Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer’s Disease and Mild Cognitive Impairment Patients

It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer’s disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD and Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients’ blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis

Reunión científica del Programa Geomateriales: durabilidad y conservación de geomateriales del patrimonio construido, 9 de octubre 2013

El Programa Geomateriales Durabilidad y conservación del geomateriales del patrimonio construido, enmarcado en el IV Plan Regional de Investigación Científica e Innovación Tecnológica (IV PRICIT), fue concedido a través de su Convocatoria de Programas de I+D en Tecnologías 2009 (orden 679/2009). Iniciado el 1 de enero de 2010 y finalizado el 31 de mayo de 2014, el programa de investigación se plantea con una clara concepción experimental, pretendiendo dar solución y optimizando las actuaciones aplicadas para mejorar la durabilidad y conservación de los geomateriales utilizados en el patrimonio construido. El consorcio que integra el programa está constituido por grupos de investigación que desarrollan su labor en la Comunidad de Madrid, pertenecientes a la Agencia Estatal del Consejo Superior de Investigaciones Científicas (CSIC), a la Universidad Complutense de Madrid (UCM) y a la Universidad de Alcalá de Henares (UAH), otros grupos, laboratorios y/o centros tecnológicos ubicados en otras provincias españolas y en países europeos así como empresas privadas y otros organismos de colaboración. El programa ha conseguido alcanzar los objetivos científico-tecnológicos planteados, en gran parte mediante la colaboración de los diferentes grupos integrantes, jugando un papel esencial la participación también en el programa del Laboratorio de Petrofísica (RedLab 217). El presente volumen recoge las ponencias presentadas en la Reunión Científica del Programa Geomateriales, celebrada el 9 de octubre de 2013. Estas ponencias se organizaron fundamentalmente en base a los objetivos científicos del programa, incidiendo en las principales actividades realizadas y resultados obtenidos, y apostando por los jóvenes investigadores incorporados. En los resúmenes incluidos se pretende resaltar, por un lado, los resultados científicos de mayor relevancia, las investigaciones que han generado el desarrollo de patentes, las colaboraciones establecidas entre los diferentes grupos y/o empresas y las previsiones futuras. Por otro, aspectos relacionados con los objetivos de formación, como la realización de tesis doctorales y movilidad de investigadores, así como la participación conjunta en los objetivos de difusión y en actividades de gestión de los diferentes miembros del programa. El Programa Geomateriales ha supuesto un importante avance del conocimiento, permitiendo los logros científicos obtenidos posicionar al consorcio en unas condiciones muy favorables respecto a las diversas temáticas implicadas en la conservación del patrimonio. Este aspecto hace del consorcio el único a nivel nacional que aborda su estudio de forma integral y confirma, una vez más, la necesidad y conveniencia de crear equipos de trabajo que apuesten por la colaboración y conjunción de esfuerzos para alcanzar mayores y mejores logros.Peer Reviewe

Global characteristics and outcomes of SARS-CoV-2 infection in children and adolescents with cancer (GRCCC): a cohort study

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (<19 years) with cancer or having received a haematopoietic stem-cell transplantation. There were no centre-specific exclusion criteria. The registry was disseminated through professional networks through email and conferences and health-care providers were invited to submit all qualifying cases. Data for demographics, oncological diagnosis, clinical course, and cancer therapy details were collected. Primary outcomes were disease severity and modification to cancer-directed therapy. The registry remains open to data collection. Findings: Of 1520 submitted episodes, 1500 patients were included in the study between April 15, 2020, and Feb 1, 2021. 1319 patients had complete 30-day follow-up. 259 (19·9%) of 1301 patients had a severe or critical infection, and 50 (3·8%) of 1319 died with the cause attributed to COVID-19 infection. Modifications to cancer-directed therapy occurred in 609 (55·8%) of 1092 patients receiving active oncological treatment. Multivariable analysis revealed several factors associated with severe or critical illness, including World Bank low-income or lower-middle-income (odds ratio [OR] 5·8 [95% CI 3·8–8·8]; p<0·0001) and upper-middle-income (1·6 [1·2–2·2]; p=0·0024) country status; age 15–18 years (1·6 [1·1–2·2]; p=0·013); absolute lymphocyte count of 300 or less cells per mm3 (2·5 [1·8–3·4]; p<0·0001), absolute neutrophil count of 500 or less cells per mm3 (1·8 [1·3–2·4]; p=0·0001), and intensive treatment (1·8 [1·3–2·3]; p=0·0005). Factors associated with treatment modification included upper-middle-income country status (OR 0·5 [95% CI 0·3–0·7]; p=0·0004), primary diagnosis of other haematological malignancies (0·5 [0·3–0·8]; p=0·0088), the presence of one of more COVID-19 symptoms at the time of presentation (1·8 [1·3–2·4]; p=0·0002), and the presence of one or more comorbidities (1·6 [1·1–2·3]; p=0·020). Interpretation: In this global cohort of children and adolescents with cancer and COVID-19, severe and critical illness occurred in one fifth of patients and deaths occurred in a higher proportion than is reported in the literature in the general paediatric population. Additionally, we found that variables associated with treatment modification were not the same as those associated with greater disease severity. These data could inform clinical practice guidelines and raise awareness globally that children and adolescents with cancer are at high-risk of developing severe COVID-19 illness. Funding: American Lebanese Syrian Associated Charities and the National Cancer Institute