Patient-reported outcomes in RA patients treated with tofacitinib or bDMARDs in real-life conditions in two Latin American countries / Desenlaces reportados por los pacientes diagnosticados con AR tratados con tofacitinib o FARME biológico bajo condiciones reales en dos países de Latinoamérica

Objective: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. Methods: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). Results: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients’ mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (−2.55[.30] vs. −2.52[.26]), HAQ-DI score (−.56[.07] vs. −.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (−2.37[.22] vs. −2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported.Conclusion: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs.(AU)

Objetivo: Describir la eficacia, la seguridad y los desenlaces reportados por los pacientes (PRO) en pacientes con artritis reumatoide (RA) con una respuesta inadecuada a los fármacos antirreumáticos modificadores de la enfermedad sintéticos convencionales (csFARME) tratados con tofacitinib o FARME biológico (bFARME) en condiciones de la vida real. Métodos: Estudio no intervencional realizado entre marzo de 2017 y septiembre de 2019 en 13 centros de Colombia y Perú. Los desenlaces evaluados al inicio y a los seis meses de seguimiento fueron la actividad de la enfermedad (puntaje Routine Assessment of Patients Index Data [RAPID3]), el estado funcional (puntaje Health Assessment Questionnaire [HAQ-DI]) y la calidad de vida (EuroQol Questionnaire [EQ-5D-3L]). El puntaje de actividad de la enfermedad-28 (DAS28-ESR) y la frecuencia de eventos adversos (EA). Se estimaron las diferencias no ajustadas y ajustadas con respecto a los valores basales y se expresaron como diferencia de medias por mínimos cuadrados (LMD). Resultados: Se recolectó información de 100 pacientes tratados con tofacitinib y 70 pacientes con bFARME. Al inicio del estudio, la edad media de los pacientes era de 53,53 años (DE 13,77) y la duración media de la enfermedad de 6,31 años (DE 7,01). El cambio con respecto al valor basal en el mes 6 no fue estadísticamente significativo en la LMD ajustada (SE) para tofacitinib vs. los bFARME para RAPID3 (−2,55 [0,30] vs. −2,52 [0,26]), puntuación HAQ-DI (−0,56 [0,07] vs. −0,50 [0,08]), puntuación EQ-5D-3L (0,39 [0,04] vs. 0,37 [0,04]) y DAS28-ESR (−2,37 [0,22] vs. −2,77 [0,20]). Los pacientes de ambos grupos presentaron proporciones similares de EA no graves y graves. Ninguna muerte fue reportada. Conclusiones: Los cambios desde el inicio no fueron estadísticamente significativos entre tofacitinib y los bFARME en RAPID3 y en los desenlaces secundarios. Los pacientes de ambos grupos presentaron proporciones similares de EA no graves y graves.(AU)

Patient-reported outcomes in RA patients treated with tofacitinib or bDMARDs in real-life conditions in two Latin American countries.

OBJECTIVE: To describe efficacy, safety, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) treated with tofacitinib or biological DMARDs (bDMARDs) in real-life conditions. METHODS: A noninterventional study was performed between March 2017 and September 2019 at 13 sites in Colombia and Peru. Outcomes measured at baseline and at the 6-month follow-up were disease activity (RAPID3 [Routine Assessment of Patients Index Data] score), functional status (HAQ-DI [Health Assessment Questionnaire] score), and quality of life (EQ-5D-3L [EuroQol Questionnaire]). The Disease Activity Score-28 (DAS28-ESR) and frequency of adverse events (AEs) were also reported. Unadjusted and adjusted differences from baseline were estimated and expressed as the least squares mean difference (LSMD). RESULTS: Data from 100 patients treated with tofacitinib and 70 patients with bDMARDs were collected. At baseline, the patients' mean age was 53.53 years (SD 13.77), the mean disease duration was 6.31 years (SD 7.01). The change from baseline at month 6 was not statistically significant different in the adjusted LSMD [SD] for tofacitinib vs. bDMARDs for RAPID3 score (-2.55[.30] vs. -2.52[.26]), HAQ-DI score (-.56[.07] vs. -.50[.08]), EQ-5D-3L score (.39[.04] vs. .37[.04]) and DAS28-ESR (-2.37[.22] vs. -2.77[.20]). Patients from both groups presented similar proportions of nonserious and serious AEs. No deaths were reported. CONCLUSION: Changes from baseline were not statistically significantly different between tofacitinib and bDMARDs in terms of RAPID3 scores and secondary outcomes. Patients from both groups presented similar proportions of nonserious and serious AEs. CLINICAL TRIAL NUMBER: NCT03073109.

Guillain-Barre syndrome associated to COVID-19 infection: a review of published case reports. / Síndrome de Guillain-Barré asociado a infección por COVID-19: revisión de casos publicados.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic is a major worldwide health disorder. There is an increasing number of neurological complications recognized with COVID-19 including patients with GBS and its variants. DEVELOPMENT: A review of the clinical cases of GBS associated to COVID-19 infection published in the last months has been developed. We included 48 patients (31 men, mean age 56.4 years). The most common COVID-19 symptoms were cough (60.4%) and fever (56.3%). Mean time from COVID-19 symptoms to neurologic manifestations was 12.1 days, but in nine patients (18.8%) developed GBS within seven days. Eleven patients (22.9%) presented cranial nerve involvement in the absence of muscle weakness; 36 presented the classic sensory motor variant (75%) and one had a pure motor variant (2.1%). The electrodiagnostic pattern was considered demyelinating in 82.4% of the generalized variants. The presence of hyposmia/dysgeusia was associated with a latency shorter than seven days to GBS onset of symptoms (30% vs 15.6%), and cranial nerve involvement in the absence of weakness (30.8% vs 17.1%). Most patients (87.5%) were treated with intravenous immunoglobulin. Neurological outcome was favorable in 64.6%; 29.2% had respiratory failure and 4.2% died shortly after being admitted. CONCLUSIONS: GBS in patients with SARS-CoV-2 infection resembles clinically and electrophysiology the classical forms. Further studies are necessary to understand whether GBS frequency is actually increased due to SARS-CoV-2 infection and explore pathogenic mechanisms.

TITLE: Síndrome de Guillain-Barré asociado a infección por COVID-19: revisión de casos publicados.Introducción. La pandemia por la enfermedad por coronavirus 2019 (COVID-19) es un importante problema para la salud mundial. Hay un incremento en las complicaciones neurológicas reconocidas por la COVID-19, incluyendo el síndrome de Guillain-Barré (SGB) y sus variantes. Desarrollo. Se realizó una revisión de los casos publicados en los últimos meses de SGB asociado a infección por COVID-19. Incluimos a 48 pacientes (31 hombres; edad media: 56,4 años). Los síntomas de COVID-19 más comunes fueron tos (60,4%) y fiebre (56,3%). El tiempo promedio entre los síntomas de COVID-19 y el SGB fue de 12,1 días, pero nueve pacientes (18,8%) desarrollaron SGB en menos de siete días. Once pacientes (22,9%) presentaron afectación de los nervios craneales en ausencia de debilidad muscular, 36 presentaron la variante clásica sensitivomotora (75%) y uno tuvo una variante motora pura (2,1%). El patrón electrofisiológico se consideró desmielinizante en el 82,4% de las variantes generalizadas. La presencia de hiposmia/disgeusia estuvo asociada con una latencia menor a los siete días hasta el inicio de los síntomas del SGB (30 frente a 15,6%) y a la afectación de los nervios craneales en ausencia de debilidad (30,8 frente a 17,1%). La mayoría de los pacientes (87,5%) fueron tratados con inmunoglobulina endovenosa. La evolución neurológica fue favorable en el 64,6%, el 29,2% tuvo insuficiencia respiratoria y hubo un 4,2% de muertes. Conclusiones. El SGB en pacientes con infección por SARS-CoV-2 es similar clínica y electrofisiológicamente a las formas clásicas. Se requieren más estudios para comprender si la frecuencia del SGB realmente aumentó debido a la pandemia por COVID-19 y explorar los mecanismos patógenos involucrados.

Validation of QTLs for Orobanche crenata resistance in faba bean (Vicia faba L.) across environments and generations.

Broomrape (Orobanche crenata Forsk.) is a major root-parasite of faba bean (Vicia faba L.), that seriously limits crop cultivation in the whole Mediterranean area. This parasitic weed is difficult to control, difficult to evaluate and the resistance identified so far is of polygenic nature. This study was conducted to identify genetic regions associated with broomrape resistance in recombinant inbred lines (RILs) and to validate their previous location in the original F(2) population derived from the cross between lines Vf6 and Vf136. A progeny consisting of 165 F(6) RILs was evaluated in three environments across two locations in 2003 and 2004. Two hundred seventy seven molecular markers were assigned to 21 linkage groups (9 of them assigned to specific chromosomes) that covered 2,856.7 cM of the V. faba genome. The composite interval mapping on the F(6) map detected more quantitative trait loci (QTL) than in the F(2) analysis. In this sense, four QTLs controlling O. crenata resistance (Oc2-Oc5) were identified in the RI segregant population in three different environments. Only Oc1, previously reported in the F(2) population, was not significant in the advanced lines. Oc2 and Oc3 were found to be associated with O. crenata resistance in at least two of the three environments, while the remaining two, Oc4 and Oc5, were only detected in Córdoba-04 and Mengíbar-04 and seemed to be environment dependent.

El lóbulo de la vena ácigos / No disponible

No disponible

Neumotórax espontáneo bilateral / Bilateral spontaneous pneumothorax

No disponible

No disponible

Cross-species amplification of Medicago truncatula microsatellites across three major pulse crops.

Model plants are facilitating the genetic characterization and comparative mapping of a number of traditional crops. Medicago truncatula has been widely accepted as a model plant to this end as it provides the essential tools for multiple aspects of legume genetics and genomics. A large set of markers from highly conserved M. truncatula gene regions is being created and used to establish a worldwide framework for comparative genomic studies in legumes. We have investigated the potential for cross-species amplification of 209 expressed sequence tag (EST)-based and 33 bacterial artificial chromosome (BAC)-based microsatellites from M. truncatula in the three most important European legume pulses-pea, faba bean and chickpea-that might facilitate future comparative mapping. Our results revealed significant transferability of M. truncatula microsatellites to the three pulses (40% in faba bean, 36.3% in chickpea and 37.6% in pea). The percentage of M. truncatula EST-SSRs (simple sequence repeats) amplified in the three crops (39-43%) was twofold higher than that of the genomic SSRs (21-24%). Sequence analysis determined that the level of conservation in the microsatellite motif was very low, while the flanking regions were generally well conserved. The variations in the sequences were mainly due to changes in the number of repeat motifs in the microsatellite region combined with indel and base substitutions. None of the functional microsatellites showed direct polymorphism among the parental genotypes tested, consequently preventing their immediate use for mapping purposes.

Restoration of genetic diversity in the dry forest tree Swietenia macrophylla (Meliaceae) after pasture abandonment in Costa Rica.

We studied the levels of genetic diversity of Swietenia macrophylla (big leaf mahogany) in five successional plots in the Santa Rosa National Park, Guanacaste, Costa Rica. We selected sites with different lengths of time since the last major disturbance (typically fire): 6, 9, 15 and 20 years. In addition, we also included a patch of mature forest that had experienced selective logging and other human activity in the past 100 years. Genetic diversity was assessed using five polymorphic DNA microsatellite loci. We found a total of 21 alleles in the five loci examined, in which the number of alleles present varied among the five sites studied. Allelic diversity varied between sites ranging from 20 to 14 alleles, and our data revealed that earlier successional sites have more alleles than older sites. There was significant heterogeneity in allele frequencies between sites; however, genetic differentiation between populations was low (FST = 0.063) indicating that most of the variation was found within sites and extensive gene flow between sites. In addition, our analysis also showed that genetic diversity of adult trees does not solely determine the diversity of seedlings and saplings found around them, also supporting the existence of extensive gene flow. The impact of these findings for the design of conservation strategies for tropical dry forests trees is discussed.

Environmental and physiological regulation of transpiration in tropical forest gap species: the influence of boundary layer and hydraulic properties.

Environmental and physiological regulation of transpiration were examined in several gap-colonizing shrub and tree species during two consecutive dry seasons in a moist, lowland tropical forest on Barro Colorado Island, Panama. Whole plant transpiration, stomatal and total vapor phase (stomatal + boundary layer) conductance, plant water potential and environmental variables were measured concurrently. This allowed control of transpiration (E) to be partitioned quantitatively between stomatal (g s) and boundary layer (g b) conductance and permitted the impact of invividual environmental and physiological variables on stomatal behavior and E to be assessed. Wind speed in treefall gap sites was often below the 0.25 m s-1 stalling speed of the anemometer used and was rarely above 0.5 m s-1, resulting in uniformly low g b (c. 200-300 mmol m-2 s-1) among all species studied regardless of leaf size. Stomatal conductance was typically equal to or somewhat greater than g b. This strongly decoupled E from control by stomata, so that in Miconia argentea a 10% change in g s when g s was near its mean value was predicted to yield only a 2.5% change in E. Porometric estimates of E, obtained as the product of g s and the leaf-bulk air vapor pressure difference (VPD) without taking g b into account, were up to 300% higher than actual E determined from sap flow measurements. Porometry was thus inadequate as a means of assessing the physiological consequences of stomatal behavior in different gap colonizing species. Stomatal responses to humidity strongly limited the increase in E with increasing evaporative demand. Stomata of all species studied appeared to respond to increasing evaporative demand in the same manner when the leaf surface was selected as the reference point for determination of external vapor pressure and when simultaneous variation of light and leaf-air VPD was taken into account. This result suggests that contrasting stomatal responses to similar leaf-bulk air VPD may be governed as much by the external boundary layer as by intrinsic physiological differences among species. Both E and g s initially increased sharply with increasing leaf area-specific total hydraulic conductance of the soil/root/leaf pathway (G t), becoming asymptotic at higher values of G t. For both E and g s a unique relationship appeared to describe the response of all species to variations in G t. The relatively weak correlation observed between g s and midday leaf water potential suggested that stomatal adjustment to variations in water availability coordinated E with water transport efficiency rather than bulk leaf water status.

The effect of environmentally induced stem temperature gradients on transpiration estimates from the heat balance method in two tropical woody species.

Commercially available sap flow gauges were used to evaluate the performance of the stem heat balance (SHB) technique for measuring sap flow in coffee (Coffea arabica L. cv. Yellow Catuai) and koa (Acacia koa Gray) plants under greenhouse and field conditions. Transpiration rates measured gravimetrically and with the SHB technique were similar in greenhouse tests, provided that insulation in addition to that supplied by the gauge manufacturer was applied to reduce radiant heating in the vicinity of the sap flow gauges. Unrealistic estimates of transpiration rates were sometimes obtained under both field and greenhouse conditions as a result of negative stem temperature differentials from below to above the gauge heater, even in the absence of power applied to the heaters. It was possible to correct this environmentally induced bias by means of additional stem insulation that minimized the rate of change in stem temperature, or by applying simple corrections using the DeltaT values for unheated gauges operated as blanks. In the field, where dense canopies reduced the radiant energy load on stems, temperature corrections were unnecessary, because DeltaT values in unheated gauges were near zero.

[A model for the extrusion of a corn:soybean blend (70:30)]. / Modelo para la extrusión de mezclas maiz:soja (70:30).

Most of the physicochemical and sensorial properties of the extrudates depend on the extent of the starch degradation. A cereal extrudate has physicochemical properties similar to those of a blend of raw, gelatinized and dextrinized starch. Based on this postulate, models of cereal: oilseed blends were prepared, and different analytical techniques for their characterization were applied. Results revealed that the corn:soy (70:30) extruded sample under study, was similar to moderately dextrinized corn:soy blend obtained in the laboratory. Therefore, it could be used to prepare "papillas" or precooked foods.