Empowerment: An Idea Whose Time Has Come in Diabetes Education

We have learned much in the past 10 years about how to help patients to acquire diabetes-related knowledge and skills and how to use strategies to help patients change behaviors. However, the application ofknowledge and techniques should be guided by a relevant, coherent, educational philosophy. Empowerment offers a practical conceptual framework for diabetes patient education. Empowering patients provides them with the knowledge, skills, and responsibility to effect change and has the potential to promote overall health and maximize the use of available resources. It is an idea whose time has come for diabetes education.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68779/2/10.1177_014572179101700108.pd

Preclinical Evaluation of Bispecific Adaptor Molecule Controlled Folate Receptor CAR-T Cell Therapy With Special Focus on Pediatric Malignancies

Chimeric antigen receptor (CAR)-T cell therapy has transformed pediatric oncology by producing high remission rates and potent effects in CD19+ B-cell malignancies. This scenario is ideal as CD19 expression is homogeneous and human blood provides a favorable environment for CAR-T cells to thrive and destroy cancer cells (along with normal B cells). Yet, CAR-T cell therapies for solid tumors remain challenged by fewer tumor targets and poor CAR-T cell performances in a hostile tumor microenvironment. For acute myeloid leukemia and childhood solid tumors such as osteosarcoma, the primary treatment is systemic chemotherapy that often falls short of expectation especially for relapsed and refractory conditions. We aim to develop a CAR-T adaptor molecule (CAM)-based therapy that uses a bispecific small-molecule ligand EC17, fluorescein isothiocyanate (FITC) conjugated with folic acid, to redirect FITC-specific CAR-T cells against folate receptor (FR)-positive tumors. As previously confirmed in rodents as well as in human clinical studies, EC17 penetrates solid tumors within minutes and is retained due to high affinity for the FR, whereas unbound EC17 rapidly clears from the blood and from receptor-negative tissues. When combined with a rationally designed CAR construct, EC17 CAM was shown to trigger CAR-modified T cell activation and cytolytic activity with a low FR threshold against tumor targets. However, maximal cytolytic potential correlated with (i) functional FR levels (in a semi-log fashion), (ii) the amount of effector cells present, and (iii) tumors' natural sensitivity to T cell mediated killing. In tumor-bearing mice, administration of EC17 CAM was the key to drive CAR-T cell activation, proliferation, and persistence against FR+ pediatric hematologic and solid tumors. In our modeling systems, cytokine release syndrome (CRS) was induced under specific conditions, but the risk of severe CRS could be easily mitigated or prevented by applying intermittent dosing and/or dose-titration strategies for the EC17 CAM. Our approach offers the flexibility of antigen control, prevents T cell exhaustion, and provides additional safety mechanisms including rapid reversal of severe CRS with intravenous sodium fluorescein. In this paper, we summarize the translational aspects of our technology in support of clinical development

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases

The second gold rush: Oakland and the East Bay in World War II

More than any event in the twentieth century, World War II marked the coming of age of America's West Coast cities. Almost overnight, new war industries prompted the mass urban migration and development that would trigger lasting social, cultural, and political changes. For the San Francisco Bay Area, argues Marilynn Johnson, the changes brought by World War II were as dramatic as those brought by the gold rush a century earlier.Focusing on Oakland, Richmond, and other East Bay shipyard boomtowns, Johnson chronicles the defense buildup, labor migration from the South and Midwest, housing issues, and social and racial conflicts that pitted newcomers against longtime Bay Area residents. She follows this story into the postwar era, when struggles over employment, housing, and civil rights shaped the urban political landscape for the 1950s and beyond. She also traces the cultural legacy of war migration and shows how Southern religion and music became an integral part of Bay Area culture.Johnson's sources are wide-ranging and include shipyard records, labor histories, police reports, and interviews. Her findings place the war's human drama at center stage and effectively recreate the texture of daily life in workplace, home, and community. Enriched by the photographs of Dorothea Lange and others, The Second Gold Rush makes an important contribution to twentieth-century urban studies as well as to California history

Foreign-born Population in Boston Area Communities, 1870–2010

This dataset underlies a choropleth map of Boston area communities in which areas are shaded according to the percentage of the population that was foreign-born during each decade. The data was drawn from the US Census of Population, as well as the American Community Survey