Is It Feasible to Use CMV-Specific T-Cell Adoptive Transfer as Treatment Against Infection in SOT Recipients?

During the last decade, many studies have demonstrated the role of CMV specific T-cell immune response on controlling CMV replication and dissemination. In fact, it is well established that transplanted patients lacking CMV-specific T-cell immunity have an increased occurrence of CMV replication episodes and CMV-related complications. In this context, the use of adoptive transfer of CMV-specific T-cells has been widely investigated and applied to Hematopoietic Stem Cell Transplant patients and may be useful as a therapeutic alternative, to reconstitute the CMV specific T-cell response and to control CMV viremia in patients receiving a transplantation. However, only few authors have explored the use of T-cell adoptive transfer in SOT recipients. We propose a novel review in which we provide an overview of the impact of using CMV-specific T-cell adoptive transfer on the control of CMV infection in SOT recipients, the different approaches to stimulate, isolate and expand CMV-specific T-cells developed over the years and a discussion of the possible use of CMV adoptive cellular therapy in this SOT population. Given the timeliness and importance of this topic, we believe that such an analysis will provide important insights into CMV infection and its treatment/prevention.This study was supported by the Spanish Ministry of Science, Innovation and University, Instituto de Salud Carlos III Grant/Award Numbers: PI17CIII-00014 (MPY110/18); DTS18CIII/00006 (MPY127/19); PI20-009 (MPY303/20). This work was supported by Plan Nacional de I + D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Science, Innovation and University, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), co-financed by European Development Regional Fund ‘A way to achieve Europe’. EG-R is supported by the Sara Borrell Program (CD18CIII/00007), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades. FM is supported by the PFIS Program (F18III/00013), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades. MN is supported by the FPU program (FPU19/05927), Ministerio de Ciencia, Innovación y Universidades.S

Evaluación estructural no destructiva de pavimento flexible mediante la solución del algoritmo AASHTO 1993, Carretera Piura-Paita, 2022

La presente investigación consiste en la resolución del algoritmo ASSHTO 1993 aplicando metodologías no destructivas para evaluar estructuralmente las condiciones mecánicas de pavimentos flexibles con fines de rehabilitación, el estudio a evaluar se realiza en la vía Piura - Paita, en dirección al oeste teniendo una población de 46 km, tomando una muestra de 10 km desde la progresiva 5+100 hasta la progresiva 15+100. Este método se aplica para obtener el diseño del refuerzo del pavimento flexible por medio de la metodología de retrocálculo explicada en la Guía ASSTHO 93, mediante el análisis de deflexiones medidas utilizando el deflectometro de impacto (FWD), de esta manera se obtiene el módulo resiliente de la subrasante, el módulo resiliente del pavimento, el número estructural existente, con la finalidad de estimar el espesor de refuerzo, para lograr una proyección de vida útil del pavimento de 15 años y de esta manera contribuir a la gestión para el desarrollo vial

Factores socioeconómicos y culturales relacionados a las prácticas de alimentación complementaria de madres de niños (as) de 6 a 12 meses que acuden al Centro de Salud Juan Parra del Riego, El Tambo - Huancayo 2016

El objetivo es determinar la relación entre los factores socioeconómicos culturales y las prácticas de alimentación complementaria de madres de niños(as) de 6 a 12 meses que acuden al Centro de Salud Juan Parra del Riego, El Tambo Huancayo 2016. Metodología: El tipo de investigación es aplicada correlacional, con diseño no experimental correlacional transversal. Resultados: Más de la mitad de madres encuestadas presentan factores socioeconómicos culturales desfavorables relacionados a prácticas de alimentación complementaria inadecuadas. Del 69.4% (50) de madres con prácticas de alimentación complementaria inadecuada el 52.8% (38) presentan factores sociales desfavorables, por otro lado un 19.4%(14) de madres con prácticas de alimentación complementaria adecuadas presentan factores sociales adecuados. Del 69.4% (50) de madres con prácticas inadecuadas el 61.1% (44) presentan factores económicos desfavorables y el 13.9% (10) presentan factores económicos favorables. Del 80.6% (58) de madres con prácticas inadecuadas el 66.7%(48) presentan factores culturales desfavorables y el 13.9% (10) presentan factores culturales favorables. Conclusión: Si existe relación directa entre los factores socioeconómicos culturales y las prácticas de alimentación complementaria de madres de niños(as) de 06 a 12 meses.Tesis de segunda especialida

Varicella-zoster virus clades circulating in Spain over two decades

BACKGROUND: Despite childhood universal VZV immunization was introduced in 2015, there are no data on VZV clade distribution in Spain. OBJECTIVES: To characterize the varicella-zoster virus strains circulating in Spain between 1997 and 2016. STUDY DESIGN: In this retrospective study, we determined the VZV clades in 294 patients with different pathologies (mainly encephalitis, zoster and varicella) by sequencing three fragments within ORF 22, ORF 21 and ORF 50 and, subsequently analyzing 7 relevant SNPs. RESULTS: Among these 294 patients, 132(44.9%) patients were infected by clade 1, 42(14.3%) patients by clade 3, 19(6.5%) by clade 5, 29(9.9%) by clade VI and 3(1%) by clade 4. Four patients (1.4%) were infected by clade 2 vOKA strains, who received one dose of live-attenuated varicella vaccine. Putative recombinant clade 1/3 was identified in 6 cases (2.0%). Results obtained from partial sequences were assigned to clade 1 or 3 in 56(19%) patients and clade 5 or VI in 3(1.0%) patients. In the multivariate analysis, encephalitis was independently associated with clades 1 and 3 and age >14y.o. (P = 0.035 and P = 0.021, respectively). Additionally, Madrid had significant fewer cases of encephalitis compared with the rest of regions analyzed (P = 0.001). CONCLUSIONS: Higher prevalence of clades 1 and 3 and their relation with encephalitis and age >14y.o. suggest earlier introduction of this clades in Spain. Putative interclade 1 and 3 recombinants are circulating in patients with encephalitis, herpes zoster and varicella. Several cases were related to vOKA vaccination but vaccine strains do not seem to circulate in the general population.This work was supported by a grant from Instituto de Salud Carlos III. Project code MPY1372/12. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Optimization of a Lambda-RED Recombination Method for Rapid Gene Deletion in Human Cytomegalovirus

Human cytomegalovirus (HCMV) continues to be a major cause of morbidity in transplant patients and newborns. However, the functions of many of the more than 282 genes encoded in the HCMV genome remain unknown. The development of bacterial artificial chromosome (BAC) technology contributes to the genetic manipulation of several organisms including HCMV. The maintenance of the HCMV BAC in E. coli cells permits the rapid generation of recombinant viral genomes that can be used to produce viral progeny in cell cultures for the study of gene function. We optimized the Lambda-Red Recombination system to construct HCMV gene deletion mutants rapidly in the complete set of tested genes. This method constitutes a useful tool that allows for the quick generation of a high number of gene deletion mutants, allowing for the analysis of the whole genome to improve our understanding of HCMV gene function. This may also facilitate the development of novel vaccines and therapeutics.This study was supported by the Spanish Ministry of Science, Innovation and University, Instituto de Salud Carlos III Grant/Award Numbers: PI17CIII-00014 (MPY110/18); PI20CIII-00009 (MPY303/20); DTS18CIII/00006 (MPY127/19). E.G.-R. is supported by the Sara Borrell Program (CD18CIII/00007), M.L.-S. is supported by the Sara Borrell Program (CD17CIIII/00017), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades.S

Impact of flour fortification with calcium on calcium intake: a simulation study in seven countries

Calcium intake is low in many countries, especially in low-income countries. Our objective was to perform a simulation exercise on the impact, effectiveness, and safety of a flour fortification strategy using the Intake Modelling, Assessment, and Planning Program. Modeling of calcium fortification scenarios was performed with available dietary intake databases from Argentina, Bangladesh, Italy, the Lao People's Democratic Republic (Lao PDR), Uganda, Zambia, and the United States. This theoretical exercise showed that simulating a fortification with 156 mg of calcium per 100 g of flour would decrease the prevalence of low calcium intake, and less than 2% of the individuals would exceed the recommended calcium upper limit (UL) in Argentina, Italy, Uganda, and Zambia. Bangladesh and the Lao PDR showed little impact, as flour intake is uncommon. By contrast, in the United States, this strategy would lead to some population groups exceeding the UL. This exercise should be replicated and adapted to each country, taking into account the updated prevalence of calcium inadequacy, flour consumption, and technical compatibility between calcium and the flour-type candidate for fortification. A fortification plan should consider the impact on all age groups to avoid the risk of exceeding the upper levels of calcium intake.Fil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Universidad Nacional de La Matanza; ArgentinaFil: Betrán, Ana Pilar. Organizacion Mundial de la Salud; ArgentinaFil: Romero, Iris Beatriz. Universidad Nacional de La Matanza; ArgentinaFil: García Casal, María de las Nieves. Organizacion Mundial de la Salud; ArgentinaFil: Perez, Surya Macarena. Universidad Nacional de La Matanza; ArgentinaFil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin

Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins

The B and T lymphocytes of the adaptive immune system are important for the control of most viral infections, including COVID-19. Identification of epitopes recognized by these cells is fundamental for understanding how the immune system detects and removes pathogens, and for antiviral vaccine design. Intriguingly, several cross-reactive T lymphocyte epitopes from SARS-CoV-2 with other betacoronaviruses responsible for the common cold have been identified. In addition, antibodies that cross-recognize the spike protein, but not the nucleoprotein (N protein), from different betacoronavirus have also been reported. Using a consensus of eight bioinformatic methods for predicting B-cell epitopes and the collection of experimentally detected epitopes for SARS-CoV and SARS-CoV-2, we identified four surface-exposed, conserved, and hypothetical antigenic regions that are exclusive of the N protein. These regions were analyzed using ELISA assays with two cohorts: SARS-CoV-2 infected patients and pre-COVID-19 samples. Here we describe four epitopes from SARS-CoV-2 N protein that are recognized by the humoral response from multiple individuals infected with COVID-19, and are conserved in other human coronaviruses. Three of these linear surface-exposed sequences and their peptide homologs in SARS-CoV-2 and HCoV-OC43 were also recognized by antibodies from pre-COVID-19 serum samples, indicating cross-reactivity of antibodies against coronavirus N proteins. Different conserved human coronaviruses (HCoVs) cross-reactive B epitopes against SARS-CoV-2 N protein are detected in a significant fraction of individuals not exposed to this pandemic virus. These results have potential clinical implications.This research was supported by grants from COV20_00679 (MPY 222-20), to M.J.M., MPY 509/19 to A.J.M.-G. and MPY 388/18 to D.L. of “Acción Estratégica en Salud” from the ISCIII.S

Further Characterization of the Electrogenicity and pH Sensitivity of the Human Organic Anion-Transporting Polypeptides OATP1B1 and OATP1B3

Organic anion-transporting polypeptides (OATPs) are involved in the liver uptake of many endogenous and xenobiotic compounds, such as bile acids and drugs, respectively. Using Xenopus laevis oocytes and Chinese hamster ovary (CHO) cells expressing rat Oatp1a1, human OATP1B1, or OATP1B3, the sensitivity of these transporters to extracellular/intracellular pH (pHo/pHi) and changes in plasma membrane potential (ΔΨ) was investigated. In X. laevis oocytes, nonspecific plasma membrane permeability increased only at pHo below 4.5. Above this value, both using oocytes and CHO cells, extracellular acidification affected differently the specific transport of taurocholic acid (TCA) and estradiol 17β-d-glucuronide (E217βG) by Oatp1a1 (stimulation), OATP1B1 (inhibition), and OATP1B3 (stimulation). Changes in substrate uptake in the presence of valinomycin (K+-ionophore), carbonyl cyanide 3-chlorophenylhydrazone and nigericin (protonophores), and amiloride (Na+/H+-inhibitor) and cation replacement in the medium were studied with fluorescent probes for measuring substrate uptake (cholylglycyl amidofluorescein) and changes in pHi (SNARF-4F) and ΔΨ [DilC1(5)]. The results suggest that activity of these three carriers is sodium/potassium-independent and affected differently by changes in pHo and ΔΨ: Oatp1a1 was confirmed to be an electroneutral anion exchanger, whereas the function of both OATP1B1 and OATP1B3 was markedly affected by the magnitude of ΔΨ. Moreover, electrophysiological measurements revealed the existence of a net anion influx associated to OATP1B1/OATP1B3-mediated transport of TCA, E217βG, and estrone-3-sulfate. Furthermore, a leakage of Na+ through OATP1B1 and OATP1B3, which is not coupled to substrate transport, was found. In conclusion, these results suggest that OATP1B1 and OATP1B3 are electrogenic transporters whose activity may be strongly affected under circumstances of displacement of local pH

Borderline personality traits mediate the relationship between low perceived social support and non-suicidal self-injury in a clinical sample of adolescents

Altres ajuts: Acord transformatiu CRUE-CSICNon-suicidal self-injury (NSSI) is a serious public health concern among adolescents, especially in clinical settings. Social support plays a critical role in the onset and maintenance of NSSI in adolescence. NSSI is closely associated with borderline personality disorder (BPD), yet no previous work has analyzed the mediating role of borderline traits in the relationship between perceived social support (PSS) and NSSI. This study aimed to address this gap