Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

VALIDEZ EN LA INVESTIGACIÓN IMAGINOLÓGICA VALIDITY IN IMAGING RESEARCH

Es habitual observar que al concepto de validez se le otorgue un significado adicional sobre la difusión de conocimientos y conclusiones científicas, no obstante esta sea una propiedad de la interpretación de valores obtenidos de instrumentos de medición. El manejo inadecuado de este concepto genera confusión y puede incurrir en una falsa legitimación de inferencias científicas. Por medio de esta revisión, es intención de los autores colaborar en la compresión de este constructo desde su perspectiva histórica y operativa, con el objetivo de permitir, tanto al usuario de la literatura imaginológica como a quienes comunican los resultados de sus investigaciones, dar un correcto uso semántico así como distinguir algunos de los recursos estadísticos prácticos para sostener esta propiedad.<br>It is common to note that the concept of validity is given added significance in the realm of knowledge and scientific finding dissemination, despite being an attribute of value interpretation of measuring instruments. Improper management of this concept generates confusion and may lead to a false legitimation of scientific inferences. Through this review, the authors intend to contribute to the understanding of this construct analyzing it from a historical and operational perspective in order to allow both the user of the imaging literature and those who report the results of their research to give the concept a semantically correct use as well as to identify some of the practical statistical resources to support this attribute

Tumor de wilms: estudio de centro único de los andes ecuatorianos. serie de casos con seguimiento

El tumor de Wilms (WT) es el tumor renal pediátrico más común entre 1 y 5 años de edad. La evidencia existente con respecto a los aspectos clínicos, terapéuticos y de supervivencia (SV) de TW es escasa. El objetivo de este estudio fue determinar las diferencias en la supervivencia general (SG) a 5 años y la supervivencia libre de enfermedad (SSE) a 5 años, en pacientes tratados con WT con quimioterapia neoadyuvante (NACT) y cirugía inicial (IS). Series de casos. Se incluyeron pacientes con TW entre 11 meses y 13 años de edad, tratados en el Instituto de Cáncer SOLCA, Cuenca, Ecuador (1994-2019). Las variables de resultado fueron OS y DFS. Una vez que se completaron sus tratamientos, los pacientes fueron seguidos clínicamente. Se aplicaron estadísticas descriptivas (medidas de tendencia central y dispersión) y analíticas (Chi2, corrección exacta y de continuidad de Fisher). Se realizaron análisis SV con curvas de Kaplan Meier y log-rank. 36 pacientes (52.8% hombres), con una mediana de edad de 44 meses; El 55.5% de los cuales tenían histología favorable fueron reclutados. La ubicación y el estadio más frecuentes fue el riñón izquierdo (55.5%) y el I (33.3%) respectivamente. El 58,3% se sometió a IC y el 41,7% de QTNA. Después de los tratamientos, 21 pacientes (58,3%) lograron la remisión completa. General OS y DFS fueron 72.0% y 69.0% respectivamente. Al comparar subgrupos con QTNA y CI. Al comparar los subgrupos con QTNA e IC, se verificaron OS y DFS de 60.0% y 81.0% (p = 0.118); y de 66.7% y 71.4% (p = 0.536) respectivamente. El OS general y el DFS observados son similares a los informados en otros estudios. No se evidenciaron diferencias con los tratamientos QTNA e IC.Wilms tumor (WT) is the most common pediatric kidney tumor between 1 and 5 years of age. The existing evidence regarding clinical, therapeutic and survival (SV) aspects of TW is scarce. The aim of this study was to determine differences in 5-year overall survival (OS) and 5-year disease-free survival (DFS), in patients treated by WT with neoadjuvant chemotherapy (NACT) and initial surgery (IS). Case series. Patients with TW between 11 months and 13 years of age, treated at SOLCA Cancer Institute, Cuenca, Ecuador (1994-2019) were included. The outcome variables were OS and DFS. Once their treatments were completed, patients were followed clinically. Descriptive (measures of central tendency and dispersion) and analytical (Chi2, Fisher's exact and continuity correction) statistics were applied. SV analysis with Kaplan Meier curves and log-rank were performed. 36 patients (52.8 % men), with a median age of 44 months; 55.5 % of which had favorable histology were recruited. The most frequent location and stage was left kidney (55.5 %) and I (33.3 %) respectively. 58.3 % underwent IC and 41.7 % QTNA. After treatments, 21 patients (58.3 %) achieved complete remission. General OS and DFS were 72.0 % and 69.0 % respectively. When comparing subgroups with QTNA and CI. When comparing the subgroups with QTNA and CI, OS and DFS of 60.0 % and 81.0 % were verified (p=0.118); and of 66.7 % and 71.4 % (p=0.536) respectively. General OS and DFS observed are similar to those reported in other studies. No differences were evidenced with QTNA and CI treatments

High intraspecific variability of Echinococcus granulosus sensu stricto in Chile

Echinococcus granulosus sensu stricto is the major cause of cystic echinococcosis in most human and animal cases in the world and the most widespread species within the E. granulosus sensu lato complex. E. granulosus s.s. remains endemic in South America together with other species of the Echinococcus genus, especially in some areas in Argentina, Brazil, Chile and Peru. Except for a single human case caused by E. canadensis (G6) described in the literature, only E. granulosus s.s. has been found in the Chilean territory. In the current study 1609bp of the cox1 gene from 69 Chilean isolates of E. granulosus s.s. from humans and animals were analysed. In total, 26 cox1 haplotypes were found, including the widespread haplotype EG01 (22 isolates) and also EGp1 (5), EgRUS7 (1), EgAus02 (1) and EgAus03 (2). Twenty-one different haplotype not previously described were identified from 38 Chilean isolates designated EgCL1-EgCL21. Previous work had described low variability of E. granulosus s.s. in South America, based on isolates from Peru. Results obtained in this work challenge the previously described idea of the low diversity of the parasite in South America, and warrant future investigation on the origin and spread of the parasite in the continent after the Spanish arrival