Within-wing isotopic (δ2H, δ13C, δ15N) variation of monarch butterflies: implications for studies of migratory origins and diet

Increasingly, stable isotope measurements are being used to assign individuals to broad geographic origins based on established relationships between animal tissues and tissue-specific isoscapes. In particular, the eastern North American population of the monarch butterfly (Danaus plexippus) has been the subject of several studies using established δ2H and δ13C wing-tissue isoscapes to infer natal origins of migrating and overwintering individuals. However, there has been no study investigating potential variance that can derive from sub-sampling different regions of the wings, especially those regions differing in pigmentation (orange versus black). Within-wing isotopic (δ2H, δ13C, δ15N) variance of 40 monarch butterflies collected from natural overwinter mortality on Mexican roost sites were split evenly into two groups: unwashed samples and those washed in a 2:1 chloroform:methanol solvent. Isotopic variance in δ2H and δ13C was related to pigment (within-wing range 5‰ and 0.5‰, respectively), but not region of subsampling. This variance was reduced 3 to 4 fold through solvent washing that removed pigmented surface scales and any adhered oils. Wing δ15N was similarly influenced by pigment (range 0.3‰), but this effect was not reduced through washing. We recommend future isotopic studies of monarchs and other butterflies for migration research to use the same region for sub-sampling consistently and to wash samples with solvent to reduce isotopic variance related to uncontrolled variance in discrimination (δ2H, δ13C, δ15N) and/or adsorbed water vapor (δ2H). These data also need to be included in description of methods

Predictive index for risk stratification of venous thromboembolic disease in patients with hematologic malignancies

Introducción: la enfermedad tromboembólica venosa es una frecuente complicación en las hemopatías malignas y tiene un significativo impacto en la morbilidad y la mortalidad. A pesar de existir múltiples scores bien validados para estratificar el riesgo de esta enfermedad en tumores sólidos, las hemopatías malignas están subrepresentadas en estos modelos.Objetivo: diseñar un índice predictivo para la estratificación del riesgo trombótico en pacientes con hemopatías malignas.Métodos: se realizó un estudio observacional analítico de casos y controles en el Hospital “Arnaldo Milián Castro” de la Provincia de Villa Clara, durante el período de octubre de 2016 a enero de 2019, en 285 pacientes hospitalizados con hemopatías malignas (94 con enfermedad tromboembólica y191 sin). Para el análisis univariado fue aplicada la prueba de Chi-cuadrado, Odds Ratio para la estimación del riesgo y V de Cramer para la fuerza de asociación. La regresión logística y la curva ROC fueron aplicadas en el análisis multivariado.Resultados: el índice predictivo de enfermedad tromboembólica quedó compuesto por cinco factores predictores: hipercolesterolemia, actividad tumoral, inmovilidad, uso de medicamentos trombogénicos y diabetes mellitus. Se definió como alto riesgo de trombosis al paciente que obtuvo cuatro puntos o más y bajo riesgo al que tuvo menos de cuatro puntos. El índice clasificó correctamente al 81,10% de los pacientes, para una sensibilidad del 59,57% y una especificidad del 92,15%. Los valores predictivos positivos y negativos fueron de 78,87% y 82,24%, respectivamente.Conclusiones: el índice elaborado representó una herramienta específica y eficaz para la predicción de enfermedad tromboembólica en el paciente hospitalizado con hemopatía maligna.Introduction: venous thromboembolic disease is a frequent complication in hematologic malignancies and has a significant impact on morbidity and mortality. Despite the existence of multiple well-validated scores to stratify the risk of this disease in solid tumors, hematological malignancies are underrepresented in these models.Objective: to design a predictive index for the stratification of the thrombotic risk in patients with hematologic malignancies.Methods: an analytical observational study of cases and controls was carried out in the “Arnaldo Milián Castro” Hospital from Villa Clara Province, during the period from October 2016 to January 2019, in 285 hospitalized patients with hematological malignancies (94 with thromboembolic disease and 191 without). For univariate analysis, Chi-square test, Odds Ratio for risk estimation and Cramer's V for strength of association were applied. Logistic regression and ROC curve were applied in the multivariate analysis.Results: the predictive index of thromboembolic disease was composed of five predictors: hypercholesterolemia, tumor activity, immobility, use of thrombogenic drugs and diabetes mellitus. High risk of thrombosis was defined as a patient who scored four points or more and low risk as a patient who scored less than four points. The index correctly classified 81.10% of the patients, for a sensitivity of 59.57% and a specificity of 92.15%. The positive and negative predictive values were 78.87% and 82.24%, respectively.Conclusions: the developed index represented a specific and effective tool for the prediction of thromboembolic disease in hospitalized patients with hematologic malignancy

Within-wing isotopic (δ2H, δ13C, δ15N) variation of monarch butterflies: implications for studies of migratory origins and diet

Increasingly, stable isotope measurements are being used to assign individuals to broad geographic origins based on established relationships between animal tissues and tissue-specific isoscapes. In particular, the eastern North American population of the monarch butterfly (Danaus plexippus) has been the subject of several studies using established δ2H and δ13C wingtissue isoscapes to infer natal origins of migrating and overwintering individuals. However, there has been no study investigating potential variance that can derive from subsampling different regions of the wings, especially those regions differing in pigmentation (orange versus black). Within-wing isotopic (δ2H, δ13C, δ15N) variance of 40 monarch butterflies collected from natural overwinter mortality on Mexican roost sites were split evenly into two groups: unwashed samples and those washed in a 2:1 chloroform:methanol solvent. Isotopic variance in δ2H and δ13C was related to pigment (within-wing range 5‰ and 0.5‰, respectively), but not region of subsampling. This variance was reduced 3 to 4 fold through solvent washing that removed pigmented surface scales and any adhered oils. Wing δ15N was similarly influenced by pigment (range 0.3‰), but this effect was not reduced through washing. We recommend future isotopic studies of monarchs and other butterflies for migration research to use the same region for subsampling consistently and to wash samples with solvent to reduce isotopic variance related to uncontrolled variance in discrimination (δ2H, δ13C, δ15N) and/or adsorbed water vapor (δ2H). These data also need to be included in description of methods

Patogenia de la aterosclerosis

La enfermedad cardiovascular arteriosclerótica es una alteración compleja en la que participan una serie de factores moleculares, genéticos, medioambientales. Las concentraciones plasmáticas elevadas de lipoproteínas de baja densidad son un factor de riesgo para el desarrollo prematuro de la aterosclerosis y cardiopatía isquémica. Las lipoproteínas de baja densidad oxidadas por los radicales libres intervienen en prácticamente todas las etapas del proceso de formación de la placa de ateroma. En la arteriogénesis intervienen múltiples factores de crecimiento, citokinas y otras sustancias producidas por las células endoteliales, las células de músculo liso y los linfocitos T que regulan la respuesta inflamatoria y la proliferación celular. Este trabajo de revisión tiene como propósito profundizar en la fisiopatología molecular de la aterosclerosis

Risankizumab for Ulcerative Colitis

Importance: The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective: To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, setting, and participants: Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions: For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main outcomes and measures: The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results: Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P < .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P < .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No adverse event signals were detected in the treatment groups. Conclusion and relevance: Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial registration: ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135