ITS. El manejo de la infección asintomática, en el marco de la atención integral tiene carácter multidisciplinario: a) Atención médica, la evaluación inicial constituye el punto de partida para elaborar el plan de manejo, que incluya la profiláxis antituberculosa y para otras infecciones oportunistas y el tratamiento antirretroviral de gran actividad (TARGA), b) Atención de Enfermería: comprende el plan de educación del paciente y de sus familiares sobre aspectos de autocuidado; c) Consejería y Apoyo Emocional, permite un mejor enfrentamiento del problema, aceptación de su condición de PVVS y un vivir con dignidad; d) Atención Social, tiene como objetivo el análisis de las posibles consecuencias sociales relacionadas con la infección por VIH (situación laboral, vivienda, entorno familiar y social, abandono social, orfandad, etc.), la intervención social incluye la visita domiciliaria, para la recuperación del inasistente o del abandono a las profilaxis y/o al tratamiento antirretroviral.

Ace2p controls the expression of genes required for cell separation in Schizosaccharomyces pombe.

Schizosaccharomyces pombe cells divide by medial fission through contraction of an actomyosin ring and deposition of a multilayered division septum that must be cleaved to release the two daughter cells. Here we describe the identification of seven genes (adg1(+), adg2(+), adg3(+), cfh4(+), agn1(+), eng1(+), and mid2(+)) whose expression is induced by the transcription factor Ace2p. The expression of all of these genes varied during the cell cycle, maximum transcription being observed during septation. At least three of these proteins (Eng1p, Agn1p, and Cfh4p) localize to a ring-like structure that surrounds the septum region during cell separation. Deletion of the previously uncharacterized genes was not lethal to the cells, but produced defects or delays in cell separation to different extents. Electron microscopic observation of mutant cells indicated that the most severe defect is found in eng1Delta agn1Delta cells, lacking the Eng1p endo-beta-1,3-glucanase and the Agn1p endo-alpha-glucanase. The phenotype of this mutant closely resembled that of ace2Delta mutants, forming branched chains of cells. This suggests that these two proteins are the main activities required for cell separation to be completed.