Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Pityriasis Rubra Pilaris: A Multicentric Case Series of 65 Spanish Patients.

INTRODUCTION: PRP is a rare entity of unknown etiopathogenesis. Lack of management guidelines makes it a challenge for clinicians. OBJECTIVE: To add our experience to increase evidence about PRP. METHODS: We performed a retrospective, descriptive and multicentric study of 65 patients with PRP, being the largest European case series of patients with PRP. RESULTS: PRP was more frequent in male patients with an average age of 51 years, but erythrodermic forms presented in older patients (average age 61 years). Six (75%) paediatric patients and ten (60%) non-erythrodermic adults controlled their disease with topical corticosteroids. On the contrary, 26 (68%) erythrodermic patients required biologic therapy as last and effective therapy line requiring an average of 6.5 months to achieve complete response. CONCLUSION: Our study showed a statistical difference in terms of outcome and response to treatment between children or patients with limited disease and patients who develop erythroderma.

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases. / Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Evaluating unintended consequences of intentional species introductions and eradications for improved conservation management.

Increasingly intensive strategies to maintain biodiversity and ecosystem function are being deployed in response to global anthropogenic threats, including intentionally introducing and eradicating species via assisted migration, rewilding, biological control, invasive species eradications, and gene drives. These actions are highly contentious because of their potential for unintended consequences. We conducted a global literature review of these conservation actions to quantify how often unintended outcomes occur and to elucidate their underlying causes. To evaluate conservation outcomes, we developed a community assessment framework for systematically mapping the range of possible interaction types for 111 case studies. Applying this tool, we quantified the number of interaction types considered in each study and documented the nature and strength of intended and unintended outcomes. Intended outcomes were reported in 51% of cases, a combination of intended outcomes and unintended outcomes in 26%, and strictly unintended outcomes in 10%. Hence, unintended outcomes were reported in 36% of all cases evaluated. In evaluating overall conservations outcomes (weighing intended vs. unintended effects), some unintended effects were fairly innocuous relative to the conservation objective, whereas others resulted in serious unintended consequences in recipient communities. Studies that assessed a greater number of community interactions with the target species reported unintended outcomes more often, suggesting that unintended consequences may be underreported due to insufficient vetting. Most reported unintended outcomes arose from direct effects (68%) or simple density-mediated or indirect effects (25%) linked to the target species. Only a few documented cases arose from more complex interaction pathways (7%). Therefore, most unintended outcomes involved simple interactions that could be predicted and mitigated through more formal vetting. Our community assessment framework provides a tool for screening future conservation actions by mapping the recipient community interaction web to identify and mitigate unintended outcomes from intentional species introductions and eradications for conservation.

Evaluación de las Consecuencias Involuntarias de las Introducciones y Erradicaciones Intencionales de Especies para el Manejo Mejorado de la Conservación Resumen Actualmente se despliegan estrategias cada vez más intensas para mantener la biodiversidad y la función del ecosistema como respuesta a las amenazas antropogénicas mundiales, incluyendo la introducción y erradicación intencionales de especies por medio de la migración asistida, el retorno a la vida silvestre, el control biológico, la erradicación de especies invasoras y la genética dirigida. Estas acciones son muy polémicas por el potencial que tienen para generar consecuencias involuntarias. Realizamos una revisión de la literatura mundial sobre estas acciones de conservación para cuantificar cuán seguido ocurren las consecuencias involuntarias y cuáles son sus causas subyacentes. Para evaluar los resultados de conservación, desarrollamos un marco de trabajo de evaluación comunitaria para mapear sistemáticamente el rango de posibles interacciones para 111 estudios de caso. Con la aplicación de esta herramienta cuantificamos el número de tipos de interacción consideradas en cada estudio y documentamos la naturaleza y la fuerza de los resultados involuntarios. Se reportaron los resultados voluntarios en 51% de los casos, una combinación de resultados voluntarios e involuntarios en 26% de los casos y estrictamente los resultados involuntarios en el 10% de los casos. Por lo tanto, los resultados involuntarios fueron reportados en el 36% de todos los casos evaluados. En la evaluación general de los resultados de conservación (sopesando los efectos voluntarios y. los involuntarios), algunos efectos involuntarios fueron bastante inocuos en relación con el objetivo de conservación, mientras que otros resultaron en consecuencias involuntarias severas para las comunidades receptoras. Los estudios que evaluaron un mayor número de interacciones comunitarias con la especie objetivo reportaron resultados involuntarios con mayor frecuencia, lo que sugiere que las consecuencias involuntarias pueden estar subvaloradas debido al escrutinio insuficiente. La mayoría de los resultados involuntarios reportados surgieron de los efectos directos (68%) o de los efectos indirectos o mediados por la densidad (25%) vinculados con la especie diana. Solamente unos cuantos casos documentados surgieron de interacciones más complejas (7%). Por lo tanto, la mayoría de los resultados involuntarios involucran interacciones simples que podrían ser pronosticadas y mitigadas por medio de un escrutinio más formal. Nuestro marco de trabajo de evaluación comunitaria proporciona una herramienta para la revisión de las acciones de conservación en el futuro mediante el mapeo de la red de interacciones entre comunidades receptoras y para la mitigación de los resultados involuntarios surgidos de las introducciones y erradicaciones intencionales de especies a favor de la conservación.

Intervention effects on self-control decrease speed of biological aging mediated by changes in substance use: A longitudinal study of African American youth.

Biological aging is a common root for multiple diseases causing morbidity and mortality, and trajectories of aging may start early in life. This study was designed to examine whether a universal family-based substance use preventive intervention to enhance self-control and reduce substance use would also result in reductions in biological aging among Black youth from the rural South. The Adults in the Making (AIM) program is a randomized controlled trial with six 2-h sessions for Black youth. The 216 youths agreeing to provide blood at age 22 included 114 who had received the AIM intervention and 102 who assigned to the control group. We examined accelerated DNA methylation (DNAm)-based aging using a recently developed measure, "GrimAge," that has been shown to predict the risk of early mortality and that is known to be more strongly affected by substance use than other DNAm-based aging indices. Relative to those randomly assigned to the control group, those receiving the intervention demonstrated significantly enhanced self-control, slower increases in substance use, and reduced Grim aging at age 22. Using a bootstrapping method with 1000 replications, we found a significant indirect effect of AIM on reduced Grim aging through its effect on self-control and substance use. Sensitivity analyses examined effects using other indices of DNAm-based aging. These findings suggest that a family-based program designed to enhance rural Black youth's self-control can have beneficial effects on self-control, enhancing young adult health and health behavior, and ultimately decreased mortality risk.

El envejecimiento biológico es una causa común de varias enfermedades que causan morbilidad y mortalidad, y las trayectorias del envejecimiento pueden comenzar en las primeras etapas de la vida. Este estudio se diseñó para analizar si una intervención preventiva familiar y universal en el abuso de sustancias orientada a mejorar el autocontrol y a reducir el consumo de sustancias también tendría como resultado disminuciones del envejecimiento biológico entre jóvenes negros del sur rural. El programa Adults in the Making (AIM) es un ensayo controlado aleatorizado con seis sesiones de dos horas para jóvenes negros. Entre los 216 jóvenes que aceptaron dar sangre a los 22 años se encontraban 114 que habían recibido la intervención del AIM y 102 asignados al grupo de referencia. Analizamos el envejecimiento basado en la metilación acelerada del ADN (ADNm) usando un método de medición desarrollado recientemente que se llama "GrimAge", el cual, según se ha demostrado, predice el riesgo de mortalidad temprana y está más marcadamente afectado por el consumo de sustancias que otros índices de envejecimiento basados en el ADNm. En relación con las personas asignadas aleatoriamente al grupo de referencia, las que recibieron la intervención demostraron un autocontrol considerablemente mayor, aumentos más lentos de consumo de sustancias y un menor envejecimiento Grim a los 22 años. Utilizando un método de muestreo con reemplazamiento con 1000 reproducciones, hallamos un efecto indirecto significativo del AIM en un menor envejecimiento Grim mediante su efecto en el autocontrol y el consumo de sustancias. Los análisis de sensibilidad examinaron los efectos utilizando otros índices de envejecimiento basados en el ADNm. Estos resultados indican que un programa familiar diseñado para aumentar el autocontrol de los jóvenes negros de zonas rurales puede tener efectos beneficiosos en el autocontrol, mejorar la salud de los adultos jóvenes y su conducta con respecto a la salud y, finalmente, disminuir el riesgo de mortalidad.

Effectiveness of Panama as an intercontinental land bridge for large mammals.

Habitat fragmentation is a primary driver of wildlife loss, and establishment of biological corridors is a common strategy to mitigate this problem. A flagship example is the Mesoamerican Biological Corridor (MBC), which aims to connect protected forest areas between Mexico and Panama to allow dispersal and gene flow of forest organisms. Because forests across Central America have continued to degrade, the functioning of the MBC has been questioned, but reliable estimates of species occurrence were unavailable. Large mammals are suitable indicators of forest functioning, so we assessed their conservation status across the Isthmus of Panama, the narrowest section of the MBC. We used large-scale camera-trap surveys and hierarchical multispecies occupancy models in a Bayesian framework to estimate the occupancy of 9 medium to large mammals and developed an occupancy-weighted connectivity metric to evaluate species-specific functional connectivity. White-lipped peccary (Tayassu pecari), jaguar (Panthera onca), giant anteater (Myrmecophaga tridactyla), white-tailed deer (Odocoileus virginianus), and tapir (Tapirus bairdii) had low expected occupancy along the MBC in Panama. Puma (Puma concolor), red brocket deer (Mazama temama), ocelot (Leopardus pardalis), and collared peccary (Pecari tajacu), which are more adaptable, had higher occupancy, even in areas with low forest cover near infrastructure. However, the majority of species were subject to ≥1 gap that was larger than their known dispersal distances, suggesting poor connectivity along the MBC in Panama. Based on our results, forests in Darien, Donoso-Santa Fe, and La Amistad International Park are critical for survival of large terrestrial mammals in Panama and 2 areas need restoration.

Efectividad de Panamá como un Puente Terrestre Intercontinental para Mamíferos Mayores Resumen La fragmentación del hábitat es un causante primario de la pérdida de biodiversidad, y el establecimiento de corredores biológicos es una estrategia común para mitigar este problema. El Corredor Biológico Mesoamericano (CBM) es un ejemplo notable que pretende conectar áreas boscosas protegidas entre México y Panamá para permitir la dispersión y flujo genético de organismos del bosque. El funcionamiento del CBM se ha cuestionado debido a que la degradación de los bosques en Centroamérica continúa, pero no se dispone de estimaciones confiables de la ocurrencia de especies. Los mamíferos grandes son indicadores adecuados del funcionamiento de los bosques tropicales Por lo tanto evaluamos su estado de conservación en el Istmo de Panamá, la sección más angosta del CBM. Utilizamos muestreos con cámaras trampa y modelos de ocupación para múltiples especies bajo un modelo Bayesiano para estimar la ocupación de 9 especies de mamíferos medianos a grandes, y desarrollamos una métrica de conectividad ponderada por la ocupación para evaluar la conectividad funcional para cada especie. El puerco de monte (Tayassu pecari), jaguar (Panthera onca), hormiguero gigante (Myrmecophaga tridactyla), venado cola blanca (Oidocoileus virginianus), y tapir (Tapirus bairdii) presentaron una ocupación baja en el CBM en Panamá. El puma (Puma concolor), venado corzo (Mazama temama), ocelote (Leopardus pardalis) y el saino (Pecari tajacu), que son más adaptables, presentaron mayor ocupación, aún en áreas con poca cobertura boscosa, cercanas a infraestructura. Sin embargo, la mayoría de las especies estuvo sujeta a ≥ 1 vacío que era mayor que sus distancias de dispersión conocidas, lo que sugiere una conectividad pobre a lo largo del CBM en Panamá. Basados en nuestros resultados, los bosques de Darién, Donoso-Santa Fé y el Parque Internacional La Amistad son críticos para la supervivencia de mamíferos terrestres grandes en Panamá mientras que 2 áreas requieren restauración.

Birds suppress pests in corn but release them in soybean crops within a mixed prairie/agriculture system.

Birds provide ecosystem services (pest control) in many agroecosystems and have neutral or negative ecological effects (disservices) in others. Large-scale, conventional row crop agriculture is extremely widespread globally, yet few studies of bird effects take place in these agroecosystems. We studied indirect effects of insectivorous birds on corn and soybean crops in fields adjacent to a prairie in Illinois (USA). We hypothesized that prairie birds would forage for arthropods in adjacent crop fields and that the magnitude of services or disservices would decrease with distance from the prairie. We used bird-excluding cages over crops to examine the net effect of birds on corn and soybean grain yield. We also conducted DNA metabarcoding to identify arthropod prey in fecal samples from captured birds. Our exclosure experiments revealed that birds provided net services in corn and net disservices in soybeans. Distance from prairie was not a significant predictor of exclosure treatment effect in either crop. Many bird fecal samples contained DNA from both beneficial arthropods and known economically significant pests of corn, but few economically significant pests of soybeans. Song Sparrows (Melospiza melodia), one of our most captured species, most commonly consumed corn rootworms, an economically significant pest of corn crops. We estimated that birds in this system provided a service worth approximately US $275 ha-1 in corn yield gain, and a disservice valued at approximately $348 ha-1 in soybean yield loss. Our study is the first to demonstrate that birds can provide substantial and economically valuable services in field corn, and disservices in soybean crops. The contrasting findings in the 2 crop systems suggest a range of bird impacts within widespread agroecosystems and demonstrate the importance of quantifying net trophic effects.

Las aves brindan servicios ecosistémicos (control de plagas) en muchos agro-ecosistemas y tienen efectos ecológicos neutrales o negativos (deservicios) en otros. La agricultura convencional a gran escala de cultivos en hilera está ampliamente distribuida a escala global, pero a pesar de esto se han realizado pocos estudios de los efectos de las aves en estos agro-ecosistemas. Estudiamos los efectos indirectos de las aves insectívoras en cultivos de maíz y soja en campos adyacentes a una pradera en Illinois (EEUU). Hipotetizamos que las aves de pradera forrajearían en busca de artrópodos en los campos de cultivo adyacentes y que la magnitud de los servicios o deservicios disminuiría con la distancia desde la pradera. Usamos jaulas de exclusión de aves sobre los cultivos para examinar el efecto neto de las aves en el rendimiento de granos de maíz y soja. También utilizamos el método de código de barras de ADN para identificar presas de artrópodos en las muestras de heces de las aves capturadas. Nuestros experimentos de exclusión revelaron que las aves brindaron servicios netos en el maíz y deservicios netos en la soja. La distancia a las praderas no fue un predictor significativo del efecto del tratamiento de exclusión en ninguno de los cultivos. Muchas muestras de heces de aves contuvieron ADN tanto de artrópodos benéficos como de plagas económicamente significativas de maíz, pero de pocas plagas económicamente significativas de soja. Melospiza melodia, una de nuestras especies más capturadas, mayormente consumió el gusano de la raíz del maíz, una plaga económicamente significativa de este cultivo. Estimamos que las aves en este sistema brindaron un servicio valuado en aproximadamente US $275 ha­1 de ganancias en rendimiento de maíz, y un deservicio valuado en aproximadamente $348 ha­1 de pérdidas en rendimiento de soja. Nuestro estudio es el primero en demostrar que las aves pueden brindar servicios substanciales y económicamente valiosos en los campos de maíz y deservicios en los cultivos de soja. Los hallazgos contrastantes en los dos sistemas de cultivo sugieren un rango de impactos de las aves dentro de los agro-ecosistemas ampliamente distribuidos y demuestra la importancia de cuantificar los efectos tróficos netos.

Compatibility between Leptolegnia chapmanii and diflubenzuron and neem oil for the control of Aedes aegypti.

Leptolegnia chapmanii is pathogenic to mosquito larvae. The compatibility between L. chapmanii and two insect growth regulators (IGR), diflubenzuron and neem oil, was evaluated. L. chapmanii was grown on culture media containing different concentrations of each IGR. The mycelial growth was significantly reduced with the highest concentrations of IGR (F6,98=268, p<0.05). However, the production of zoospores (F6,56=0.93, p>0.05) and the larval mortality of Aedes aegypti (F6,56=0.95, p>0.05) were not significantly different among treatments. Furthermore, the percentage of adult emergence in the presence of different concentrations of diflubenzuron or a neem formulation was determined, and the pathogenic activity of zoospores was evaluated at the concentrations that inhibit the emergence at 30, 50 and 90%. The pathogenicity of zoospores was not significantly different among treatments (F6,14=0.54, p>0.05), and the larval mortalities were above 90% in all cases.

[Genetic characterization of rice endophytic bacteria (Oryza sativa L.) with antimicrobial activity against Burkholderia glumae]. / Caracterización genética de bacterias endofíticas de arroz (Oryza sativa L.) con actividad antimicrobiana contra Burkholderia glumae.

The aim of the present study was to isolate, select and characterize endophytic bacteria in rice inhibiting Burkholderia glumae THT as well as to characterize the genetic diversity and virulence factors in strains of B. glumae and Burkholderia gladioli of rice. Rice plants were collected in 4 departments from the northern region of Peru, isolating endophytic bacteria, after tissue sterilization, at 30°C (48h) in Trypticase Soy Agar (TSA), evaluating the antimicrobial activity against B. glumae THT, production of siderophores, resistance of toxoflavine and partial sequencing of the 16S rRNA gene. Furthermore, B. glumae and B. gladioli were isolated in selective medium (pH 4.5) at 41°C/72h. Molecular identification was performed using BOX-PCR and sequencing of the 16S rRNA gene, in addition to the production of extracellular enzymes, motility tests and sensitivity/resistance to bactericides. One hundred and eighty nine (189) endophytic bacteria were isolated, and only 9 strains showed antimicrobial activity against B. glumae THT, highlighting Burkholderia vietnamiensis TUR04-01, B. vietnamiensis TUR04-03 and Bacillus aryabhattai AMH12-02. The strains produced siderophores and at least 55.5% were resistant to toxoflavin. Additionally, 17 strains were grouped into 9 BOX-PCR profiles, where 16 had similarity with B. glumae LMG2196T (100%) and 1 with B. gladioli NBRC 13700T (99.86%). High diversity was found according to geographical origin and virulence factors. In conclusion, strains of the genus Bacillus and Burkholderia are potential biocontrol agents against B. glumae.

Identification of an Argentinean isolate of Spodoptera frugiperda granulovirus.

The fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is an important maize pest. Due to the environmental impact and emergence of resistance caused by chemical pesticides and transgenic events, the use of baculoviruses becomes a safe and useful alternative for its control in integrated pest management strategies. Here we report the identification of a novel isolate of a granulovirus of S. frugiperda native to the central region of Argentina, named SfGV ARG. We observed that larvae infected with SfGV ARG showed a yellowish coloration, swollen body and, in some cases, severe lesions in the last abdominal segments. We confirmed the identity of the isolate by sequencing fragments of the lef-8, lef-9 and granulin genes and by calculating evolutionary distances using the Kimura-2-Parameter model. SfGV ARG DNA restriction pattern allowed to estimate a genome of at least 135 kb.

Vedolizumab, an option in patients with inflammatory bowel disease intolerant to thiopurines and refractory to biological agents. / Vedolizumab, una opción en pacientes con enfermedad inflamatoria intestinal intolerantes a tiopurinas y refractarios a biológicos.

Vedolizumab (VDZ), a human monoclonal antibody that binds specifically to α4ß7-integrin, and is approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC), has demonstrated its efficacy in controlled clinical trials. OBJECTIVE: To describe a population treated with VDZ and to evaluate its long-term efficacy and safety in clinical practice. METHODS: An observational and multicentre study was carried out on patients with inflammatory bowel disease treated with VDZ for at least one year. An evaluation was performed on the activity indices, faecal calprotectin and C-reactive protein levels, hospital admissions, surgeries, and adverse events. RESULTS: A total of 73 patients were analysed (43 UC and 30 CD). More than one anti-TNF and more than one immunosuppressive was previously used by 74 and 23%, respectively, of UC patients, and 90 and 37%, respectively of CD patients. VDZ was stopped in 17 (23%) patients, 10 UC and 7 CD, due to a lack or loss of response before the first year, or due to adverse events. An intensification of the dose was required in 26 (63%) UC, and 16 (53%) CD patients. At 6 months, 70 and 42% of UC patients, and 80 and 43% of CD patients achieved a clinical response and remission, respectively. At one year, 58 and 35% of UC patients and 47 and 43% of CD patients, maintained the clinical response and remission, respectively. The C-reactive protein decreased significantly in both CD and UC patients. However, the decrease in faecal calprotectin was only achieved during follow-up in UC, but not in CD patients. Eight patients with CD that had been treated previously with ustekinumab avoided surgery at one year. A colectomy was performed on 8 (18.6%) UC patients, and 4 (13.3%) CD patients needed surgery. Six patients (8%) (5 UC and 1 CD) had adverse events. The concomitant use of corticosteroids or immunomodulators did not increase the efficacy. Those with a higher number of previous anti-TNF treatments showed less remissions in UC and responses in CD. CONCLUSIONS: After one year of VDZ, a clinical response and remission was induced in a considerable percentage of patients refractory to different biological or immunosuppressive therapies. VDZ can be considered as an alternative in those intolerant to immunosuppressives, with few adverse events.

[Effectiveness of Beauveria bassiana (Baubassil®) on the common cattle tick Rhipicephalus microplus in the Department of Guajira, Colombia]. / Efectividad de Beauveria bassiana (Baubassil®) sobre la garrapata común del ganado bovino Rhipicephalus microplus en el Departamento de la Guajira, Colombia.

The effectiveness of Baubassil®(Beauveria bassiana) on the tick Rhipicephalus (Boophilus) microplus was evaluated. In the in vitro phase, the optimal germination temperature of the fungus was determined by microcultures at 25, 30 and 35°C and the mortality of ticks. In the field, in a randomized design, 30 cebuine cows; 15 cows were treated with Baubassil® once a week at a 1×106 conidia/ml, and a control group was left untreated. It was observed that at temperatures of 25, 30 and 35°C, germination of the entomopathogen was 97.5, 94.7 and 6.3%, respectively. In animals treated with Baubassil® obtained a corrected effectiveness of 96.8% on ticks in the fifth week of application. The use of Baubassil® would be a valid alternative for controlling the cattle tick under the agroecological conditions of the Dry Caribbean.

In vitro effect of Chrysosporium indicum and Chrysosporium keratinophylum on Toxocara canis eggs.

The degree of antagonism exercised by fungi on geohelminth development varies according to the morphological alterations caused by different fungal species. Saprophytic fungi may exert ovicidal or ovistatic effects. The aim of this study was to apply scanning electron microscopy (SEM) to observe the action of two soil saprophytic species of Chrysosporium (C. indicum and C. keratinophylum) on Toxocara canis eggs. The fungal strains to be tested were incubated for 28 days at 28°C in 2% water agar with a suspension of unembryonated T. canis eggs. A suspension of T. canis eggs in 2% water agar was used as control group. The assay was done in triplicate for each fungus and the control group. SEM observations were performed on the 4th, 7th, 14th, 21st, and 28th day after inoculation. The effect of the fungi on eggs was evaluated in accordance with the alterations observed on the surface and the changes in the normal characteristics of the eggs. Hyphae around the eggs, appresoria penetrating the shell and changes in the typical egg membrane were observed in this assay. Type 3 effect (alterations that occur both in the embryo and the shell, and hyphal penetration of the eggs) was the prevalent effect. SEM allowed us to observe clearly the morphological alterations in T. canis eggs due to the effect of C. indicum and C. keratinophylum. Both saprophytic species of Chrysosporium alter the egg structure and alterations increase as exposure increases.

Efficacy of epiphytic bacteria to prevent northern leaf blight caused by Exserohilum turcicum in maize.

Eight potential biological control agents (BCAs) were evaluated in planta in order to assess their effectiveness in reducing disease severity of northern leaf blight caused by Exserohilum turcicum. The assay was carried out in greenhouse. Twenty-six-day-old plants, V4 phenological stage, were inoculated with antagonists by foliar spray. Only one biocontrol agent was used per treatment. Ten days after this procedure, all treatments were inoculated with E. turcicum by foliar application. Treatments performed were: C-Et: control of E. turcicum; T1: isolate 1 (Enterococcus genus)+E. turcicum; T2: isolate 2 (Corynebacterium genus)+E. turcicum; T3: isolate 3 (Pantoea genus)+E. turcicum; T4: isolate 4 (Corynebacterium genus)+E. turcicum; T5: isolate 5 (Pantoea genus)+E. turcicum; T6: isolate 6 (Bacillus genus)+E. turcicum; T7: isolate 7 (Bacillus genus)+E. turcicum; T8: isolate 8 (Bacillus genus)+E. turcicum. Monitoring of antagonists on the phyllosphere was performed at different times. Furthermore, the percentage of infected leaves and, plant and leaf incidence were determined. Foliar application of different bacteria significantly reduced the leaf blight between 30-78% and 39-56% at 20 and 39 days respectively. It was observed that in the V10 stage of maize plants, isolate 8 (Bacillus spp.) caused the greatest effect on reducing the severity of northern leaf blight. Moreover, isolate 8 was the potential BCA that showed more stability in the phyllosphere. At 39 days, all potential biocontrol agents had a significant effect on controlling the disease caused by E. turcicum.

The role of automated feedback in training and retaining biological recorders for citizen science.

The rapid rise of citizen science, with lay people forming often extensive biodiversity sensor networks, is seen as a solution to the mismatch between data demand and supply while simultaneously engaging citizens with environmental topics. However, citizen science recording schemes require careful consideration of how to motivate, train, and retain volunteers. We evaluated a novel computing science framework that allowed for the automated generation of feedback to citizen scientists using natural language generation (NLG) technology. We worked with a photo-based citizen science program in which users also volunteer species identification aided by an online key. Feedback is provided after photo (and identification) submission and is aimed to improve volunteer species identification skills and to enhance volunteer experience and retention. To assess the utility of NLG feedback, we conducted two experiments with novices to assess short-term (single session) and longer-term (5 sessions in 2 months) learning, respectively. Participants identified a specimen in a series of photos. One group received only the correct answer after each identification, and the other group received the correct answer and NLG feedback explaining reasons for misidentification and highlighting key features that facilitate correct identification. We then developed an identification training tool with NLG feedback as part of the citizen science program BeeWatch and analyzed learning by users. Finally, we implemented NLG feedback in the live program and evaluated this by randomly allocating all BeeWatch users to treatment groups that received different types of feedback upon identification submission. After 6 months separate surveys were sent out to assess whether views on the citizen science program and its feedback differed among the groups. Identification accuracy and retention of novices were higher for those who received automated feedback than for those who received only confirmation of the correct identification without explanation. The value of NLG feedback in the live program, captured through questionnaires and evaluation of the online photo-based training tool, likewise showed that the automated generation of informative feedback fostered learning and volunteer engagement and thus paves the way for productive and long-lived citizen science projects.

Rabbit biocontrol and landscape-scale recovery of threatened desert mammals.

Funding for species conservation is insufficient to meet the current challenges facing global biodiversity, yet many programs use expensive single-species recovery actions and neglect broader management that addresses threatening processes. Arid Australia has the world's worst modern mammalian extinction record, largely attributable to competition from introduced herbivores, particularly European rabbits (Oryctolagus cuniculus) and predation by feral cats (Felis catus) and foxes (Vulpes vulpes). The biological control agent rabbit hemorrhagic disease virus (RHDV) was introduced to Australia in 1995 and resulted in dramatic, widespread rabbit suppression. We compared the area of occupancy and extent of occurrence of 4 extant species of small mammals before and after RHDV outbreak, relative to rainfall, sampling effort, and rabbit and predator populations. Despite low rainfall during the first 14 years after RHDV, 2 native rodents listed by the International Union for Conservation of Nature (IUCN), the dusky hopping-mouse (Notomys fuscus) and plains mouse (Pseudomys australis), increased their extent of occurrence by 241-365%. A threatened marsupial micropredator, the crest-tailed mulgara (Dasycercus cristicauda), underwent a 70-fold increase in extent of occurrence and a 20-fold increase in area of occupancy. Both bottom-up and top-down trophic effects were attributed to RHDV, namely decreased competition for food resources and declines in rabbit-dependent predators. Based on these sustained increases, these 3 previously threatened species now qualify for threat-category downgrading on the IUCN Red List. These recoveries are on a scale rarely documented in mammals and give impetus to programs aimed at targeted use of RHDV in Australia, rather than simply employing top-down threat-based management of arid ecosystems. Conservation programs that take big-picture approaches to addressing threatening processes over large spatial scales should be prioritized to maximize return from scarce conservation funding. Further, these should be coupled with long-term ecological monitoring, a critical tool in detecting and understanding complex ecosystem change.

[Safety in the Microbiology laboratory]. / Seguridad en el laboratorio de Microbiología Clínica.

The normal activity in the laboratory of microbiology poses different risks - mainly biological - that can affect the health of their workers, visitors and the community. Routine health examinations (surveillance and prevention), individual awareness of self-protection, hazard identification and risk assessment of laboratory procedures, the adoption of appropriate containment measures, and the use of conscientious microbiological techniques allow laboratory to be a safe place, as records of laboratory-acquired infections and accidents show. Training and information are the cornerstones for designing a comprehensive safety plan for the laboratory. In this article, the basic concepts and the theoretical background on laboratory safety are reviewed, including the main legal regulations. Moreover, practical guidelines are presented for each laboratory to design its own safety plan according its own particular characteristics.

An Auto-Ethnographic Study of "Open Dialogue": The Illumination of Snow.

This auto-ethnographic study describes the changes in the author's thinking and clinical work connected to her first-hand experience of Open Dialogue, which is an innovative, psychosocial approach to severe psychiatric crises developed in Tornio, Finland. In charting this trajectory, there is an emphasis on three interrelated themes: the micropolitics of U.S. managed mental health care; the practice of "dialogicality" in Open Dialogue; and the historical, cultural, and scientific shifts that are encouraging the adaptation of Open Dialogue in the United States. The work of Gregory Bateson provides a conceptual framework that makes sense of the author's experience and the larger trends. The study portrays and underscores how family and network practices are essential to responding to psychiatric crises and should not be abandoned in favor of a reductionist, biomedical model.

Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time.

BACKGROUND: With the advent of biologic drugs in the management of moderate to severe psoriasis, there may have been a shift in therapeutic approach from rotational strategies to a unidirectional progression from topical treatments to the highest rung of the therapeutic ladder. We studied the frequency of switching from classic to biologic therapy and vice versa in a cohort of patients with psoriasis over a period of up to 5 years. METHODS: Patients are included in the BIOBADADERM prospective registry when they are first prescribed any specific conventional or biologic systemic treatment. The data for each patient refer to the follow-up period from the time they entered the cohort until October 2013. To describe the pattern of switches from classic to biologic therapy and vice versa, we used the data in the registry on the first day of every 365-day period following the date each patient was included in the cohort. RESULTS: In total, 47.3% of the patients (926/1956) were prescribed a classic systemic drug and 52.7% (1030/1956) a biologic agent on entry into the study. Of the 741 patients who accumulated 5 years of follow-up, 21.9% (155) were receiving nonbiologic drugs and 78.1% (553) were on biologic therapy on the first day of their 5th year of follow-up. CONCLUSIONS: The proportion of patients receiving biologic therapy increased with longer follow-up.