Detection and characterization of amplitude defects using spectral kurtosis

Peer Reviewe

Apresentação do dossiê: A Historiografia sobre as Missões Jesuíticas: a Escrita e o Tempo

Dossier "History of historiography in Brazil and Portugal: future past of national histories in a restless present"Apresentação do dossiê: A Historiografia sobre as Missões Jesuíticas: a Escrita e o Temp

Epidemiology of Carbapenemase-Producing Klebsiella pneumoniae in a Hospital, Portugal

We aimed to provide updated epidemiologic data on carbapenem-resistant Klebsiella pneumoniae in Portugal by characterizing all isolates (N = 46) recovered during 2013– 2018 in a 123-bed hospital in Lisbon. We identified blaKPC-3 (n = 36), blaOXA-181 (n = 9), and blaGES-5 (n = 8) carbapenemase genes and observed co-occurrence of blaKPC-3 and blaGES-5 in 7 isolates. A single GES-5–producing isolate co-produced the extended-spectrum β-lactamase BEL-1; both corresponding genes were co- located on the same ColE1-like plasmid. The blaOXA-181 gene was always located on an IncX3 plasmid, whereas blaKPC-3 was carried on IncN, IncFII, IncFIB, and IncFIIA plasmid types. The 46 isolates were distributed into 13 pulsotypes and 9 sequence types. All isolates remained susceptible to ceftazidime/avibactam, but some exhibited reduced antimicrobial susceptibility (MIC = 3 mg/L)

Techno-economic evaluation and comparison of PAC-MBR and ozonation-UV revamping for organic micro-pollutants removal from urban reclaimed wastewater

The presence of sewage-borne Organic Micro-Pollutants (OMP) in Wastewater Treatment Plants (WWTP) effluents represents an increasing concern when water is reclaimed for irrigation or even indirect potable reuse. During eighteen months, an innovative hybrid water reclamation scheme based on a Membrane Biological Reactor (MBR) enhanced with Powder Activated Carbon (PAC) was operated at pilot-scale (70 m3/d) in order to compare it with state-of-the art Wastewater Reclamation System (WWRS) also revamped with a final step of ozonation-UV. Removal of persistent OMP, water quality and treatment costs were evaluated and compared for the different treatment schemes. OMP removal efficiency results for the different schemes concluded that established technologies, such as physico-chemical and filtration systems as well as MBR, do not remove significantly (>15%) the most recalcitrant compounds. The upgrading of these two systems through the addition of ozonation-UV step and PAC dosing allowed improving average recalcitrant OMP removal to 85±2 and 75±5 %, respectively. In term of costs, PAC-MBR represents an increase of 37 % of costs regarding conventional systems but presents improvements of 50 % reduction in space and water quality. On the other hand, ozonation requires up to a 15% increase of foot-print; nevertheless, represents lower costs and lower carbon footprint. Ozonation-UV seems to be the best option for upgrading existing facilities, while PAC- MBR should be considered when space represents a critical limitation and produced water is reused for high water quality purposes.Postprint (author's final draft

Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis

BACKGROUND & AIMS: Steatohepatitis (SH) is associated with mitochondrial dysfunction and excessive production of superoxide, which can then be converted into H(2)O(2) by SOD2. Since mitochondrial GSH (mGSH) plays a critical role in H(2)O(2) reduction, we explored the interplay between superoxide, H(2)O(2), and mGSH in nutritional and genetic models of SH, which exhibit mGSH depletion. METHODS: We used isolated mitochondria and primary hepatocytes, as well as in vivo SH models showing mGSH depletion to test the consequences of superoxide scavenging. RESULTS: In isolated mitochondria and primary hepatocytes, superoxide scavenging by SOD mimetics or purified SOD decreased superoxide and peroxynitrite generation but increased H(2)O(2) following mGSH depletion, despite mitochondrial peroxiredoxin/thioredoxin defense. Selective mGSH depletion sensitized hepatocytes to cell death induced by SOD mimetics, and this was prevented by RIP1 kinase inhibition with necrostatin-1 or GSH repletion with GSH ethyl ester (GSHee). Mice fed the methionine-choline deficient (MCD) diet or MAT1A(-/-) mice exhibited reduced SOD2 activity; in vivo treatment with SOD mimetics increased liver damage, inflammation, and fibrosis, despite a decreased superoxide and 3-nitrotyrosine immunoreactivity, effects that were ameliorated by mGSH replenishment with GSHee, but not NAC. As a proof-of-principle of the detrimental role of superoxide scavenging when mGSH was depleted transgenic mice overexpressing SOD2 exhibited enhanced susceptibility to MCD-mediated SH. CONCLUSIONS: These findings underscore a critical role for mGSH in the therapeutic potential of superoxide scavenging in SH, and suggest that the combined approach of superoxide scavenging with mGSH replenishment may be important in SH

NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial

Simple Summary Multiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis. Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients

Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.This work was supported by the Coordinated Research Activities at the Centro Nacional de Microbiología (CNM, Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM) and a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This work was also supported by the Spanish Ministry of Economy and Competitiveness (PID2019 110275RB-I00); the Spanish AIDS Research Network RD16CIII/0002/0001 that is included in Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2016-2020, Instituto de Salud Carlos III, European Region Development Fund (ERDF); Miguel Servet - AESI, MPY 341/21. The work of ML-H and SR is financed by NIH grant R01AI143567. The work of MT is supported by Instituto de Salud Carlos III (COV20_00679). The work of LV is supported by a predoctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER).S

IDENTIFICAÇÃO DO CULTIVO AGRÍCOLA E DO MANEJO DE PRAGAS E DOENÇAS EM PRODUÇÃO ORGÂNICA EM ALAGOAS

A agricultura familiar é de grande importância para o Brasil, por ser a principal fonte de renda de muitos produtores rurais no País. Ademais, o cultivo de alimentos orgânicos em propriedades familiares aumentou nos últimos anos. Objetivou-se identificar as espécies agrícolas de interesse econômico e as práticas de manejo de pragas e doenças nos cultivos orgânicos em um assentamento de Reforma Agrária no estado de Alagoas. As espécies cultivadas são raízes, hortaliças e frutíferas. Rotação e consorciação de culturas, poda das plantas comprometidas pelo ataque das pragas, SAF’s e aplicação de substâncias naturais de fácil aquisição nas propriedades rurais são práticas de controle de pragas e doenças usadas pelos agricultores. Estas técnicas de manejo de pragas estão de acordo com as exigências do Ministério da Agricultura, Pecuária e Abastecimento para a classificação destes produtores como orgânicos, conforme a Legislação Brasileira que garante a permanência destes no Cadastro Nacional de Produtores Orgânicos

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe

Efecto de la raza paterna en características de la canal de corderos para carne en Hidalgo, México

Efecto de la raza paterna en características de la canal de corderos para carne en Hidalgo, México   El objetivo del estudio fue evaluar los efectos de la raza paterna (Charollais, Dorset y Texel), utilizando ovejas Hampshire, sexo y tipo de nacimiento de la cría, en características de la canal de los corderos. Después del destete (74±8 días), 45 corderos de estas cruzas se finalizaron durante 63 días, consumiendo una dieta balanceada con 14% de PC y 2.82 Mcal de EM/kg de MS. Los corderos se pesaron y se sacrificaron a los 137 días de edad; posteriormente, se tomaron medidas de peso y rendimiento de la canal caliente y fría, área del ojo de chuleta, espesor de grasa subcutánea, longitud de canal, longitud de pierna, perímetro de grupa y se calculó el índice de compacidad de la canal; además se determinó la composición regional de la canal (espaldilla, bajos, badal, pierna, cuello, y costillar). Los datos se analizaron utilizando un modelo mixto. Los corderos de padre Charollais tuvieron el mayor (P<0.05) área del ojo de chuleta (20.1±0.5 cm2), mientras que los de padre Dorset fueron superiores (P<0.05) en longitud interna de la canal (66.3±0.9 cm) y longitud de pierna (34.8±0.3 cm). Los machos superaron a las hembras (P<0.05) en la mayoría de las variables analizadas. Los corderos de parto sencillo tuvieron medias mayores que los de parto doble (P<0.05) en espesor de la grasa subcutánea y longitud de la pierna. En general, las cruzas con Charollais y Dorset mostraron superioridad en las características de la canal.     Efecto de la raza paterna en características de la canal de corderos para carne en Hidalgo, México   El objetivo del estudio fue evaluar los efectos de la raza paterna (Charollais, Dorset y Texel), utilizando ovejas Hampshire, sexo y tipo de nacimiento de la cría, en características de la canal de los corderos. Después del destete (74±8 días), 45 corderos de estas cruzas se finalizaron durante 63 días, consumiendo una dieta balanceada con 14% de PC y 2.82 Mcal de EM/kg de MS. Los corderos se pesaron y se sacrificaron a los 137 días de edad; posteriormente, se tomaron medidas de peso y rendimiento de la canal caliente y fría, área del ojo de chuleta, espesor de grasa subcutánea, longitud de canal, longitud de pierna, perímetro de grupa y se calculó el índice de compacidad de la canal; además se determinó la composición regional de la canal (espaldilla, bajos, badal, pierna, cuello, y costillar). Los datos se analizaron utilizando un modelo mixto. Los corderos de padre Charollais tuvieron el mayor (P<0.05) área del ojo de chuleta (20.1±0.5 cm2), mientras que los de padre Dorset fueron superiores (P<0.05) en longitud interna de la canal (66.3±0.9 cm) y longitud de pierna (34.8±0.3 cm). Los machos superaron a las hembras (P<0.05) en la mayoría de las variables analizadas. Los corderos de parto sencillo tuvieron medias mayores que los de parto doble (P<0.05) en espesor de la grasa subcutánea y longitud de la pierna. En general, las cruzas con Charollais y Dorset mostraron superioridad en las características de la canal.     The objective of the study was to evaluate the effects of sire breed (Charollais, Dorset and Texel), utilizing Hampshire ewes, lamb sex and birth type, on carcass traits of the lambs. After weaning (74±8 d), 45 lambs from these crosses were fattened during 63 d, consuming a balanced diet with 14% CP and 2.82 Mcal of ME/kg of DM. Lambs were weighed and slaughtered at 137 d of age; later, measures on slaughter weight and yield of hot and cold carcass, rib eye area, subcutaneous fat, carcass length, leg length, and rump perimeter were taken and the carcass compactness index was calculated. In addition, the carcass regional composition (shoulder, chest-belly, anterior-loin, leg, neck, and rear-loin) was determined. Data were analyzed utilizing a mixed model. Charollais-sired lambs had the highest (P<0.05) rib eye area (20.1±0.5 cm2), while Dorset-sired lambs were superior (P<0.05) in carcass length (66.3±0.9 cm) and leg length (34.8±0.3 cm). Ram lambs surpassed ewe lambs (P<0.05) in most traits analyzed. Lambs born as singles had higher means than twin lambs (P<0.05) in subcutaneous fat and leg length. In general, crosses with Charollais and Dorset showed superiority in carcass traits