Designer transcription activator-like effectors enable discovery of cell death-inducer genes.

TALEs (transcription activator-like effectors) in plant-pathogenic Xanthomonas bacteria activate expression of plant genes and support infection or cause a resistance response. PthA4AT is a TALE with a particularly short DNA-binding domain harbouring only 7.5-repeats which triggers cell death in Nicotiana benthamiana; however, the genetic basis for this remains unknown. To identify possible target genes of PthA4AT that mediate cell death in N. benthamiana, we exploited the modularity of TALEs to stepwise enhance their specificity and reduce potential target sites. Substitutions of individual repeats suggested that PthA4AT-dependent cell death is sequence-specific. Stepwise addition of repeats to the C-terminal or N-terminal end of the repeat region narrowed the sequence requirements in promoters of target genes. Transcriptome profiling and in silico target prediction allowed the isolation of two cell death-inducer genes, which encode a patatin-like protein and a bifunctional monodehydroascorbate reductase/carbonic anhydrase protein. These two proteins are not linked to known TALE-dependent resistance genes. Our results show that the aberrant expression of different endogenous plant genes can cause a cell death reaction, which supports the hypothesis that TALE-dependent executor resistance genes can originate from various plant processes. Our strategy further demonstrates the use of TALEs to scan genomes for genes triggering cell death and other relevant phenotypes.

Severe infections in systemic necrotizing vasculitis.

Infections in patients with systemic vasculitis represent one of the main causes of mortality. Corticosteroid use, immunosuppressive therapy, age, associated organic involvement and dialysis dependence are risk factors of infection. OBJECTIVES: To determine the prevalence of severe infection and associated factors in patients diagnosed with ANCA-associated vasculitis (AAV) and Polyarteritis Nodosa (PAN). METHODS: retrospective study was conduced in a single rheumatology center (2000-2018). We included patients diagnosed with AAV (Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (PAM) and Polyarteritis nodosa (PAN). Serious infectious events requiring hospitalisation or prolonged antibiotic/antiviral treatment, recurrent infection of Herpes Zoster Virus or opportunistic infections were evaluated. Sites of infection, isolated microorganisms and mortality related were analyzed. RESULTS: 105 patients were analyzed, follow-up time median 18 m, 58.7% were women and median age was 52 years. Types of vasculitis: 41.9% PAM, 16.2% EPGA, 40% GPA, 1.9% PAN. Constitutional, pulmonary, renal and otorhinolaryngology manifestations were the most frequent. PREVALENCE OF INFECTION: 34.2%, with a median of 3 months from diagnosis of vasculitis to the infectious event. Low respiratory tract (42.8%), sepsis (31.4%), and urinary tract (14.3%) were the most common sites of infections. Bacterial aetiology was the most prevalent (67.7%). Mortality at the first event was 14.3% and a 72.2% of patients were in the induction phase of treatment. Infectious events were significantly associated with age > 65 years (p = 0.030), presence of lung (p = 0.016) and renal involvement (p = 0.001), BVASv3 > 15, mortality (p = 0.0002). CONCLUSIONS: The prevalence of infection was 34.2%. Lower airway infections, septicemia and urinary tract infections were the most prevalent. Infections were associated with renal and pulmonary involvement, age older than 65 years and score BVAS > 15. Severe infections were associated with mortality, especially in elderly patients.

Consultas tardías en los servicios de emergencias pediátricas durante la pandemia por COVID-19 en Uruguay, entre el 13 de marzo y el 29 de julio de 2020

En diciembre de 2019, en Wuhan, China, se detectaron los primeros casos de SARS-CoV-2. En Uruguay, desde el 16 de marzo de 2020 se suspendieron las actividades de enseñanza, deportivas y espectáculos públicos. Varios países reportaron una marcada disminución de las visitas a urgencias. Algunos niños presentaron enfermedades ocasionales o descompensaciones de enfermedades crónicas, consultando en forma tardía con el riesgo que ello implica. El objetivo de este trabajo es realizar una descripción de las consultas tardías durante la pandemia. Se realizó un estudio multicéntrico y descriptivo entre el 13 de marzo y el 29 de julio de 2020. Se definió consulta tardía como los ingresos por injurias agudas con más de 6 horas de evolución, fiebre mayor a 72 horas de evolución, dificultad respiratoria con más de 12 horas de evolución, síntomas agudos, como dolor abdominal, de más de 24 horas de evolución, síntomas de más de 12 horas de evolución en niños con enfermedades crónicas que determinaron descompensación e ingreso. Se incluyeron 27 centros. Se registraron un total de 34.260 consultas en urgencia, se incluyeron 189 niños para el estudio. El promedio de edad fue de 6 años; 17 pacientes requirieron ingreso a unidad de cuidados intensivos (UCI). Predominó la apendicitis entre los diagnósticos al alta. Esta investigación puso en evidencia la existencia de consultas tardías en nuestro país. Esto contribuye a ponderar el impacto negativo de la pandemia en la población pediátrica.

Summary: In December 2019, the first cases of SARS-CoV-2 were detected in Wuhan. In Uruguay, since March 16, teaching, sports and public entertainment activities were suspended. Several countries reported a marked decrease in emergency room visits. Some children presented occasional illnesses or decompensations from chronic illnesses, consulting late with the risk that this implies. The objective of the work is to make a description of late consultations during the pandemic. A multicenter and descriptive study was carried out between March 13 and July 29, 2020. "Late consultation" was defined as admissions for: Acute injuries with more than 6 hours of evolution, fever greater than 72 hours of evolution, difficulty respiratory disease with more than 12 hours of evolution, acute symptoms such as abdominal pain of more than 24 hours of evolution, symptoms of more than 12 hours of evolution in children with chronic diseases that determined decompensation and admission. 27 centers were included. A total of 34260 emergency consultations were registered, 189 children were included for the study. The average age was 6 years. 17 patients required admission to the ICU. Appendicitis predominated among the diagnoses at discharge. This research revealed the existence of late consultations in our country. This helps to weigh the negative impact of the pandemic on the pediatric population.

Em dezembro de 2019, em Wuhan, foram detectados os primeiros casos de SARS-CoV-2. No Uruguai, desde 16 de março, as atividades de ensino, esporte e entretenimento público foram suspensas. Vários países relataram uma diminuição acentuada nas visitas ao pronto-socorro. Algumas crianças apresentavam doenças ocasionais ou descompensações de doenças crônicas, consultando tardiamente os riscos que isso implica. O objetivo do trabalho é fazer uma descrição das consultas tardias durante a pandemia. Um estudo multicêntrico e descritivo foi realizado entre 13 de março e 29 de julho de 2020. Consulta tardia foi definida como internações por: Lesões agudas com mais de 6 horas de evolução, febre maior que 72 horas de evolução, dificuldade respiratória com mais de 12 horas de evolução, sintomas agudos como dor abdominal com mais de 24 horas de evolução, sintomas com mais de 12 horas de evolução em crianças com doenças crônicas que determinaram descompensação e internação. 26 centros foram incluídos. Um total de 34.260 consultas de emergência foram registradas, 189 crianças foram incluídas no estudo. A idade média era de 6 anos. 17 pacientes necessitaram de internação na UTI. Apendicite predominou entre os diagnósticos na alta. Esta pesquisa revelou a existência de consultas tardias em nosso país. Isso ajuda a pesar o impacto negativo da pandemia na população pediátrica.

Frecuencia de eventos cardiovasculares en pacientes con lupus eritematoso sistémico / Frequency of cardiovascular events in patients with systemic lupus erythematosus

Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.

Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.

Priming crop plants with rosemary (Salvia rosmarinus Spenn, syn Rosmarinus officinalis L.) extract triggers protective defense response against pathogens.

Plant bioactive compounds provide novel straightforward approaches to control plant diseases. Rosemary (Salvia rosmarinus)-derived extracts carry many prominent pharmacological activities, including antimicrobial and antioxidant, mainly due to its phenolic compounds, rosmarinic acid (RA), carnosic acid and carnosol. However, the effects of these extracts on plant diseases are still unknown, which constrains its potential application as bioprotectant in the agricultural production. In this study we demonstrate the antiviral effect of the aqueous rosemary extract (ARE) against tobacco necrosis virus strain A (TNVA) in ARE-treated tobacco (Nicotiana tabacum) plants. Our results show that ARE-treatment enhances plant defense response, contributing to reduce virus replication and systemic movement in tobacco plants. RA, the main phenolic compound detected in this extract, is one of the main inducers of TNVA control. The ARE-induced protection in TNVA-infected plants was characterized by the expression of H2O2 scavengers and defense-related genes, involving salicylic acid- and jasmonic acid-regulated pathways. Furthermore, treatment with ARE in lemon (Citrus limon) and soybean (Glycine max) leaves protects the plants against Xanthomonas citri subsp. citri and Diaporthe phaseolorum var. meridionalis, respectively. Additionally, ARE treatment also promotes growth and development, suggesting a biostimulant activity in soybean. These results open the way for the potential use of ARE as a bioprotective agent in disease management.

Validation of an indirect in-house ELISA using synthetic peptides to detect antibodies anti-gp90 and gp45 of the equine infectious anaemia virus.

BACKGROUND: Equine infectious anaemia (EIA) is controlled by the identification of seropositive animals. The official diagnostic method is the agar gel immunodiffusion (AGID) test, which detects antibodies against a viral core protein (p26). Although AGID is inexpensive and specific, the report of results takes considerable time and the test has low analytical sensitivity. OBJECTIVE: To validate our in-house indirect ELISAgp90/45 , following the World Organization of Animal Health (OIE) criteria. STUDY DESIGN: Test validation. METHODS: Synthetic peptides gp90 and gp45 were used as antigens in ELISAgp90/45 . Tests used for validation, calibration and linear working operating range, analytical and diagnostic sensitivity and specificity, repeatability and reproducibility were assessed by comparing them with the AGID test and using 1844 equine sera grouped into five different panels. RESULTS: We were able to replace the National References Sera with our Internal Reference Sera. ELISAgp90/45 had acceptable repeatability and reproducibility. Analytical sensitivity of the ELISAgp90/45 was 800 times greater than that of AGID test for positive sera and 400 times greater for weak positive sera. ELISAgp90/45 also showed optimal analytical specificity, since no cross-reactivity was detected with antibodies against other equine viruses. One sample was positive by AGID test and negative by ELISAgp90/45. ELISAgp90/45 was performed using 243 EIA positive and 878 negative equid sera, and showed a diagnostic sensitivity of 99.59% [CI 97.73%-99.99%] and a diagnostic specificity of 90.32% [CI 88.17%-92.19%], compared to AGID test; thus, it was demonstrated to be a robust test. MAIN LIMITATIONS: Samples were derived from naturally infected equid populations showing heterogeneous clinical states: therefore, their status was uncertain and some horses were sampled more than once. The AGID test may not be the most useful gold standard. CONCLUSION: ELISAgp90/45 is a useful tool for the diagnosis of EIAV infection and meets validation requirements established by the OIE.

A serralysin-like protein of Candidatus Liberibacter asiaticus modulates components of the bacterial extracellular matrix.

Huanglongbing (HLB), the current major threat for Citrus species, is caused by intracellular alphaproteobacteria of the genus Candidatus Liberibacter (CaL), with CaL asiaticus (CLas) being the most prevalent species. This bacterium inhabits phloem cells and is transmitted by the psyllid Diaphorina citri. A gene encoding a putative serralysin-like metalloprotease (CLIBASIA_01345) was identified in the CLas genome. The expression levels of this gene were found to be higher in citrus leaves than in psyllids, suggesting a function for this protease in adaptation to the plant environment. Here, we study the putative role of CLas-serralysin (Las1345) as virulence factor. We first assayed whether Las1345 could be secreted by two different surrogate bacteria, Rhizobium leguminosarum bv. viciae A34 (A34) and Serratia marcescens. The protein was detected only in the cellular fraction of A34 and S. marcescens expressing Las1345, and increased protease activity of those bacteria by 2.55 and 4.25-fold, respectively. In contrast, Las1345 expressed in Nicotiana benthamiana leaves did not show protease activity nor alterations in the cell membrane, suggesting that Las1345 do not function as a protease in the plant cell. Las1345 expression negatively regulated cell motility, exopolysaccharide production, and biofilm formation in Xanthomonas campestris pv. campestris (Xcc). This bacterial phenotype was correlated with reduced growth and survival on leaf surfaces as well as reduced disease symptoms in N. benthamiana and Arabidopsis. These results support a model where Las1345 could modify extracellular components to adapt bacterial shape and appendages to the phloem environment, thus contributing to virulence.

Taller de concordancia en la evaluación de imágenes capilaroscópicas / Reliability of nailfold videocapillaroscopy workshop

Introducción: la capilaroscopia es un método no invasivo que permite observar la microvasculatura en el área periungueal. Los resultados informados pueden ser altamente variables entre distintos observadores. A lo largo del tiempo surgieron métodos cuantitativos y semicuantitativos para mejorar la reproducibilidad. Objetivos: conocer el nivel de acuerdo intra e interobservador al informar los diferentes patrones capilaroscópicos en individuos con diferente nivel de entrenamiento. Materiales y métodos: estudio de corte transversal. Participaron médicos reumatólogos especialistas y en formación que habían realizado previamente un curso virtual de capacitación en capilaroscopia. Recibieron 40 imágenes capilaroscópicas proyectadas en una presentación de PowerPoint y debían responder a través de un cuestionario digital. Se evaluó la concordancia de respuestas intra e interobservador. Resultados: se encontró un alto nivel de concordancia global con un kappa 0,66 IC 95% (0,63-0,70) p<0,0000. También en otros grupos como reumatólogos en formación: kappa 0,65 IC 95% (0,60-0,71) p=0,0000, y médicos reumatólogos: kappa 0,67 IC 95% (0,62-0,72) p=0,0000. Conclusiones: el nivel de concordancia encontrado fue globalmente alto, independientemente del nivel de entrenamiento de los profesionales, y de ser o no reumatólogo. La concordancia fue superior cuando se comparó a quienes tenían más de 4 años de experiencia en la realización de videocapilaroscopia.

Introduction: videoapillaroscopy is a non-invasive method that allows the observation of the microvasculature in the periungual area. Reported results can be highly variable between different observers. Over time, quantitative and semi-quantitative methods emerged to improve reproducibility. Objetives: to know the level of intra and interobserver agreement when reporting the different capillaroscopic patterns in individuals with different levels of training. Materials and methods: cross section study. Specialist rheumatologists and those in training who had previously completed a virtual capillaroscopy training course participated. They received 40 capillaroscopic images projected in a PowerPoint presentation and had to issue their response through a digital questionnaire. Concordance of intra and interobserver responses was evaluated. Results: a high level of global agreement was found with a kappa 0.66 CI 95% (0.63-0.70) p<0.0000, also in other groups such as rheumatologists in training: kappa 0.65 CI 95% (0.60-0.71) p=0.0000, physicians rheumatologists: kappa 0.67 95% CI (0.62-0.72) p=0.0000. Conclusions: the level of agreement found was globally high, regardless of the level of training of the professionals, and whether or not they were a rheumatologist. Concordance was higher when compared to those who had more than 4 years of experience performing videocapillaroscopy.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Consenso de inmunizaciones en adultos con enfermedades reumáticas inflamatorias crónicas autoinmunes / Consensus on immunizations in adults with autoimmune chronic inflammatory rheumatic diseases

Aumento del riesgo de infecciones prevenibles y sus complicaciones en pacientes con enfermedades reumáticas inflamatorias crónicas (ERICA), con y sin tratamiento con inmunosupresores (IS), y beneficios de la vacunación.

Lupus en Argentina. Pacientes no respondedores al tratamiento estándar y belimumab como posible opción. Datos del registro RELESSAR / Lupus in Argentina. Non-responders to standard treatment and belimumab as a possible option. RELESSAR record data

Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.

Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.

Vasculitis cutáneas: etiología y características clínicas en pacientes adultos en un centro de tercer nivel / Cutaneous vasculitis: etiology and clinical characteristics in adult patients at a third-level center

Introducción: Diversas entidades clínicas, como enfermedades autoinmunes, infecciones, neoplasias y fármacos pueden manifestarse con lesiones vasculíticas en la piel. Debido a la heterogeneidad de las causas, suelen representar un desafío diagnóstico. El objetivo de este estudio es describir la etiología de las vasculitis cutáneas (VC) y evaluar las características clínicas, histológicas y de laboratorio halladas en estos pacientes. Material y métodos: Se realizó un estudio retrospectivo con revisión de historias clínicas de pacientes mayores de 16 años con VC por diagnóstico clínico y/o histológico evaluados en el período 2010-2018. Resultados: Se incluyeron 74 pacientes. El 69% son mujeres con una edad media al diagnóstico de 41 años (DE 16.5, rango 16-75). Las causas más frecuentes asociadas a las VC fueron las enfermedades autoinmunes (EAI) en un 50% de los pacientes evaluados. En el 29.7% de los casos no pudo identificarse una causa subyacente. En el 2.7% de los casos se asoció a neoplasias, otro 2.7% a fármacos y un 12% a otras etiologías. El 76% de los pacientes presentaron formas clínicas no severas, predominando la púrpura palpable en el 65% de los casos. Entre los pacientes biopsiados, el 76% fueron vasculitis leucocitoclásticas (VLC). Como manifestaciones extracutáneas asociadas, predominó el compromiso articular (43,2%). En las vasculitis asociadas a EAI, el 33 % presentó compromiso renal, en tanto que éste no se observó en ninguno de los pacientes con vasculitis idiopáticas. El 78% de los pacientes recibieron glucocorticoides sistémicos. Conclusión: En nuestro centro, la etiología más común de VC fue la asociada a EAI. La mayoría de los pacientes eran mujeres. Clínicamente predominaron las manifestaciones cutáneas no severas y la VLC fue el hallazgo más frecuente en las biopsias.

Background: Various clinical entities, such as autoimmune diseases, infections, neoplasms and drugs can manifest with vasculitic lesions on the skin. Due to the heterogeneity of causes, they often represent a diagnostic challenge. The aim of this study is to describe the etiology of cutaneous vasculitis (CV) and to assess the clinical, histological and laboratory characteristics found in these patients. Material and methods: A retrospective study was carried out with a review of the medical records of patients over 16 years old with CV by clinical and/or histological diagnosis evaluated in the period 2010-2018. Results: 74 patients were included. 69% are women with a mean age at diagnosis of 41 years (SD 16.5, range 16-75). The most frequent causes associated with CVs were autoimmune diseases (AID) in 50% of the patients evaluated. In 29.7% of the cases, an underlying cause could not be identified. In 2.7% of the cases it was associated with neoplasms, another 2.7% with drugs, and 12% with other etiologies. 76% of the patients presented non-severe clinical forms, with palpable purpura predominant in 65% of the cases. Among the biopsied patients, 76% were leukocytoclastic vasculitis (LCV). As associated extracutaneous manifestations, joint involvement predominated (43.2%). In vasculitis associated with AID, 33% presented renal involvement, while this was not observed in any of the patients with idiopathic vasculitis. 78% of the patients received systemic glucocorticoids. Conclusion: In our center, the most common etiology of CV was associated with AID. Most of the patients were women. Clinically, non-severe skin manifestations predominated and VLC was the most frequent finding in biopsies.

PthA4AT , a 7.5-repeats transcription activator-like (TAL) effector from Xanthomonas citri ssp. citri, triggers citrus canker resistance.

Transcription activator-like effectors (TALEs) are important effectors of Xanthomonas spp. that manipulate the transcriptome of the host plant, conferring susceptibility or resistance to bacterial infection. Xanthomonas citri ssp. citri variant AT (X. citri AT ) triggers a host-specific hypersensitive response (HR) that suppresses citrus canker development. However, the bacterial effector that elicits this process is unknown. In this study, we show that a 7.5-repeat TALE is responsible for triggering the HR. PthA4AT was identified within the pthA repertoire of X. citri AT followed by assay of the effects on different hosts. The mode of action of PthA4AT was characterized using protein-binding microarrays and testing the effects of deletion of the nuclear localization signals and activation domain on plant responses. PthA4AT is able to bind DNA and activate transcription in an effector binding element-dependent manner. Moreover, HR requires PthA4AT nuclear localization, suggesting the activation of executor resistance (R) genes in host and non-host plants. This is the first case where a TALE of unusually short length performs a biological function by means of its repeat domain, indicating that the action of these effectors to reprogramme the host transcriptome following nuclear localization is not limited to 'classical' TALEs.

The mitochondrial copper chaperone COX19 influences copper and iron homeostasis in arabidopsis.

KEY MESSAGE: The mitochondrial metallochaperone COX19 influences iron and copper responses highlighting a role of mitochondria in modulating metal homeostasis in Arabidopsis. The mitochondrial copper chaperone COX19 participates in the biogenesis of cytochrome c oxidase (COX) in yeast and humans. In this work, we studied the function of COX19 in Arabidopsis thaliana, using plants with either decreased or increased COX19 levels. A fusion of COX19 to the red fluorescent protein localized to mitochondria in vivo, suggesting that Arabidopsis COX19 is a mitochondrial protein. Silencing of COX19 using an artificial miRNA did not cause changes in COX activity levels or respiration in plants grown under standard conditions. These amiCOX19 plants, however, showed decreased expression of the low-copper responsive miRNA gene MIR398b and an induction of the miR398 target CSD1 relative to wild-type plants. Plants with increased COX19 levels, instead, showed induction of MIR398b and other low-copper responsive genes. In addition, global transcriptional changes in rosettes of amiCOX19 plants resembled those observed under iron deficiency. Phenotypic analysis indicated that the roots of amiCOX19 plants show altered growth responses to copper excess and iron deficiency. COX activity levels and COX-dependent respiration were lower in amiCOX19 plants than in wild-type plants under iron deficiency conditions, suggesting that COX19 function is particularly important for COX assembly under iron deficiency. The results indicate that the mitochondrial copper chaperone COX19 has a role in regulating copper and iron homeostasis and responses in plants.

Mitochondria and copper homeostasis in plants.

Copper (Cu) and other transition metals are essential for living organisms but also toxic when present in excess. To cope with this apparent paradox, organisms have developed sophisticated mechanisms to acquire, transport and store these metals. Particularly, plant mitochondria require Cu for the assembly and function of cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. COX assembly is a complex process that requires the action of multiple factors, many of them involved in the delivery and insertion of Cu into the enzyme. In this review, we summarize what is known about the processes involved in Cu delivery to mitochondria and how these processes impact in Cu homeostasis at the cellular level. We also discuss evidence indicating that metallochaperones involved in COX assembly play additional roles in signaling pathways related to changes in Cu and redox homeostasis and the response of plants to stress. We propose that cysteine-rich proteins present in the mitochondrial intermembrane space are excellent candidates as sensors of these changes and transducers of signals originated in the organelle to the rest of the cell.

Effect of two synthetic peptides mimicking conserved regions of equine infectious anemia virus proteins gp90 and gp45 upon cytokine mRNA expression.

Gp90 and gp45 synthetic peptides, which mimic conserved sequences of native viral proteins, are recognized by antibodies to equine infectious anemia virus (EIAV) in asymptomatic carrier horses and generate humoral and cellular responses in immunized mice. Cytokine mRNA levels were evaluated in equine peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with gp90 and gp45 with the aim of determining the cytokine profile associated with the proliferative response. Stimulation index (SI) values indicate that 100 and 60% of EIAV-infected horses recognized gp90 and gp45, respectively. A strong positive correlation was found between IL-12p40 and SI, IFN-gamma and SI, and IL-12p40 and IFN-gamma (p < 0.001). These results suggest the presence of specific memory cells that would contribute to maintain reinfection resistance and that conserved viral regions represented by gp90 and gp45 synthetic peptides may be good candidates for inclusion in vaccine strategies against EIAV.

Comportamiento que adoptan las parejas ante la infertilidad

Se estudiaron 30 parejas de nivel socio-económico ajo que consultaron a la Clínica de Infertilidad del Instituto Materno Infantil de Bogotá durante el período enero /88 y febrero/89, con el fin de conocer el comportmiento adoptado ante el Diagnóstico de Infertilidad. Se encuentra que la relación de pareja es buena en el 33.3 por ciento y regular/mala 23.3 por ciento. Se presenta un "cambio en la relación de pareja" en el 66.6 por ciento, manifestado por enfriamiento de la relación conyugal (58.8 por ciento) maltrato (17.6 por ciento) y Adulterio (17.6 por ciento). La expresión afectiva se modifica: con disminución del cariño en el 29.7 por ciento, convivir por obligación en el 24.3 por ciento, insatisfacción sexual 21.6 por ciento, despreocupación 18.9 por ciento. La búsqueda de tratamiento se encuentra en el 60 por ciento y la conducta compensatoria inacción 40 por ciento búsqueda de empleo 23.3 por ciento cuidar niños ajenos 20 por ciento y deportes 10 por ciento. La adopción como medida copensatoria es rechazada por los perjuicios que tienen sobre ésta. Se recomienda el trabajo de un equipo multidisciplinarios de ginecólogos, enfermeras, psicólogos, terapeutas física y ocupacional, trabajadoras sociales como punto de apoyo para el menejo de las parejas que consultan por Infertilidad

Salud mental escolar. I. El niño y su medio

El hogar y la escuela proporcionan al niño sus primeras experiencias socializadoras y el concepto de autoridad que son la base de sus actitudes y conducta en la vida futura; por esta razón se considera decisivo el ambiente que rodea al niño en la edad escolar, ya que si se le brindan todos los aportes físicos, psicosociales y culturales que requiere, se favorece su desarrollo integral y se previene la aparición de problemas mentales que limiten su desenvolvimiento como ser útil y productivo. En el presente artículo se hace una descripción de los factores que en el hogar como en la escuela se dan, y que afectan positica o negativamente el desarrollo psicosocial del niño escolar