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The current World Health Organization (WHO) classification of central nervous system (CNS) tumours includes several neoplasms that, while occurring in this location, are more frequently seen extracranially. These include mesenchymal, melanocytic and haematolymphoid neoplasms, as well as metastases. A few of these entities are exclusive of the CNS and have no extracranial counterpart. Despite their diverse histogenesis, these neoplasms share a peculiar predilection for involving meningeal structures. In fact, in the context of an intraoperative pathologic consultation of a meningeal tumour, virtually all these entities should be considered as potential diagnoses. Metastases in the CNS are very common. Most are carcinomas that cytologically resemble their site of origin. Loss of differentiation with cell dissociation and anaplasia and presence of accompanying fibrillary brain parenchyma can be a source of diagnostic problems. In this review, we intend to show the most relevant cytologic features of these tumours, and it is especially aimed at their analysis during intraoperative studies., (© 2023 John Wiley & Sons Ltd.)

Despite common histogenesis meningiomas have a wide morphologic spectrum, and the World Health Organization (WHO) recognizes 15 subtypes. They are the most common brain tumour in adults and typically have an extra-axial location. Although there have been important advances in the molecular biology of meningiomas its diagnosis is based on histopathologic features. The great majority are benign WHO grade 1 tumours. There are specific criteria for assigning WHO grade 2 and 3 that can be applied to all meningioma subtypes. Regardless of these criteria, chordoid and clear cell morphologic subtypes are considered grade 2. WHO grade 3 tumours exhibit a very high mitotic index, frank anaplasia or specific molecular abnormalities. The impressive morphologic diversity shown by meningiomas makes them a diagnostic challenge, which can be even greater in intraoperative studies. The focus of this article is to describe and illustrate their main cytologic features, with emphasis on the most infrequent subtypes., (© 2023 John Wiley & Sons Ltd.)

The expanding presence of red foxes ( Vulpes vulpes ) in urban and suburban regions could potentially lead to increased instances of human aggression towards this species. We studied 10 deceased red foxes that were submitted by law enforcement agencies in the metropolitan area of Madrid in 2014-2022 because of suspected abuse. Forensic autopsies were performed to establish the cause and manner of death. In 4 of the 10 cases, the cause of death was deemed unnatural, involving blunt-force trauma ( n  = 2), asphyxia resulting from hanging ( n  = 1), and firearm injury ( n  = 1). Among the remaining cases, most had succumbed to natural causes ( n  = 4), often marked by severe emaciation and a high burden of parasites, primarily Sarcoptes scabiei . In 2 cases, death was undetermined given the poor preservation of the carcass. The growing prevalence of wildlife species in urban areas, particularly red foxes, may require forensic veterinary investigation of deaths potentially related to abuse., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this paper.

Background: Errors in the pre-analytical phase of the microbiology laboratory reduce patient safety and generate additional expenses. In Mexico we do not have systems for evaluation and monitoring of the pre-analytical phase; quality indicators are proposed for continuous improvement., Objective: Identify the main reasons for rejection of respiratory samples in the microbiology laboratory and evaluate the usefulness of preanalytical quality indicators., Material and Methods: Cross-sectional study. Review of microbiology laboratory applications from August 2022 to July 2023, calculated the frequency of rejection and identification of the main reasons for it, it was analyzed using quality indicators based on the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)., Results: Of 3530 processing requests, 582 were for respiratory samples (16.48%), 44 samples rejected due to pre-analytical errors (7.56%), the main causes identified: Transcription error 22.7%, identification error 20.4%, Samples that do not comply Murray-Washington criteria 25.0%, Errors in obtaining/collecting samples 20.4%, Samples with defects in conservation 4.5%, Unidentified samples: 6.8., Conclusions: The main causes of rejection were identified; upon analysis with the preanalytical quality indicators, they were found at desirable levels and in reference ranges; only 4 were useful for long-term implementation., (Licencia CC 4.0 (BY-NC-ND) © 2024 Revista Médica del Instituto Mexicano del Seguro Social.)

Undifferentiated anaplastic thyroid tumours are uncommon and constitute a diagnostic challenge on fine needle aspiration. A case showing large, single neoplastic cells in a background of Hashimoto's disease is presented., (© 2023 John Wiley & Sons Ltd.)

COL1A1-PDGFB gene fusion uterine sarcoma is a recently described entity which shows some overlapping features with dermatofibrosarcoma protuberans. To date, only 4 cases have been reported in the literature. Due to its rarity, succinct clinicopathologic characteristics are yet to be established. We report a fifth case initially mistaken as a uterine fibroid which histologically proved to be a CD34 + high-grade spindle cell proliferation which on fluorescence in situ hybridization analysis displayed COL1A1-PDGFB gene rearrangement. With this case description we hope to raise awareness and aid in the characterization of this emerging entity., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 by the International Society of Gynecological Pathologists.)

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL), the most frequent non-Hodgkin's lymphoma subtype, is characterized by strong biological, morphological, and clinical heterogeneity, but patients are treated with immunochemotherapy in a relatively homogeneous way. Here, we have used a customized NanoString platform to analyze a series of 197 homogeneously treated DLBCL cases. The platform includes the most relevant genes or signatures known to be useful for predicting response to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) in DLBCL cases. We generated a risk score that combines the International Prognostic Index with cell of origin and double expression of MYC/BCL2 , and stratified the series into three groups, yielding hazard ratios from 0.15 to 5.49 for overall survival, and from 0.17 to 5.04 for progression-free survival. Group differences were highly significant ( p  < 0.0001), and the scoring system was applicable to younger patients (<60 years of age) and patients with advanced or localized stages of the disease. Results were validated in an independent dataset from 166 DLBCL patients treated in two distinct clinical trials. This risk score combines clinical and biological data in a model that can be used to integrate biological variables into the prognostic models for DLBCL cases., Competing Interests: M.A.P. declares having received lecture fees and advisory board fees from Millennium/Takeda, Jansen, NanoString, Kyowa Kirin, Gilead, and Celgene.The authors declare that they have no significant relationships with, or financial interests, in any commercial companies pertaining to this article., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Legislation regulating Spanish and European academic curricula prescribes a certain level of knowledge and skills any student must master. Spanish universities freely decide the number of credits assigned to each subject and in which year the subject will be taught. We hypothesize that this flexibility may give way to excessively heterogeneous training across universities in nursing degrees. Such curricula heterogeneity hinders inter-university transfers and weakens educational excellence., Objectives: 1) To review the existing differences in nursing degrees in Spanish universities; 2) to compare our results against current legislation; 3) to propose changes in the legislation, if necessary., Design: Mixed-methods approach., Setting: Spain., Methods: We reviewed nursing degree curricula of all 60 Spanish universities. Inter-university differences were analyzed and checked against current legislation. A focus group proposed legislative changes accordingly., Results: Several differences between public and private universities were statistically significant. During the first cycle, public universities´ course loads include more theoretical teachings, more credits in core subjects during the first year, and more compulsory subjects in second year. Private universities are more likely to offer external internships during the first cycle whereas the public ones are more likely to offer them during the second cycle. Public universities offer more credits under the following curricular blocks than private ones: "Nutrition/Dietetics," "Psychiatry," "Public and Community Health," and "Geriatrics." In turn, private universities offer more credits in the areas of "Theory/Methodology," "Ethics/Legislation," "English," and "Theology." Academic curricula meet most of the criteria established by the Spanish and European legislation. The proposed legislative changes aim at standardizing curricula by associating specific credits and their timeline to the teaching blocks., Conclusions: Nursing degree curricula among Spanish universities are highly heterogeneous. Legislative changes to homogenize teaching blocks would facilitate credit validations and student mobility across universities, in addition to increasing nursing degrees´ standardization and excellence., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Peripheral T-cell lymphoma (PTCL) is a clinically aggressive disease, with a poor response to therapy and a low overall survival rate of approximately 30% after 5 years. We have analyzed a series of 105 cases with a diagnosis of PTCL using a customized NanoString platform (NanoString Technologies, Seattle, WA) that includes 208 genes associated with T-cell differentiation, oncogenes and tumor suppressor genes, deregulated pathways, and stromal cell subpopulations. A comparative analysis of the various histological types of PTCL (angioimmunoblastic T-cell lymphoma [AITL]; PTCL with T follicular helper [TFH] phenotype; PTCL not otherwise specified [NOS]) showed that specific sets of genes were associated with each of the diagnoses. These included TFH markers, cytotoxic markers, and genes whose expression was a surrogate for specific cellular subpopulations, including follicular dendritic cells, mast cells, and genes belonging to precise survival (NF-κB) and other pathways. Furthermore, the mutational profile was analyzed using a custom panel that targeted 62 genes in 76 cases distributed in AITL, PTCL-TFH, and PTCL-NOS. The main differences among the 3 nodal PTCL classes involved the RHOAG17V mutations (P < .0001), which were approximately twice as frequent in AITL (34.09%) as in PTCL-TFH (16.66%) cases but were not detected in PTCL-NOS. A multivariate analysis identified gene sets that allowed the series of cases to be stratified into different risk groups. This study supports and validates the current division of PTCL into these 3 categories, identifies sets of markers that can be used for a more precise diagnosis, and recognizes the expression of B-cell genes as an IPI-independent prognostic factor for AITL., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

In this study, the effects of co-administration with biscuit flour and fermented defatted "alperujo" (FDA) on gut health were evaluated in a batch of laying hens (Hy-Line 2015) on a commercial farm. Animals were divided into two groups: control group and treatment group; and histological and morphometric analyses of all sections of the intestine (duodenum, jejunum, ileum, cecum and rectum) were performed at 10, 18, 25, 50 and 75 weeks of age. During the whole productive period, a decrease in the mortality rate ( p = 0.01) was observed in treated hens, as well as an increase in the number of eggs produced ( p < 0.001), their size ( p < 0.025), and weight ( p < 0.024). In the early and late stages of production (10, 18 and 50 weeks), a significant increase ( p < 0.001) in the height and depth of the intestinal villi was observed in the treatment group. Villi height was also significantly higher ( p < 0.001) in the treatment group up to week 50 in the cecum, and at weeks 18 and 50 in the rectum. We concluded that an economical and sustainable feeding system with less environmental impact, such as co-supplementation with biscuit flour and FDA, could maintain gut health without negatively impacting laying hens' productive performance.

Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.

Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.

Background: Neoplasms from the ventricular system share a common location but have highly variable histogenesis. Many are slowly growing tumors that behave in a benign fashion. They can be classified as primary and secondary tumors. The most common primary tumors are ependymomas, subependymomas, subependymal giant cell astrocytomas, central neurocytomas, choroid plexus tumors, meningiomas, germinomas, pineal parenchymal tumors, papillary tumors of the pineal region, chordoid gliomas, rosette-forming glioneuronal tumors of the fourth ventricle, and craniopharyngiomas. Pilocytic astrocytomas, medulloblastomas, and atypical teratoid/rhabdoid tumors often show secondary involvement of the ventricular system., Summary: Advances in neurosurgery have facilitated access to the ventricular system increasing the number of cases in which such tumors can be biopsied. In this context, cytology has been proven to be an extremely useful diagnostic tool during intraoperative pathologic consultations. Many ventricular tumors are infrequent, and the cytologic information available is limited. In this review, we describe the cytologic features of the uncommon ventricular tumors and report on unusual findings of the more common ones. For the cytologic evaluation of brain tumors, many neuropathologists prefer formalin fixation and hematoxylin and eosin staining. In this review, we highlight the cytologic findings as seen with Diff-Quik, a very popular staining method among cytopathologists. In fact, when pathologists are unfamiliar with cytology, it is common to request the assistance of cytopathologists during the evaluation of intraoperative procedures. Key Message: Ventricular tumors of the central nervous system comprise a group of heterogeneous tumors with very different cytologic features. The cytomorphology of these tumors, including rare entities, is often very characteristic, allowing a precise recognition during intraoperative pathologic consultations. Diff-Quik is a valuable staining method that can be used alone or as a complement to hematoxylin and eosin staining. Diff-Quik allows for clear visualization of the overall architecture, cytoplasmic details, and extracellular material., (© 2021 S. Karger AG, Basel.)

Companion animal abuse is an issue that concerns not only veterinarians and law enforcement agencies but also society in general. Animals that die under suspicious or violent circumstances should be submitted to reference laboratories for a postmortem examination by veterinary forensic pathologists trained to recognize animal abuse. Nevertheless, the low notification rate of such cases in Spain may explain the country's lag in the development of veterinary forensics and the limited information available on animal abuse epidemiology in comparison with other countries. By sharing information among the entities involved in recognizing animal abuse, we can better address these issues, thus improving veterinary forensics in Spain (and elsewhere). In this study, we analysed the cause and manner of death of 96 dog and cat carcasses suspected of animal abuse. These cases were submitted to our diagnostic laboratory for forensic postmortem examination by public agencies and animal protection centres. To our knowledge, this is the first study to focus on the postmortem analysis of forensic cases of suspected dog and cat abuse in Spain. On the basis of gross and histopathological findings, we distinguished between natural and non-natural abuse-related deaths, classifying the latter. We confirmed that most of the dog deaths were related with abuse, though the suspected abuse and the cause of death did not always coincide. In contrast, cause of death was determined to be natural in many of the cat suspected abuse cases. The most frequent non-natural abuse-related cause of death in dogs was blunt force trauma (n=24, 43.64%), followed by firearm injuries (n=10, 18.18%), asphyxia (n=5, 9.09%), heatstroke (n=3, 5.45%), starvation (n=2, 3.64%), bite injury (n=1, 1.82%), and sharp force trauma (n=1, 1.82%). In cats, the most common cause of death was blunt force trauma (n=9, 21.95%), followed by firearm injuries (n=3, 7.32%) and bite injury (n=2, 4.88%). The main goal of our study is to share our results with the scientific community to advance the field of veterinary forensics in Spain, which will lead to more successful prosecutions by law enforcement agencies. Finally, we highlight that veterinarians who can accurately recognize signs of animal abuse may be able to better respond to cases of companion animal cruelty, which in turn, may prevent possible escalation to interpersonal violence., Competing Interests: Declaration of Competing Interest The author report no declarations of interest., (Published by Elsevier B.V.)

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called "red-to-yellow" transition. Following hematopoietic recovery, such as upon BM transplantation, a "yellow-to-red" transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-μCT) upon osmium-tetroxide lipid staining. Due to user-dependent variables, reproducibility in longitudinal studies is a challenge for both methods. Here we report the development of a semi-automated image analysis plug-in, MarrowQuant , which employs the open-source software QuPath, to systematically quantify multiple bone components in H&E sections in an unbiased manner. MarrowQuant discerns and quantifies the areas occupied by bone, adipocyte ghosts, hematopoietic cells, and the interstitial/microvascular compartment. A separate feature, AdipoQuant , fragments adipocyte ghosts in H&E-stained sections of extramedullary adipose tissue to render adipocyte area and size distribution. Quantification of BM hematopoietic cellularity with MarrowQuant lies within the range of scoring by four independent pathologists, while quantification of the total adipocyte area in whole bone sections compares with volumetric measurements. Employing our tool, we were able to develop a standardized map of BM hematopoietic cellularity and adiposity in mid-sections of murine C57BL/6 bones in homeostatic conditions, including quantification of the highly predictable red-to-yellow transitions in the proximal section of the caudal tail and in the proximal-to-distal tibia. Additionally, we present a comparative skeletal map induced by lethal irradiation, with longitudinal quantification of the "red-to-yellow-to-red" transition over 2 months in C57BL/6 femurs and tibiae. We find that, following BM transplantation, BM adiposity inversely correlates with kinetics of hematopoietic recovery and that a proximal to distal gradient is conserved. Analysis of in vivo recovery through magnetic resonance imaging (MRI) reveals comparable kinetics. On human trephine biopsies MarrowQuant successfully recognizes the BM compartments, opening avenues for its application in experimental, or clinical contexts that require standardized human BM evaluation., (Copyright © 2020 Tratwal, Bekri, Boussema, Sarkis, Kunz, Koliqi, Rojas-Sutterlin, Schyrr, Tavakol, Campos, Scheller, Sarro, Bárcena, Bisig, Nardi, de Leval, Burri and Naveiras.)

Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), a cerebrovascular condition with occlusive lesions and compensatory angiogenesis. Mysterin mutations, together with exposure to environmental trigger factors, lead to an elevated stroke risk since childhood. Mysterin is induced during cell stress, to function as cytosolic AAA+ ATPase and ubiquitylation enzyme. Little knowledge exists, in which context mysterin is needed. Here, we found that genetic ablation of several mitochondrial matrix factors, such as the peptidase ClpP, the transcription factor Tfam, as well as the peptidase and AAA+ ATPase Lonp1, potently induces Rnf213 transcript expression in various organs, in parallel with other components of the innate immune system. Mostly in mouse fibroblasts and human endothelial cells, the Rnf213 levels showed prominent upregulation upon Poly(I:C)-triggered TLR3-mediated responses to dsRNA toxicity, as well as upon interferon gamma treatment. Only partial suppression of Rnf213 induction was achieved by C16 as an antagonist of PKR (dsRNA-dependent protein kinase). Since dysfunctional mitochondria were recently reported to release immune-stimulatory dsRNA into the cytosol, our results suggest that mysterin becomes relevant when mitochondrial dysfunction or infections have triggered RNA-dependent inflammation. Thus, MMD has similarities with vasculopathies that involve altered nucleotide processing, such as Aicardi-Goutières syndrome or systemic lupus erythematosus. Furthermore, in MMD, the low penetrance of RNF213 mutations might be modified by dysfunctions in mitochondria or the TLR3 pathway.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 ± 2) and moderate motivation to stop smoking (4.9 ± 3), 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.

In recent years, cases of hepatitis E virus (HEV) infection have increased in Europe in association with the consumption of contaminated food, mainly from pork products but also from wild boars. The animal's serum is usually tested for the presence of anti-HEV antibodies and viral RNA but, in many cases such as during hunting, an adequate serum sample cannot be obtained. In the present study, liver transudate was evaluated as an alternative matrix to serum for HEV detection. A total of 125 sera and liver transudates were tested by enzyme-linked immunosorbent assay at different dilutions (1:2, 1:10, 1:20), while 58 samples of serum and liver transudate were checked for the presence of HEV RNA by RT-qPCR. Anti- HEV antibodies were detected by ELISA in 68.0% of the serum samples, and in 61.6% of the undiluted transudate, and in 70.4%, 56.8%, and 44.8% of 1:2, 1:10, or 1:20 diluted transudate, respectively. The best results were obtained for the liver transudate at 1:10 dilution, based on the Kappa statistic (0.630) and intraclass correlation coefficient (0.841). HEV RNA was detected by RT-qPCR in 22.4% of the serum samples and 6.9% of the transudate samples, all samples used for RT-qPCR were positive by ELISA. Our results indicate that liver transudate may be an alternative matrix to serum for the detection of anti-HEV antibodies.

Mitochondria are mostly inherited by maternal via, that is, only mitochondria from eggs are retained in the embryos. However, this general assumption of uniparentally transmitted, homoplasmic and non-recombining mitochondrial genomes is becoming more and more controversial. The presence of different sequences of mtDNA within a cell or individual, known as heteroplasmy, is increasingly reported in several taxon of animals, such as molluscs, arthropods and vertebrates. In this work, a considerable frequency of heteroplasmy were detected in the COI and 16S genes of the spider crab Maja brachydactyla, possibly associated to hybridisation with the congeneric species Maja squinado. This finding is a fact to keep in mind before addressing molecular analyses based on mitochondrial markers, since the assumption of maternal inheritance could lead to erroneous results. As M. brachydactyla is a commercial species, heteroplasmy is an important aspect to take into account for the fisheries management of this resource, since effective population size could be overestimated., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Information provided by health care professionals is crucial to create a climate of social opinion. This is important in organ donation and transplantation (ODT), where the participation of the general public is essential to obtain organs., Objective: To determine the attitude toward the Law of Presumed Consent (LPC) among Spanish university students and to analyze their relation with attitude toward ODT., Methods: and design. The type of study was a sociologic, multicenter, observational study. The population included medical and nursing students in Spanish universities. Database of Collaborative International Donor Project was used stratified by geographic area and academic course. A validated questionnaire (Collaborative International Donor Project, organ donation and transplantation questionnaire in Spanish [PCID-DTO-RIOS]) was self-administered and completed anonymously. A sample of 9598 medical and 10,566 nursing students was analyzed (99% confidence and precision of ±1%) and stratified by geographic area and year of study., Results: Completion rate was 90%. Regarding attitude toward LPC, 66% of the students were against the law, whereas 34% accepted it. Of the students surveyed, 9% considered the law as a gesture of solidarity, 25% as an effective way of not wasting organs, 48% as an abuse of power, and 18% as offenses against the family. Those students who were in favor of LPC also had a more favorable attitude toward ODT (86% vs 76%; P < .001). Comparing groups, nursing students were less in favor of LPC than medical students (32% vs 36%; P < .000)., Conclusion: Sixty-six percent of Spanish university medical and nursing students were against the LPC. The favorable attitude toward ODT is associated with considering the law as a gesture of solidarity or as an effective way of not wasting organs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A primary care physician (PCP) not only accompanies the patient in the process of an illness, but throughout his or her life. The confidence we have in these health professionals is fundamental, and their favorable attitude toward organ donation and transplantation (ODT) has a significant influence on the population., Objective: To analyze trust in PCPs among Spanish medical and nursing students, the relationship with their attitude toward ODT, and the factors that condition it., Methods and Design: A sociologic, multicenter, and observational study., Population: medical and nursing students in Spanish universities., Database: Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. A sample of 9598 medical and 10,566 nursing students (99% confidence and precision of ±1%), stratified by geographic area and year of study., Results: Completion rate: 90%. With respect to students' trust in their physician, 18% (n = 3267) of them totally trust (completely), 45% (n = 8101) trust enough, 30% (n = 5478) of them have not enough trust, and 7% not at all. Comparing groups, medical students totally trust more in PCPs than nursing students (55% vs 45%; P < .000), however, nursing students have less than enough trust in their PCP than medical students (53% vs 47%; P < .000). Students that totally trust in their PCP were more in favor toward ODT than students with not enough trust (83% vs 77%; P < .000)., Conclusion: Only 18% of Spanish medical and nursing students totally trust in their PCP. Attitude toward ODT is related to a higher level of trust in PCPs among these students., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Zoonotic hepatitis E, mainly caused by hepatitis E virus (HEV) genotype (gt) 3, is a foodborne disease that has emerged in Europe in recent decades. The main animal reservoir for genotype 3 is domestic pigs. Pig liver and liver derivates are considered the major risk products, and studies focused on the presence of HEV in pig muscles are scarce. The objective of the present study was to evaluate the presence of HEV in different organs and tissues of 45 apparently healthy pigs from nine Spanish slaughterhouses (50% national production) that could enter into the food supply chain. Anti-HEV antibodies were evaluated in serum by an ELISA test. Ten samples from each animal were analyzed for the presence of HEV RNA by reverse transcription real-time PCR (RT-qPCR). The overall seroprevalence obtained was 73.3% (33/45). From the 450 samples analyzed, a total of 26 RT-qPCR positive samples were identified in the liver (7/45), feces (6/45), kidney (5/45), heart (4/45), serum (3/45), and diaphragm (1/45). This is the first report on detection of HEV RNA in kidney and heart samples of naturally infected pigs. HEV RNA detection was negative for rib, bacon, lean ham, and loin samples. These findings indicate that pig meat could be considered as a low risk material for foodborne HEV infection., (Copyright © 2020 García, Hernández, Gutierrez-Boada, Valero, Navarro, Muñoz-Chimeno, Fernández-Manzano, Escobar, Martínez, Bárcena, González, Avellón, Eiros, Fongaro, Domínguez, Goyache and Rodríguez-Lázaro.)

Pediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma-related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.

The olive oil sector is currently adapting its traditional function to also become a supplier of high-value by-products that possess antioxidant, anti-inflammatory and antimicrobial properties. In this study, we evaluated the effect of the fermented defatted alperujo (FDA) on the intestinal health of laying hens. The morphology of the duodenal and cecal mucosa, the composition of the intestinal microbiota and the productivity of a batch of laying hens were evaluated after FDA supplementation. At early life stages, significant differences ( p < 0.001) were observed in duodenal villi height and in crypt depth of both the duodenum and the cecum in the FDA-supplemented group, indicating improved intestinal health in this group. Microbiota composition in the hatchery group supplemented with FDA had a higher abundance of Actinobacteria, Firmicutes and Proteobacteria, and higher bacterial diversity. During the production period, significant differences ( p < 0.05) were observed in the number of broken eggs from the supplemented group. We conclude that FDA supplementation improves the absorption capacity of the intestinal mucosa and modifies the intestinal microbiota to favor a greater immune response, leading to an increase in egg production.

Health care professionals and the information that they provide to the public on organ donation and transplantation (ODT) influence attitudes toward this option., Objective: The objective was to analyze the knowledge of university nursing students at Spanish universities toward ODT and the factors affecting it., Methods and Design: The methods and design included a multicenter, sociologic, and observational study including university nursing diploma students in a complete academic year., Participants: A sample of 10,566 students was selected stratified by geographic area and year., Instrument: A validated questionnaire of knowledge toward ODT (PCID-DTO RIOS), self-administered and completed anonymously., Results: Questionnaire completion rate: 85% (n = 9001). Only 18% (n = 1580) believed that their knowledge about ODT was good, 40% (n = 3578) believed that the information they had was normal, and 39% believed that their knowledge was sparse. Of the students, 96% believed that organ needs are not covered and 79% that they might need a transplant in the future. Only 39% (n = 3493) had attended a talk about ODT. Furthermore, 83% (n = 7435) believed that attending a talk would be interesting. The following variables were associated with having a more adequate knowledge: gender (62% men vs 57% women; P < .001); academic year (P < .001); knowing a donor (P < .001); knowing a transplant patient (P < .001); believing the possibility of needing a transplant oneself in the future (P < .001); attitude toward deceased donation (P < .001); and interest in receiving an informative talk about ODT (P < .001)., Conclusion: Only 18% of nursing students in Spain believed that their knowledge about ODT was adequate. These results must be considered for possible training plans for these future professionals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Research on healthy aging shows that lifespan reductions are often caused by mitochondrial dysfunction. Thus, it is very interesting that the deletion of mitochondrial matrix peptidase LonP1 was observed to abolish embryogenesis, while deletion of the mitochondrial matrix peptidase Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit (ClpP) prolonged survival. To unveil the targets of each enzyme, we documented the global proteome of LonP1 +/- mouse embryonal fibroblasts (MEF), for comparison with ClpP -/- depletion. Proteomic profiles of LonP1 +/- MEF generated by label-free mass spectrometry were further processed with the STRING (Search tool for the retrieval of interacting genes) webserver Heidelberg for protein interactions. ClpP was previously reported to degrade Eral1 as a chaperone involved in mitoribosome assembly, so ClpP deficiency triggers the accumulation of mitoribosomal subunits and inefficient translation. LonP1 +/- MEF also showed Eral1 accumulation, but no systematic effect on mitoribosomal subunits. In contrast to ClpP -/- profiles, several components of the respiratory complex-I membrane arm, of the glutathione pathway and of lysosomes were accumulated, whereas the upregulation of numerous innate immune defense components was similar. Overall, LonP1, as opposed to ClpP, appears to have no effect on translational machinery, instead it shows enhanced respiratory dysfunction; this agrees with reports on the human CODAS syndrome (syndrome with cerebral, ocular, dental, auricular, and skeletal anomalies) caused by LonP1 mutations.

The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways 1,2 . Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer 3-6 , but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.

Background: Chronic hepatic inflammation leads to liver fibrosis, which may progress to cirrhosis, a condition with high morbidity. Our aim was to assess the as yet unknown role of innate immunity protein CD5L in liver fibrosis., Methods: CD5L was measured by ELISA in plasma samples from cirrhotic (n = 63) and hepatitis (n = 39) patients, and healthy controls (n = 7), by immunohistochemistry in cirrhotic tissue (n = 12), and by quantitative RT-PCR in mouse liver cell subsets isolated by cell sorting. Recombinant CD5L (rCD5L) was administered into a murine model of CCl 4 -induced fibrosis, and damage, fibrosis and hepatic immune cell infiltration, including the LyC6 hi (pro-fibrotic)-LyC6 low (pro-resolutive) monocyte ratio were determined. Moreover, rCD5L was added into primary human hepatic stellate cells to study transforming growth factor β (TGFβ) activation responses., Findings: Cirrhotic patients showed elevated plasma CD5L concentrations as compared to patients with hepatitis and healthy controls (Mann-Whitney test p < 0·0001). Moreover, plasma CD5L correlated with disease progression, FIB4 fibrosis score (r:0·25, p < 0·0001) and tissue expression (r = 0·649; p = 0·022). Accordingly, CCl 4 -induced damage increased CD5L levels in total liver, particularly in hepatocytes and macrophages. rCD5L administration attenuated CCl 4 -induced injury and fibrosis as determined by reduced serum transaminase and collagen content. Moreover, rCD5L inhibited immune cell infiltration and promoted a phenotypic shift in monocytes from LyC6 hi to LyC6 low . Interestingly, rCD5L also had a direct effect on primary human hepatic stellate cells promoting SMAD7 expression, thus repressing TGFβ signalling., Interpretation: Our study identifies CD5L as a key pleiotropic inhibitor of chronic liver injury. FUND: Fundació Marató TV3, AGAUR and the ISCIII-EDRF., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Recent immunological and transgenic advances are a promising alternative using limited materials of human origin for transplantation. However, it is essential to achieve social acceptance of this therapy., Objective: To analyze the attitude of nursing students from Spanish universities toward organ xenotransplantation (XTx) and to determine the factors affecting their attitude., Materials and Methods: Type of study: A sociological, multicentre, and observational study., Study Population: Nursing students enrolled in Spain (n = 28,000)., Sample Size: A sample of 10 566 students estimating a proportion of 76% (99% confidence and precision of ±1%), stratified by geographical area and year of study. Instrument of measurement: A validated questionnaire (PCID-XenoTx-RIOS) was handed out to every student in a compulsory session. This survey was self-administered and self-completed voluntarily and anonymously by each student in a period of 5-10 min., Statistical Analysis: descriptive analysis, Student's t test, the chi-square test, and a logistic regression analysis., Results: A completion rate: 84% (n = 8913) was obtained. If the results of XTx were as good as in human donation, 74% (n = 6564) would be in favor and 22% (n = 1946) would have doubts. The following variables affected this attitude: age (P < 0.001); sex (P < 0.001); geographical location (P < 0.001); academic year of study (P < 0.001); attitude toward organ donation (P < 0.001); belief in the possibility of needing a transplant (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); and the opinion of one's partner (P < 0.001). The following variables persisted in the multivariate analysis: being a male (OR = 1.436; P < 0.001); geographical location (OR = 1.937; P < 0.001); an attitude in favor of donation (OR = 1.519; P < 0.001); belief in the possibility of needing a transplant (OR = 1.497; P = 0.036); and having spoken about the issue with family (OR = 1.351; P < 0.001) or friends (OR = 1.240; P = 0.001)., Conclusions: The attitude of nursing students toward organ XTx is favorable and is associated with factors of general knowledge about organ donation and transplantation and social interaction., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale: LonP1 is an essential mitochondrial protease, which is crucial for maintaining mitochondrial proteostasis and mitigating cell stress. However, the importance of LonP1 during cardiac stress is largely unknown., Objective: To determine the functions of LonP1 during ischemia/reperfusion (I/R) injury in vivo, and hypoxia-reoxygenation (H/R) stress in vitro., Methods and Results: LonP1 was induced 2-fold in wild-type mice during cardiac ischemic preconditioning (IPC), which protected the heart against ischemia-reperfusion (I/R) injury. In contrast, haploinsufficiency of LonP1 (LONP1 +/- ) abrogated IPC-mediated cardioprotection. Furthermore, LONP1 +/- mice showed significantly increased infarct size after I/R injury, whereas mice with 3-4 fold cardiac-specific overexpression of LonP1 (LonTg) had substantially smaller infarct size and reduced apoptosis compared to wild-type controls. To investigate the mechanisms underlying cardioprotection, LonTg mice were subjected to ischemia (45 min) followed by short intervals of reperfusion (10, 30, 120 min). During early reperfusion, the left ventricles of LonTg mice showed substantially reduced oxidative protein damage, maintained mitochondrial redox homeostasis, and showed a marked downregulation of both Complex I protein level and activity in contrast to NTg mice. Conversely, when LonP1 was knocked down in isolated neonatal rat ventricular myocytes (NRVMs), an up-regulation of Complex I subunits and electron transport chain (ETC) activities was observed, which was associated with increased superoxide production and reduced respiratory efficiency. The knockdown of LonP1 in NRVMs caused a striking dysmorphology of the mitochondrial inner membrane, mitochondrial hyperpolarization and increased hypoxia-reoxygenation (H/R)-activated apoptosis. Whereas, LonP1 overexpression blocked H/R-induced cell death., Conclusions: LonP1 is an endogenous mediator of cardioprotection. Our findings show that upregulation of LonP1 mitigates cardiac injury by preventing oxidative damage of proteins and lipids, preserving mitochondrial redox balance and reprogramming bioenergetics by reducing Complex I content and activity. Mechanisms that promote the upregulation of LonP1 could be beneficial in protecting the myocardium from cardiac stress and limiting I/R injury., (Copyright © 2018. Published by Elsevier Ltd.)

Methionine restriction, i.e., a partial depletion of the essential sulfur amino acid methionine from nutrition, extends lifespan in model organisms including yeast, nematodes, mice and rats. Recent results indicate that this strategy also prolongs health span and longevity in 2 short-lived strains of mice (with the Lmna G609G/G609G or zmpste24 -/- genotypes) that represent animal models of Hutchinson-Gilford progeria syndrome (HGPS). The beneficial effects of methionine restriction on HGPS could be linked to reduced inflammation, and improved DNA stability, as well as the normalization of lipid and bile acid metabolism. Previous work has established that behavioral, nutritional, pharmacological and genetic manipulations that extend longevity in model organisms are only efficient if they induce increased autophagic flux. Methionine restriction extends lifespan in Saccharomyces cerevisiae in an Atg5- and Atg7-dependent fashion, supporting the notion that methionine restriction may indeed mediate its antiaging effects through the induction of macroautophagy/autophagy as well. Based on these findings, we speculate that autophagy might constitute an actionable therapeutic target to treat progeroid syndromes.