Trastornos del ciclo de la metilación en pacientes con fenilcetonuria

En este trabajo demostramos que los pacientes con fenilcetonuria (PKU) que siguen un tratamiento dietético estricto, con escasos aportes de proteínas naturales y alto aporte de suplementos dietéticos exentos de fenilalanina y enriquecidos en vitaminas y minerales, reciben una cantidad excesiva de vitamina B12 y de ácido fólico que conlleva una alteración en el ciclo de la metilación. Así, se produce un aumento de la vía de la remetilación, que se pone de manifiesto en el descenso de los niveles de homocisteína, metionina, arginina y citrulina, así como un aumento de la trans-sulfuración (manifestada en la elevación de cisteína, glicina y ornitina). Ello supone una menor disponibilidad de grupos metilo para otras reacciones metabólicas; nosotros hemos estudiado las relacionadas con la vía Arg-ADMA-NO y la vía Arg-GAA-Cr, comprobando que en efecto existe una menor producción de dimetilarginina asimétrica (ADMA) y creatinina (Crn). La determinación de estos metabolitos podría ser utilizada para el control dietético de los pacientes, lo que en el caso de la Crn es especialmente importante, dada la rapidez y el bajo coste de su determinación. Si bien estudios previos habían sugerido alteraciones en estos metabolitos, ninguno hasta la fecha había estudiado la vía de la metilación en los pacientes PKU ni la había puesto en relación con el tratamiento dietético de estos pacientes

Postnatal exposure to organic pollutants in maternal milk in north-western Spain

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGEvaluation of postnatal exposure to organic pollutants is especially important for suckling infants during breastfeeding, a crucial perinatal growth period when organs and hormonal systems develop. We determined levels of 60 pollutants, including organochlorine pesticides (OCPs), organophosphorus pesticides (OPPs), pyrethroids (PYRs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs), in 81 breast milk samples from breastfeeding mothers from Santiago de Compostela (north-western Spain). For most detected organic pollutants, levels were correlated with the season of milk sampling, maternal age at delivery, and place of residence. Dietary consumption habits (eggs, molluscs, and vegetable oils) were also correlated with OCP, OPP, PCB, PBDE and PYR levels. We also assessed the risk to infant health of exposure to organic pollutants in breast milk. PAHs, OCPs, OPPs, and PYRs accounted for almost 95% of the targeted organic pollutants in the samples analysed.Xunta de Galicia | Ref. GRC-ED431C 2022/35Instituto de Salud Carlos III (ISCIII) | Ref. RD21/ 001

Non-invasive biomonitoring of infant exposure to environmental organic pollutants in north-western Spain based on hair analysis. Identification of potential sources

Recent years have seen growing interest in hair sample analysis to detect organic pollutants (OPs). This biological matrix can be analysed non-invasively for biomonitoring of OPs over a wide exposure window. Obtaining hair sample amounts that meet the needs of the analytical methodology required for the determination of the POs of interest can be challenging, especially in infants. As a result, studies assessing organic pollutants in infant hair have been very scarce. We quantified levels of about 60 OPs, including persistent organic pollutants (POPs), in 110 hair samples from a patient cohort (60 mothers and 50 infants) from Santiago de Compostela (north-western Spain). For each participant we examined relationship between OP levels and corresponding epidemiological parameters using correlations, principal component analysis (PCA), hierarchical cluster analysis, and Multivariate analysis of variance (MANOVA). For many OPs we observed significant correlations with place of residence, parity, and maternal age, as well as pet ownership. Evaluation of dietary habits showed significant associations between levels some OPs and the consumption of fish, molluscs, and cereal. There were significant associations between chlorpyrifos and deltamethrin levels and infant birth characteristics such as birthweight and head circumference. Relations between OP levels in the hair of mothers and their infants were also examined, revealing common sources of exposure for dioxin-like polychlorinated biphenyls (DLPCBs), non-dioxin-like polychlorinated biphenyls (NDLPCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs). Levels of fluoranthene (F), pyrene (P), endrin, and some PBDEs in maternal hair were significantly correlated with those in infant hair. Our findings identified common sources of exposure to OPs of distinct chemical classes.Xunta de Galicia | Ref. GRC-ED431C 2022/35Universidade de Vigo/CISU

Newborn screening for Fabry disease in the north-west of Spain

Fabry disease is an X-linked lysosomal storage disorder caused by the impairment of α-galactosidase A. Enzyme replacement therapy is available to treat patients, who often experience delayed diagnosis. A newborn screening for Fabry disease was performed to study the prevalence of the pathology and to evaluate the possibility to implement the test in systematic screenings. We collected 14,600 dried blood spot samples (7575 males and 7025 females) and carried out a diagnostic study by fluorometric measurement of α-galactosidase A enzymatic activity and GLA gene sequencing. We detected one patient with a mutation in GLA associated with classical Fabry Disease (M290I), ten subjects carrying genetic variants of uncertain diagnosis (S126G, R118C, A143T), and a girl with the non-characterized variant F18Y, which was not previously described. Additional 25 samples presented nucleotide substitutions described as polymorphisms (D313Y, rs2071225, and rs2071397). The estimated prevalence for Fabry disease in north-western Spanish males is of 0.013%. Conclusion: These results confirm that the prevalence of Fabry disease is underestimated and systematic screening is feasible; however, further characterization of variants of uncertain clinical significance is necessary to establish protocols of patients’ managementThis studied was founded by the Spanish National Institute of Health-Instituto Carlos III/EU-FEDER, grant no. PI11-00842, to Ortolano S. and FEEL Foundation to Cristobal ColónS

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Структурный подход к использованию бетонов с низким содержанием цемента

Лопухов В. Ю. Структурный подход к использованию бетонов с низким содержанием цемента / В. Ю. Лопухов, Ю. А. Беленцов, В. М. Золотов // Вестник БГТУ им. В. Г. Шухова. - 2014. - №6. - С. 96-99.Области применения бетона на цементном вяжущем разнообразны. Можно с уверенностью сказать, что сегодня бетон является строительным материалом номер один в мире. Но с ростом его потребления растѐт спрос на цемент процесс производства, которого дорог и экологически вреден. Одним из способов снижения затрат цемента может быть уплотнение упаковки бетонной смеси по средствам подбора оптимального гранулометрического зернового состава заполнителей с наименьшей водопотребностью. Проведенные расчеты и опыты подтверждают суждение о способности уплотнения бетонной смеси при жестком каркасе упаковки из зерен заполнителя и оптимальном соотношении объемов связующего (цемента) и заполнителя. Так в смесях на многофракционном заполнителе 3-5 фракций реализуется эффект упрочнения. Что позволяет при применении наименьшего количества цемента сохранить прочность бетона близкой к исходной. По расчетам экономия цемента при создание такой плотной упаковки составит 120 кг