How to treat localized Hodgkin lymphoma?

Purpose Of Review: We aim to summarize the current knowledge on the management of early-stage classical Hodgkin lymphoma, with a focus on conventional strategies, incorporation of immunotherapies and exploration of novel prognostic markers.

Recent Findings: Long-term data on combined modalities (associating chemotherapy and radiotherapy) still supports their benefit in terms of progression free survival compared to chemotherapy alone in both early favourable and early unfavourable interim PET-negative classical Hodgkin Lymphoma. Novel agents, such as Brentuximab Vedotin and checkpoints inhibitors show promising and impressive results when added to first-line treatment.

Epicardially secreted fibronectin drives cardiomyocyte maturation in 3D-engineered heart tissues.

Ischemic heart failure is due to irreversible loss of cardiomyocytes. Preclinical studies showed that human pluripotent stem cell (hPSC)-derived cardiomyocytes could remuscularize infarcted hearts and improve cardiac function. However, these cardiomyocytes remained immature.

African Nova Scotian nurses' perceptions and experiences of leadership: a qualitative study informed by Black feminist theory.

Background: People of African Nova Scotian (ANS) ancestry are a culturally distinct group who experience numerous socioeconomic inequities and health disparities, secondary to structural and social determinants of health. Understanding the experiences of ANS health practitioners is important in addressing anti-Black racism in health care. We sought to critically examine the leadership experiences of ANS nurses in health care practice.

Inducible apelin receptor knockdown reduces differentiation efficiency and contractility of hESC-derived cardiomyocytes.

Aims: The apelin receptor, a G protein-coupled receptor, has emerged as a key regulator of cardiovascular development, physiology, and disease. However, there is a lack of suitable human in vitro models to investigate the apelinergic system in cardiovascular cell types. For the first time we have used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and a novel inducible knockdown system to examine the role of the apelin receptor in both cardiomyocyte development and to determine the consequences of loss of apelin receptor function as a model of disease.

Black nurses in the nursing profession in Canada: a scoping review.

Background: With migration occurring over a series of centuries, dating back to the 1600's, the circumstance regarding Black people in Canada is a complex account. A plethora of social issues and the failure to adequately acknowledge and reconcile historical issues, has resulted in health inequity, disparities and knowledge gaps, related to the Black population in Canada. In nursing, historical records indicate a legacy of discrimination that continues to impact Black nurses.

A Comparability of Renal Length and Volume Measurements in MRI and Ultrasound in Children.

Despite the significant increase in use of magnetic resonance imaging (MRI) in children, there is still a lack of normal reference values of renal size in this method and reference values are being interpolated from the ultrasound (US) studies. The study provides comparative analysis of agreement in renal length and volume measurements between MRI and ultrasound. Ninety-three children with a mean age of 8.

African Canadian nurses in the nursing profession in Canada: a scoping review protocol.

Objective: The objective of this review is to synthesize the evidence on African Canadian nurses in the nursing profession in Canada.

Introduction: With approximately 1.2 million people of African descent, Canada has committed to addressing the United Nations' decade for people of African descent.

BNC1 regulates cell heterogeneity in human pluripotent stem cell-derived epicardium.

The murine developing epicardium heterogeneously expresses the transcription factors TCF21 and WT1. Here, we show that this cell heterogeneity is conserved in human epicardium, regulated by BNC1 and associated with cell fate and function. Single cell RNA sequencing of epicardium derived from human pluripotent stem cells (hPSC-epi) revealed that distinct epicardial subpopulations are defined by high levels of expression for the transcription factors BNC1 or TCF21.

Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells.

Method to Synchronize Cell Cycle of Human Pluripotent Stem Cells without Affecting Their Fundamental Characteristics.

Cell cycle progression and cell fate decisions are closely linked in human pluripotent stem cells (hPSCs). However, the study of these interplays at the molecular level remains challenging due to the lack of efficient methods allowing cell cycle synchronization of large quantities of cells. Here, we screened inhibitors of cell cycle progression and identified nocodazole as the most efficient small molecule to synchronize hPSCs in the G2/M phase.

A Novel Human Pluripotent Stem Cell-Derived Neural Crest Model of Treacher Collins Syndrome Shows Defects in Cell Death and Migration.

The neural crest (NC) is a transient multipotent cell population present during embryonic development. The NC can give rise to multiple cell types and is involved in a number of different diseases. Therefore, the development of new strategies to model NC in vitro enables investigations into the mechanisms involved in NC development and disease.

Bacterial Community Dynamics in Dichloromethane-Contaminated Groundwater Undergoing Natural Attenuation.

The uncontrolled release of the industrial solvent methylene chloride, also known as dichloromethane (DCM), has resulted in widespread groundwater contamination in the United States. Here we investigate the role of groundwater bacterial communities in the natural attenuation of DCM at an undisclosed manufacturing site in New Jersey. This study investigates the bacterial community structure of groundwater samples differentially contaminated with DCM to better understand the biodegradation potential of these autochthonous bacterial communities.

"You feel you have to be made of steel": The strong Black woman, health, and well-being in Nova Scotia.

The "strong Black woman" construct has been well-documented in the United States as both an aspirational icon and a constricting burden for African-heritage women. It has not been examined among African-Canadians. Drawing on qualitative interviews and standardized measures with 50 African-heritage women in Eastern Canada, our analysis reveals their perceptions of the construct as both strongly endorsed as a source of cultural pride, yet also acknowledged to take a terrible toll on health and well-being.

Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs.

Inducible loss of gene function experiments are necessary to uncover mechanisms underlying development, physiology and disease. However, current methods are complex, lack robustness and do not work in multiple cell types. Here we address these limitations by developing single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms.

An iPSC-derived vascular model of Marfan syndrome identifies key mediators of smooth muscle cell death.

Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in FBN1, which encodes the extracellular matrix protein fibrillin-1. To investigate the pathogenesis of aortic aneurysms in MFS, we generated a vascular model derived from human induced pluripotent stem cells (MFS-hiPSCs). Our MFS-hiPSC-derived smooth muscle cells (SMCs) recapitulated the pathology seen in Marfan aortas, including defects in fibrillin-1 accumulation, extracellular matrix degradation, transforming growth factor-β (TGF-β) signaling, contraction and apoptosis; abnormalities were corrected by CRISPR-based editing of the FBN1 mutation.

Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation.

Unlabelled: Vascular smooth muscle cells (SMCs) from distinct anatomic locations derive from different embryonic origins. Here we investigated the respective potential of different embryonic origin-specific SMCs derived from human embryonic stem cells (hESCs) to support endothelial network formation in vitro. SMCs of three distinct embryological origins were derived from an mStrawberry-expressing hESC line and were cocultured with green fluorescent protein-expressing human umbilical vein endothelial cells (HUVECs) to investigate the effects of distinct SMC subtypes on endothelial network formation.

Robust derivation of epicardium and its differentiated smooth muscle cell progeny from human pluripotent stem cells.

The epicardium has emerged as a multipotent cardiovascular progenitor source with therapeutic potential for coronary smooth muscle cell, cardiac fibroblast (CF) and cardiomyocyte regeneration, owing to its fundamental role in heart development and its potential ability to initiate myocardial repair in injured adult tissues. Here, we describe a chemically defined method for generating epicardium and epicardium-derived smooth muscle cells (EPI-SMCs) and CFs from human pluripotent stem cells (HPSCs) through an intermediate lateral plate mesoderm (LM) stage. HPSCs were initially differentiated to LM in the presence of FGF2 and high levels of BMP4.

Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation.

Obesity increases the risk of developing life-threatening metabolic diseases including cardiovascular disease, fatty liver disease, diabetes, and cancer. Efforts to curb the global obesity epidemic and its impact have proven unsuccessful in part by a limited understanding of these chronic progressive diseases. It is clear that low-grade chronic inflammation, or metaflammation, underlies the pathogenesis of obesity-associated type 2 diabetes and atherosclerosis.

Temporal and embryonic lineage-dependent regulation of human vascular SMC development by NOTCH3.

Vascular smooth muscle cells (SMCs), which arise from multiple embryonic progenitors, have unique lineage-specific properties and this diversity may contribute to spatial patterns of vascular diseases. We developed in vitro methods to generate distinct vascular SMC subtypes from human pluripotent stem cells, allowing us to explore their intrinsic differences and the mechanisms involved in SMC development. Since Notch signaling is thought to be one of the several key regulators of SMC differentiation and function, we profiled the expression of Notch receptors, ligands, and downstream elements during the development of origin-specific SMC subtypes.

Ca(2+) signals evoked by histamine H1 receptors are attenuated by activation of prostaglandin EP2 and EP4 receptors in human aortic smooth muscle cells.

Background And Purpose: Histamine and prostaglandin E2 (PGE2 ), directly and via their effects on other cells, regulate the behaviour of vascular smooth muscle (VSM), but their effects on human VSM are incompletely resolved.

Experimental Approach: The effects of PGE2 on histamine-evoked changes in intracellular free Ca(2+) concentration ([Ca(2+) ]i ) and adenylyl cyclase activity were measured in populations of cultured human aortic smooth muscle cells (ASMCs). Selective ligands of histamine and EP receptors were used to identify the receptors that mediate the responses.

Awareness of palliative care and end-of-life options among African Canadians in Nova Scotia.

Purpose: To assess, using qualitative methods, the knowledge African Canadians living in Nova Scotia have regarding their options for palliative and end-of-life (EOL) care.

Design: This project engaged caregivers in a Black community in Nova Scotia, Canada, in an exploration of palliative and EOL care. A group of six caregivers who cared for someone who had died were recruited through purposive sampling.