Selective Recognition of Carbohydrate Antigens by Germline Antibodies Isolated from AID Knockout Mice.

Germline antibodies, the initial set of antibodies produced by the immune system, are critical for host defense, and information about their binding properties can be useful for designing vaccines, understanding the origins of autoantibodies, and developing monoclonal antibodies. Numerous studies have found that germline antibodies are polyreactive with malleable, flexible binding pockets. While insightful, it remains unclear how broadly this model applies, as there are many families of antibodies that have not yet been studied. In addition, the methods used to obtain germline antibodies typically rely on assumptions and do not work well for many antibodies. Herein, we present a distinct approach for isolating germline antibodies that involves immunizing activation-induced cytidine deaminase (AID) knockout mice. This strategy amplifies antigen-specific B cells, but somatic hypermutation does not occur because AID is absent. Using synthetic haptens, glycoproteins, and whole cells, we obtained germline antibodies to an assortment of clinically important tumor-associated carbohydrate antigens, including Lewis Y, the Tn antigen, sialyl Lewis C, and Lewis X (CD15/SSEA-1). Through glycan microarray profiling and cell binding, we demonstrate that all but one of these germline antibodies had high selectivity for their glycan targets. Using molecular dynamics simulations, we provide insights into the structural basis of glycan recognition. The results have important implications for designing carbohydrate-based vaccines, developing anti-glycan monoclonal antibodies, and understanding antibody evolution within the immune system.

Abortion in women with severe preeclampsia and eclampsia prior to 24 weeks gestation.

OBJECTIVE: Due to poor prognosis, obstetric care providers often recommend abortion for women diagnosed with severe preeclampsia prior to fetal viability. However, there is limited available evidence to guide the counseling regarding risks. STUDY DESIGN: This study is a retrospective case series that describes outcomes of all women who underwent abortions with the diagnosis of severe preeclampsia or eclampsia prior to 24 weeks gestation. RESULTS: This case series describes 11 women who underwent abortion prior to 24 weeks gestation due to severe preeclampsia or eclampsia, 9 by dilation and evacuation and 2 by labor induction. The majority of women underwent dilation and evacuation and no women undergoing either induction of labor or dilation and evacuation had severe complications directly related to the abortion. CONCLUSIONS: This case series provides information on the safety of abortion procedures in women with severe preeclampsia and eclampsia syndrome.

Crossing borders: a systematic review identifying potential mechanisms of intergenerational trauma transmission in asylum-seeking and refugee families.

Background: As displacement and forced migration continue to exhibit global growth trends, new and surviving generations of children are being born and spending their formative years in host countries. Refugee children who have not been exposed to traumatic events may still be at risk for adverse developmental and mental health outcomes via intergenerational trauma transmission. Objective: To identify and synthesize potential mechanisms of intergenerational trauma transmission in forcibly displaced families where parents have experienced direct war-related trauma exposure, but children have no history of direct trauma exposure. Methods: PRISMA systematic review guidelines were adhered to. Searches were conducted across seven major databases and included quantitative, qualitative and mixed methods literature from 1945 to 2019. The search resulted in 752 citations and 8 studies (n = 1,684) met review inclusion criteria. Results: Findings suggest that parental trauma exposure and trauma sequelae indirectly affect child well-being via potential mechanisms of insecure attachment; maladaptive parenting styles; diminished parental emotional availability; decreased family functioning; accumulation of family stressors; dysfunctional intra-family communication styles and severity of parental symptomology. Conclusion: Further research is needed to assess independent intergenerational effects and mechanisms of trauma transmission in this population.

Antecedentes: A medida que el desplazamiento y la migración forzada exhiben de manera continua tendencias de crecimiento global, las nuevas y sobrevivientes generaciones de niños nacen y pasan sus años de formación en los países de acogida. Los niños refugiados que no han estado expuestos a eventos traumáticos aún pueden estar en riesgo de consecuencias adversas para el desarrollo y la salud mental a través de la transmisión intergeneracional del trauma.Objetivo: Identificar y sintetizar mecanismos potenciales de transmisión intergeneracional de traumas en familias desplazadas por la fuerza donde los padres han experimentado una exposición directa al trauma relacionada con la guerra, pero los niños no tienen antecedentes de exposición directa al trauma.Métodos: Se siguieron las pautas de revisión sistemática PRISMA. Las búsquedas se realizaron en siete bases de datos principales e incluyeron literatura sobre métodos cuantitativos, cualitativos y mixtos desde 1945 al 2019. La búsqueda resultó en 752 citas y 8 estudios (n = 1.684) cumplieron con los criterios de inclusión de la revisión.Resultados: Los resultados sugieren que la exposición al trauma parental y las secuelas del trauma afectan indirectamente el bienestar del niño a través de mecanismos de apego inseguro; estilos de parentalidad maladaptativos; disminución de la disponibilidad emocional parental; disminución del funcionamiento familiar; acumulación de estresores familiares; estilos de comunicación intrafamiliar disfuncionales y gravedad de la sintomatología parental.Conclusión: existe una clara necesidad de apoyar a los padres y a sus hijos que han estado expuestos a traumas de guerra. Se necesita más investigación para evaluar los efectos intergeneracionales independientes de la transmisión del trauma en esta población.

Training the next generation of psychotraumatologists: COllaborative Network for Training and EXcellence in psychoTraumatology (CONTEXT).

In this paper we present a description of the Horizon2020, Marie Sklodowska-Curie Action funded, research and training programme CONTEXT: COllaborative Network for Training and EXcellence in psychoTraumatology. The three objectives of the programme are put forward, each of which refers to a key component of the CONTEXT programme. First, we summarize the 12 individual research projects that will take place across three priority populations: (i) refugees and asylum seekers, (ii) first responders, and (iii) perpetrators and survivors of childhood and gender-based violence. Second, we detail the mentoring and training programme central to CONTEXT. Finally, we describe how the research, together with the training, will contribute towards better policy, guidelines, and practice within the field of psychotraumatology.

En este artículo presentamos una descripción de un nuevo programa de investigación y formación, Horizon2020, con fondos de Marie Sklodowska-Curie Action, llamado CONTEXT o 'Red coordinadora para la formación y la excelencia en psicotraumatología'. Se presentan los tres objetivos del programa y cada uno de los cuales hace referencia a un componente clave del programa CONTEXT. Primero, resumimos los doce proyectos individuales de investigación que se llevarán a cabo en tres poblaciones prioritarias: (i) refugiados y solicitantes de asilo, (ii) personal de respuesta en emergencias y (iii) perpetradores y sobrevivientes de violencia infantil y de género. En segundo lugar, detallamos el programa de tutoría y formación, eje central de CONTEXT. Finalmente, describimos cómo la investigación, junto con la formación, contribuirá a una mejor política, directrices y práctica en el campo de la psicoterapia.

Perspectives on Anti-Glycan Antibodies Gleaned from Development of a Community Resource Database.

Antibodies are used extensively for a wide range of basic research and clinical applications. While an abundant and diverse collection of antibodies to protein antigens have been developed, good monoclonal antibodies to carbohydrates are much less common. Moreover, it can be difficult to determine if a particular antibody has the appropriate specificity, which antibody is best suited for a given application, and where to obtain that antibody. Herein, we provide an overview of the current state of the field, discuss challenges for selecting and using antiglycan antibodies, and summarize deficiencies in the existing repertoire of antiglycan antibodies. This perspective was enabled by collecting information from publications, databases, and commercial entities and assembling it into a single database, referred to as the Database of Anti-Glycan Reagents (DAGR). DAGR is a publicly available, comprehensive resource for anticarbohydrate antibodies, their applications, availability, and quality.