Ofatumumab as part of reduced intensity conditioning in high risk B-cell lymphoma patients: final long-term analysis from a prospective multicenter Phase-II Trial.

Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.

Evolving Risk Classifications in AML in a Real-Life Scenario: After Changes upon Changes, Is It More and More Adverse?

Acute myeloid leukemia (AML) is a heterogeneous disease classified into three risk categories (favorable, intermediate and adverse) with significant differences in outcomes. Definitions of risk categories evolve overtime, incorporating advances in molecular knowledge of AML. In this study, we analyzed the impacts of evolving risk classifications in 130 consecutive AML patients in a single-center real-life experience. Complete cytogenetic and molecular data were collected using conventional qPCR and targeted Next Generation Sequencing (NGS). Five-year OS probabilities were consistent among all classification models (roughly 50-72%, 26-32% and 16-20% for favorable, intermediate and adverse risk groups, respectively). In the same way, the medians of survival months and prediction power were similar in all models. In each update, around 20% of patients were re-classified. The adverse category consistently increased over time (31% in MRC, 34% in ELN2010, 50% in ELN2017), reaching up to 56% in the recent ELN2022. Noteworthily, in multivariate models, only age and the presence of TP53 mutations remained statistically significant. With updates in risk-classification models, the percentage of patients assigned to the adverse group is increasing, and so will the indications for allogeneic stem cell transplantation.

Corrigendum: Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines.

[This corrects the article DOI: 10.3389/fimmu.2022.986823.].

Suitability of potyviral recombinant virus-like particles bearing a complete food allergen for immunotherapy vaccines.

Virus-like particles (VLPs) have been gaining attention as potential platforms for delivery of cargos in nanomedicine. Although animal viruses are largely selected due to their immunostimulatory capacities, VLPs from plant viruses constitute a promising alternative to be considered. VLPs derived from Turnip mosaic virus (TuMV) have proven to present a tridimensional structure suited to display molecules of interest on their surface, making them interesting tools to be studied in theragnostic strategies. Here, we study their potential in the treatment of food allergy by genetically coupling TuMV-derived VLPs to Pru p 3, one of the most dominant allergens in Mediterranean climates. VLPs-Pru p 3 were generated by cloning a synthetic gene encoding the TuMV coat protein and Pru p 3, separated by a linker, into a transient high-expression vector, followed by agroinfiltration in Nicotiana benthamiana plants. The generated fusion protein self-assembled in planta to form the VLPs, which were purified by exclusion chromatography. Their elongated morphology was confirmed by electron microscopy and their size (~400 nm), and monodispersity was confirmed by dynamic light scattering. Initial in vitro characterization confirmed that they were able to induce proliferation of human immune cells. This proliferative capability was enhanced when coupled with the natural lipid ligand of Pru p 3. The resultant formulation, called VLP-Complex, was also able to be transported by intestinal epithelial cells, without affecting the monolayer integrity. In light of all these results, VLP-Complex was furtherly tested in a mouse model of food allergy. Sublingual administration of VLP-Complex could effectively reduce some serological markers associated with allergic responses in mice, such as anti-Pru p 3 sIgE and sIgG2a. Noteworthy, no associated macroscopic, nephritic, or hepatic toxicity was detected, as assessed by weight, blood urea nitrogen (BUN) and galectin-3 analyses, respectively. Our results highlight the standardized production of allergen-coated TuMV-VLPs in N. benthamiana plants. The resulting formula exerts notable immunomodulatory properties without the need for potentially hazardous adjuvants. Accordingly, no detectable toxicity associated to their administration was detected. As a result, we propose them as good candidates to be furtherly studied in the treatment of immune-based pathologies.

Antitumor applications of polyphenol-conjugated turnip mosaic virus-derived nanoparticles.

Background: Filamentous plant virus-derived nanoparticles are biodegradable and noninfectious to humans. Their structure is also amenable to chemical modifications. They constitute an appealing material for biomedical applications including imaging and drug delivery. We had previously used turnip mosaic virus-derived nanoparticles (TuMV-NPs) to increase antibody-sensing in vivo, to prevent biofilm formation and to build biological nanoscaffolds. Materials & methods: We analyzed TuMV-NP biodistribution and tumor homing using in vivo imaging. We studied in vitro the interaction with human cancer cell lines and the antiproliferative effect of epigallocatechin gallate-functionalized TuMV-NPs. Results & conclusion: TuMV-NPs are efficiently internalized by human cells and show good tumor homing. The antiproliferative effect of epigallocatechin gallate-TuMV-NPs suggests that they could offer a potential anticancer therapy.

Cancer is the second leading cause of death worldwide, just behind cardiovascular disease. It accounts for nearly 10 million deaths annually, and new strategies to improve early detection and drug delivery are urgently needed. Nanoparticles are small structures within the nanometer range (1 billionth of a meter) that can be used to deliver either an imaging probe (tracer) to allow the detection of a tumor or drugs to kill tumor cells. There are many types of nanoparticles; those based on plant viruses are especially appealing for biomedical purposes because they are biodegradable and noninfectious to humans. Also, their physicochemical properties, such as symmetry, uniformity and loading capacity, make them excellent nanocarriers. We report here for the first time the ability of nanoparticles derived from the turnip mosaic virus (TuMV), a well-known virus naturally infecting cruciferous plants (e.g., broccoli, turnip, radish, cabbage) but not humans, to deliver a fluorescent imaging probe that allows tumor detection in vivo. Moreover, TuMV nanoparticles were used to deliver a natural chemotherapeutic agent of plant origin to different types of tumor cells (lung, colorectal, breast, and head and neck), showing increased antiproliferative capacity compared to the nonvehiculized drug.

Nursing students faced with organ donation: Multicenter stratified national study.

AIM: To analyze the attitude of university nursing students at Spanish universities toward organ donation and transplantation and the factors affecting to their attitude. BACKGROUND: The opinion of future nurses toward organ transplant donation could have an important influence on the population. Knowing that opinion and what factors influence it is important to improve the attitude towards organ donation and transplantation. DESIGN: A multicenter, sociological, interdisciplinary and observational study including university nursing diploma students in a complete academic year. METHODS: Selected and randomized sample was taken of students from 52 of the 111 faculties and nursing schools and faculties in Spain with teaching activity PARTICIPANTS: A sample of 10,566 students was selected stratified by geographical area and year. MEASUREMENT INSTRUMENT: The instrument used was a validated questionnaire of attitude toward organ donation and transplantation, self-administered and completed anonymously. RESULTS: Completion rate: 85 % (n = 9001). Of the students surveyed, 78 % (n = 7040) would donate their organs after dying. Variables related to a favourable attitude: (1) Interest in listening to a talk about organ donation and transplantation [Odds ratio 1.66, 95 % confidence interval 2.05-1.35]; (2) Family discussion [Odds ratio 2.30, 95 % confidence interval 2.79-1.90] or discussion with friends about organ donation and transplantation [Odds ratio 1.56, 95 % confidence interval 1.86-1.31]; (3) Knowing that one's father [Odds ratio 1.54, 95 % confidence interval 1.94-1.22], mother's [Odds ratio 1.44, 95 % confidence interval 1.82-1.13] or partner [Odds ratio 1.28, 95 % confidence interval 1.60-1.03] has a favourable opinion; (4) Having a good self-assessment of information about organ donation and transplantation [Odds ratio 2.94, 95 % confidence interval 4.90-1.78]; (5) Not being worried about possible mutilation of the body after donation [Odds ratio 2.73, 95 % confidence interval 3.36-1.72]. CONCLUSIONS: Nursing students in Spain tend to have a favourable attitude toward organ donation and transplantation although more than 20 % of those surveyed are not in favour. TWEETABLE ABSTRACT: To maintain a high rate of organ donation for organ transplantation, it is necessary to improve the social awareness of future generations of nurses towards organ donation.

Mediational Effect of Fairburn's Transdiagnostic Mechanisms Between Attachment to the Mother and Eating Disorder Symptoms in a Clinical Sample.

Objective: Research has supported a link between insecure attachment and eating disorders (EDs); however, little is known about how this influence is exerted in young female EDs patients. This study tested, for the first time, a multiple mediational model, wherein the four Fairburn's transdiagnostic mechanisms mediated the relationship between attachment to the mother and ED symptoms. Methods: A total of 101 female young EDs patients aged 15-24 were administered the Inventory of Parent and Peer Attachment, Eating Disorder Inventory-3 and Eating Attitudes Test-26 to assess attachment, the four transdiagnostic maintaining mechanisms and ED symptoms, respectively. Results: Comparison analyses showed that there were no significant differences between the diagnostic groups in terms of attachment and the transdiagnostic variables. Multiple mediational analyses indicated that low self-esteem and clinical perfectionism were significant mediators between insecure attachment to the mother and ED symptoms, while controlling for depressive symptoms. Conclusion: These findings suggest that the distal risk influence of insecure attachment to the mother in the development of ED symptoms might be explained by low self-esteem and high clinical perfectionism, controlling for depressive symptoms. Further investigation into the efficacy of cognitive-behavioral treatments targeting insecure attachment representations for young EDs patients is recommended.

Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience.

Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7-66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years' survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.

Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC.

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy. Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249). Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar. Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors. Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival. © 2022 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Regulatory mechanisms of mitochondrial BKCa channels.

The mitochondrial BKCa channel (mitoBKCa) is a splice variant of plasma membrane BKCa (Maxi-K, BKCa, Slo1, KCa1.1). While a high-resolution structure of mitoBKCa is not available yet, functional and structural studies of the plasma membrane BKCa have provided important clues on the gating of the channel by voltage and Ca2+, as well as the interaction with auxiliary subunits. To date, we know that the control of expression of mitoBKCa, targeting and voltage-sensitivity strongly depends on its association with its regulatory ß1-subunit, which overall participate in the control of mitochondrial Ca2+-overload in cardiac myocytes. Moreover, novel regulatory mechanisms of mitoBKCa such as ß-subunits and amyloid-ß have recently been proposed. However, major basic questions including how the regulatory BKCa-ß1-subunit reaches mitochondria and the mechanism through which amyloid-ß impairs mitoBKCa channel function remain to be addressed.

Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish hematopoietic transplantation and cell therapy group.

The potential role of active CMV infection in promoting acute Graft-versus-Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real-time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%-52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%-50.1%), and of grade II-IV aGvHD, 30.7 (95% CI, 24.9%-36.4%). Overall, development of CMV DNAemia at any level resulted in an increased risk of subsequent all grade (HR, 1.38; 95% CI, 1.08 - 1.76; P = .009) or grade II-IV (HR, 1.58; 95% CI, 1.22 - 2.06; P = .001) aGvHD. The increased risk of aGvHD linked to prior occurrence of CMV DNAemia was similar to the above when only clinically significant episodes were considered for the analyses (HR for all grade aGvHD, 1.48; 95% CI, 1.13 - 1.91; P = .041, and HR for grade II-IV aGvHD, 1.53; 95% CI. 1.13-1.81; P = .04). The CMV DNA doubling time in blood was comparable overall in episodes of CMV DNAemia whether followed by aGvHD or not. Whether CMV replication is a surrogate risk marker of aGvHD or it is causally involved is an important question to be addressed in future experimental research.

Consumo de alimentos ultraprocesados y obesidad: una revisión sistemática / Ultra-processed food consumption and obesity-a systematic review

INTRODUCCIÓN Y OBJETIVO: cada vez son más numerosos los estudios que relacionan el consumo de alimentos ultraprocesados con la prevalencia de la obesidad. Esta clase de alimentos se caracteriza porque aportan gran cantidad de azúcares libres y grasas saturadas, lo que contribuye a aumentar la ingesta energética. En las últimas décadas, el consumo de estos alimentos ha aumentado hasta el punto de convertirse en una importante fuente de energía diaria en algunas poblaciones. De esta manera se desplazan los alimentos ricos en fibra, hidratos de carbono complejos y grasas beneficiosas para la salud que pertenecen a los patrones de alimentación saludables. El objetivo de esta revisión sistemática fue recopilar la información existente en la literatura sobre la relación entre alimentos ultraprocesados y obesidad. MATERIAL Y MÉTODOS: se realizó una revisión sistemática en la base de datos PubMed. Se siguieron los criterios PRISMA para identificar los artículos publicados desde el año 2000 hasta abril de 2020 que cumplían los siguientes criterios: eran artículos originales (en inglés o español), realizados en sujetos humanos y excluyendo a mujeres embarazadas. La búsqueda se realizó utilizando los términos "Ultra-processed food and obesity" y "ultra-processed food and overweight", de manera que se incluyeron un total de 12 artículos: 7 estudios transversales, 3 estudios prospectivos de cohortes y 2 estudios ecológicos. RESULTADOS: se encontró una asociación positiva entre el consumo de ultraprocesados y la obesidad en 9 de los 12 artículos incluidos en la revisión. Sin embargo, existen limitaciones con respecto a la heterogeneidad de las metodologías de los diversos estudios o la utilización de distintos sistemas de clasificación de alimentos en función del grado de procesamiento. CONCLUSIÓN: es necesario realizar más estudios que permitan establecer con mayor evidencia la relación entre el consumo de ultraprocesados y la prevalencia e incidencia de la obesidad

BACKGROUND AND OBJECTIVES: a number of studies suggest a relationship between the intake of ultra-processed foods and the prevalence of obesity. Specifically, this type of food provides large amounts of free sugars and saturated fats, which contribute to a high energy intake. In the last few decades, consumption of these products has increased to the point of representing an important amount of calories in the daily diet of several populations. As a result, foods that are usually consumed in healthy eating patterns containing fiber, complex carbohydrates and fats are displaced. This systematic review aimed to compile the information in the literature, and to examine the scientific evidence about the relationship between ultra-processed food and obesity. MATERIAL AND METHODS: a systematic review was performed of the PubMed database. PRISMA criteria were applied to identify those papers published from 2000 to April 2020 that met the following criteria: original articles (in English or Spanish), dealing with research in human subjects, with exclusion of pregnant women. The search was performed using the terms "ultra-processed food and obesity" and "ultra-processed food and overweight", which resulted in a total of 12 references: 7 cross-sectional studies, 3 prospective cohort studies, and 2 ecological studies. RESULTS: a positive association was found between ultra-processed food consumption and obesity in 9 of the 12 papers included in the review. However, limitations exist regarding the heterogeneity of methodologies or use of different food classification systems according to processing degree. CONCLUSION: further studies are needed to establish the relationship between ultra-processed food consumption and the prevalence and incidence of obesity

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group.

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.

[Ultra-processed food consumption and obesity-a systematic review]. / Consumo de alimentos ultraprocesados y obesidad: una revisión sistemática.

INTRODUCTION: A number of studies suggest a relationship between the intake of ultra-processed foods and the prevalence of obesity. Specifically, this type of food provides large amounts of free sugars and saturated fats, which contribute to a high energy intake. In the last few decades the consumption of these products has increased to the point of representing an important amount of calories in the daily diet of several populations. As a result, foods that are usually consumed in healthy eating patterns, containing fiber, complex carbohydrates, and good fats, have been displaced. This systematic review aims to compile the information available in the literature, and to examine the scientific evidence about the relationship between ultra-processed food and obesity. Nevertheless, there are a number of limitations due to the heterogeneity of the methodologies or food classification systems used in the different studies, which makes it difficult to draw definitive conclusions on the relationship between consumption of ultra-processed food and development of obesity.

INTRODUCCIÓN: Cada vez son más numerosos los estudios que relacionan el consumo de alimentos ultraprocesados con la prevalencia de la obesidad. Esta clase de alimentos se caracteriza porque aportan gran cantidad de azúcares libres y grasas saturadas, lo que contribuye a aumentar la ingesta energética. En las últimas décadas, el consumo de estos alimentos está aumentado hasta el punto de convertirse en una importante fuente de energía diaria en algunas poblaciones. De esta manera, resultan desplazados alimentos ricos en fibra, hidratos de carbono complejos y grasas beneficiosas para la salud que pertenecen a patrones de alimentación saludables. Esta revisión sistemática se propone recopilar la información existente en la literatura sobre la relación entre alimentos ultraprocesados y obesidad. Sin embargo, hay que reconocer que existen limitaciones con respecto a la heterogeneidad de las metodologías empleadas en los diversos estudios o la utilización de distintos sistemas de clasificación de alimentos en función del grado de procesamiento, lo que dificulta el establecimiento, de manera definitiva, de una asociación entre el consumo de ultraprocesados y el desarrollo de obesidad.

Clinical outcomes of allogeneic hematopoietic stem cell transplant recipients developing Cytomegalovirus DNAemia prior to engraftment.

There is limited information on the impact of CMV DNAemia episodes developing prior to engraftment (pre-CMV DNAemia) on clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This issue was addressed in the current retrospective multicenter study including 878 patients. All participant centers used preemptive antiviral therapy strategies for prevention of CMV disease. CMV DNA load in blood was monitored by real-time PCR assays. A total of 144 patients (cumulative incidence 16.5%, 95% CI, 14%-19%) had an episode of pre-CMV DNAemia at a median of 10 days after allo-HSCT. Patients who developed pre-CMV DNAemia had a significantly higher (P = < 0.001) probability of recurrent episodes (50%) than those who experienced post-CMV DNAemia (32.9%); Nevertheless, the incidence of CMV disease was comparable (P = 0.52). Cumulative incidences of overall mortality (OM) and non-relapse mortality (NRM) at 1-year after allo-HSCT were 32% (95% CI, 29-35%) and 23% (95% CI 20-26%), respectively. The risk of OM and NRM in adjusted models appeared comparable in patients developing a single episode of CMV DNAemia, regardless of whether it occurred before or after engraftment, in patients with pre- and post-engraftment CMV DNAemia episodes or in those without CMV DNAemia.

Maternal immune response in the placenta of sheep during recrudescence of natural congenital infection of Neospora caninum.

In order to gain further insight into the pathogenesis and transmission of ovine neosporosis, the serological response of 13 naturally infected pregnant sheep was monitored. All sheep were euthanized upon the detection of a sharp increase in the level of specific antibodies against N. caninum in order to study the maternal immune response after the recrudescence of a chronic infection. Ten sheep were euthanized between 84 and 118 days of gestation, whereas the three remaining and three control not infected, pregnant sheep were euthanized at 135 days of gestation after no sharp increase in antibodies was detected. Vertical transmission was confirmed in 11 sheep by detection of N. caninum-DNA in at least one fetus, confirming recrudescence. Not all of fetuses showed pathologic microscopic lesions, however, multifocal non-purulent encephalitis was the main finding. Furthermore, nine out of the 11 vertical transmission positive sheep had lesions in placentomes (mainly multifocal necrotic foci), and the parasite was detected in eight out of 11 placentas by PCR and/or immunohistochemestry. The placentomes from sheep that suffered recrudescence showed an increased number of T lymphocytes CD3+ (CD4/CD8 < 1) and macrophages (MHC-II+), assessed by immunohistochemestry, together with an up-regulation of IFN-γ, IL-10, IL-4, TNFα, IL-2 and IL-18. IL-17 was only upregulated in the three infected sheep that did not have a sharp increase in antibody levels. In the sheep that showed fetal death at the time of euthanasia (n = 3) the placental microscopic lesions were more severe, the inflammatory infiltrate was higher, and the upregulation of cytokines was greater than in those sheep carrying viable fetuses. This study suggests that, similarly to bovine neosporosis, the time of gestation when recrudescence occurs determines the viability of the fetuses and, thus, seems to be related to the severity of lesions and immune response in the placenta. These results suggest that there might be a correlation, either as cause or as a consequence, between protection against vertical transmission of the parasite and a milder maternal serological response together with a high level of transcription of IL-17 in the placenta.

Turnip Mosaic Virus Coat Protein Deletion Mutants Allow Defining Dispensable Protein Domains for 'in Planta' eVLP Formation.

The involvement of different structural domains of the coat protein (CP) of turnip mosaic virus, a potyvirus, in establishing and/or maintaining particle assembly was analyzed through deletion mutants of the protein. In order to identify exclusively those domains involved in protein-protein interactions within the particle, the analysis was performed by agroinfiltration "in planta", followed by the assessment of CP accumulation in leaves and the assembly of virus-like particles lacking nucleic acids, also known as empty virus-like particles (eVLP). Thus, the interactions involving viral RNA could be excluded. It was found that deletions precluding eVLP assembly did not allow for protein accumulation either, probably indicating that non-assembled CP protein was degraded in the plant leaves. Deletions involving the CP structural core were incompatible with particle assembly. On the N-terminal domain, only the deletion avoiding the subdomain involved in interactions with other CP subunits was incorporated into eVLPs. The C-terminal domain was shown to be more permissive to deletions. Assembled eVLPs were found for mutants, eliminating the whole domain. The C-terminal domain mutants were unusually long, suggesting some role of the domain in the regulation of particle length. The identification of the CP domains responsible for eVLP formation will allow for new approaches to protein stretch replacement with peptides or proteins of nanobiotechnological interest. Finally, specific cases of application are considered.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

Smoking in nursing students: A prevalence multicenter study.

The role of nursing students as future health promoters of healthy behaviors is influenced by their attitude towards smoking. A cross-sectional study using a self-administered survey was performed to analyze smoking prevalence among undergraduate the nursing students who attend nursing faculties in 2 European countries (Spain and Portugal) during academic period 2015 to 2016. A total of 1469 subjects were surveyed (response rate of 79.8%). An 80% of the students were female with a mean age of 21.9 (4.8) years. The overall prevalence of tobacco use was 18.9%, with an average percentage of 16.2% in Portugal and 18.3% in Spain. Statistical significance was observed in relation to smoke and previous studies (16.4% vs 27.1%; P < .001). Only 1.1% of the students reported using electronic cigarette. 15.8% of smokers started smoking while at university with statistical gender and previous studies differences (P < .001). Fagerström and Richmond test showed low nicotine dependence (2.8 ±â€Š2) and moderate motivation to stop smoking (4.9 ±â€Š3), respectively. Smoking prevalence among nursing students was slightly higher than the general European population. For that reason, measures to reduce tobacco use have to be focused on students and university policies on tobacco control should be a challenge in the future.

Exploring Health Science Students' Notions on Organ Donation and Transplantation: A Multicenter Study.

The knowledge acquired during university education about organ donation and transplantation (ODT) decisively influences the information future health professionals transmit. This is important in ODT where the participation of the general public is essential to obtain organs. OBJECTIVE: To determine notions of Spanish medicine and nursing students on ODT and its relationship with attitude toward ODT. METHODS AND DESIGN: and design. We conducted a sociologic, multicenter, and observational study. The population for our study consisted of medical and nursing students in Spanish universities. Our database was the Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. Our sample consisted of 9598 medical and 10,566 nursing students (99% confidence interval; precision of ±1%), stratified by geographic area and year of study. RESULTS: The completion rate for our study was 90%. Only 20% (n=3640) of students thought their notions on ODT were good; 41% (n=7531) thought their notions were normal; 36% (n=6550) thought their notions were scarce. Comparing groups, there were differences between those who believed that their notions on ODT were good (44% nursing vs 56% medical students; P < .000), and those who believed it scarce (54% nursing vs 46% medical students; P < .000). Notions on ODT were related with attitude toward the donation of one's own organs: those who considered their notions were good were more in favor then those who considered it scarce (88% vs 72%; P < .000). CONCLUSION: Only 20% of Spanish medical and nursing students thought their notions on ODT were good. Having good knowledge is related to a favorable attitude towards ODT. Receiving specific information on the subject could improve their knowledge about ODT during their training.