Valoración de la exposición a plaguicidas en cultivos extensivos de Argentina y su potencial impacto sobre la salud

Los plaguicidas configuran un aspecto central de las prácticas agrícolas. El área pampeana agrupa un IEP mayor al promedio nacional y los IIAT superiores, correspondientes al 2,4-D y clorpirifos. El aumento en ambos índices de exposición se asoció a incrementos en las tasas de mortalidad por cáncer a nivel departamental. El daño genotóxico en aplicadores no se asoció a los niveles de exposición; sí la disminución de la actividad de butirilcolinesterasa. Los instrumentos "índices" y resultados alcanzados brindan valiosos elementos para vigilar la exposición a plaguicidas en Argentina.http://ref.scielo.org/tfp3m2publishedVersionFil: Butinof, Mariana. Universidad Nacional de Córdoba; Argentina.Fil: Fernández, Ricardo. Universidad Católica de Córdoba; Argentina.Fil: Muñoz, Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas Instituto Nacional de Investigaciones en Ciencias de la Salud; Argentina.Fil: Lerda, Daniel. Universidad Católica de Córdoba; Argentina.Fil: Blanco, Marcelo. Universidad Nacional de Córdoba; Argentina.Fil: Lantieri, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas Instituto Nacional de Investigaciones en Ciencias de la Salud; Argentina.Fil: Antolini, Luciana. Universidad Nacional de Córdoba; Argentina.Fil: Gieco, Marbela. Consejo Nacional de Investigaciones Científicas y Técnicas Instituto Nacional de Investigaciones en Ciencias de la Salud; Argentina.Fil: Ortiz, Pablo. Universidad Nacional de córdoba; Argentina.Fil: Filippi, Iohanna. Universidad Nacional de Córdoba; Argentina.Fil: Franchini, Germán. Consejo Nacional de Investigaciones Científicas y Técnicas Instituto Nacional de Investigaciones en Ciencias de la Salud; Argentina.Fil: Eandi, Mariana. Universidad Nacional de Córdoba; Argentina.Fil: Montedoro, Franco. Universidad Nacional de Córdoba; Argentina.Fil: María del Pilar Díaz. Consejo Nacional de Investigaciones Científicas y Técnicas Instituto Nacional de Investigaciones en Ciencias de la Salud; Argentina.Salud Pública y Medioambienta

Phenotypic profiling of CD34⁺ cells by advanced flow cytometry improves diagnosis of juvenile myelomonocytic leukemia

Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B-cell and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs versus controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML versus patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single eight-color antibody combination.</p

Phenotypic profiling of CD34⁺ cells by advanced flow cytometry improves diagnosis of juvenile myelomonocytic leukemia

Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B-cell and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs versus controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML versus patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single eight-color antibody combination.</p

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%

The reaction of the acetates of alpha-chloro methyl hemiacetals with nucleophiles. Synthesis of 2-hydroxy-1,4-dithianes

The acetates of the methyl hemiacetals of alpha-halo aldehydes, 1, easily undergo nucleophilic attack by lithium thiolates or ethane dithiolate affording alpha-thioalkyl aldehydes 2 or 2-hydroxy-1,4-dithianes 3, respectively. 3-monosubstituted dithianes 3 smoothly dehydrate to 2,3-dihydro-1,4-dithiines 4, whereas 3,3-disubstituted derivatives give dimers 6. The single-crystal X-ray analysis of 6b shows that it crystallises in a racemic form, with the dithiane ring in a chair conformation and the exocyclic S(3) atom axially bonded to the ring. The crystal packing appears to be determined mainly by a weak C-H ... O hydrogen bonding interaction

Note Illustrative della Carta geologica d'Italia alla scala 1:50.000 Foglio 254 Modigliana. Servizio Geologico d'Italia.

Note illustrative redatte per il Foglio geologico n. 254 Modigliana della Carta Geologica d'Italia alla scala 1:50.000. 117 pp