Cytosine base editing enables quadruple-edited allogeneic CART cells for T-ALL.

Allogeneic chimeric antigen receptor T-cell (CART) therapies require multiple gene edits to be clinically tractable. Most allogeneic CARTs have been created using gene editing techniques that induce DNA double-stranded breaks (DSBs), resulting in unintended on-target editing outcomes with potentially unforeseen consequences. Cytosine base editors (CBEs) install C•G to T•A point mutations in T cells, with between 90% and 99% efficiency to silence gene expression without creating DSBs, greatly reducing or eliminating undesired editing outcomes following multiplexed editing as compared with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). Using CBE, we developed 7CAR8, a CD7-directed allogeneic CART created using 4 simultaneous base edits. We show that CBE, unlike CRISPR-Cas9, does not impact T-cell proliferation, lead to aberrant DNA damage response pathway activation, or result in karyotypic abnormalities following multiplexed editing. We demonstrate 7CAR8 to be highly efficacious against T-cell acute lymphoblastic leukemia (T-ALL) using multiple in vitro and in vivo models. Thus, CBE is a promising technology for applications requiring multiplexed gene editing and can be used to manufacture quadruple-edited 7CAR8 cells, with high potential for clinical translation for relapsed and refractory T-ALL.

Impacto del confinamiento por COVID-19 en la calidad de vida y salud mental / Impact of COVID-19 confinement on quality of life and mental health

Introducción:La pandemia por SARS-Cov-2 ha tenido un impacto negativo en múltiplesaspectosdelavidahumana,tantoenlofísico,psicológico, económico, social y cultural. Las afecciones de la calidad de vida están asociadas al confinamiento y la libertad de salir, de pasar tiempo con sus amigos o familiares, o de realizar actividades; por lo que se ven privados de la mayor parte de su interacción social. El objetivo de este presente artículo es brindar información sobre cómo afecta el confinamiento y aislamiento social por la pandemia a la calidad de vida y salud mental.

Introduction:The SARS-Cov-2 pandemic has had a negative impact on multiple aspects of human life, both physical, psychological, economic, social and cultural. Quality of life conditions are associated with confinement and freedom to go out, to spend time with friends or family, or to carry out activities; so they are deprived of most of their social interaction. The objective of this present article is to provide information on how confinement and social isolation due to the pandemic affects quality of life and mental health

Impacto del confinamiento por COVID-19 en la calidad de vida y salud mental / Impact of COVID-19 confinement on quality of life and mental health

RESUMEN Introducción: La pandemia por SARS-Cov-2 ha tenido un impacto negativo en múltiples aspectos de la vida humana, tanto en lo físico, psicológico, económico, social y cultural. Las afecciones de la calidad de vida están asociadas al confinamiento y la libertad de salir, de pasar tiempo con sus amigos o familiares, o de realizar actividades; por lo que se ven privados de la mayor parte de su interacción social. El objetivo de este presente artículo es brindar información sobre cómo afecta el confinamiento y aislamiento social por la pandemia a la calidad de vida y salud mental.

ABSTRACT Introduction: The SARS-Cov-2 pandemic has had a negative impact on multiple aspects of human life, both physical, psychological, economic, social and cultural. Quality of life conditions are associated with confinement and freedom to go out, to spend time with friends or family, or to carry out activities; so they are deprived of most of their social interaction. The objective of this present article is to provide information on how confinement and social isolation due to the pandemic affects quality of life and mental health

Patient experience assessment in pediatric hospitals in Argentina.

OBJECTIVE: To create a hospital pediatric inpatient experience survey based on the Consumer Assessment of Healthcare Providers and Systems Hospital Survey (CAHPS® Hospital Survey). DESIGN: Survey development based on: (i) Translation and back translation, (ii) Review by experts, (iii) Cultural adaptation: qualitative evaluation of dimensions with reformulation and adaptation of items, (iv) Local cognitive evaluation and (v) Final measurement of its psychometric properties. Inspection, content validity and reliability assessment through internal consistency (Cronbach's alpha coefficient) and inter-item correlation. Factor analysis matrix: extraction, selection and rotation. SETTING: Two pediatric hospitals in Buenos Aires, Argentina: Hospital de Pediatría 'Garrahan' (HG) and Hospital de Niños 'Ricardo Gutiérrez' (HRG). PARTICIPANTS: Parents or caregivers of pediatric patients hospitalized for at least 24 h. RESULTS: A feasible and easy to administer 21-item instrument was developed. One thousand and thirty-two surveys were analyzed, 630 (61%) in HG and 402 (39%) in HRG. Population: mothers of admitted children were interviewed 85% of the time, 61% (625) had completed minor schooling to high school education; 365 families (35%) had unsatisfied basic needs and 51% (529) did not have health insurance. Reliability: adequate Cronbach's alpha scores were found with correlation 0.7 or higher in most domains. Validity: a direct correlation was observed between overall positive opinion and quality of care perceived with the survey, and an indirect correlation (perceived low quality) with higher level of schooling and health insurance ownership. CONCLUSION: An instrument with adequate psychometric properties was adapted to evaluate patients and families' perceptions of quality of care received during children's hospitalization.

Growth in very young children undergoing chronic peritoneal dialysis.

Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescription and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is not well understood. Here, we analyzed data from 153 children in 18 countries who commenced chronic peritoneal dialysis at <24 months of age. From diagnosis to last observation, 57 patients were fed on demand, 54 by NG tube, and 10 by gastrostomy; 26 switched from NG to gastrostomy; and 6 returned from NG to demand feeding. North American and European centers accounted for nearly all feeding by gastrostomy. Standardized body mass index (BMI) uniformly decreased during periods of demand feeding and increased during NG and gastrostomy feeding. Changes in BMI demonstrated significant regional variation: 26% of North American children were obese and 50% of Turkish children were malnourished at last observation (P < 0.005). Body length decreased sharply during the first 6 to 12 months of life and then tended to stabilize. Time fed by gastrostomy significantly associated with higher lengths over time (P < 0.001), but adjustment for baseline length attenuated this effect. In addition, the use of biocompatible peritoneal dialysate and administration of growth hormone independently associated with improved length, even after adjusting for regional factors. In summary, growth and nutritional status vary regionally in very young children treated with chronic peritoneal dialysis. The use of gastrostomy feeding, biocompatible dialysis fluid, and growth hormone therapy associate with improved linear growth.

Diagnóstico socioestomatológico de los municipios de Sensuntepeque, Ilobasco y cantón Maquilishuat, caserío Santa Lucia del departamento de Cabañas, de la República de El Salvador, durante el periodo de abril a septiembre de 2001 / Socio-stomatological diagnosis of the municipalities of Sensuntepeque, Ilobasco and Maquilishuat canton, Santa Lucia hamlet of the department of Cabañas, of the Republic of El Salvador, during the period from April to September 2001

Esta investigación describe la situación actual y real de la atención estomatológica por parte del Ministerio de Salud; esta es desarrollada en unidades de salud, hospitales nacionales específicamente, los cuales son de carácter público, así como también la problemática de salud en general de la nación que habita en las diferentes localidades de dicho departamento. Por otra parte esta investigación pretende crear conciencia de que la salud bucal no debe tomarse aislada del contexto socioeconómico y político del país; ya que estos están ligados íntimamente a esta, y son factores influyentes en ella. En lo que se refiere al contenido de la investigación esta consta de cuatro capítulos. Capítulo I: Este describe los objetivos relacionados cada cual con sus indicadores, siendo estos el esqueleto de la investigación y en la cual se fundamenta; explica porqué se realizó este trabajo, cuales fueron sus alcances, problemas y limitaciones que se presentaron al realizarla. El capítulo II se establece un marco teórico, este comprende toda la parte teórica acerca del estado general de las poblaciones tomando en cuenta los factores que más influyen en la situación estomatológica de estas como son: el social, económico, político, educativo, demográfico, cultural y ecológico. El capitulo III abarca lo que se refiere a metodología este abarca las técnicas y métodos de índole estadísticos que han sido aplicados a la investigación, para así darle mayor validez y exactitud a dicho trabajo. Finalmente el capítulo IV, muestra los resultados de toda la información obtenida. Presentada mediante cuadros estadísticos, un breve análisis y discusión de los mismos por cada municipio en estudio, y las recomendaciones hechas por el grupo a diferentes organismos y entidades del país.

This research describes the current and real situation of dental care by the Ministry of Health; This is developed in health units, specifically national hospitals, which are of a public nature, as well as the general health problems of the nation that lives in the different localities of said department. On the other hand, this research aims to create awareness that oral health should not be taken in isolation from the socioeconomic and political context of the country; since these are closely linked to it, and are influencing factors in it. Regarding the content of the research, it consists of four chapters. Chapter I: This describes the objectives each related to its indicators, these being the skeleton of the research and on which it is based; It explains why this work was carried out, what were its scope, problems and limitations that arose when it was carried out. Chapter II establishes a theoretical framework, this includes all the theoretical part about the general state of populations taking into account the factors that most influence the stomatological situation of these, such as: social, economic, political, educational, demographic, cultural and ecological. Chapter III covers what refers to methodology, this covers the techniques and methods of a statistical nature that have been applied to the investigation, in order to give greater validity and accuracy to said work. Finally, chapter IV shows the results of all the information obtained. Presented through statistical tables, a brief analysis and discussion of them for each municipality under study, and the recommendations made by the group to different agencies and entities in the country.