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Recent discoveries of at least two heart fields and dynamic nature of cardiac development as well as controversies regarding the participation of heart fields in development of different heart structures led us to investigate the dynamics of incorporation of the first and second heart fields and prospective fate of the straight heart tube by labeling chicken embryos in vivo with the fluorescent lipophilic dye DiI. The cephalic and caudal limits of the anterior and posterior segments of the straight heart tube were labeled in two groups of embryos. Labels were tracked along the "C," "S," and "U" loops up to the tetracavitary or mature heart (n = 30 embryos/group; torsion and looping stage). To determine whether the atria and atrioventricular canal are derived from the first heart field the straight heart tube was cultured in vitro and immunodetection of Sox-9 and troponin I was performed to identify the mesenchymal and myocardial lineages respectively. Proliferating cell nuclear antigen (PCNA) immunodetection was used to determine the involvement of cell proliferation in heart tube development during torsion and looping. Embryological constitution of the straight heart tube and heart looping (C, S, and U) were not consistent with current descriptions. In fact, right ventricle precursors were absent in the straight heart tube derived from the first heart field. During torsion and looping, the cephalic segment of the straight heart tube gradually shifted into the heart tube until it was located at the myocardial interventricular septum in the tetracavitary heart. In contrast, the caudal segment of the straight heart tube was elongated and remodeled to become the first heart field derived left ventricle and the proximal part of the ventricular inlets. The ventricular outflows, right ventricle, distal part of the ventricular inlets, and atria developed from the second heart field.

Background: The COVID-19 pandemic has prompted a transformation of medical training. Although there were obvious medical education and social interaction challenges, e-learning presented some advantages, which may have generated medical curricula innovation and adjustments to novel technological methodologies. This study aims to generate consensuses among medical students regarding medical education provided during the pandemic in the resource-limited context of a Global South university., Methods: The implementation of a participatory Delphi method included a recruitment campaign, training, constitution of Delphi panels and questions, and development of the Delphi exercises. Students from the second to the sixth year of medicine of a university in Quito, Ecuador, constituted two Delphi panels, developed questions about the education received during the pandemic, and answered them over 3.5 rounds., Findings: Twenty-two medical students participated in the Delphi exercises about their perception of medical education during the COVID-19 pandemic. The analysis consisted of a total of 22 Delphi questions divided into five distinct categories: adaptations and innovations, curriculum and assessment changes, virtual clinical practice, time management, and mental health. The authors established high, medium, and low consensuses for analysis., Conclusions: Consensuses were reached based on students' academic year and focused on the changes in lecture delivery, the usage of new technologies, patient care skills, the impact of the educational routine, and the mental health of the COVID-19 pandemic. The way the pandemic affected medical education in the Global South set the stage for the need for a comprehensive review of tools, skills, and curricula for students from culturally diverse backgrounds. This study offers a highly replicable methodology to generate consensuses and introduce students to academic research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ortiz Riofrio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Delayed intervention for ST-segment elevation myocardial infarction (STEMI) is associated with higher mortality. The association of door-to-ECG (D2E) with clinical outcomes has not been directly explored in a contemporary US-based population. Methods: This was a three-year, 10-center, retrospective cohort study of ED-diagnosed patients with STEMI comparing mortality between those who received timely (<10 min) vs. untimely (>10 min) diagnostic ECG. Among survivors, we explored left ventricular ejection fraction (LVEF) dysfunction during the STEMI encounter and recovery upon post-discharge follow-up. Results: Mortality was lower among those who received a timely ECG where one-week mortality was 5% (21/420) vs. 10.2% (26/256) among those with untimely ECGs ( p = 0.016), and in-hospital mortality was 6.0% (25/420) vs. 10.9% (28/256) ( p = 0.028). Data to compare change in LVEF metrics were available in only 24% of patients during the STEMI encounter and 46.5% on discharge follow-up. Conclusions: D2E within 10 min may be associated with a 50% reduction in mortality among ED STEMI patients. LVEF dysfunction is the primary resultant morbidity among STEMI survivors but was infrequently assessed despite low LVEF being an indication for survival-improving therapy. It will be difficult to assess the impact of STEMI care interventions without more consistent LVEF assessment., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article.

Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation., (© 2024 The Authors New Phytologist © 2024 New Phytologist Foundation.)

Introduction: Trauma video review of Emergency Medical Services (EMS) handoffs demonstrates frequent problems including interruptions and incomplete information transfer. This study aimed to perform a regional needs assessment of handoff perceptions and expectations to guide future standardization efforts., Methods: A multidisciplinary team of trauma providers through consensus building created an anonymous survey which was then distributed through the North Central Texas Trauma Regional Advisory Council and four regional level-1 trauma institutions. Qualitative data underwent content analysis; quantitative data are presented with descriptive statistics., Results: Survey responses (n = 249) were submitted by trauma nurses (38%), EMS (24%), emergency physicians (14%), and trauma physicians (13%). Median overall handoff quality was rated well (4, scale 1-5) despite some variability between hospitals (3, scale 1-5). The top five most important handoff details were the same for both stable and unstable patients: primary mechanism, blood pressure, heart rate, Glasgow Coma Scale, and location of injuries. While providers felt neutral about the data order, the vast majority supported immediate bed transfer and primary survey in unstable patients. The majority of receiving providers report interrupting handoff at least once (78%); and 66% of EMS clinicians found interruptions disruptive. Content analysis revealed top priority categories for improvement: environment, communication, information relayed, team dynamics, and flow of care., Conclusion: Although our data demonstrated satisfaction and concordance with respect to the EMS handoff, 84% of EMS clinicians reported some to high amounts of variability across institutions. Gaps in the development of standardized handoffs identified include exposure, education, and enforcement of these protocols., (Copyright © 2023 Elsevier Inc. All rights reserved.)

An increasingly common output arising from the analysis of shotgun metagenomic datasets is the generation of metagenome-assembled genomes (MAGs), with tens of thousands of MAGs now described in the literature. However, the discovery and comparison of these MAG collections is hampered by the lack of uniformity in their generation, annotation and storage. To address this, we have developed MGnify Genomes, a growing collection of biome-specific non-redundant microbial genome catalogues generated using MAGs and publicly available isolate genomes. Genomes within a biome-specific catalogue are organised into species clusters. For species that contain multiple conspecific genomes, the highest quality genome is selected as the representative, always prioritising an isolate genome over a MAG. The species representative sequences and annotations can be visualised on the MGnify website and the full catalogue and associated analysis outputs can be downloaded from MGnify servers. A suite of online search tools is provided allowing users to compare their own sequences, ranging from a gene to sets of genomes, against the catalogues. Seven biomes are available currently, comprising over 300,000 genomes that represent 11,048 non-redundant species, and include 36 taxonomic classes not currently represented by cultured genomes. MGnify Genomes is available at https://www.ebi.ac.uk/metagenomics/browse/genomes/., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Understanding the spatial and temporal frameworks of species diversification is fundamental in evolutionary biology. Assessing the geographic origin and dispersal history of highly diverse lineages of rapid diversification can be hindered by the lack of appropriately sampled, resolved, and strongly supported phylogenetic contexts. The use of currently available cost-efficient sequencing strategies allows for the generation of a substantial amount of sequence data for dense taxonomic samplings, which together with well-curated geographic information and biogeographic models allow us to formally test the mode and tempo of dispersal events occurring in quick succession. Here, we assess the spatial and temporal frameworks for the origin and dispersal history of the expanded clade K, a highly diverse Tillandsia subgenus Tillandsia (Bromeliaceae, Poales) lineage hypothesized to have undergone a rapid radiation across the Neotropics. We assembled full plastomes from Hyb-Seq data for a dense taxon sampling of the expanded clade K plus a careful selection of outgroup species and used them to estimate a time- calibrated phylogenetic framework. This dated phylogenetic hypothesis was then used to perform biogeographic model tests and ancestral area reconstructions based on a comprehensive compilation of geographic information. The expanded clade K colonized North and Central America, specifically the Mexican transition zone and the Mesoamerican dominion, by long-distance dispersal from South America at least 4.86 Mya, when most of the Mexican highlands were already formed. Several dispersal events occurred subsequently northward to the southern Nearctic region, eastward to the Caribbean, and southward to the Pacific dominion during the last 2.8 Mya, a period characterized by pronounced climate fluctuations, derived from glacial-interglacial climate oscillations, and substantial volcanic activity, mainly in the Trans-Mexican Volcanic Belt. Our taxon sampling design allowed us to calibrate for the first time several nodes, not only within the expanded clade K focal group but also in other Tillandsioideae lineages. We expect that this dated phylogenetic framework will facilitate future macroevolutionary studies and provide reference age estimates to perform secondary calibrations for other Tillandsioideae lineages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vera-Paz, Granados Mendoza, Díaz Contreras Díaz, Jost, Salazar, Rossado, Montes-Azcué, Hernández-Gutiérrez, Magallón, Sánchez-González, Gouda, Cabrera, Ramírez-Morillo, Flores-Cruz, Granados-Aguilar, Martínez-García, Hornung-Leoni, Barfuss and Wanke.)

Fourteen species of the genus Epidendrum , recently collected in the Área de Conservación Privada La Pampa del Burro (ACPPB), five of them new to science ( Epidendrumechinatiantherum sp. nov. , E.imazaense sp. nov. , E.parvireflexilobum sp. nov. , E.rosulatum sp. nov. , and E.ochrostachyum sp. nov. ), are described and illustrated. The other species include a new record for Peru ( E.acrobatesii ) and four for the department of Amazonas ( E.brachyblastum , E.forcipatum , E.mavrodactylon , and E.tridens ). Epidendrumenantilobum is here considered a synonym of Epidendrumbrachyblastum . The type locality of Epidendrumcryptorhachis , originally stated as Ecuador, Guayabamba, is corrected to indicate that it refers to the valley of Guayabamba, Rodríguez de Mendoza, Amazonas, Peru. Our results show the need to continue conducting botanical exploration in the ACPPB as a baseline for subsequent studies, including a full inventory of the orchid diversity., Competing Interests: No conflict of interest was declared., (Jessy Patricia Arista, Eric Hágsater, Elizabeth Santiago, José D. Edquén, Elí Pariente, Manuel Oliva, Gerardo A. Salazar.)

Motivation: The visualization of biological data is a fundamental technique that enables researchers to understand and explain biology. Some of these visualizations have become iconic, for instance: tree views for taxonomy, cartoon rendering of 3D protein structures or tracks to represent features in a gene or protein, for instance in a genome browser. Nightingale provides visualizations in the context of proteins and protein features., Results: Nightingale is a library of re-usable data visualization web components that are currently used by UniProt and InterPro, among other projects. The components can be used to display protein sequence features, variants, interaction data, 3D structure, etc. These components are flexible, allowing users to easily view multiple data sources within the same context, as well as compose these components to create a customized view., Availability and Implementation: Nightingale examples and documentation are freely available at https://ebi-webcomponents.github.io/nightingale/. It is distributed under the MIT license, and its source code can be found at https://github.com/ebi-webcomponents/nightingale., Competing Interests: A.B. is an Editor-in-Chief of Bioinformatics Advances, but was not involved in the editorial process of this manuscript. The remaining authors have no conflicts of interest to declare., (© The Author(s) 2023. Published by Oxford University Press.)

Intimate partner violence (IPV) and emergency medicine intersect when individuals experiencing IPV present to emergency departments for medical care, either on their own or when brought in by law enforcement authorities for medical evaluation and social services. Coordination of care is required, with particular attention paid to the sensitive nature of the patient's presentation and with an emphasis on trauma-informed care. Emergent medical needs must be balanced with concerns for the patient's emotional well-being and the need for advocacy and social services. This supplement reviews best practices and evidence-based recommendations for the evaluation and management of patients who have experienced IPV, with a focus on the considerations for traumatic injuries in these patients.

Liparisaltomayoënsis sp. nov. is described, illustrated, and tentatively assigned to the Neotropical section Decumbentes on the basis of its branching, prostrate rhizomes and upright stems bearing several leaves. Vegetatively, the new species is distinguished by its short, upward stems bearing 3-6 leaves, these with undulate, translucent margins and reticulate, prominent veining on the upper surface. Florally, it is distinctive in the labellum with fleshy basal one-half provided with a central, rounded cavity limited on each side by a prominent, bilobulate ridge and apically by a lunate ridge, and membranaceous, trilobulate apical one-half deflexed ca. 90°. In contrast with other species of section Decumbentes, in which fruit formation is infrequent, in L.altomayoënsis a high proportion (⁓50-100%) of flowers develop into a fruit; in some flowers the pollinaria rotate and contact the stigma, apparently resulting in at least facultative self-pollination. The main differences among the six species of L.sectionDecumbentes hitherto known are contrasted in a dichotomous key. The new species is known only from three populations located in the Bosque de Protección Alto Mayo, on the Amazonian slope of the Andes in northeastern Peru but appears to be under no foreseeable threats., (José D. Edquén, Jessy P. Arista, Alexander Damián, Gerardo A. Salazar.)

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. Here, we report recent developments with InterPro (version 90.0) and its associated software, including updates to data content and to the website. These developments extend and enrich the information provided by InterPro, and provide a more user friendly access to the data. Additionally, we have worked on adding Pfam website features to the InterPro website, as the Pfam website will be retired in late 2022. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB. Moreover, we report the development of a card game as a method of engaging the non-scientific community. Finally, we discuss the benefits and challenges brought by the use of artificial intelligence for protein structure prediction., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: Emergency medical services (EMS) workforce demographics in the United States do not reflect the diversity of the population served. Despite some efforts by professional organizations to create a more representative workforce, little has changed in the last decade. This scoping review aims to summarize existing literature on the demographic composition, recruitment, retention, and workplace experience of underrepresented groups within EMS., Methods: Peer-reviewed studies were obtained from a search of PubMed, CINAHL, Web of Science, ProQuest Thesis and Dissertations, and non-peer-reviewed ("gray") literature from 1960 to present. Abstracts and included full-text articles were screened by two independent reviewers trained on inclusion/exclusion criteria. Studies were included if they pertained to the demographics, training, hiring, retention, promotion, compensation, or workplace experience of underrepresented groups in United States EMS by race, ethnicity, sexual orientation, or gender. Studies of non-EMS fire department activities were excluded. Disputes were resolved by two authors. A single reviewer screened the gray literature. Data extraction was performed using a standardized electronic form. Results were summarized qualitatively., Results: We identified 87 relevant full-text articles from the peer-reviewed literature and 250 items of gray literature. Primary themes emerging from peer-reviewed literature included workplace experience (n = 48), demographics (n = 12), workforce entry and exit (n = 8), education and testing (n = 7), compensation and benefits (n = 5), and leadership, mentorship, and promotion (n = 4). Most articles focused on sex/gender comparisons (65/87, 75%), followed by race/ethnicity comparisons (42/87, 48%). Few articles examined sexual orientation (3/87, 3%). One study focused on telecommunicators and three included EMS physicians. Most studies (n = 60, 69%) were published in the last decade. In the gray literature, media articles (216/250, 86%) demonstrated significant industry discourse surrounding these primary themes., Conclusions: Existing EMS workforce research demonstrates continued underrepresentation of women and nonwhite personnel. Additionally, these studies raise concerns for pervasive negative workplace experiences including sexual harassment and factors that negatively affect recruitment and retention, including bias in candidate testing, a gender pay gap, and unequal promotion opportunities. Additional research is needed to elucidate recruitment and retention program efficacy, the demographic composition of EMS leadership, and the prevalence of racial harassment and discrimination in this workforce.

Full plastome sequences for land plants have become readily accessible thanks to the development of Next Generation Sequencing (NGS) techniques and powerful bioinformatic tools. Despite this vast amount of genomic data, some lineages remain understudied. Full plastome sequences from the highly diverse (>1,500 spp.) subfamily Tillandsioideae (Bromeliaceae, Poales) have been published for only three (i.e., Guzmania , Tillandsia , and Vriesea ) out of 22 currently recognized genera. Here, we focus on core Tillandsioideae, a clade within subfamily Tillandsioideae, and explore the contribution of individual plastid markers and data categories to inform deep divergences of a plastome phylogeny. We generated 37 high quality plastome assemblies and performed a comparative analysis in terms of plastome structure, size, gene content and order, GC content, as well as number and type of repeat motifs. Using the obtained phylogenetic context, we reconstructed the evolution of these plastome attributes and assessed if significant shifts on the evolutionary traits' rates have occurred in the evolution of the core Tillandsioideae. Our results agree with previously published phylogenetic hypotheses based on plastid data, providing stronger statistical support for some recalcitrant nodes. However, phylogenetic discordance with previously published nuclear marker-based hypotheses was found. Several plastid markers that have been consistently used to address phylogenetic relationships within Tillandsioideae were highly informative for the retrieved plastome phylogeny and further loci are here identified as promising additional markers for future studies. New lineage-specific plastome rearrangements were found to support recently adopted taxonomic groups, including large inversions, as well as expansions and contractions of the inverted repeats. Evolutionary trait rate shifts associated with changes in size and GC content of the plastome regions were found across the phylogeny of core Tillandsioideae., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vera-Paz, Díaz Contreras Díaz, Jost, Wanke, Rossado, Hernández-Gutiérrez, Salazar, Magallón, Gouda, Ramírez-Morillo, Donadío and Granados Mendoza.)

An important virulence trait of Salmonella enterica serovar Typhimurium ( S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe 2+ , biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.

Cellulitis and other skin and soft-tissue infections (SSTIs) are common presentations in the emergency department. This review describes the varied etiologies and patient presentations of the more common SSTIs: cellulitis, abscesses, and necrotizing soft-tissue infections. A discussion of the common diagnoses masquerading as SSTIs is presented, as well as a stepwise approach to avoiding misdiagnosis. Diagnostic studies are also evaluated, including discussions on ultrasound, computed tomography, and clinical decision rules. This review also provides an evidence-based analysis of the controversies in management of abscesses, including the commonly utilized techniques of incision and drainage, irrigation, packing, and concurrent antibiotic therapy.

Objective: The objective of this study was to assess the predictive significance of anti-Scl-70 (anti-topoisomerase I) antibodies, as determined by three different methods, for decline in forced vital capacity (FVC) within the first year of follow-up in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD)., Methods: Patients in the Genetics Versus Environment in Scleroderma Outcome Study cohort who had ILD (verified by imaging) and available FVC% at enrollment, plus 12 to 18 months thereafter, were examined. All patients had a disease duration of 5 years or less at enrollment. The annualized percentage change in FVC% at 1 year follow-up was the outcome variable. Anti-Scl-70 antibodies were determined by passive immunodiffusion (ID) against calf thymus extract, chemiluminescent immunoassay (CIA), and line blot immunoassay (LIA)., Results: Ninety-one patients with a mean disease duration of 2.36 years were included. Anti-Scl-70 antibodies by ID predicted a faster rate of FVC% decline (b = -0.06, P = 0.04). None of the other clinical or serological variables significantly predicted ILD progression. Interestingly, anti-Scl-70 antibodies as determined by CIA and LIA were not significant predictors of FVC decline (P = 0.26 and 0.64, respectively). The observed level of agreement between ID and LIA was moderate (κ = 0.568), whereas it was good between ID and CIA (κ = 0.66)., Conclusion: Anti-Scl-70 antibodies determined by ID predicted faster FVC decline in patients with SSc-related ILD. Notably, both CIA and LIA for the same antibody did not predict rate of FVC decline at their current cutoffs of positivity. The discrepancy observed between anti-Scl-70 antibody assays can have relevant implications for clinical care and trial enrichment strategies in SSc-ILD., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Determine relationships between skin gene expression and systemic sclerosis (SSc) clinical disease features, and changes in skin gene expression over time., Methods: A total of 339 forearm skin biopsies were obtained from 113 SSc patients and 44 matched healthy controls. 105 SSc patients had a second biopsy, and 76 had a third biopsy. Global gene expression profiling was performed, and differentially expressed genes and cell type-specific signatures in SSc were evaluated for relationships to modified Rodnan Skin Score (mRSS) and other clinical variables. Changes in skin gene expression over time were analysed by mixed effects models and principal component analysis. Immunohistochemical staining was performed to validate conclusions., Results: Gene expression dysregulation was greater in SSc patients with affected skin than in those with unaffected skin. Immune cell and fibroblast signatures positively correlated with mRSS. High baseline immune cell and fibroblast signatures predicted higher mRSS over time, but were not independently predictive of longitudinal mRSS after adjustment for baseline mRSS. In early diffuse cutaneous SSc, immune cell and fibroblast signatures declined over time, and overall skin gene expression trended towards normalisation. On immunohistochemical staining, most early diffuse cutaneous SSc patients with high baseline T cell and macrophage numbers had declines in these numbers at follow-up., Conclusions: Skin thickness in SSc is related to dysregulated immune cell and fibroblast gene expression. Skin gene expression changes over time in early diffuse SSc, with a tendency towards normalisation. These observations are relevant for understanding SSc pathogenesis and could inform treatment strategies and clinical trial design., Competing Interests: Competing interests: MDM reports support from Mitsubishi-Tanabe, Boehringer Ingelheim, EICOS and Corbus to her institution outside the submitted work, and fees from Medtelligence, Actelion Pharma, Mitsubishi-Tanabe, Boehringer Ingelheim and EICOS to her outside the submitted work. SA reports grant support from Momenta, Boehringer Ingelheim, Janssen, and the Scleroderma Research Foundation to his institution outside the submitted work; consulting fees from Boehringer Ingelheim, Novartis, Corbus, CSL Behring, Abbvie, AstraZeneca to him outside the submitted work; honorarium from Boehringer Ingelheim for lectures and payment from the American College of Rheumatology to him outside the submitted work. BS, MAL, WRS, GS, MW, TMT, JC and CPV have no relevant competing interests to declare., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: The authors declare no conflict of interest.

Salmonella enterica is a common source of food and water-borne infections, causing a wide range of clinical ailments in both human and animal hosts. Immunity to Salmonella involves an interplay between different immune responses, which are rapidly initiated to control bacterial burden. However, Salmonella has developed several strategies to evade and modulate the host immune responses. In this sense, the main knowledge about the pathogenicity of this bacterium has been obtained by the study of mouse models with non-typhoidal serovars. However, this knowledge is not representative of all the pathologies caused by non-typhoidal serovars in the human. Here we review the most important features of typhoidal and non-typhoidal serovars and the diseases they cause in the human host, describing the virulence mechanisms used by these pathogens that have been identified in different models of infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schultz, Melo-Gonzalez, Salazar, Porto, Riedel, Kalergis and Bueno.)

Clinical Presentation: A 52-year-old man presented with hemoptysis of 2 weeks' duration. He had been experiencing hoarseness, right-sided pleuritic chest pain, subjective fevers, chills, night sweats, and 10 pounds weight loss for the previous 2 months. He additionally reported severe frontal headaches, nasal congestion, and intermittent epistaxis, which had been present for a year before his current presentation. He had worked in construction and denied tobacco or illicit drug use., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The Pfam database is a widely used resource for classifying protein sequences into families and domains. Since Pfam was last described in this journal, over 350 new families have been added in Pfam 33.1 and numerous improvements have been made to existing entries. To facilitate research on COVID-19, we have revised the Pfam entries that cover the SARS-CoV-2 proteome, and built new entries for regions that were not covered by Pfam. We have reintroduced Pfam-B which provides an automatically generated supplement to Pfam and contains 136 730 novel clusters of sequences that are not yet matched by a Pfam family. The new Pfam-B is based on a clustering by the MMseqs2 software. We have compared all of the regions in the RepeatsDB to those in Pfam and have started to use the results to build and refine Pfam repeat families. Pfam is freely available for browsing and download at http://pfam.xfam.org/., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

TGF-β is a master regulator of fibrosis, driving the differentiation of fibroblasts into apoptosis-resistant myofibroblasts and sustaining the production of extracellular matrix (ECM) components. Here, we identified the nuclear long noncoding RNA (lncRNA) H19X as a master regulator of TGF-β-driven tissue fibrosis. H19X was consistently upregulated in a wide variety of human fibrotic tissues and diseases and was strongly induced by TGF-β, particularly in fibroblasts and fibroblast-related cells. Functional experiments following H19X silencing revealed that H19X was an obligatory factor for TGF-β-induced ECM synthesis as well as differentiation and survival of ECM-producing myofibroblasts. We showed that H19X regulates DDIT4L gene expression, specifically interacting with a region upstream of the DDIT4L gene and changing the chromatin accessibility of a DDIT4L enhancer. These events resulted in transcriptional repression of DDIT4L and, in turn, in increased collagen expression and fibrosis. Our results shed light on key effectors of TGF-β-induced ECM remodeling and fibrosis.

A new species of Liparis sect. Decumbentes, Liparis sessilis Damián, Salazar & Rimarachín, sp. nov is described and illustrated from Amazonas (Perú), including color photographs, a detailed comparison and an identification key to all the species of Liparis sect. Decumbentes. In addition, we report Liparis brachystalix Rchb.f. for the first time for the orchid flora of Peru, and select a lectotype for its synonym, L. commelinoides Schltr., (Alexander Damián, Gerardo A. Salazar, Leyda Rimarachín.)

Patients with concomitant HIV-1 infection and systemic lupus erythematosus (SLE) followed longitudinally at an HIV outpatient clinic from 1994 to 2019 were examined. Patients met 1982 and 1997 ACR classification criteria for SLE at the Thomas Street clinic from 1994 to 2019. Clinical and demographic comparisons were made with a non HIV-SLE patient cohort, the Lupus in Minorities Studies, Nature versus Nurture (LUMINA) study. Twenty-two patients with concomitant HIV-1 infection and SLE were identified, including 18 females, 3 males, and 1 male to female transgender. Overall, 81.8% of SLE-HIV patients were African-American compared to 55.3% of the 5856 patients seen at the HIV clinic from 2016 to 2017 (p = 0.02, OR = 3.6). There were 12 patients that developed HIV-1 in the setting of SLE and 10 patients that developed SLE in the setting HIV-1. This demographic distribution was significant when compared with the 1604 unique patients in the HIV rheumatology clinic from 1994 to 2019 (p = 0.03, OR = 5.9) and also significant when compared with the 5856 patients attending the county HIV clinic overall in 2016-2017 (p = 0.008, OR = 7.2). When comparing with the non-HIV SLE cohort, anti-dsDNA antibodies were noted less frequently in all HIV-SLE patients (p = 0.0002) including all sub-cohorts of our patients. Skin/mucosal involvement (p = 0.0003) and cytopenias (p = 0.0001) occurred less frequently in the patients that were diagnosed with HIV after their SLE diagnosis compared to non-HIV SLE patients. In a large county HIV clinic setting, the prevalence of SLE was significantly higher in African American women. Anti-dsDNA antibodies were less frequent in HIV-1 positive SLE patients.Key Points• This paper presents clinical and laboratory data on the largest cohort of SLE patients with HIV-1 infection reported to date.• The prevalence of SLE in a large outpatient HIV-1 clinic was larger than reported in HIV negative population studies.• The prevalence of SLE was particularly high in black HIV-1 infected women.• Skin/mucosal involvement and anti-ds DNA antibodies were less common in patients with HIV-1 and SLE compared to patients with SLE without SLE>.

Universal angiosperm enrichment probe sets designed to enrich hundreds of putatively orthologous nuclear single-copy loci are increasingly being applied to infer phylogenetic relationships of different lineages of angiosperms at a range of evolutionary depths. Studies applying such probe sets have focused on testing the universality and performance of the target nuclear loci, but they have not taken advantage of off-target data from other genome compartments generated alongside the nuclear loci. Here we do so to infer phylogenetic relationships in the orchid genus Epidendrum and closely related genera of subtribe Laeliinae. Our aims are to: 1) test the technical viability of applying the plant anchored hybrid enrichment (AHE) method (Angiosperm v.1 probe kit) to our focal group, 2) mine plastid protein coding genes from off-target reads; and 3) evaluate the performance of the target nuclear and off-target plastid loci in resolving and supporting phylogenetic relationships along a range of taxonomical depths. Phylogenetic relationships were inferred from the nuclear data set through coalescent summary and site-based methods, whereas plastid loci were analyzed in a concatenated partitioned matrix under maximum likelihood. The usefulness of target and flanking non-target nuclear regions and plastid loci was assessed through the estimation of their phylogenetic informativeness. Our study successfully applied the plant AHE probe kit to Epidendrum , supporting the universality of this kit in angiosperms. Moreover, it demonstrated the feasibility of mining plastome loci from off-target reads generated with the Angiosperm v.1 probe kit to obtain additional, uniparentally inherited sequence data at no extra sequencing cost. Our analyses detected some strongly supported incongruences between nuclear and plastid data sets at shallow divergences, an indication of potential lineage sorting, hybridization, or introgression events in the group. Lastly, we found that the per site phylogenetic informativeness of the ycf1 plastid gene surpasses that of all other plastid genes and several nuclear loci, making it an excellent candidate for assessing phylogenetic relationships at medium to low taxonomic levels in orchids., (Copyright © 2020 Granados Mendoza, Jost, Hágsater, Magallón, van den Berg, Lemmon, Lemmon, Salazar and Wanke.)

Genome3D (https://www.genome3d.eu) is a freely available resource that provides consensus structural annotations for representative protein sequences taken from a selection of model organisms. Since the last NAR update in 2015, the method of data submission has been overhauled, with annotations now being 'pushed' to the database via an API. As a result, contributing groups are now able to manage their own structural annotations, making the resource more flexible and maintainable. The new submission protocol brings a number of additional benefits including: providing instant validation of data and avoiding the requirement to synchronise releases between resources. It also makes it possible to implement the submission of these structural annotations as an automated part of existing internal workflows. In turn, these improvements facilitate Genome3D being opened up to new prediction algorithms and groups. For the latest release of Genome3D (v2.1), the underlying dataset of sequences used as prediction targets has been updated using the latest reference proteomes available in UniProtKB. A number of new reference proteomes have also been added of particular interest to the wider scientific community: cow, pig, wheat and mycobacterium tuberculosis. These additions, along with improvements to the underlying predictions from contributing resources, has ensured that the number of annotations in Genome3D has nearly doubled since the last NAR update article. The new API has also been used to facilitate the dissemination of Genome3D data into InterPro, thereby widening the visibility of both the annotation data and annotation algorithms., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introducción: El deterioro cognitivo leve es una alteración de la función cognitiva que no afecta de manera negativa a las actividades diarias de la persona. Factores de riesgo modificables como la hipertensión arterial podrían intervenir en el aceleramiento de este proceso y afectar a personas menores de 65 años. Una detección temprana del deterioro cognitivo leve por medio del Montreal Cognitive Assesment (MoCA) en personas con hipertensión arterial ayudaría a idear medidas para su control eficaz., Materiales Y Métodos: Se diseñó un estudio de tipo observacional transversal. La población se integra con pacientes hipertensos de 45 a 65 años de Guayaquil. De una base de datos de 570 pacientes, se realizó un llamado a sujetos que cumplieran los criterios de inclusión y exclusión, para la evaluación de la función cognitiva por medio del MoCA., Resultados: El 93.3% de los participantes sometidos a la prueba MoCA presentó un puntaje menor de 26. El promedio del puntaje total fue de 18.9 y el 51.6% de los participantes reveló deterioro cognitivo leve. Se obtuvo una correlación negativa del 40% (-0.40) con una p = 0.0015 entre años con hipertensión arterial y el resultado total de la prueba MoCA., Conclusiones: Por medio del MoCA se pudo cuantificar la magnitud del deterioro cognitivo en estos pacientes. Se identificó que la mayoría de los participantes examinados presentaba un puntaje promedio menor del intervalo normal. Las cifras obtenidas de los valores de correlación de Pearson muestran una actividad tendencial y relación de la hipertensión arterial con el deterioro de la función cognitiva., Introduction: Mild cognitive impairment is an alteration of cognitive function that does not negatively affect the daily activities of the person. Modifiable risk factors such as hypertension could be involved in the acceleration of this process affecting people under 65 years of age. Early detection of mild cognitive impairment through the Montreal Cognitive Assessment (MoCA) in people with high blood pressure, would help to formulate strategies for its effective control., Materials and Methods: A cross-sectional observational study was designed. The population is hypertensive patients between 45 and 65 years old in Guayaquil. From a database of 570 patients, a call was made to patients who met the inclusion and exclusion criteria, for the evaluation of cognitive function through MoCA., Results: 93.3% of the participants who underwent the MoCA test had a score lower than 26. The average of the total score was 18.9, with 51.6% of the participants suffering from mild cognitive impairment. A negative correlation of 40% (-0.40) was obtained with a p = 0.0015 between years with arterial hypertension and the total result of the MoCA test., Conclusions: Through MoCA, the magnitude of cognitive deterioration in these patients could be quantified. It was detected that the majority of the examined participants had a lower average score of the normal range. The figures obtained from the Pearson correlation values show trend activity, relating arterial hypertension and deterioration of cognitive function., (Copyright: © 2020 Permanyer.)

Pathogenicity island excision is a phenomenon that occurs in several Salmonella enterica serovars and other members of the family Enterobacteriaceae. ROD21 is an excisable pathogenicity island found in the chromosome of S. Enteritidis, S. Dublin and S. Typhi among others, which contain several genes encoding virulence-associated proteins. Excision of ROD21 may play a role in the ability of S. Enteritidis to cause a systemic infection in mice. Our previous studies have shown that Salmonella strains unable to excise ROD21 display a reduced ability to colonize the liver and spleen. In this work, we determined the kinetics of ROD21 excision in vivo in C57BL/6 mice and its effect on virulence. We quantified bacterial burden and excision frequency in different portions of the digestive tract and internal organs throughout the infection. We observed that the frequency of ROD21 excision was significantly increased in the bacterial population colonizing mesenteric lymph nodes at early stages of the infective cycle, before 48 hours post-infection. In contrast, excision frequency remained very low in the liver and spleen at these stages. Interestingly, excision increased drastically after 48 h post infection, when intestinal re-infection and mortality begun. Moreover, we observed that the inability to excise ROD21 had a negative effect on S. Enteritidis capacity to translocate from the intestine to deeper organs, which correlates with an abnormal transcription of invA in the S. Enteritidis strain unable to excise ROD21. These results suggest that excision of ROD21 is a genetic mechanism required by S. Enteritidis to produce a successful invasion of the intestinal epithelium, a step required to generate systemic infection in mice., Competing Interests: The authors have declared that no competing interests exist.

The main environmental risk factor associated with the development of Crohn's disease (CD) is cigarette smoking. Although the mechanism is still unknown, some studies have shown that cigarette exposure affects the intestinal barrier of the small bowel. Among the factors that may be involved in this process are Paneth cells. These specialized epithelial cells are located into the small intestine, and they are able to secrete antimicrobial peptides, having an essential role in the control of the growth of microorganisms. Alterations in its function are associated with inflammatory processes, such as CD. To study how cigarette components impact ileum homeostasis and Paneth cells integrity, we used intragastric administration of cigarette smoke condensate (CSC) in mice. Our results showed that inflammation was triggered after mucosal exposure of CSC, which induced particular alterations in Paneth cells granules, antimicrobial peptide production, and a reduction of bactericidal capacity. In fact, exposure to CSC generated an imbalance in the fecal bacterial population and increased the susceptibility of mice to develop ileal damage in response to bacterial infection. Moreover, our results obtained in mice unable to produce interleukin 10 (IL-10 -/- mice) suggest that CSC treatment can induce a symptomatic enterocolitis with a pathological inflammation in genetically susceptible individuals., (Copyright © 2019 Berkowitz, Pardo-Roa, Salazar, Salazar-Echegarai, Miranda, Ramírez, Chávez, Kalergis, Bueno and Álvarez-Lobos.)

Carbapenem-resistant Klebsiella pneumoniae sequence type 258 (CRKP-ST258) can cause chronic infections in lungs and airways, with repeated episodes of bacteremia. In this report we addressed whether the recruitment of myeloid cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) modulates the clearance of CKRP-ST258 in the lungs and establishes bacterial persistence. Our data demonstrate that during pneumonia caused by a clinical isolate of CRKP-ST258 (KP35) there is an early recruitment of monocyte-myeloid-derived suppressor cells (M-MDSCs) and neutrophils that actively produce IL-10. However, M-MDSCs were the cells that sustained the production of IL-10 over the time of infection evaluated. Using mice unable to produce IL-10 (IL-10 -/- ), we observed that the production of this cytokine during the infection caused by KP35 is important to control bacterial burden, to prevent lung damage, to modulate cytokine production, and to improve host survival. Importantly, intranasal transfer of bone marrow-derived M-MDSCs from mice able to produce IL-10 at 1 day prior to infection improved the ability of IL-10 -/- mice to clear KP35 in the lungs, decreasing their mortality. Altogether, our data demonstrate that IL-10 produced by M-MDSCs is required for bacterial clearance, reduction of lung tissue damage, and host survival during KP35 pneumonia., (Copyright © 2019 American Society for Microbiology.)

Background: Given the considerable role played by Salmonella in the incidence of food poisoning around the world, surveillance of this infection is prioritized by both food producers and health care authorities. Data remains insufficient concerning the prevalence of Salmonella in poultry systems in Ecuador and in Latin America in general. Methods: In this study we evaluated the prevalence and diversity of Salmonella serovars in samples taken from 21 layer farms and backyard layers in central Ecuador during August-November 2017.   Salmonella was isolated following standardized methods (ISO 6579) and the serovar determination was carried out by PCR. Results: A significant presence of Salmonella was detected, with an incidence of 76% (95% confidence interval (CI): 58-94) in farms, 33% (95%CI: 13-53) in pooled cloacal swabs from layer hens, 33% (95%CI: 12-55) on feed samples, and 10% (95%CI: 0-22) in backyard layer feces from traditional local markets. The dominant serovars detected were S. Infantis and S. Typhimurium. Conclusions: This study forms a basis for further surveillance of Salmonella serovars in layer farms in central Ecuador., Competing Interests: No competing interests were disclosed.

Automatic annotation of protein function is routinely applied to newly sequenced genomes. While this provides a fine-grained view of an organism's functional protein repertoire, proteins, more commonly function in a coordinated manner, such as in pathways or multimeric complexes. Genome Properties (GPs) define such functional entities as a series of steps, originally described by either TIGRFAMs or Pfam entries. To increase the scope of coverage, we have migrated GPs to function as a companion resource utilizing InterPro entries. Having introduced GPs-specific versioned releases, we provide software and data via a GitHub repository, and have developed a new web interface to GPs (available at https://www.ebi.ac.uk/interpro/genomeproperties). In addition to exploring each of the 1286 GPs, the website contains GPs pre-calculated for a representative set of proteomes; these results can be used to profile GPs phylogenetically via an interactive viewer. Users can upload novel data to the viewer for comparison with the pre-calculated results. Over the last year, we have added ∼700 new GPs, increasing the coverage of eukaryotic systems, as well as increasing general coverage through automatic generation of GPs from related resources. All data are freely available via the website and the GitHub repository.

The last few years have witnessed significant changes in Pfam (https://pfam.xfam.org). The number of families has grown substantially to a total of 17,929 in release 32.0. New additions have been coupled with efforts to improve existing families, including refinement of domain boundaries, their classification into Pfam clans, as well as their functional annotation. We recently began to collaborate with the RepeatsDB resource to improve the definition of tandem repeat families within Pfam. We carried out a significant comparison to the structural classification database, namely the Evolutionary Classification of Protein Domains (ECOD) that led to the creation of 825 new families based on their set of uncharacterized families (EUFs). Furthermore, we also connected Pfam entries to the Sequence Ontology (SO) through mapping of the Pfam type definitions to SO terms. Since Pfam has many community contributors, we recently enabled the linking between authorship of all Pfam entries with the corresponding authors' ORCID identifiers. This effectively permits authors to claim credit for their Pfam curation and link them to their ORCID record.

The InterPro database (http://www.ebi.ac.uk/interpro/) classifies protein sequences into families and predicts the presence of functionally important domains and sites. Here, we report recent developments with InterPro (version 70.0) and its associated software, including an 18% growth in the size of the database in terms on new InterPro entries, updates to content, the inclusion of an additional entry type, refined modelling of discontinuous domains, and the development of a new programmatic interface and website. These developments extend and enrich the information provided by InterPro, and provide greater flexibility in terms of data access. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB, and discuss how our evaluation of residue coverage may help guide future curation activities.

Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe 2+ , biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.

Objective: The 2 pneumoproteins, KL-6 and CCL-18, are promising biomarkers in systemic sclerosis (SSc)-related interstitial lung disease (ILD). Our goal was to determine their predictive significance for forced vital capacity % (FVC%) decline within the first year of followup in patients with early SSc-ILD., Methods: Early SSc patients with imaging-verified ILD enrolled in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) cohort were included. Annualized rate of change in FVC% based on the baseline and followup measurement within 12-18 months was used as the surrogate outcomes for ILD progression., Results: Eighty-two early SSc-ILD patients with mean disease duration of 2.3 years were investigated. FVC% change ranged from -23% to 38%. Baseline KL-6 levels were higher in patients than healthy controls (p < 0.0001). Higher KL-6 levels were predictive of faster FVC% decline at the 1-year followup (r = -0.23, p = 0.037). Upon categorizing KL-6 using a previously published cutoff of 1273 U/ml, its predictive significance remained in the univariable model (b = -0.07, p = 0.01), indicating that patients with positive KL-6 had on average 7% more decline in annualized percent change of FVC%. Moreover, KL-6 remained an independent predictor after adjustment for sex, disease type, anti-Scl-70, and immunosuppressive treatment status in multivariable models. Although CCL-18 was higher in patients than controls (p < 0.001), its levels did not predict FVC decline rate (p = 0.458)., Conclusion: KL-6 but not CCL-18 is predictive of early SSc-ILD progression. KL-6 is a promising pneumoprotein that can contribute to SSc-ILD clinical trial enrichment.

Chronic intestinal inflammations are triggered by genetic and environmental components. However, it remains unclear how specific changes in the microbiota, host immunity, or pathogen exposure could promote the onset and exacerbation of these diseases. Here, we evaluated whether Salmonella enterica serovar Typhimurium ( S . Typhimurium) infection increases the susceptibility to develop intestinal inflammation in mice. Two mouse models were used to evaluate the impact of S . Typhimurium infection: the chemical induction of colitis by dextran sulfate sodium (DSS) and interleukin (IL)-10 -/- mice, which develop spontaneous intestinal inflammation. We observed that S . Typhimurium infection makes DSS-treated and IL-10 -/- mice more susceptible to develop intestinal inflammation. Importantly, this increased susceptibility is associated to the ability of S . Typhimurium to persist in liver and spleen of infected mice, which depends on the virulence proteins secreted by Salmonella Pathogenicity Island 2-encoded type three secretion system (TTSS-2). Although immunization with a live attenuated vaccine resulted in a moderate reduction of the IL-10 -/- mice susceptibility to develop intestinal inflammation due to previous S . Typhimurium infection, it did not prevent bacterial persistence. Our results suggest that persistent S . Typhimurium infection may increase the susceptibility of mice to develop inflammation in the intestine, which could be associated with virulence proteins secreted by TTSS-2.

Introduction: Only a few scales have been validated in Spanish for the assessment of suicide risk, and none of them have achieved predictive validity., Objective: To determine the validity and reliability of the Beck Hopelessness Scale in patients with suicide risk attending the specialist clinic., Methods: The Beck Hopelessness Scale, reasons for living inventory, and the suicide behaviour questionnaire were applied in patients with suicide risk attending the psychiatric clinic and the emergency department. A new assessment was made 30 days later to determine the predictive validity of suicide or suicide attempt., Results: The evaluation included a total of 244 patients, with a mean age of 30.7±13.2 years, and the majority were women. The internal consistency was .9 (Kuder-Richardson formula 20). Four dimensions were found which accounted for 50% of the variance. It was positively correlated with the suicidal behaviour questionnaire (Spearman .48, P<.001), number of suicide attempts (Spearman .25, P<.001), severity of suicide risk (Spearman .23, P<.001). The correlation with the reasons for living inventory was negative (Spearman -.52, P<.001). With a cut-off ≥12, the negative predictive value was 98.4% (95% CI: 94.2-99.8), and the positive predictive value was 14.8% (95% CI: 6.6-27.1)., Conclusion: The Beck Hopelessness Scale in Colombian patients with suicidality shows results similar to the original version, with adequate reliability and moderate concurrent and predictive validity., (Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cigarette smoking is a major risk factor for gastrointestinal disorders, such as peptic ulcer, Crohn's disease (CD), and several cancers. The mechanisms proposed to explain the role of smoking in these disorders include mucosal damage, changes in gut irrigation, and impaired mucosal immune response. Paradoxically, cigarette smoking is a protective factor for the development and progression of ulcerative colitis (UC). UC and CD represent the two most important conditions of inflammatory bowel diseases, and share several clinical features. The opposite effects of smoking on these two conditions have been a topic of great interest in the last 30 years, and has not yet been clarified. In this review, we summarize the most important and well-understood effects of smoking in the gastrointestinal tract; and particularly, in intestinal inflammation, discussing available studies that have addressed the causes that would explain the opposite effects of smoking in CD and UC.

EBI metagenomics (http://www.ebi.ac.uk/metagenomics) provides a free to use platform for the analysis and archiving of sequence data derived from the microbial populations found in a particular environment. Over the past two years, EBI metagenomics has increased the number of datasets analysed 10-fold. In addition to increased throughput, the underlying analysis pipeline has been overhauled to include both new or updated tools and reference databases. Of particular note is a new workflow for taxonomic assignments that has been extended to include assignments based on both the large and small subunit RNA marker genes and to encompass all cellular micro-organisms. We also describe the addition of metagenomic assembly as a new analysis service. Our pilot studies have produced over 2400 assemblies from datasets in the public domain. From these assemblies, we have produced a searchable, non-redundant protein database of over 50 million sequences. To provide improved access to the data stored within the resource, we have developed a programmatic interface that provides access to the analysis results and associated sample metadata. Finally, we have integrated the results of a series of statistical analyses that provide estimations of diversity and sample comparisons., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

We conducted a pilot study using Anchored Hybrid Enrichment to resolve relationships among a mostly Neotropical sage lineage that may have undergone a recent evolutionary radiation. Conventional markers (ITS, trnL-trnF and trnH-psbA) have not been able to resolve the relationships among species nor within portions of the backbone of the lineage. We sampled 12 representative species of subgenus Calosphace and included one species of Salvia's s.l. closest relative, Lepechinia, as outgroup. Hybrid enrichment and sequencing were successful, yielding 448 alignments of individual loci with an average length of 704bp. The performance of the phylogenomic data in phylogenetic reconstruction was superior to that of conventional markers, increasing both support and resolution. Because the captured loci vary in the amount of net phylogenetic informativeness at different phylogenetic depths, these data are promising in phylogenetic reconstruction of this group and likely other lineages within Lamiales. However, special attention should be placed on the amount of phylogenetic noise that the data could potentially contain. A prior exploration step using phylogenetic informativeness profiles to detect loci with sites with disproportionately high substitution rates (showing "phantom" spikes) and, if required, the ensuing filtering of the problematic data is recommended. In our dataset, filtering resulted in increased support and resolution for the shallow nodes in maximum likelihood phylogenetic trees resulting from concatenated analyses of all the loci. Additionally, it is expected that an increase in sampling (loci and taxa) will aid in resolving weakly supported, short deep internal branches., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: There are few clinical predictors of the progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). The purpose of this study was to examine the predictive significance of key cytokines for long-term progression of ILD and survival in 2 independent cohorts of patients with early SSc., Methods: Plasma levels of 11 Th1/Th2 cytokines (interleukin-1β [IL-1β], IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor, CCL2, interferon-inducible T cell α chemoattractant, and interferon-γ-inducible 10-kd protein) were measured in 266 patients with early SSc in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) discovery cohort. Levels of CCL2, IL-10, and IL-6 were measured in 171 patients with early SSc in the Canadian Scleroderma Research Group (CSRG) replication cohort. The primary outcome measure was a decline in the forced vital capacity percent predicted (FVC%) value over time. A joint analysis of longitudinal FVC% values and survival was performed., Results: After adjustment for age, sex, and ethnicity, CCL2 and IL-10 were found to be significant predictors of ILD progression in the discovery cohort. Higher CCL2 levels predicted a faster decline in FVC% values (b = -0.57, P = 0.032), while higher IL-10 levels predicted a slower decline (b = 0.26, P = 0.01). A higher CCL2 value was also predictive of poorer survival (hazard ratio 1.76, P = 0.030). In the CSRG replication cohort, higher CCL2 levels predicted a faster decline in FVC% values (b = -0.58, P = 0.038), but neither IL-10 nor IL-6 had predictive significance. A higher CCL2 level also predicted poorer survival (hazard ratio 3.89, P = 0.037)., Conclusion: Higher CCL2 levels in the circulation were predictive of ILD progression and poorer survival in patients with early SSc, findings that support the notion that CCL2 has a role as a biomarker and potential therapeutic target., (© 2017, American College of Rheumatology.)

Salmonella enterica serovar Typhimurium ( S . Typhimurium) is a Gram-negative bacterium that produces disease in numerous hosts. In mice, oral inoculation is followed by intestinal colonization and subsequent systemic dissemination, which leads to severe pathogenesis without the activation of an efficient anti- Salmonella immune response. This feature suggests that the infection caused by S . Typhimurium may promote the production of anti-inflammatory molecules by the host that prevent efficient T cell activation and bacterial clearance. In this study, we describe the contribution of immune cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) to the systemic infection caused by S . Typhimurium in mice. We observed that the production of IL-10 was required by S . Typhimurium to cause a systemic disease, since mice lacking IL-10 (IL-10 -/- ) were significantly more resistant to die after an infection as compared to wild-type (WT) mice. IL-10 -/- mice had reduced bacterial loads in internal organs and increased levels of pro-inflammatory cytokines in serum at 5 days of infection. Importantly, WT mice showed high bacterial loads in tissues and no increase of cytokines in serum after 5 days of S . Typhimurium infection, except for IL-10. In WT mice, we observed a peak of il-10 messenger RNA production in ileum, spleen, and liver after 5 days of infection. Importantly, the adoptive transfer of T or B cells from WT mice restored the susceptibility of IL-10 -/- mice to systemic S . Typhimurium infection, suggesting that the generation of regulatory cells in vivo is required to sustain a systemic infection by S . Typhimurium. These findings support the notion that IL-10 production from lymphoid cells is a key process in the infective cycle of S . Typhimurium in mice due to generation of a tolerogenic immune response that prevents bacterial clearance and supports systemic dissemination.

Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue, and sheds light on new mechanisms of platelet activation and platelet-mediated immune and inflammatory responses.

Inflammatory bowel disease (IBD) includes a set of pathologies that result from a deregulated immune response that may affect any portion of the gastrointestinal tract. The most prevalent and defined forms of IBD are Crohn's disease and ulcerative colitis. Although the etiology of IBD is not well defined, it has been suggested that environmental and genetic factors contribute to disease development and that the interaction between these two factors can trigger the pathology. Diet, medication use, vitamin D status, smoking, and bacterial infections have been proposed to influence or contribute to the onset or development of the disease in susceptible individuals. The infection with pathogenic bacteria is a key factor that can influence the development and severity of this disease. Here, we present a comprehensive review of studies performed in human and mice susceptible to IBD, which supports the notion that infection with bacterial pathogens, such as Salmonella , could promote the onset of IBD due to permanent changes in the intestinal microbiota, disruption of the epithelial barrier and alterations of the intestinal immune response after infection.

Interleukin-10 (IL-10) is recognized as an anti-inflammatory cytokine that downmodulates inflammatory immune responses at multiple levels. In innate cells, production of this cytokine is usually triggered after pathogen recognition receptor (PRR) engagement by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patters (DAMPs), as well as by other soluble factors. Importantly, IL-10 is frequently secreted during acute bacterial infections and has been described to play a key role in infection resolution, although its effects can significantly vary depending on the infecting bacterium. While the production of IL-10 might favor host survival in some cases, it may also result harmful for the host in other circumstances, as it can prevent appropriate bacterial clearance. In this review we discuss the role of IL-10 in bacterial clearance and propose that this cytokine is required to recover from infection caused by extracellular or highly pro-inflammatory bacteria. Altogether, we propose that IL-10 drives excessive suppression of the immune response upon infection with intracellular bacteria or in non-inflammatory bacterial infections, which ultimately favors bacterial persistence and dissemination within the host. Thus, the nature of the bacterium causing infection is an important factor that needs to be taken into account when considering new immunotherapies that consist on the modulation of inflammation, such as IL-10. Indeed, induction of this cytokine may significantly improve the host's immune response to certain bacteria when antibiotics are not completely effective., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc., Methods: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc., Results: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (β = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (β = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (β = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort., Conclusions: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.