Speciation Gamma-Spectrometry: the Fate of Environmental Radio-Nuclides in Hard-Water Lakes

Abstract A sequential fractionation method for simultaneous and absolute measurement of environmental radio-nuclides, 241 Am, 210 Pb, 226 Ra, 137 Cs, 40 K and 234 Th/ 238 U, by gamma-spectrometry was tested and applied to hard-water lake-sediments. The carbonate, fulvic, humic and mineral insoluble fractions were extracted from the sediments. Correction of self-absorption and geometrical effects, arising from the conditioning of bulk and fractionated sediments, were done using Monte Carlo simulations. This "non-destructive" fractionation procedure allows further analysis of other chemical species in the same fractions thus creating possibilities to study the dynamics of self-cleaning mechanism in lakes. The results demonstrate that the procedure is quantitative and suitable for the determination of environmental key radio-tracers in different fractions. Unlike other fresh-water sediments the major part of the environmental radio-nuclides is associated with "mineral" fractions. This speciation gamma-spectrometry procedure was supplemented by isotope-dilution alpha-spectrometry 210 Po ( 210 Pb), for determining the acid-soluble organic fractions in fresh-water lakes. The overall speciation procedure demonstrated that carbonate fractions, extracted from hard-water lake sediments, could be separated either free from, or associated with, fulvic-compounds. This speciation procedure can be applied to other aquatic deposits, however supplementary steps can be added if other data are required

HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets

We conducted this study to determine the HLA class II allele associations in a large cohort of patients of homogeneous ethnic derivation with systemic lupus erythematosus (SLE). The large sample size allowed us to stratify patients according to their clinical and serologic characteristics. We studied 577 European Caucasian patients with SLE. Antinuclear antibodies (Hep-2 cells), anti-dsDNA antibodies (Crithidia luciliae), and antibodies to extractable nuclear antigens Ro (SS-A), La (SS-B), U1-RNP, Sm, Jo1, SCL70, and PCNA, were detected in all patients. Molecular typing of HLA-DRB1, DRB3, DQA1, and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. We found a significantly increased frequency of DRB1*03, DRB1*15, DRB1*16, DQA1*0102, DQB1*0502, DQB1*0602, DQB1*0201, DQB1*0303, and DQB1*0304 in lupus patients as compared with healthy controls. In addition, DRB1*03 was associated with anti-Ro, anti-La, pleuritis, and involvement of lung, kidney, and central nervous system. DRB1*15 and DQB1*0602 were associated with anti-dsDNA antibodies; DQB1*0201 with anti-Ro and anti-La, leukopenia, digital skin vasculitis, and pleuritis; and DQB1*0502 was associated with anti-Ro, renal involvement, discoid lupus, and livedo reticularis. In conclusion, our study shows some new HLA clinical and serologic associations in SLE and further confirms that the role of MHC genes is mainly to predispose to particular serologic and clinical manifestations of this disease

A Metabolomic Approach to the Study of Wine Micro-Oxygenation

Wine micro-oxygenation is a globally used treatment and its effects were studied here by analysing by untargeted LC-MS the wine metabolomic fingerprint. Eight different procedural variations, marked by the addition of oxygen (four levels) and iron (two levels) were applied to Sangiovese wine, before and after malolactic fermentation

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

As repercussões do cuidado na vida do cuidador familiar do idoso com demência de Alzheimer

Nos últimos anos tem aumentado progressivamente o número de famílias que se tem confrontado com a situação de cuidar de familiares idosos em condição de dependência, principalmente quando esta é provocada em virtude da Doença de Alzheimer (DA). O objetivo deste estudo é o de investigar as repercussões do cuidado na vida do cuidador familiar de idoso com demência de Alzheimer. Através da epistemologia qualitativa utilizou-se a técnica da entrevista na modalidade de história de vida temática aplicada a vinte cuidadores de idosos cadastrados na Associação Brasileira de Alzheimer do estado do Amazonas (ABRAZ-AM). Os resultados mostraram que as renúncias aparecem nos depoimentos dos familiares como uma repercussão significativa do cuidado. A privação social em função do cuidado é uma realidade presente na vida dos cuidadores deste estudo. A raiva, a impaciência, o medo, a solidão e a vergonha são sentimentos vivenciados pelos cuidadores em seu cotidiano, que se alternam com sentimentos de satisfação, felicidade, compaixão e de retribuição. É importante salientar que neste estudo, a situação de cuidado vivenciada pelos cuidadores é permeada por sentimentos que se contrapõem, em determinados momentos se configurando como desagradáveis e em outros momentos como agradáveis. Sendo assim, percebe-se que é possível e relevante os profissionais da saúde identificarem esses aspectos favorecedores de prazer na relação de cuidado, buscando exaltá-los perante os outros. Dessa forma, a possibilidade de enfrentar da melhor forma os percalços deve ser considerada uma realidade eminentemente presente no cotidiano de cuidado.In recent years there has been a progressive increase in the number of families confronted with the situation of caring for elderly relatives in a dependent condition, principally as a result of Alzheimer's disease. The objective of the present study was to investigate the repercussions of such care in the life of family caregivers of elderly relatives with Alzheimer's disease. By means of qualitative epistemology, the interview technique was used in the thematic life history modality, and applied to 20 caregivers of elderly individuals enrolled in the Brazilian Association of Alzheimer's Disease in the State of Amazonas, Northern Brazil. The results showed that renouncements emerge in the caregivers' testimonies as a significant repercussion of care. Social deprivation is a reality that is present in the lives of all the caregivers who took part in this study. Anger, impatience, fear, loneliness and shame are feelings experienced by the caregivers in their everyday lives, intermingling with feelings of satisfaction, happiness, compassion and retribution. It is important to highlight that in the present study the care situation lived by the caregivers was permeated by opposing feelings, being considered unpleasant in certain moments and pleasant in others. Thus, it is perceived that it is possible and relevant for the health professionals to identify the pleasure-promoting aspects in the care relationship, praising them before the others. Therefore, the possibility of facing the mishaps in the best possible way should be considered as an eminently present reality in the daily routine of care

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality