Antimicrobial Effect of Titanium Dioxide Nanoparticles

The widespread use of antibiotics has led to the emergence of multidrug-resistant bacterial strains, and therefore a current concern for food safety and human health. The interest for new antimicrobial substances has been focused toward metal oxide nanoparticles. Specifically, titanium dioxide (TiO2) has been considered as an attractive antimicrobial compound due to its photocatalytic nature and because it is a chemically stable, non-toxic, inexpensive, and Generally Recognized as Safe (GRAS) substance. Several studies have revealed this metal oxide demonstrates excellent antifungal and antibacterial properties against a broad range of both Gram-positive and Gram-negative bacteria. These properties were significantly improved by titanium dioxide nanoparticles (TiO2 NPs) synthesis. In this chapter, latest developments on routes of synthesis of TiO2 NPs and antimicrobial activity of these nanostructures are presented. Furthermore, TiO2 NPs favor the inactivation of microorganisms due to their strong oxidizing power by free radical generation, such as hydroxyl and superoxide anion radicals, showing reductions growth against several microorganisms, such as Escherichia coli and Staphylococcus aureus. Understanding the main mechanisms of antimicrobial action of these nanoparticles was the second main purpose of this chapter

Palaeoecological analysis of two Late Pleistocene continental mollusc assemblages from Uruguay

Ponencia presentada en World Congress of Malacology, 1-5 Aug. 2022, Münich - Alemania, organizado por UNITAS Malacologica y Ludwig-Maximilians-Universität.Extant continental (freshwater and terrestrial) molluscs are very informative from an environmental point of view. The specific environmental requirements of different taxa can be extrapolated to the fossil assemblages in order to reconstruct past environments. This is especially true for the Quaternary, when fossil assemblages are mostly composed by extant species. We analysed two associations of continental molluscs from the Late Pleistocene of Uruguay, with the goal of reconstruct the depositional environments for each assemblage. For this analysis, 11 localities from the Sopas Formation and 10 from the Dolores Formation were selected. The statistical analyses aimed to understand the diversity of each locality and to make comparisons among them, using traditional diversity indices (Shannon, Simpson, Equitability). To estimate the diversity Rarefaction and Chao1 were applied. Lastly, the species occurrence in all localities were compared, using several multivariate analyses: NMDS with axes rotation by Principal Components Analysis, Correspondence Analysis, and Cluster Analysis. The multivariate analyses show that all local assemblages are distributed in two main associations: one composed mostly by Sopas Formation localities (Sopas Association) and the other composed mostly by Dolores Formation localities (Dolores Association). Only one locality from each Formation was interchanged. The Sopas Association records mostly the families Cyrenidae (36.1 %), Tateidae (32 %), Cochliopidae (26.1 %), and the only record of the family Chilinidae. Also, the large, massive species Diplodon charruanus, D. wymanii and D. peraeformis are present. Meanwhile, the Dolores Association records mostly representatives of Cochliopidae (54.4 %), Planorbinae (20.2 %), Sphaeridae (16 %), and has the only records of Physidae and Succineidae. Cochliopidae (Heleobia) are present in both associations, which is logical since currently they are quite ubiquitous in most lotic and lentic environments. Ampullariidae and the subfamily Ancylinae are also present in both associations, along with the delicate species Diplodon rhuacoicus, which is the only Diplodon from the Dolores Association. Presently, the communities that include Sopas-like assemblages are mostly found in high to moderate current lotic environments, with rocky to coarse bottoms. Meanwhile, the communities that include the taxa typical of the Dolores Association are common in lentic or very calm lotic environments, with fine sediments and abundant aquatic vegetation.ANII: FCE_3_2018_1_148922ANII: POS_NAC_2015_1_10947

CARACTERÍSTICAS DE LA FORMACIÓN DEPORTIVA DE LOS PARTICIPANTES EN LOS IV JUEGOS ESCOLARES CENTROAMERICANOS Y DEL CARIBE, ARMENIA 2013

Objetivo: Caracterizar la formación deportiva de participantes en los IV Juegos Deportivos EscolaresCentroamericanos y del Caribe, Armenia, 2013. Materiales y métodos: Estudio cuantitativo, prospectivo,con alcance descriptivo y de corte transversal. De un universo de 683 participantes, fue seleccionadaintencionalmente una muestra no probabilística de 233 deportistas (102 hombres y 131 mujeres),entre 15 y 17 años de edad, pertenecientes a nueve delegaciones participantes, quienes respondieronuna encuesta que indagaba sobre la formación deportiva. Resultados: Los deportistas encuestadosafirman que la organización del deporte en la escuela se da en clubes deportivos, los deportistaspertenecen a entidades deportivas independientes a su institución educativa y dichas entidades noposeen convenios con las instituciones educativas; el promedio de edad de inicio es 9,57 años, enentidades deportivas independientes de su institución; al 52,3 % de los deportistas se les realizaronpruebas para identificar talento; y de ellas las más utilizadas fueron las pruebas físicas. Dentro delcontrol se encuentra que el 89,2 % realizó pruebas permanentemente y las más utilizadas son las físicas,se identifica que los deportistas tienen un bagaje en competencias internacionales y un promediode 7 competencias por año; finalmente, se establece que el principal agente motivador son los padres

The presence of both HLA-DRB1[*]04:01 and HLA-B[*]15:01 increases the susceptibility to cranial and extracranial giant cell arteritis.

Objectives: To determine if patients with the predominant extracranial large-vessel-vasculitis (LVV) pattern of giant cell arteritis (GCA) have a distinctive HLA-B association, different from that reported in biopsy-proven cranial GCA patients. In a further step we assessed if the combination of HLA-B and HLA-DRB1 alleles confers an increased risk for GCA susceptibility, either for the cranial and extracranial LVV phenotypes. Methods: A total of 184 patients with biopsy-proven cranial GCA, 105 with LVV-GCA and 486 healthy controls were included in our study. We compared HLA-B phenotype frequencies between the three groups. Results: HLA-B*15 phenotype was significantly increased in patients with classic cranial GCA compared to controls (14.7% versus 5.8%, respectively; p<0.01; OR [95% CI] =2.81 [1.54-5.11]). It was mainly due to the HLA-B*15:01 allele (12.5% versus 4.0%, respectively; p<0.01; OR [95% CI] =3.51 [1.77-6.99]) and remained statistically significant after Bonferroni correction. Similar HLA-B*15 association was observed in patients with the LVV-GCA (11.4% versus 5.8%, p=0.04, OR [95% CI] =2.11 [1.04-4.30]). This association was also mainly due to the HLA-B*15:01 allele (10.5% versus 4.0%, respectively; p=0.0054; OR [95% CI] =2.88 [1.19-6.59]). Noteworthy, the presence of HLA-B*15:01 together with HLA-DRB1*04:01 led to an increased risk of developing both cranial and extracranial LVV-GCA. Conclusions: Susceptibility to GCA is strongly related to the HLA region, regardless of the clinical phenotype of expression of the disease.This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from ‘‘Instituto de Salud Carlos III’’ (ISCIII) (Spain). However, this research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors

Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network

Objetivos: Describir la presentación clínica, el manejo y los resultados de la enfermedad de Kawasaki (EK) en Latinoamérica y evaluar los indicadores pronósticos tempranos de aneurisma de la arteria coronaria (AAC). Diseño del estudio: Se realizó un estudio observacional basado en el registro de la EK en 64 centros pediátricos participantes de 19 países latinoamericanos de forma retrospectiva entre el 1 de enero de 2009 y el 31 de diciembre de 2013, y de forma prospectiva desde el 1 de junio de 2014 hasta el 31 de mayo de 2017. Se recopilaron datos demográficos, clínicos y de laboratorio iniciales. Se utilizó una regresión logística que incorporaba factores clínicos y la puntuación z máxima de la arteria coronaria en la presentación inicial (entre 10 días antes y 5 días después de la inmunoglobulina intravenosa [IGIV]) para desarrollar un modelo pronóstico de AAC durante el seguimiento (>5 días después de la IGIV). Resultados: De 1853 pacientes con EK, el ingreso tardío (>10 días tras el inicio de la fiebre) se produjo en el 16%, el 25% tuvo EK incompleta y el 11% fue resistente a la IGIV. Entre los 671 sujetos con puntuación z de la arteria coronaria notificada durante el seguimiento (mediana: 79 días; IQR: 36, 186), el 21% presentaba AAC, incluido un 4% con aneurismas gigantes. Un modelo pronóstico simple que utilizaba sólo una puntuación z de la arteria coronaria máxima ≥2,5 en la presentación inicial fue óptimo para predecir la AAC durante el seguimiento (área bajo la curva: 0,84; IC del 95%: 0,80, 0,88). Conclusiones: De nuestra población latinoamericana, la puntuación z de la arteria coronaria ≥2,5 en la presentación inicial fue el factor pronóstico más importante que precedió a la AAC durante el seguimiento. Estos resultados resaltan la importancia de la ecocardiografía temprana durante la presentación inicial de la EK. © 2023 Los autoresObjectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). Study design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). Conclusion: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD. © 2023 The Author(s