How Does the Burden of Respiratory Syncytial Virus Compare to Influenza in Spanish Adults?

BACKGROUND: Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at-risk populations. This study is aimed at assessing hospital burden and healthcare resource utilization (HRU) of RSV and influenza in adults in Spain. METHODS: Data were obtained from the Projected Hospitalisation Database of inpatient episodes (ages: younger adults 18-50 and 51-64 years; older adults 65-74, 75-84, and ≥ 85 years) during 2015, 2017, and 2018 in Spanish public hospitals. Incidence, mean hospitalization, and HRU assessments, including length of stay (LOS), intensive care unit (ICU) usage, and age-standardized mortality rates, were collected and stratified by age group, with analyses focusing on the adult population (≥ 18 years old). RESULTS: Mean hospitalization rate in the population across all years was lower in individuals with RSV versus influenza (7.2/100,000 vs. 49.7/100,000 individuals). ICU admissions and median LOS were similar by age group for both viruses. Age-standardized mortality was 6.3/100,000 individuals and 6.1/100,000 individuals in patients with RSV and influenza, respectively, and mortality rates were similar in older adults (≥ 65 years) for both viruses. CONCLUSIONS: RSV and influenza infection were associated with considerable HRU. There is a substantial disease burden for RSV infection in older adults ≥ 65 years. While RSV hospitalization rates in adults reported here appeared lower than influenza, RSV is still underdiagnosed in the hospital setting and its incidence might be similar to, or higher than, influenza.

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

ABSTRACT: Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery. We established a tibial fracture mouse model that recapitulates clinically relevant orthopedic trauma surgery, which causes changes in neuropeptide levels in dorsal root ganglia and sustained neuroinflammation in the spinal cord. Here, we monitored extended pain behavior in this model, observing chronic bilateral hindpaw mechanical allodynia in both male and female C57BL/6J mice that persisted for >3 months after surgery. We also tested the analgesic effects of a novel, minimally invasive, bioelectronic approach to percutaneously stimulate the vagus nerve (termed percutaneous vagus nerve stimulation [pVNS]). Weekly pVNS treatment for 30 minutes at 10 Hz for 3 weeks after the surgery strongly reduced pain behaviors compared with untreated controls. Percutaneous vagus nerve stimulation also improved locomotor coordination and accelerated bone healing. In the dorsal root ganglia, vagal stimulation inhibited the activation of glial fibrillary acidic protein-positive satellite cells but without affecting microglial activation. Overall, these data provide novel evidence supportive of the use of pVNS to prevent postoperative pain and inform translational studies to test antinociceptive effects of bioelectronic medicine in the clinic.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury.

Background: Links between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI. Methods: We have applied a three-dose paradigm of 10µg/40µl intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging. Results: Three doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment. Conclusions: Overall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.

Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury.

Background: Links between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI. Methods: We have applied a three-dose paradigm of 10µg/40µl intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging. Results: Three doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment. Conclusions: Overall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.

New Patients in Treatment for Opioid Addiction in Spain.

Introduction: Patients seeking first time treatment for opioid consumption reflect the characteristics of the consumer population. This group has not been studied in Spain in decades. The objective of this study was to characterize the opioid user population seeking first time treatment (incidents) and compare them group with those with prior treatment (prevalents). Methods: Cross-sectional study (N = 3325) with patients with opioid addiction seeking care at public addiction centers in the Community of Madrid from 2017 through 2019. Differentiation and comparisons were carried out using bivariate analysis, adjusted by sociodemographic characteristics related and those related to substance use consumption in incident and prevalent patients. Results: About 12.2% were incidents. Compared to prevalents, there were more foreigners (34.1% vs 19.1% P < .001), but with a better social network. Regarding opioid use, incidents were less likely to use injection (10.7% compared to 16.8% P = .008), but had greater daily frequency (75.8% vs 52.2%, P < .001). The age of initial consumption was greater (27 years vs 21.3 years, (P < .001)). About 15.5% of incidents sought care for non-heroin opioids, compared to 4.8% of prevalents (P < .001). Women sought care at twice the rate of men (29.3% vs 12.3%; P > .001). Discussion: New patients presented a profile with many stable characteristics, but which highlighted an increase in the use of other opioids, as occurs in the international context. Surveillance of the new patient characteristics can serve as an early indicator of consumption changes in. Thus, periodic monitoring is important.

A Trypanosoma cruzi phosphoglycerate kinase isoform with a Per-Arnt-Sim domain acts as a possible sensor for intracellular conditions.

Per-ARNT-Sim (PAS) domains constitute a family of domains present in a wide variety of prokaryotic and eukaryotic organisms. They form part of the structure of various proteins involved in diverse cellular processes. Regulation of enzymatic activity and adaptation to environmental conditions, by binding small ligands, are the main functions attributed to PAS-containing proteins. Recently, genes for a diverse set of proteins with a PAS domain were identified in the genomes of several protists belonging to the group of kinetoplastids, however, until now few of these proteins have been characterized. In this work, we characterize a phosphoglycerate kinase containing a PAS domain present in Trypanosoma cruzi (TcPAS-PGK). This PGK isoform is an active enzyme of 58 kDa with a PAS domain located at its N-terminal end. We identified the protein's localization within glycosomes of the epimastigote form of the parasite by differential centrifugation and selective permeabilization of its membranes with digitonin, as well as in an enriched mitochondrial fraction. Heterologous expression systems were developed for the protein with the N-terminal PAS domain (PAS-PGKc) and without it (PAS-PGKt), and the substrate affinities of both forms of the protein were determined. The enzyme does not exhibit standard Michaelis-Menten kinetics. When evaluating the dependence of the specific activity of the recombinant PAS-PGK on the concentration of its substrates 3-phosphoglycerate (3PGA) and ATP, two peaks of maximal activity were found for the complete enzyme with the PAS domain and a single peak for the enzyme without the domain. Km values measured for 3PGA were 219 ± 26 and 8.8 ± 1.3 µM, and for ATP 291 ± 15 and 38 ± 2.2 µM, for the first peak of PAS-PGKc and for PAS-PGKt, respectively, whereas for the second PAS-PGKc peak values of approximately 1.1-1.2 mM were estimated for both substrates. Both recombinant proteins show inhibition by high concentrations of their substrates, ATP and 3PGA. The presence of hemin and FAD exerts a stimulatory effect on PAS-PGKc, increasing the specific activity by up to 55%. This stimulation is not observed in the absence of the PAS domain. It strongly suggests that the PAS domain has an important function in vivo in T. cruzi in the modulation of the catalytic activity of this PGK isoform. In addition, the PAS-PGK through its PAS and PGK domains could act as a sensor for intracellular conditions in the parasite to adjust its intermediary metabolism.

Computed tomography angiography aids in predicting resectability of isolated liver tumors in dogs.

OBJECTIVE: To assess the accuracy of CT angiography (CTA) in predicting resectability, degree of surgical difficulty, and individual factors that may impact resectability of isolated hepatic masses in dogs. ANIMALS: Prospective study of 20 dogs with 21 isolated hepatic masses. PROCEDURES: All CTAs and surgeries were performed between June 16, 2013, and November 30, 2016, at The Animal Medical Center in New York. Preoperative CTA images were evaluated by a board-certified surgeon (n = 2). A preoperative assessment was completed, documenting several predetermined factors aimed at predicting resectability of each mass and the degree of surgical difficulty. Resectability was divided into gross resectability and complete histologic excision. Following surgery, the surgeon completed a postoperative assessment documenting the intraoperative findings. Independently, a blinded board-certified radiologist analyzed the images and completed an identical preoperative assessment. RESULTS: The radiologist was more accurate in lesion localization compared to the surgeon (P = .023). Seventeen (17/21) masses were grossly resectable in surgery. Two additional (2/21) masses that were deemed grossly resectable were incompletely excised on histopathologic analysis. Both the surgeon and radiologist were accurate in their prediction of gross resectability and complete excision. Major vascular involvement, multilobar involvement, and right-sided laterality negatively affected resectability. The surgeon was significantly more accurate in predicting the degree of surgical difficulty (κ = 0.50) when compared to the radiologist (κ = 0.38). CLINICAL RELEVANCE: Preoperative CTA of isolated hepatic masses is useful in prediction of surgical difficulty and resectability, as well as identifying several factors that impact resectability.

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Postoperative pain is a major clinical problem imposing a significant burden on our patients and society. Up to 57% of patients experience persistent postoperative pain 2 years after orthopedic surgery [49]. Although many studies have contributed to the neurobiological foundation of surgery-induced pain sensitization, we still lack safe and effective therapies to prevent the onset of persistent postoperative pain. We have established a clinically relevant orthopedic trauma model in mice that recapitulates common insults associated with surgery and ensuing complications. Using this model, we have started to characterize how induction of pain signaling contributes to neuropeptides changes in dorsal root ganglia (DRG) and sustained neuroinflammation in the spinal cord [62]. Here we have extended the characterization of pain behaviors for >3 months after surgery, describing a persistent deficit in mechanical allodynia in both male and female C57BL/6J mice after surgery. Notably, we have applied a novel minimally invasive bioelectronic approach to percutaneously stimulate the vagus nerve (termed pVNS) [24] and tested its anti-nociceptive effects in this model. Our results show that surgery induced a strong bilateral hind-paw allodynia with a slight decrease in motor coordination. However, treatment with pVNS for 30-minutes at10 Hz weekly for 3 weeks prevented pain behavior compared to naïve controls. pVNS also improved locomotor coordination and bone healing compared to surgery without treatment. In the DRGs, we observed that vagal stimulation fully rescued activation of GFAP positive satellite cells but did not affect microglial activation. Overall, these data provide novel evidence for the use of pVNS to prevent postoperative pain and may inform translational studies to test anti-nociceptive effects in the clinic.

Psychometric properties of the Spanish adaptation of the Externalizing Spectrum Inventory-Brief Form (ESI-BF).

The Externalizing Spectrum Inventory-Brief Form (ESI-BF) measures tendencies toward disinhibition, lack of control, aggression, and substance use. This study adapts the ESI-BF to the Spanish population and assesses its psychometric properties. The study included 742 community adults obtained by stratified random sampling with proportional allocation according to gender, age, and geographical area of the Spanish territory and a clinical sample consisting of 333 patients. All participants completed the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (PID-5) and the Alcohol Substance Dependence Severity Scale, in addition to the Spanish version of the ESI-BF. Reliability was quantified using McDonald's omega and Cronbach's α reliability coefficients. Validity evidences were studied applying confirmatory factor analysis (CFA) and correlations. Results indicated adequate reliability of scores on the ESI-BF's general factors and most of its facets. Regarding internal structure, and in line with previous studies, both symmetric and S-1 hierarchical two-subfactor (bifactor) emerged as the best-fitting models. Considering both criticisms of symmetric models and parsimony, the S-1 bifactor model, which showed configural invariance across gender and samples, was retained. Validity evidence based on the relationship with other measures of personality and alcohol consumption show correlations values theoretically expected in both clinical and community samples. Findings suggest that the Spanish adaptation of the ESI-BF shows functional near-equivalence to the original version. Its effective psychometric properties make it useful instrument for further research related to the externalizing spectrum. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice.

BACKGROUND: Peripheral surgical trauma can trigger neuroinflammation and ensuing neurological complications, such as delirium. The mechanisms whereby surgery contributes to postoperative neuroinflammation remain unclear and without effective therapies. Here, we developed a microfluidic-assisted blood-brain barrier (BBB) device and tested the effects of omega-3 fatty acids on neuroimmune interactions after orthopaedic surgery. METHODS: A microfluidic-assisted BBB device was established using primary human cells. Tight junction proteins, vascular cell adhesion molecule 1 (VCAM-1), BBB permeability, and astrocytic networks were assessed after stimulation with interleukin (IL)-1ß and in the presence or absence of a clinically available omega-3 fatty acid emulsion (Omegaven®; Fresenius Kabi, Bad Homburg, Germany). Mice were treated 1 h before orthopaedic surgery with 10 µl g-1 body weight of omega-3 fatty acid emulsion i.v. or equal volumes of saline. Changes in pericytes, perivascular macrophages, BBB opening, microglial activation, and inattention were evaluated. RESULTS: Omega-3 fatty acids protected barrier permeability, endothelial tight junctions, and VCAM-1 after exposure to IL-1ß in the BBB model. In vivo studies confirmed that omega-3 fatty acid treatment inhibited surgery-induced BBB impairment, microglial activation, and delirium-like behaviour. We identified a novel role for pericyte loss and perivascular macrophage activation in mice after surgery, which were rescued by prophylaxis with i.v. omega-3 fatty acids. CONCLUSIONS: We present a new approach to study neuroimmune interactions relevant to perioperative recovery using a microphysiological BBB platform. Changes in barrier function, including dysregulation of pericytes and perivascular macrophages, provide new targets to reduce postoperative delirium.

Conserved YKL-40 changes in mice and humans after postoperative delirium.

Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the "Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults" (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms.

Patologías broncopulmonares asociadas a la exposición laboral a Fibras Minerales Artificiales: revisión sistemática / Lung diseases associated with occupational exposure to artificial mineral fibers: systematic review

Introducción: las fibras minerales artificiales (FMA) representan un grupo de fibras manufacturadas utilizadas principalmente para aislamiento térmico y acústico y de forma general en el ámbito de la construcción. Debido a que tienen una estructura similar a la fibra de amianto, se tiende a pensar que también pueden desarrollar patologías pulmonares como el cáncer, resultando de interés estudiar la exposición laboral a estas fibras y sus posibles consecuencias en la salud del trabajador. Método: revisión sistemática de la literatura científica mediante la búsqueda bibliográfica en MEDLINE a través de PUBMED, SCOPUS, EMBASE, WOS, Cochrane Library Plus, IBECS, LILACS y CISDOC. Se han recuperado artículos publicados en los últimos 10 años (2.008 al 2.018). Resultados: se obtuvieron 137 referencias de las que tras aplicar los criterios de inclusión y exclusión se recuperaron 8 artículos. Según el diseño del estudio contamos con 2 estudios de cohortes, 5 casos y controles y 1 transversal. En algunos estudios se encontró una asociación positiva pero no estadísticamente significativa entre la exposición laboral y el desarrollo de patología pulmonar. Conclusiones: aún no se dispone de suficiente evidencia científica que apoye una relación directa entre la exposición laboral a fibras minerales artificiales y sus implicaciones en el desarrollo de patología broncopulmonar, por lo tanto, se hace necesario realizar más estudios a largo plazo que aporten evidencia sobre este tema, en vista de la gran cantidad de trabajadores expuestos a estas fibras (AU)

Introduction: man-made mineral fibers represent a group of manufactured fibers used mainly for thermal and acoustic insulation and generally in the field of construction. Because these fibers have a similar structure to asbes-tos, it is a reason to think thatthey can develop pulmonary pathologies such as cancer, resulting in the interest to study the occupational exposure to these fibers and their possible consequences on the worker’s health.Method: Systematic review of scientific articles through bibliographic search in MEDLINE (PUBMED), SCOPUS, EM-BASE, WOS, Cochrane Library Plus, IBECS, LILACS and CISDOC, published over the last 10 years (2.008 to 2.018).Results: 137 references were retrieved, 8 articles remained after applying the inclusion and exclusion criteria. Ac-cording to this, there are 2 cohort studies, 5 cases and controls and 1 cross-sectional study. In some of these studies, a positive but not statistically significant association was found between occupational exposure to man-made min-eral fibers and the development of pulmonary pathology.Conclusions: there is not enough scientific evidence to support a direct relationship between occupational ex-posure to man-made mineral fibers and its implications in the development of bronchopulmonary pathologies, therefore it is necessary to conduct more long-term studies that provide evidence on this subject, in view of the large number of workers exposed to these fibers (AU)

Consumption of Galactose by Trypanosoma cruzi Epimastigotes Generates Resistance against Oxidative Stress.

In this study, we demonstrate that Trypanosoma cruzi epimastigotes previously grown in LIT medium supplemented with 20 mM galactose and exposed to sub-lethal concentrations of hydrogen peroxide (100 µM) showed two-fold and five-fold viability when compared to epimastigotes grown in LIT medium supplemented with two different glucose concentrations (20 mM and 1.5 mM), respectively. Similar results were obtained when exposing epimastigotes from all treatments to methylene blue 30 µM. Additionally, through differential centrifugation and the selective permeabilization of cellular membranes with digitonin, we found that phosphoglucomutase activity (a key enzyme in galactose metabolism) occurs predominantly within the cytosolic compartment. Furthermore, after partially permeabilizing epimastigotes with digitonin (0.025 mg × mg-1 of protein), intact glycosomes treated with 20 mM galactose released a higher hexose phosphate concentration to the cytosol in the form of glucose-1-phosphate, when compared to intact glycosomes treated with 20 mM glucose, which predominantly released glucose-6-phosphate. These results shine a light on T. cruzi's galactose metabolism and its interplay with mechanisms that enable resistance to oxidative stress.

Delineating transitions during the evolution of specialised peroxisomes: Glycosome formation in kinetoplastid and diplonemid protists.

One peculiarity of protists belonging to classes Kinetoplastea and Diplonemea within the phylum Euglenozoa is compartmentalisation of most glycolytic enzymes within peroxisomes that are hence called glycosomes. This pathway is not sequestered in peroxisomes of the third Euglenozoan class, Euglenida. Previous analysis of well-studied kinetoplastids, the 'TriTryps' parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp., identified within glycosomes other metabolic processes usually not present in peroxisomes. In addition, trypanosomatid peroxins, i.e. proteins involved in biogenesis of these organelles, are divergent from human and yeast orthologues. In recent years, genomes, transcriptomes and proteomes for a variety of euglenozoans have become available. Here, we track the possible evolution of glycosomes by querying these databases, as well as the genome of Naegleria gruberi, a non-euglenozoan, which belongs to the same protist supergroup Discoba. We searched for orthologues of TriTryps proteins involved in glycosomal metabolism and biogenesis. Predicted cellular location(s) of each metabolic enzyme identified was inferred from presence or absence of peroxisomal-targeting signals. Combined with a survey of relevant literature, we refine extensively our previously postulated hypothesis about glycosome evolution. The data agree glycolysis was compartmentalised in a common ancestor of the kinetoplastids and diplonemids, yet additionally indicates most other processes found in glycosomes of extant trypanosomatids, but not in peroxisomes of other eukaryotes were either sequestered in this ancestor or shortly after separation of the two lineages. In contrast, peroxin divergence is evident in all euglenozoans. Following their gain of pathway complexity, subsequent evolution of peroxisome/glycosome function is complex. We hypothesize compartmentalisation in glycosomes of glycolytic enzymes, their cofactors and subsequently other metabolic enzymes provided selective advantage to kinetoplastids and diplonemids during their evolution in changing marine environments. We contend two specific properties derived from the ancestral peroxisomes were key: existence of nonselective pores for small solutes and the possibility of high turnover by pexophagy. Critically, such pores and pexophagy are characterised in extant trypanosomatids. Increasing amenability of free-living kinetoplastids and recently isolated diplonemids to experimental study means our hypothesis and interpretation of bioinformatic data are suited to experimental interrogation.

Bridge Nodes between Personality Traits and Alcohol-Use Disorder Criteria: The Relevance of Externalizing Traits of Risk Taking, Callousness, and Irresponsibility.

BACKGROUND: Personality disorders show strong comorbidities with alcohol-use disorder (AUD), and several personality traits have been found to be more frequent in people with AUD. This study analyzes which personality facets of those proposed in the Alternative Model of Personality Disorder (AMPD) of DSM-5 are associated with the diagnostic criteria of AUD. METHODS: The sample was composed of 742 participants randomly selected from the Spanish population, and 243 patients attending mental health services. All participants were of legal age and signed an informed consent form. The instruments were administered to the community sample in an online format, and a psychologist conducted individual face-to-face interviews with the patients. AMPD facets were assessed through the Personality Inventory of DSM-5 Short-Form, and the AUD criteria through the Substance Dependence Severity Scale. A network analysis was applied to identify the personality facets mostly associated with the AUD criteria. RESULTS: The network analysis showed the existence of three communities, grouping the AUD criteria, externalizing spectrum facets, and internalizing spectrum facets, respectively. Risk taking, callousness, and irresponsibility facets showed the strongest association with the AUD criteria, bridging externalizing personality traits with AUD criteria. CONCLUSIONS: The facets of risk taking, callousness, and irresponsibility should be accurately assessed in patients with AUD to differentiate between a possible primary personality disorder and a syndrome induced by alcohol addiction.

Norms According to Age and Gender for the Spanish Version of the Inventory of Depression and Anxiety Symptoms (IDAS-II).

Inventory of Depression and Anxiety Symptoms-II (IDAS-II) constitutes a useful measurement tool with demonstrated psychometric properties that is contributing to the advancement of knowledge of emotional disorders within transdiagnostic models. To implement its use in clinical settings it is important that the scores can be interpreted in order to guide clinical decisions. This study aims to develops normative data for the Spanish version of the IDAS-II. An anonymous online survey was applied to 1,072 subjects, recruited through a stratified random sampling procedure taking into account population gender, age, and geographical region of Spain. Results show that women tend to score higher than men, particularly on the Dysphoria, General Depression, Appetite Gain, and Lassitude scales. Largest effect sizes for differences in the scores according to age were found for Lassitude, Dysphoria, and General Depression. Therefore, normative data according to gender and age group for each IDAS-II scale is provided. The norms provided in this work complement those already available, facilitating the decision-making of clinical professionals. Evidence of unidimensionality is provided for the 19 IDAS-II scales that allows researchers and clinicians to use specific IDAS-II scales independently.

Incapacidad laboral permanente por patología vestibular en conductores profesionales: un estudio transversal / Permanent work disability due to vestibular pathology in professional drivers: a cross-sectional study

Introducción: la Patología Vestibular afecta a la capacidad laboral y personal de los pacientes que sufren esta enfermedad. Método: estudio observacional, descriptivo, analítico y transversal. Como población de estudio se ha comparado a los conductores profesionales frente al resto de profesiones. Las variables usadas han sido: comunidad autónoma, género, edad, patología vestibular, situación de incapacidad temporal, tipo de contingencia, régimen de cotización, CNAE-2009, profesión (CNO-11), tipo de inicio de expediente, calificación, resolución del expediente y tiempo que tarda en resolverse en función de la resolución del expediente. Resultados: la muestra de expedientes estudiados ha sido de 597, que corresponden a los expedientes por incapacidad permanente presentados en España durante el 2018 para obtener la calificación de incapacitado permanente, o bien denegar dicha prestación. Del total de expedientes valorados, 72 (12.06%) corresponde a conductores profesionales y 525 (87.94%) al resto de categorías. El sexo mayoritario corresponde a hombres (326, 54.61%) con una franja de edad >55 años (276, 46.23%). Con la categoría de enfermedad común aparecen 574 expedientes (96.15%) y el 53.94% (n=322) de estos se inician de oficio. De todos los expedientes presentados, el 55.61% (n=270) tienen una calificación de no incapacitado y el 35.85% (n=214) de incapacidad total. En el contraste de hipótesis hemos obtenido una Odds Ratio de 2.42 (IC95%: 1.42-4.19) con p<0.001. Conclusiones: ser conductor profesional es un factor de riesgo para que un expediente de incapacidad permanente por patología vestibular se resuelva de forma favorable. (AU)

Introduction: vestibular disease affects occupational and personal capacities of those patients who suffers this disease. Method: observational, descriptive, analytic and transversal study. As population for study, we compare the professional drivers to the rest of professional workers. The variables used are: Autonomous community, gender, age, vestibular disease, temporal disability situation, type of contingency, contribution rates, CNAE-2009, Profession (CON-11), start of record, qualifications, expedient resolution, and the time it takes for a case resolution according to case resolution variable. Results: the total sample of study shows 597 cases, those are the cases that have been evaluated for permanent disability by vestibular disease in Spain during 2008, that eventually are qualified for permanent disability or whether not. Of the total sample of cases evaluated, 72 (12.06%) correspond to professional drivers and 525 (87.94%) to the rest of professionals. The majority gender group correlates to males, with a total of 326 cases (54.61%) with an age group superior to 55 years old (276, 46.23%). In the category of Common diseases it appears 574 cases (96.15%) and all of these, 53.94% (n=322) were initiated ex officio. Of all cases presented, 55.61% (n=270) present a resolution of not disabled and the 35.85% (n=214) with total disability. In the hypothesis testing we obtain an Odds’ ratio result of 2.42 (IC95%: 1.42-4.19) with p<0.001. Conclusions: being professional driver is a risk factor for those cases where permanent disability would be resolved in a favourable way. (AU)

IgE antibodies against Trypanosoma cruzi arginine kinase in patients with chronic Chagas disease.

Arginine kinase (AK) is an enzyme present in various invertebrates, as well as in some trypanosomatids such as T. cruzi, the etiological agent that causes Chagas disease. In invertebrates, this protein acts as an allergen inducing an IgE-type humoral immune response. Since AK is a highly conserved protein, we decided to study whether patients with chronic Chagas disease (CCD) produce specific antibodies against T. cruzi AK (TcAK). Plasma from patients with CCD, with and without cardiac alterations and non-infected individuals were evaluated for the presence of anti-TcAK IgG and IgE antibodies by ELISA, including detection of specific IgG subclasses. Our results showed that the levels of specific anti-TcAK IgG and IgE were different between infected and non-infected individuals, but comparable between those with different clinical manifestations. Interestingly, anti-TcAK IgG4 antibodies associated with IgE-mediated allergenic processes were also increased in CCD patients. Finally, we found that several of the predicted B cell epitopes in TcAK matched allergenic peptides previously described for its homologues in other organisms. Our results revealed for the first time a parasite's specific IgE antibody target and suggest that TcAK could contribute to delineate an inefficient B cell response by prompting a bias towards a Th2 profile. These findings also shed light on a potential allergenic response in the context of T. cruzi infection.

Errores de registro en las mediciones de presión arterial realizadas en dos centros de atención primaria de la salud de la ciudad de Salta, Argentina / Innacuracy in records of blood pressure measurements in two primary health centers of Salta City, Argentine

RESUMEN Introducción: El diagnóstico de hipertensión arterial (HTA) se realiza por la toma de la presión arterial (PA) en el consultorio médico (C) o en enfermería (E). Es frecuente aproximar los valores obtenidos a múltiplos de 10. Esto puede causar imprecisiones en el diagnóstico y el control de la HTA. Objetivo: Determinar cuántos registros de PA terminaban en cero en las mediciones realizadas en E y en C en dos centros de atención primaria de la salud de la ciudad de Salta. Material y métodos: Se efectuó un estudio descriptivo, transversal, de febrero a diciembre de 2018. Se utilizó un tensiómetro digital. A cada paciente se le midió la PA dos veces, primero en E y luego en C. Se utilizaron las pruebas de Chi2 y de Wilcoxon. Resultados: Se estudiaron 311 individuos, 60,77% mujeres. Edad media: 56,15 ± 13,8 años. Los registros terminados en cero tuvieron las siguientes frecuencias: PA sistólica en E: 36%; PA diastólica en E: 40,51%; PA sistólica en C: 11,58%; PA diastólica en C: 7,72% (p <0,0001). La PA sistólica y diastólica terminaron simultáneamente en cero en el 30,87% de los casos cuando se midieron en E y en el 0,64% de los casos cuando se midieron en C (p <0,0001). Conclusiones: La PA sistólica y la PA diastólica terminaron en cero con una frecuencia 3 y 5 veces mayor en E que en C, respectivamente, y la frecuencia de registros de PA sistólica y diastólica coincidentemente terminados en cero fue 48 veces mayor en E que en C. Estos resultados refuerzan la necesidad de una capacitación permanente para mejorar el registro en la medición de la PA.

ABSTRACT Background: The diagnosis of hypertension is established by blood pressure (BP) measurements in doctor (DO) or nursing offices (NO). Frecuently BP measurements are recorded as multiples of ten. This can lead to inaccuracy in diagnosis and control of hypertension. Objetive: To determine the percentage of BP measurements ending in zero in DO and NO, in the records of two health primary centers of Salta city. Methods: Observational study from february to december of 2018. Digital blood pressure monitor was used. Each patient BP was measured twice, first in NO and then in DO. Data were analyzed using the Chi2 and Wilcoxon tests. Results: 311 indivuals were enrolled, 60,77% were female. The average age was 56,15 ± 13,8 years. In NO the systolic BP and diastolic BP ending in zero were 36 and 40,51% respectively, while in DO were 11,58 and 7,72% (p <0,0001). The systolic BP and diastolic BP ending in zero simultaneously in NO was 30,87%, while in DO was 0,64% (p <0,0001). Conclusions: The systolic BP and the diastolic BP records ending in zero were three and five times more frequent in NO than in DO. The systolic BP and diastolic BP ending in zero simultaneously in NO were forty-eight times more frequent than in DO. These results reinforce the need of health personnel permanent training to improve precision for measuring and recording BP in medical centers.