Anti-HLA serological response to CD38-targeting desensitization therapy is challenged by peripheral memory B-cells in highly sensitized kidney transplant candidates.

High HLA sensitization (HS) limits access to compatible transplantation. New CD38-targeting agents have shown to reduce anti-HLA antibodies, although with important inter-patient variability thus, pre-treatment identification of responder and non-responder patients is needed for treatment decision-making. We analyzed 26 HS patients from two desensitization trials using anti-CD38 mAb. Hierarchical clustering identified three serological responder groups: high, low, and non-responders. Spectral flow-cytometry and functional HLA-specific memory B-cell (mBc) assessment was first conducted on PBMC and bone marrow samples from 16 patients treated with isatuximab (NCT04294459). Isatuximab effectively depleted bone marrow plasma cells, peripheral CD38-expressing plasmablasts, plasma cells, transitional B cells, and class-switch mBc, ultimately reducing frequencies of HLA-specific IgG-producing mBc. Multidimensional spectral flow cytometry with PLS-DA analysis revealed that pre-treatment abundance of specific circulating mBcs phenotypes, especially CD38neg class-switch mBc, accurately distinguished between high serological responders and low or non-responders (AUC 0.958, 0.860-1.000, p=0.009), who also displayed significantly lower frequencies of HLA-specific IgG-producing mBc (p<0.0001). This phenotypical mBc signature predicting response to therapy was validated in an external HS patient cohort (n=10) receiving daratumumab (NCT04204980). This study identifies critical circulating mBc subset phenotypes that distinguish HS patients with successful serological response to CD38-targeting desensitization therapies, potentially guiding treatment decision-making.

Corrigendum: Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept.

[This corrects the article DOI: 10.3389/fimmu.2022.918887.].

High-dimensional mass cytometry identified circulating natural killer T-cell subsets associated with protection from cytomegalovirus infection in kidney transplant recipients.

Cytomegalovirus (CMV) infection is associated with poor kidney transplant outcomes. While innate and adaptive immune cells have been implicated in its prevention, an in-depth characterization of the in vivo kinetics of multiple cell subsets and their role in protecting against CMV infection has not been achieved. Here, we performed high-dimensional immune phenotyping by mass cytometry, and functional assays, on 112 serially collected samples from CMV seropositive kidney transplant recipients. Advanced unsupervised deep learning analysis was used to assess immune cell populations that significantly correlated with prevention against CMV infection and anti-viral immune function. Prior to infection, kidney transplant recipients who developed CMV infection showed significantly lower CMV-specific cell-mediated immune (CMI) frequencies than those that did not. A broad diversity of circulating cell subsets within innate and adaptive immune compartments were associated with CMV infection or protective CMV-specific CMI. While percentages of CMV (tetramer-stained)-specific T cells associated with high CMI responses and clinical protection, circulating CD3+CD8midCD56+ NK-T cells overall strongly associated with low CMI and subsequent infection. However, three NK-T cell subsets sharing the CD11b surface marker associated with CMV protection and correlated with strong anti-viral CMI frequencies in vitro. These data were validated in two external independent cohorts of kidney transplant recipients. Thus, we newly describe the kinetics of a novel NK-T cell subset that may have a protective role in post-transplantation CMV infection. Our findings pave the way to more mechanistic studies aimed at understanding the function of these cells in protection against CMV infection.

Insights into the spatial ecology of severely injured free-living felids: Iberian lynx, bobcat, and snow leopard.

Severe musculoskeletal diseases, such as those associated with congenital or traumatic events, that result in missing limbs may compromise the fitness and survival of free-living felids. Here we report the space use of four amputee individuals from three felid species captured from 2017 to 2022 in Missouri (USA), Toledo and Badajoz (Spain), and Suitai Khairkhan Mountain (Mongolia). We describe home ranges and daily travel distances post-release of free-living felids that had either suffered a traumatic amputation or following a surgical amputation. We compared these data with those reported in the literature for felids without amputations. Forelimb or hindlimb amputation did not affect the hunting, mating, or territory patrolling behavior of any of the individuals. However, we recorded significant differences in the daily movement before and after the traumatic event of the Iberian lynx forelimb amputee. We attribute this difference to the physical impairment, although we consider other variables that may have played a role. Nevertheless, all animals appeared to cope well with their limb loss, showing home ranges and daily distances within those recorded for their sex and species. Unless amputee felids represent a threat to domestic livestock or humans, our data suggest these individuals may remain free-living as they contribute to local population persistence and appear to maintain good general health and welfare.

Prevalencia de la soledad entre los adolescentes de los centros educativos de las zonas básicas de salud de dos centros de salud de Madrid / Prevalence of loneliness in secondary school adolescents from two primary care health centres in Madrid

Objetivo: Conocer la prevalencia de la soledad nodeseada en adolescentes de centros educativosvinculados a dos zonas básicas de salud, así comodescribir su perfil según las variables analizadas.Diseño. Estudio descriptivo de corte transversal.Emplazamiento. Centros educativos correspondientes a dos zonas básicas de salud de Madrid.Participantes. Adolescentes que cursaban tercero ycuarto de ESO durante el curso lectivo 2021-2022.Variables. Nivel de soledad medido por la escalaDJGLS (0-11 puntos) y variables sociodemográficas y de ocio.Resultados. Un 47,1% de los participantes manifiesta que se siente solo con una intensidad moderada, mientras que el 6,51% manifiestan sufrirsoledad extrema y un 11,3% soledad severa. Un34,9% de los participantes no sufre soledad.Conclusiones. Nuestros resultados ponen de relieve que la soledad no deseada es un problemaque afecta a adolescentes, siendo esto importantepara el desarrollo de políticas de salud e intervenciones adaptadas a este momento del ciclo vital. (AU)

Objective: To evaluate the prevalence of unwantedloneliness in adolescents from educational centres belonging to two “basic health areas”. Moreover, to report their profile according to the variables analyzed.Design. Cross-sectional descriptive study.Location. Educational centres belonging to two “basichealth areas” of Madrid.Participants. Adolescents who were studying thirdand fourth year of secondary school during the 2021-2022 school year.Variables. Degree of loneliness as measured by theDJGLS scale (0-11 points) as well as sociodemographicand leisure variables.Results. A total of 47.1%, 6.51% and 11.3% of participants reported moderate, extreme and severe loneliness, respectively. Only 34.9% of participants did notsuffer from loneliness.Conclusions. Our study highlights that unwanted loneliness is an adolescents’ issue as well as the importance of developing health policies in this regard. Interventions need to be tailored to this developmentalstage. (AU)

Multicomponent cognitive-behavioral therapy for intermittent explosive disorder by videoconferencing: a case study / Terapia Cognitivo-Conductual multicomponente para el tratamiento del Trastorno Explosivo Intermitente por videoconferencia: un estudio de caso

Cognitive-behavioral Therapy (CBT) for the treatment of Intermittent Explosive Disorder (IED) has proved to be effective, with moderate to large effect sizes both in individual and group interventions. Videoconferencing has been used effectively to treat different mental disorders but its use for IED patients is as yet unknown. The aim of this study is to provide preliminary evidence of the possibility of treating IED by videoconference. We present a case-study experiment of a Spanish male, aged 33 years, living and working in China. After the intervention, the patient’s aggressive episodes decreased dramatically, as well as his negative affect. In contrast, he showed an important increment in positive emotions and self-esteem. There were also positive changes in some personality dimensions and facets measured by NEO-PI-R, specifically in neuroticism, extraversion, and agreeableness. The benefits were maintained at 3-, 8- and 18-month follow-ups. These preliminary results reveal that CBT by videoconference oriented to increasing emotion regulation skills was effective when implemented in a case study of a person suffering from IED

La Terapia Cognitivo-Conductual (TCC) para el tratamiento del Trastorno Explosivo Intermitente (TEI) ha probado ser eficaz, con tamaños del efecto de moderados a altos, tanto en intervenciones individuales como grupales. La videoconferencia ha sido utilizada eficazmente para tratar distintos trastornos mentales, pero su utilización en pacientes con TEI es todavía desconocida. El objetivo de este estudio es ofrecer evidencias preliminares sobre la posibilidad de tratar el TEI a través de videoconferencia. Presentamos un experimento de estudio de caso de un varón español, de 33 años de edad, que vive y trabaja en China. Después de la intervención, los episodios agresivos del paciente disminuyeron de manera importante así como el afecto negativo. Por otro lado, el paciente mostró un importante incremento en emociones positivas y autoestima. Se produjeron también cambios positivos en algunas dimensiones de personalidad y sus facetas, evaluadas con el NEO-PI-R, específicamente en neuroticismo, extraversión y amabilidad. Los beneficios se mantuvieron en los seguimientos a los 3, 8 y 18 meses. Estos resultados preliminares revelan que la TCC por videoconferencia, orientada al incremento de las habilidades en regulación emocional, fue eficaz en un estudio de caso con TEI

Evaluación de los boletines de análisis de las materias primas para formulación magistral / Evaluation of analysis sheets of raw substances used in pharmaceutical compounding

Los boletines de análisis de las materias primas para formulación magistral son de obligada tenencia si no se desea realizar los controles analíticos en la farmacia o servicio de farmacia que prepara la formula magistral o el preparado oficial. Objetivo: Evaluar la calidad de los boletines de análisis y su adecuación a las normas de la Real Farmacopea Española (RFE). Métodos: Se seleccionaron los 200 boletines válidos de productos recibidos en una farmacia comunitaria en funcionamiento habitual. Se excluyeron los que no aparecían en la RFE. Se analizó su contenido en cuanto a características, ensayos e identificación y su similitud con las pruebas especificadas en la RFE. Resultados: Se analizaron 140 boletines, de los que 3 declaraban cumplir las normas de la RFE, 45 las de la Farmacopea Europea, 50 otras normas y 42 ninguna. Presentan 5,7 pruebas de características (RFE presenta 6,0), y coinciden 3,1. Presentan 7,5 pruebas de ensayos (RFE presenta 6,6), pero coinciden 3,7. En la RFE aparecen condiciones de conservación en el 62% de las monografías analizadas, y en los boletines en el 70%. Conclusiones: La accesibilidad de los boletines es alta, pero su grado de ajuste a la RFE es bajo en todas las variables evaluadas (AU)

Analysis sheets for raw substances used for pharmaceutical compounding are obligatory unless analytical control is made in the pharmacy or the hospital pharmacy service which prepares the compounding or the officinal preparation. Objective: To evaluate the quality of the analysis sheets and their suitability to the norms of the Real Farmacopea Española [Royal Spanish Pharmacopoeia] (RFE). Methods: The selection of 200 valid analysis sheets of products received in a community pharmacy in normal function was made. Those that did not appear in the RFE were excluded. Their content as far as characteristics, tests and identification and their similarity to specific tests in the RFE were evaluated. Results: 140 analysis sheets were evaluated, of which 3 stated they complied the test norms of the RFE, 45 those of the European Pharmacopoeia, 50 other norms and 42 none. They presented and average of 5,7 characteristic tests (RFE presents 6,0), and 3,1 coincided. They presented 7,5 analysis tests (RFE presents 6,6) but 3,7 coincided. in the RFE preservation conditions appeared in 62% of the evaluated monographs and 70% in the sheets. Conclusions: The accessibility to the sheets is high, but their rate of concordance to the RFE is low in all the variables evaluated (AU)