Subconjunctival liposomal sirolimus vs. cyclosporine or tacrolimus as treatment of keratoconjunctivitis sicca in dogs: A double-blind, randomized study.

PURPOSE: To compare the safety and efficacy of a 100 microgram subconjunctival injection of liposome-encapsulated sirolimus (SCJS) to cyclosporine (CsA) or tacrolimus (CsA/T) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. METHODS: Dogs with signs and symptoms of KCS were block-randomized to one of two treatment groups: Biweekly SCJS or conventional treatment (CsA/T). Schirmer tear test 1 (STT-1) scores, conjunctival hyperemia (CH) scores, corneal opacity (CO) scores, and clinical evaluation of potential side effects were recorded every 2 weeks for 14 weeks for both groups. Differences between groups were analyzed using the mixed results ANOVA and U-Mann Whitney tests (p < .05 was considered significant). RESULTS: A total of 30 eyes were included in the study, of which 20 eyes completed follow-up. There was no statistically significant interaction between the treatment group and time on STT-1 score (p = .165), and median CH and CO scores showed no statistically significant differences between groups (p = .353 and p = .393, respectively). There were no clinically significant side effects present in any subject at any time. CONCLUSION: In this trial, a 1 mg/mL (100 micrograms) SCJS every 2 weeks showed similar safety and efficacy profiles as daily CsA/T in dogs with KS after 14 weeks of treatment. Larger studies should be performed to further assess SCJS as an alternative treatment for KCS.

Specific targeting to the Mycobacterium tuberculosis P-type ATPase Membrane Transporter, CtpF, of antituberculous compounds obtained by structure-based design.

Background: The resurgence of Mycobacterium tuberculosis (Mtb) strains that resist anti-tuberculosis (anti-TB) drugs used currently stresses the search for more effective low-toxicity drugs against new targets. Due to their role in ion homeostasis and virulence, Mtb plasma membrane P-type ATPases are interesting anti-TB targets, in particular, the Ca2+ transporting P2-type ATPase CtpF which is involved in oxidative stress response and persistence. Methods: In this study, the effect on the transcription level of the ctpF gene and other Mtb P2-type ATPases of two anti-Mtb hits was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Both anti-Mtb hits ZINC14541509 and ZINC63908257 had been previously identified using pharmacophore-based virtual screening and MM-GBSA binding free energy. In addition, the bacterial activity of both compounds on Mycobacterium bovis was evaluated to see whether or not there is an effect on other mycobacteria of the Mtb complex. Results: qRT-PCR experiments showed that the ctpF transcription level was significantly higher in the presence of both compounds, especially ZINC14541509, strongly suggesting that CtpF may be a specific target of the selected compound. Conclusions: ZINC14541509 should be considered as an alternative for the structural-based design of novel anti-TB drugs.

Hemoptisis, diagnóstico y estrategias de tratamiento en un hospital de tercer nivel / Hemoptysis: diagnosis and treatment strategies in a third level hospital

La hemoptisis se define como la expectoración de sangre del árbol traqueobronquial, por lo general se origina en las arterias bronquiales. Una vez confirmada la presencia y el sitio de sangrado se debe elegir entre los diferentes métodos de manejo de la hemoptisis, cada uno con sus beneficios y limitaciones. La embolización de arterias bronquiales es una técnica endovascular mínimamente invasiva. Se ha convertido en el método de elección para tratar hemoptisis masiva y recurrente. Tiene una tasa de éxito en el primer episodio superior al 80%. La tasa de recurrencia posterior al procedimiento va de un 10% a un 55%, en el cual la cirugía llega a tener un papel de importancia. Objetivos: Describir las características demográficas, clínicas, diagnóstico etiológico y tratamiento de pacientes con hemoptisis en un hospital de tercer nivel de la Ciudad de México. Material y métodos: Estudio retrospectivo de pacientes con diagnóstico de hemoptisis en el periodo comprendido entre enero de 2014 a diciembre de 2016. Los datos fueron obtenidos del expediente clínico. Resultados: Se estudiaron 34 pacientes media de edad 52 años, con predominio en hombres (52,9%). La etiología de la hemoptisis fue tuberculosis (45,5%), neoplasias (20,6%), bronquiectasias (15,2%), malformación arteriovenosa (6,1%). El sitio de embolización más frecuente fue la arteria bronquial superior derecha (56,6%), seguido de la arteria bronquial inferior izquierda (23,3%) y un grupo de 6 pacientes (18,7%) requirieron un segundo evento de embolización por recurrencia del sangrado. Conclusión: El manejo de la hemoptisis debe de ser integral. El objetivo principal es mantener una vía aérea permeable y evaluar cada paciente para un manejo óptimo de acuerdo al tipo y etiología de la hemoptisis.

Hemoptysis is defined as the expectoration of blood from the tracheobronchial tree, typically originating from bronchial arteries. Once the presence and bleeding site are confirmed, one must choose among different methods for managing hemoptysis, each with its own benefits and limitations. Bronchial artery embolization is a minimally inva sive endovascular technique. It has become the method of choice for treating massive and recurrent hemoptysis. Its success rate in the first episode is over 80%. The recur rence rate after the procedure ranges from 10% to 55%, in which surgery may play an important role. Objectives: to describe the demographic and clinical characteristics, the etiological diagnosis and treatment of patients with hemoptysis at a tertiary care level hospital in the City of Mexico. Materials and methods: retrospective study of patients diagnosed with hemoptysis during the period from January 2014 to December 2016. The data were obtained from the clinical records. Results: a total of 34 patients with a mean age of 52 years were studied, with a pre dominance of males (52.9%). The etiology of hemoptysis was tuberculosis (45.5%), neoplasms (20.6%), bronchiectases (15.2%), and arteriovenous malformation (6.1%). The most frequent embolization site was the right upper bronchial artery (56.6%), followed by the left lower bronchial artery (23.3%); and a group of 6 patients (18.7%) required a second embolization procedure due to recurrence of bleeding. Conclusion: the management of hemoptysis should be comprehensive. The main objective is to maintain airway permeability and evaluate each patient for optimal man agement based on the type and etiology of the hemoptysis.

Novel scaffolds targeting Mycobacterium tuberculosis plasma membrane Ca2+ transporter CtpF by structure-based strategy.

CtpF is a Ca2+ transporter P-type ATPase key to the response to stress conditions and to Mycobacterium tuberculosis virulence, therefore, an interesting target for the design of novel anti-Mtb compounds. In this work, molecular dynamics simulations of four previously identified CtpF inhibitors allowed recognizing the key protein-ligand (P-L) interactions, which were then used to perform a pharmacophore-based virtual screening (PBVS) of 22 million compounds from ZINCPharmer. The top-rated compounds were then subjected to molecular docking, and their scores were refined by MM-GBSA calculations. In vitro assays showed that ZINC04030361 (Compound 7) was the best promising candidate, showing a MIC of 25.0 µg/mL, inhibition of Ca2+-ATPase activity (IC50) of 3.3 µM, cytotoxic activity of 27.2 %, and hemolysis of red blood cells lower than 0.2 %. Interestingly, the ctpF gene is upregulated in the presence of compound 7, compared to other alkali/alkaline P-type ATPases coding genes, strongly suggesting that CtpF is a compound 7-specific target.

Specific identification of Mycobacterium bovis by Loop-Mediated Isothermal Amplification (LAMP) targeting the Region of Difference 12 (RD12) of the M. tuberculosis complex.

Bovine tuberculosis is a prevalent zoonotic disease that causes high risks for production animals, dairy producers and consumers, together with significant economic losses. Thus, methods for easy, fast and specific detection of Mycobacterium bovis in small and medium-sized livestock under field conditions are very required. In this work, a Loop-Mediated Isothermal Amplification LAMP-PCR targeting the Region of Difference 12 (RD12) of M. bovis genome was designed for the purpose of identification. A set of six primers designed for the isothermal amplification of five different genomic fragments led to the specific identification of M. bovis from other mycobacterial species. A basic colorimetric reaction was clearly observed at first sight under natural light, indicating positive identification of M. bovis in a maximum of 30 min of isothermal amplification at 65 °C. The limit of detection was near 50 fg of M. bovis genomic DNA, corresponding approximately to 10 copies of the genome. •The proposed LAMP-PCR amplification of M. bovis genomic DNA might be performed by untrained laboratory personnel.•Specific identification of M. bovis LAMP is possible in 30 min at 65.. C using a simple water bath.•The basic colorimetric reaction for M. bovis identification could be observed with the naked eye under natural light.

Mycobacterium leprae's Infective Capacity Is Associated with Activation of Genes Involved in PGL-I Biosynthesis in a Schwann Cells Infection Model.

Peripheral nerves and Schwann cells (SCs) are privileged and protected sites for initial colonization, survival, and spread of leprosy bacillus. Mycobacterium leprae strains that survive multidrug therapy show a metabolic inactivation that subsequently induces the recurrence of typical clinical manifestations of leprosy. Furthermore, the role of the cell wall phenolic glycolipid I (PGL-I) in the M. leprae internalization in SCs and the pathogenicity of M. leprae have been extensively known. This study assessed the infectivity in SCs of recurrent and non-recurrent M. leprae and their possible correlation with the genes involved in the PGL-I biosynthesis. The initial infectivity of non-recurrent strains in SCs was greater (27%) than a recurrent strain (6.5%). In addition, as the trials progressed, the infectivity of the recurrent and non-recurrent strains increased 2.5- and 2.0-fold, respectively; however, the maximum infectivity was displayed by non-recurrent strains at 12 days post-infection. On the other hand, qRT-PCR experiments showed that the transcription of key genes involved in PGL-I biosynthesis in non-recurrent strains was higher and faster (Day 3) than observed in the recurrent strain (Day 7). Thus, the results indicate that the capacity of PGL-I production is diminished in the recurrent strain, possibly affecting the infective capacity of these strains previously subjected to multidrug therapy. The present work opens the need to address more extensive and in-depth studies of the analysis of markers in the clinical isolates that indicate a possible future recurrence.

Ligilactobacillus murinus Strains Isolated from Mice Intestinal Tract: Molecular Characterization and Antagonistic Activity against Food-Borne Pathogens.

Considering the objectives of "One Health" and the Sustainable development Goals "Good health and well-being" for the development of effective strategies to apply against bacterial resistance, food safety dangers, and zoonosis risks, this project explored the isolation and identification of Lactobacillus strains from the intestinal tract of recently weaned mice; as well as the assessment of antibacterial activity against clinical and zoonotic pathogens. For molecular identification, 16S rRNA gene-specific primers were used and, via BLAST-NCBI, 16 Ligilactobacillus murinus, one Ligilactobacillus animalis, and one Streptococcus salivarius strains were identified and registered in GenBank after the confirmation of their identity percentage and the phylogenetic analysis of the 16 Ligilactobacillus murinus strains and their association with Ligilactobacillus animalis. The 18 isolated strains showed antibacterial activity during agar diffusion tests against Listeria monocytogenes ATCC 15313, enteropathogenic Escherichia coli O103, and Campylobacter jejuni ATCC 49943. Electrophoretic and zymographic techniques confirmed the presence of bacteriolytic bands with a relative molecular mass of 107 kDa and another of 24 kDa in Ligilactobacillus murinus strains. UPLC-MS analysis allowed the identification of a 107 kDa lytic protein as an N-acetylmuramoyl-L-amidase involved in cytolysis and considered a bacteriolytic enzyme with antimicrobial activity. The 24 kDa band displayed similarity with a portion of protein with aminopeptidase function. It is expected that these findings will impact the search for new strains and their metabolites with antibacterial activity as an alternative strategy to inhibit pathogens associated with major health risks that help your solution.

Hydroelectrolytic and Acid-Base Parameters after 80 to 115 km Endurance Races (Raid Uruguayo) and Their Association with the Comfort Index.

The Raid Uruguayo (RAID) is an equestrian endurance competition. This study characterized the hydroelectrolytic parameters (Na+, K+, Cl-, tCa++, and iCa++), hematocrit (Ht), total plasma protein (TPP), and blood pH from 900 equine athletes (finishers and non-finishers) competing over distances of 80 to 115 km under different climate conditions. Paired blood samples were taken prior to the start of the competition (sample 1) and at the end of the race or at the time of leaving the competition (sample 2). The association of the comfort index (CI: low, moderate, and high) with blood parameters was evaluated. Of the 900 horses included, 550 were not able to finish the trial. The comfort index was not associated with success in completing the race. In the horses that finished the race, the CI was not associated with Ht, pH, TPP, or Na+ concentrations in samples taken after finishing the RAID. In contrast, the decreases in chloride, K+, tCa++, and iCa++ concentrations found after the race were more pronounced at moderate and high CI values when compared with low CI values. In horses that did not finish the race, the CI was associated with all variables except for Ht. The data confirmed the relevance of considering the impact of the comfort index in hydroelectrolytic losses in the RAID, as it influence ssuccess or failure in the performance of endurance horses finishing the competition.

El debate de los principios y reglas en la normatividad contable internacional / The debate on principles and rules in international accounting standards / A discussão de princípios e regras nas normas internacionais de contabilidade

RESUMEN El análisis conceptual de los estándares de información financiera internacional trae implícita una discusión jurídica, que se puede remontar al debate entre el pensamiento iuspositivista - iusnaturalista del derecho, debate que puede dar pautas para dilucidar si los estándares del International Accounting Standards Board (lASB) están basados en principios o reglas, así como también, aportar en la conceptualización del marco teórico de las políticas contables. La discusión sobre las bases de la normatividad contable generalmente carece de una visión transdisciplinar acadêmica y práctica. Se utilizó una metodología conceptual e interpretativa para comprender; desde la teorïa del derecho y desde la perspectiva del análisis económico del derecho, el dilema sobre principios o reglas, esto contribuye a la reflexión sobre la elección de las políticas contables adecuadas para la representación financiera y contable de las organizaciones.

AВSTRАСT The conceptual analysis of international financial reporting standards implies a legal discussion, which can be traced back to the debate between the iuspositivist - iusnaturalist thinking of law, a debate that can provide guidelines to elucidate whether the standards of the International Accounting Standards Board (IASB) are based on principles or rules, as well as to contribute to the conceptualization of the theoretical framework of accounting policies. The discussion on the basis of accounting standards generally lacks a transdisciplinary academic and practical vision. A conceptual and interpretative methodology was used to understand, from the theory of law and from the perspective of the economic analysis of law, the dilemma of principles or rules, which contributes to the reflection on the choice of appropriate accounting policies for the financial and accounting representation of organizations.

RESUMO A análise conceitual das normas internacionais de relato financeiro envolve uma discussão jurídica, que pode ser rastreada até o debate entre o pensamento iuspositivista - iusnaturalista da lei, um debate que pode fornecer diretrizes para esclarecer se as normas do International Accounting Standards Board (IASB) são baseadas em princípios ou regras, bem como para contribuir para a conceitualização da estrutura teórica das políticas contábeis. A discussão com base nas normas contábeis geralmente carece de uma visão acadêmica e prática transdisciplinar Uma metodologia conceitual e interpretativa foi utilizada para compreender a partir da teoria do direito e da perspectiva da análise econômica do direito, o dilema dos princípios ou regras, o que contribui para a reflexão sobre a escolha de políticas contábeis apropriadas para a representação financeira e contábil das organizações.

Early effects of gene duplication on the robustness and phenotypic variability of gene regulatory networks.

BACKGROUND: Research on gene duplication is abundant and comes from a wide range of approaches, from high-throughput analyses and experimental evolution to bioinformatics and theoretical models. Notwithstanding, a consensus is still lacking regarding evolutionary mechanisms involved in evolution through gene duplication as well as the conditions that affect them. We argue that a better understanding of evolution through gene duplication requires considering explicitly that genes do not act in isolation. It demands studying how the perturbation that gene duplication implies percolates through the web of gene interactions. Due to evolution's contingent nature, the paths that lead to the final fate of duplicates must depend strongly on the early stages of gene duplication, before gene copies have accumulated distinctive changes. METHODS: Here we use a widely-known model of gene regulatory networks to study how gene duplication affects network behavior in early stages. Such networks comprise sets of genes that cross-regulate. They organize gene activity creating the gene expression patterns that give cells their phenotypic properties. We focus on how duplication affects two evolutionarily relevant properties of gene regulatory networks: mitigation of the effect of new mutations and access to new phenotypic variants through mutation. RESULTS: Among other observations, we find that those networks that are better at maintaining the original phenotype after duplication are usually also better at buffering the effect of single interaction mutations and that duplication tends to enhance further this ability. Moreover, the effect of mutations after duplication depends on both the kind of mutation and genes involved in it. We also found that those phenotypes that had easier access through mutation before duplication had higher chances of remaining accessible through new mutations after duplication. CONCLUSION: Our results support that gene duplication often mitigates the impact of new mutations and that this effect is not merely due to changes in the number of genes. The work that we put forward helps to identify conditions under which gene duplication may enhance evolvability and robustness to mutations.

Commercial Vaccines Do Not Confer Protection against Two Genogroups of Piscirickettsia salmonis, LF-89 and EM-90, in Atlantic Salmon.

In Atlantic salmon, vaccines have failed to control and prevent Piscirickettsiosis, for reasons that remain elusive. In this study, we report the efficacy of two commercial vaccines developed with the Piscirickettsia salmonis isolates AL100005 and AL 20542 against another two genogroups which are considered highly and ubiquitously prevalent in Chile: LF-89 and EM-90. Two cohabitation trials were performed to mimic field conditions and vaccine performance: (1) post-smolt fish were challenged with a single infection of LF-89, (2) adults were coinfected with EM-90, and a low level coinfection of sea lice. In the first trial, the vaccine delayed smolt mortalities by two days; however, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 60.3%, vaccinated: 56.7%; p = 0.28). In the second trial, mortality started three days later for vaccinated fish than unvaccinated fish. However, unvaccinated and vaccinated fish did not show significant differences in survival (unvaccinated: 64.6%, vaccinated: 60.2%, p = 0.58). Thus, we found no evidence that the evaluated vaccines confer effective protection against the genogroups LF-89 and EM-90 of P. salmonis with estimated relative survival proportions (RPSs) of -9% and -12%, respectively. More studies are necessary to evaluate whether pathogen heterogeneity is a key determinant of the lack of vaccine efficacy against P. salmonis.

Brush-like Polyaniline with Optical and Electroactive Properties at Neutral pH and High Temperature.

In this research, a brush-like polyaniline (poly(2-acrylamide-2-methyl-1-propanesulfonate)-g-polyaniline)-b-poly(N-vinylcarbazole) (BL PAni) was developed as a strategy to overcome the limited processability and dedoping above pH 4 of conventional polyaniline (PAni). For the BL PAni synthesis, RAFT polymerization (homopolymer), RAFT-mediated surfactant-free emulsion polymerization (block copolymer), and interfacial oxidative polymerization were applied to graft the PAni chains. NMR and FT-IR spectroscopies were performed to confirm the structural elucidation of the reaction pathways, while the thermal properties were analyzed by TGA and DSC. Notably, the BL PAni presents absorption throughout the visible region and up to the near-infrared, showing dedoping resistance at up to 80 °C and at a neutral pH. The absorption range of the BL PAni, block copolymer, and homopolymer were studied by UV-Vis spectroscopy in solid-state and dispersion/solution, highlighting BL PAni and poly(anilinium 2-acrylamide-2-methyl-1-propanesulfonate)-b-poly(N-vinylcarbazole) (PAAMP-b-PVK) due to the π-stacking between the anilinium and carbazole groups. The cyclic voltammetry confirmed the persistence of electroactivity at a pH near 7.

The ctpF Gene Encoding a Calcium P-Type ATPase of the Plasma Membrane Contributes to Full Virulence of Mycobacterium tuberculosis.

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.

Dibutyl Itaconate and Lauryl Methacrylate Copolymers by Emulsion Polymerization for Development of Sustainable Pressure-Sensitive Adhesives.

Renewable polymers possess the potential to replace monomers from petrochemical sources. The design and development of polymeric materials from sustainable materials are a technological challenge. The main objectives of this study were to study the microstructure of copolymers based on itaconic acid (IA), di-n-butyl itaconate (DBI), and lauryl methacrylate (LMA); and to explore and to evaluate these copolymers as pressure-sensitive adhesives (PSA). The copolymer synthesis was carried out through batch emulsion radical polymerization, an environmentally friendly process. IA was used in a small fixed amount as a functional comonomer, and LMA was selected due to low glass transition temperature (Tg). The structure of synthesized copolymers was studied by FTIR, 1H-NMR, Soxhlet extraction, and molecular weight analyses by GPC. Furthermore, the viscoelastic and thermal properties of copolymer films were characterized by DMA, DSC, and TGA. The single Tg displayed by the poly(DBI-LMA-IA) terpolymers indicates that statistical random composition copolymers were obtained. Moreover, FTIR and NMR spectra confirm the chemical structure and composition. It was found that a cross-linked microstructure and higher molecular weight are observed with an increase of LMA in the feed led. The Tg and modulus (G') of the copolymers film can be tuned with the ratio of DBI:LMA providing a platform for a wide range of applications as a biobased alternative to produce waterborne PSA.

El juego como herramienta de intervención en las orientaciones técnicas de los programas ambulatorios de SENAME, una mirada crítica desde la Terapia Ocupacional / The use of play as an intervention tool in the technical orientations of sename's outpatient programs, documentary review; a critical analysis from the perspective of occupational therapy

Introducción: Desde la perspectiva de Terapia Ocupacional y Ciencia de la Ocupación, la participación en ocupaciones es primordial para la adquisición y fortalecimiento de las destrezas y habilidades para la vida, siendo el juego en la niñez y adolescencia, fundamental para fortalecer el desarrollo y crecimiento integral. Objetivo: El objetivo de este estudio es identificar la importancia que se le asigna a las ocupaciones significativas, para los niños, niñas y adolescentes, específicamente el juego y su incorporación como herramienta de intervención en los programas ambulatorios del SENAME. Metodología: La metodología utilizada en la investigación fue la revisión y análisis descriptivo de documentos de orientaciones técnicas utilizados en los programas ambulatorios de SENAME. Resultados: Se observa que, en la mayoría de estas directrices, no considera el juego o actividades recreativas como estrategia de intervención terapéutica, con los niños, niñas y adolescentes. Conclusiones: Desde la mirada de la Terapia Ocupacional, se realiza un análisis y reflexión considerando el enfoque de derechos humanos, justicia ocupacional y ciencia de la ocupación, acerca de la relevancia de incorporar en las orientaciones técnicas, el juego dentro del proceso terapéutico de los involucrados.

Introduction: From the perspective of Occupational Therapy and Occupational Science, participation in occupations is essential for the acquisition and strengthening of skills and abilities to face challenges of everyday life, therefore, play in childhood and adolescence is fundamental to strengthen their development and integral growth. Objective: The objective of this study is to identify the importance assigned to significant occupations for children and adolescents, specifically play and its incorporation as an intervention tool in SENAME's outpatient programs. Methodology: The methodology carried out in this research was reviewing and making a descriptive analysis of technical guideline documents used in SENAME's outpatient programs. Results: It is observed that in most of SENAME's guidelines, play or recreational activities are not considered as a therapeutic intervention strategy to apply in children and adolescents. Conclusions: From the perspective of Occupational Therapy, an analysis and reflection is carried out considering the approach of human rights, occupational justice and science of the occupation about the relevance of incorporating play in the technical orientations in the therapeutic process of those involved.

Interactive web-based tool for evaluating the spread of bovine tuberculosis and brucellosis in Colombia / Herramienta interactiva basada en la web para evaluar la propagación de la tuberculosis bovina y la brucelosis en Colombia / Ferramenta interativa baseada na web para avaliar a disseminação da tuberculose e brucelose bovina na Colômbia

Abstract Background: Bovine tuberculosis (BTB) and brucellosis are associated with devastating losses in the livestock sector in Colombia and even in developed countries. Real-time disease surveillance is a key strategy to control and eradicate infectious disease outbreaks. Objective: To design an epidemiological tool for monitoring BTB and brucellosis in Colombia. Methods: An interactive platform for disease mapping of BTB and brucellosis during an observation period between years 2004 and 2019 was designed. Results: Our analysis showed that the provinces of Cundinamarca and Valle del Cauca are regions affected by BTB and brucellosis epidemics, respectively (p<0.001). Furthermore, increased case detection of BTB was reported in 2012 and brucellosis in 2019 (p<0.001). Conclusions: This epidemiological platform allows tracking BTB and tuberculosis hotspots, identifying trends over time, and provides useful information to animal health authorities for designing new strategies in control programs.

Resumen Antecedentes: La tuberculosis bovina (TBB) y la brucelosis están asociadas con problemas persistentes en la ganadería Colombiana e incluso en los países desarrollados. La vigilancia de enfermedades en tiempo real es una estrategia clave para controlar y erradicar brotes de enfermedades infecciosas. Objetivo: Diseñar una herramienta epidemiológica para monitorear TBB y brucelosis en Colombia. Métodos: Se diseñó un panel de control interactivo para el mapeo de ambas enfermedades durante el periodo de observación entre los años 2004 y 2019. Resultados: El análisis de la herramienta mostró que las Provincias de Cundinamarca y Valle del Cauca han sido áreas epidémicas para TBB y brucelosis, respectivamente (p<0,001). Además, se encontró un aumento de la detección de casos de TBB en 2012 y de brucelosis durante 2019 (p<0,001). Conclusiones: Este panel epidemiológico permite el seguimiento de puntos críticos de TBB y tuberculosis, identificando sus tendencias a lo largo del tiempo, y proporciona información útil para las autoridades de sanidad animal que diseñan nuevas estrategias para los programas de control.

Resumo Antecedentes: A tuberculose bovina (TBB) e a brucelose estão associadas a problemas persistentes no campo da pecuária na Colômbia e até em países desenvolvidos. Portanto, a vigilância de doenças em tempo real é uma estratégia essencial para controlar e erradicar surtos de doenças infecciosas. Objetivo: Projetar uma ferramenta epidemiológica para monitorar a TB e a brucelose na Colômbia. Métodos: Um painel de controle interativo foi projetado para o mapeamento de ambas as doenças entre 2004 e 2019 como período de observação. Resultados: A análise da ferramenta mostrou que as Províncias de Cundinamarca e Valle del Cauca foram áreas epidêmicas para TBB e brucelose, respectivamente (p<0,001). Além disso, foi encontrado um aumento na detecção de casos em 2012 para TBB e brucelose durante 2019 (p<0,001). Conclusões: Esse painel epidemiológico poderia permitir o monitoramento de pontos críticos dessas doenças, identificando tendências ao longo do tempo, fornecendo informações úteis para as autoridades de saúde animal que elaboram novas estratégias para programas de controle.

Recombination facilitates genetic assimilation of new traits in gene regulatory networks.

A new phenotypic variant may appear first in organisms through plasticity, that is, as a response to an environmental signal or other nongenetic perturbation. If such trait is beneficial, selection may increase the frequency of alleles that enable and facilitate its development. Thus, genes may take control of such traits, decreasing dependence on nongenetic disturbances, in a process called genetic assimilation. Despite an increasing amount of empirical studies supporting genetic assimilation, its significance is still controversial. Whether genetic assimilation is widespread depends, to a great extent, on how easily mutation and recombination reduce the trait's dependence on nongenetic perturbations. Previous research suggests that this is the case for mutations. Here we use simulations of gene regulatory network dynamics to address this issue with respect to recombination. We find that recombinant offspring of parents that produce a new phenotype through plasticity are more likely to produce the same phenotype without requiring any perturbation. They are also prone to preserve the ability to produce that phenotype after genetic and nongenetic perturbations. Our work also suggests that ancestral plasticity can play an important role for setting the course that evolution takes. In sum, our results indicate that the manner in which phenotypic variation maps unto genetic variation facilitates evolution through genetic assimilation in gene regulatory networks. Thus, we contend that the importance of this evolutionary mechanism should not be easily neglected.

Interferon Gamma Induces the Increase of Cell-Surface Markers (CD80/86, CD83 and MHC-II) in Splenocytes From Atlantic Salmon.

Type II interferon gamma (IFNγ) is a pleiotropic cytokine capable of modulating the innate and adaptive immune responses which has been widely characterized in several teleost families. In fish, IFNγ stimulates the expression of cytokines and chemokines associated with the pro-inflammatory response and enhances the production of nitrogen and oxygen reactive species in phagocytic cells. This work studied the effect of IFNγ on the expression of cell-surface markers on splenocytes of Atlantic salmon (Salmo salar). In vitro results showed that subpopulations of mononuclear splenocytes cultured for 15 days were capable of increasing gene expression and protein availability of cell-surface markers such as CD80/86, CD83 and MHC II, after being stimulated with recombinant IFNγ. These results were observed for subpopulations with characteristics associated with monocytes (51%), and features that could be related to lymphocytes (46.3%). In addition, a decrease in the expression of zbtb46 was detected in IFNγ-stimulated splenocytes. Finally, the expression of IFNγ and cell-surface markers was assessed in Atlantic salmon under field conditions. In vivo results showed that the expression of ifnγ increased simultaneously with the up-regulation of cd80/86, cd83 and mhcii during a natural outbreak of Piscirickettsia salmonis. Overall, the results obtained in this study allow us to propose IFNγ as a candidate molecule to stimulate the phenotypic progression of a small population of immune cells, which will increase antigen presenting cells markers. Thereby, modulatory strategies using IFNγ may generate a robust and coordinated immune response in fish against pathogens that affect aquaculture.