Brucella neotomae Infection in Humans, Costa Rica

Several species of Brucella are known to be zoonotic, but B. neotomae infection has been thought to be limited to wood rats. In 2008 and 2011, however, B. neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis. The nonzoonotic status of B. neotomae should be reassessed

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Brucella abortus ornithine lipids are dispensable outer membrane components devoid of a marked pathogen-associated molecular pattern

The brucellae are α-Proteobacteria facultative intracellular parasites that cause an important zoonosis. These bacteria escape early detection by innate immunity, an ability associated to the absence of marked pathogen-associated molecular patterns in the cell envelope lipopolysaccharide, lipoproteins and flagellin. We show here that, in contrast to the outer membrane ornithine lipids (OL) of other Gram negative bacteria, Brucella abortus OL lack a marked pathogen-associated molecular pattern activity. We identified two OL genes (olsB and olsA) and by generating the corresponding mutants found that olsB deficient B. abortus did not synthesize OL or their lyso-OL precursors. Liposomes constructed with B. abortus OL did not trigger IL-6 or TNF-α release by macrophages whereas those constructed with Bordetella pertussis OL and the olsB mutant lipids as carriers were highly active. The OL deficiency in the olsB mutant did not promote proinflammatory responses or generated attenuation in mice. In addition, OL deficiency did not increase sensitivity to polymyxins, normal serum or complement consumption, or alter the permeability to antibiotics and dyes. Taken together, these observations indicate that OL have become dispensable in the extant brucellae and are consistent within the trend observed in α-Proteobacteria animal pathogens to reduce and eventually eliminate the envelope components susceptible of recognition by innate immunity

Canine brucellosis in Costa Rica reveals widespread Brucella canis infection and the recent introduction of foreign strains

Brucellosis is a prevalent disease in Costa Rica (CR), with an increasing number of human infections. Close to half of homes in CR have one or more dogs, corresponding to ∼1.4 million canines, most of them in the Central Valley within or near the cities of San José, Heredia, and Alajuela. From 302 dog sera collected from this region, 19 were positive for Brucella canis antigens, and five had antibodies against smooth lipopolysaccharide, suggesting infections by both B. canis and other Brucella species. B. canis strains were isolated in the Central Valley from 26 kennel dogs and three pet dogs, all displaying clinical signs of canine brucellosis. We detected three recent introductions of different B. canis strains in kennels: two traced from Mexico and one from Panama. Multiple locus-variable number tandem repeats (MLVA-16) and whole-genome sequencing (WGSA) analyses showed that B. canis CR strains comprise three main lineages. The tree topologies obtained by WGSA and MLVA-16 just partially agreed, indicating that the latter analysis is not suitable for phylogenetic studies. The fatty acid methyl ester analysis resolved five different B. canis groups, showing less resolution power than the MLVA-16 and WGSA. Lactobacillic acid was absent in linages I and II but present in linage III, supporting the recent introductions of B. canis strains from Mexico. B. canis displaying putative functional cyclopropane synthase for the synthesis of lactobacillic acid are phylogenetically intertwined with B. canis with non-functional protein, indicating that mutations have occurred independently in the various lineages.La brucelosis es una enfermedad prevalente en Costa Rica (CR), con un número creciente de infecciones humanas. Cerca de la mitad de los hogares de CR tienen uno o más perros, lo que corresponde a ∼1,4 millones de caninos, la mayoría de ellos en el Valle Central dentro o cerca de las ciudades de San José, Heredia y Alajuela. De 302 sueros caninos recogidos en esta región, 19 resultaron positivos a los antígenos de Brucella canis, y cinco tenían anticuerpos contra el lipopolisacárido liso, lo que sugiere infecciones tanto por B. canis como por otras especies de Brucella. En el Valle Central se aislaron cepas de B. canis en 26 perros de perrera y tres perros de compañía, todos ellos con signos clínicos de brucelosis canina. Se detectaron tres introducciones recientes de diferentes cepas de B. canis en perreras: dos trazadas desde México y una desde Panamá. Los análisis de repeticiones en tándem de número variable de locus múltiples (MLVA-16) y de secuenciación del genoma completo (WGSA) mostraron que las cepas de B. canis CR comprenden tres linajes principales. Las topologías del árbol obtenidas por WGSA y MLVA-16 sólo coincidieron parcialmente, lo que indica que este último análisis no es adecuado para los estudios filogenéticos. El análisis de ésteres metílicos de ácidos grasos resolvió cinco grupos diferentes de B. canis, mostrando un menor poder de resolución que el MLVA-16 y el WGSA. El ácido lactobacilo estaba ausente en los linajes I y II, pero presente en el linaje III, lo que apoya las recientes introducciones de cepas de B. canis procedentes de México. Las cepas de B. canis que presentan una putativa ciclopropano sintasa funcional para la síntesis del ácido lactobacilo están filogenéticamente entrelazadas con las de B. canis con proteína no funcional, lo que indica que las mutaciones se han producido de forma independiente en los distintos linajes.Universidad Nacional, Costa RicaUniversidad de Costa RicaMinisterio de Agricultura y Ganadería, Costa RicaWellcome Sanger Institute, Reino UnidoUniversidad del Norte de Arizona, Estados UnidosEscuela de Medicina Veterinari

The differential interaction of Brucella and Ochrobactrum with innate immunity reveals traits related to the evolution of stealthy pathogens

Background: During evolution, innate immunity has been tuned to recognize pathogen-associated molecular patterns. However, some alpha-Proteobacteria are stealthy intracellular pathogens not readily detected by this system. Brucella members follow this strategy and are highly virulent, but other Brucellaceae like Ochrobactrum are rhizosphere inhabitants and only opportunistic pathogens. To gain insight into the emergence of the stealthy strategy, we compared these two phylogenetically close but biologically divergent bacteria. Methodology/principal Findings: In contrast to Brucella abortus, Ochrobactrum anthropi did not replicate within professional and non-professional phagocytes and, whereas neutrophils had a limited action on B. abortus, they were essential to control O. anthropi infections. O. anthropi triggered proinflammatory responses markedly lower than Salmonella enterica but higher than B. abortus. In macrophages and dendritic cells, the corresponding lipopolysaccharides reproduced these grades of activation, and binding of O. anthropi lipopolysaccharide to the TLR4 co-receptor MD-2 and NF-kappaB induction laid between those of B. abortus and enteric bacteria lipopolysaccharides. These differences correlate with reported variations in lipopolysaccharide core sugars, sensitivity to bactericidal peptides and outer membrane permeability. Conclusions/significance: The results suggest that Brucellaceae ancestors carried molecules not readily recognized by innate immunity, so that non-drastic variations led to the emergence of stealthy intracellular parasites. They also suggest that some critical envelope properties, like selective permeability, are profoundly altered upon modification of pathogen-associated molecular patterns, and that this represents a further adaptation to the host. It is proposed that this adaptive trend is relevant in other intracellular alpha-Proteobacteria like Bartonella, Rickettsia, Anaplasma, Ehrlichia and Wolbachia

Reproductive biology of Oligosarcus argenteus (Gunther, 1864) adult males and description of the gonadal maturation stages

Oligosarcus argenteus belongs to the Acestrorhynchinae subfamily, being restricted to South America, and found in several Brazilian hydrographic basins, in lotic and lentic environments, where they are able to reproduce. With the purpose of studying the reproductive biology of the males from this species, many morphological parameters were analyzed during a 24 month period, as well as characterizing the different testicular maturation stages. A maturity scale, with three stages (I - Initial Maturing, II - Intermediate Maturing, III - Final Maturing) was proposed for the adult males of Oligosarcus argenteus. The reproductive period was established by the bimonthly frequency of spermatogenesis and by the gonadal maturation stages.<br>Oligosarcus argenteus é uma espécie pertencente à subfamília Acestrorhynchinae, restrita à América do Sul, sendo comumente encontrada nas várias bacias hidrográficas brasileiras, em ambientes lóticos e lênticos, onde se reproduzem. Com o objetivo de estudar a biologia reprodutiva de machos desta espécie, vários parâmetros morfológicos foram analisados durante um período de 24 meses, assim como foram caracterizados os diferentes estádios de maturação testicular. Estes foram descritos, considerando-se exemplares adultos, em: Estádio I - Maturação Inicial, Estádio II - Maturação Intermediária e Estádio III - Maturação Final. Pela freqüência bimestral das células germinativas e dos estádios de maturação gonadal, a época de reprodução foi determinada

Essential Features of an Interstitial Lung Disease Multidisciplinary Meeting An International Delphi Survey

Rationale: The interstitial lung disease (ILD) multidisciplinary meetings (MDM), composed of pulmonologists, radiologists, and pathologists, is integral to the rendering of an accurate ILD diagnosis. However, there is significant heterogeneity in the conduct of ILD MDMs, and questions regarding their best practices remain unanswered. Objectives: To achieve consensus among ILD experts on essential components of an ILD MDM. Methods: Using a Delphi methodology, semi-structured interviews with ILD experts were used to identify key themes and features of ILD MDMs. These items informed two subsequent rounds of online questionnaires that were used to achieve consensus among a broader, international panel of ILD experts. Experts were asked to rate their level of agreement on a five-point Likert scale. An a priori threshold for consensus was set at a median score 4 or 5 with an interquartile range of 0. Results: We interviewed 15 ILD experts, and 102 ILD experts participated in the online questionnaires. Five items and two exploratory statements achieved consensus on being essential for an ILD MDM following two questionnaire rounds. There was consensus that the presence of at least one radiologist, a quiet setting with a visual projection system, a high-quality chest high-resolution computed tomography, and a standardized template summarizing collated patient data are essential components of an ILD MDM. Experts also agreed that it would be useful for ILD MDMs to undergo an annual benchmarking process and a validation process by fulfilling a minimum number of cases annually. Twenty-seven additional features were considered to be either highly desirable or desirable features based on the degree of consensus. Although our findings on desirable features are similar to the current literature, several of these remain controversial and warrant further research. The study also showed an agreement among participants on several future concepts to improve the ILD MDM, such as performing regular self-assessments and conducting research into shared practices to develop an international expert guideline statement on ILD MDMs. Conclusions: This Delphi study showed consensus among international ILD experts on essential and desirable features of an ILD MDM. Our data represent an important step toward potential collaborative research into future standardization of ILD MDMs

Latin America: situation and preparedness facing the multi-country human monkeypox outbreak

Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Risaralda, Colombia / Universidad Científica del Sur. Master of Clinical Epidemiology and Biostatistics. Lima, Peru / Latin American network of Monkeypox Virus Research. Pereira, Risaralda, ColombiaUniversity of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina.Hospital Britanico de Buenos Aires. Servicio de Infectología. Buenos Aires, Argentina.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muniz. Buenos Aires, Argentina.University of Buenos Aires. Cátedra de Enfermedades Infecciosas. Buenos Aires, Argentina / Hospital de Enfermedades Infecciosas F. J. Muniz. Buenos Aires, Argentina.Hospital Clínico Viedma. Cochabamba, Bolivia.Gobierno Autonomo Municipal de Cochabamba. Secretaría de Salud. Centros de Salud de Primer Nivel. Direction. Cochabamba, Bolivia.Franz Tamayo University. National Research Coordination. La Paz, Bolivia.Paulista State University Júlio de Mesquita Filho. Botucatu Medical School. Infectious Diseases Department. São Paulo, SP, Brazil / Brazilian Society for Infectious Diseases. Sãao Paulo, SP, Brazil.Universidade de São Paulo. Faculdade de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, Brazil.Institute of Infectious Diseases Emilio Ribas. São Paulo, Brazil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Centro de Referencia de Salud Dr. Salvador Allende Gossens. Policlínico Neurología. Unidad Procedimientos. Santiago de Chile, Chile.Pontificia Universidad Católica de Chile. School of Medicine. Department of Pediatric Infectious Diseases and Immunology. Santiago de Chile, Chile.Universidad Austral de Chile. Facultad de Medicina. Instituto de Salud Publica. Valdivia, Chile.Ministerio de Salud. Hospital de San Fernando. San Fernando, VI Region, Chile.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigación Biomedicina. Pereira, Risaralda, Colombia.Universidad Nacional de Colombia. Department of Pediatrics. Bogota, DC, Colombia / Hospital Pediatrico La Misericordia. Division of Infectious Diseases. Bogota, DC, Colombia.Hemera Unidad de Infectología IPS SAS. Bogota, Colombia.Hospital San Vicente Fundacion. Rionegro, Antioquia, Colombia.Clinica Imbanaco Grupo Quironsalud. Cali, Colombia / Universidad Santiago de Cali. Cali, Colombia / Clinica de Occidente. Cali, Colombia / Clinica Sebastian de Belalcazar. Valle del Cauca, Colombia.National Institute of Gastroenterology. Epidemiology Unit. La Habana, CubaHospital Salvador Bienvenido Gautier. Santo Domingo, Dominican Republic.Pontificia Universidad Catolica Madre y Maestra. Santiago, Dominican Republic.International University of Ecuador. School of Medicine. Quito, Ecuador.Universidad Tecnica de Ambato. Ambato, Ecuador.Hospital Roosevelt. Guatemala City, Guatemala.Universidad Nacional Autonoma de Honduras. Faculty of Medical Sciences. School of Medical. Unit of Scientific Research. Tegucigalpa, Honduras.Hospital Infantil de Mexico. Federico Gomez, Mexico City, Mexico.Hospital General de Tijuana. Departamento de Infectología. Tijuana, Mexico.Hospital General de Tijuana. Departamento de Infectología. Tijuana, Mexico.Asociacion de Microbiólogos y Químicos Clínicos de Nicaragua. Managua, Nicaragua.Hospital Santo Tomas. Medicine Department-Infectious Diseases Service. Panama City, Panama / Instituto Oncologico Nacional. Panama city, Panama.University of Arizona College of Medicine-Phoenix. Division of Endocrinology. Department of Medicine. Phoenix, AZ, USA / Indian School Rd. Phoenix, AZ, USA.Dirección Nacional de Vigilancia Sanitaria. Dirección de Investigación. Asunción, Paraguay.Universidad Nacional de Asuncion. Faculty of Medical Sciences. Division of Dermatology. Asuncion, Paraguay.Instituto Nacional de Salud del Nino San Borja. Infectious Diseases Division. Lima, Peru / Universidad Privada de Tacna. Facultad de Ciencias de la Salud. Tacna, Peru.Universidad San Juan Bautista. Lima, Peru.Universidad San Ignacio de Loyola. Vicerrectorado de Investigación. Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud. Lima, Peru.Hospital Evangelico de Montevideo. Montevideo, Uruguay.Icahn School of Medicine at Mount Sinai. Molecular and Cell-based Medicine. Department of Pathology. Molecular Microbiology Laboratory. New York, USA / Universidad del Rosario. Facultad de Ciencias Naturales. Centro de Investigaciones en Microbiología y Biotecnología-UR. Bogota, Colombia.Hospital Evangélico de Montevideo. Montevideo, Uruguay / Venezuelan Science Incubator and the Zoonosis and Emerging Pathogens Regional Collaborative Network. Infectious Diseases Research Branch. Cabudare, Lara, Venezuela.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela.Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela / Biomedical Research and Therapeutic Vaccines Institute. Ciudad Bolivar, Venezuela.Universidad Central de Venezuela. Tropical Medicine Institute, Infectious Diseases Section. Caracas, Venezuela.Instituto Conmemorativo Gorgas de Estudios de la Salud. Clinical Research Department. Investigador SNI Senacyt Panama. Panama City, Panama