Pediatric residents have limited experience with pediatric end-of-life care and highly varied educational experiences and do not feel adequately trained to fulfill the responsibilities associated with providing end-of-life care for children. Overall, this perception does not improve with increased level of training. This study identifies several target areas for curricular intervention that may ultimately improve the end-of-life experience for our pediatric patients and their families and the young physicians who care for them.
Epidemiological studies have highlighted the disparate impact of coronavirus disease 2019 (COVID-19) on racial and ethnic minority and socioeconomically disadvantaged populations, but data at the neighborhood-level is sparse. The objective of this study was to investigate the disparate impact of COVID-19 on disadvantaged neighborhoods and racial/ethnic minorities in Chicago, Illinois. Using data from the Cook County Medical Examiner, we conducted a neighborhood-level analysis of COVID-19 decedents in Chicago and quantify age-standardized years of potential life lost (YPLL) due to COVID-19 among demographic subgroups and neighborhoods with geospatial clustering of high and low rates of COVID-19 mortality. We show that age-standardized YPLL was markedly higher among the non-Hispanic (NH) Black (559 years per 100,000 population) and the Hispanic (811) compared with NH white decedents (312). We demonstrate that geomapping using residential address data at the individual-level identifies hot-spots of COVID-19 mortality in neighborhoods on the Northeast, West, and South areas of Chicago that reflect a legacy of residential segregation and persistence of inequality in education, income, and access to healthcare. Our results may contribute to ongoing public health and community-engaged efforts to prevent the spread of infection and mitigate the disproportionate loss of life among these communities due to COVID-19 as well as highlight the urgent need to broadly target neighborhood disadvantage as a cause of pervasive racial inequalities in life and health.
Low density lipoprotein receptor-related protein (LRP) is a multifunctional receptor, expressed by vascular smooth muscle cells (VSMCs) in normal arteries and in atherosclerotic lesions. In this investigation, we demonstrate a novel mechanism for the regulation of LRP activity in cultured rat aortic VSMCs. Cells that were treated with platelet-derived growth factor-BB (PDGF-BB) or epidermal growth factor (EGF) for 24 h bound increased amounts of the LRP ligand, activated ␣ 2 -macroglobulin (␣ 2 M), at 4°C. The B max for activated ␣ 2 M was increased from 56 ؎ 5 to 178 ؎ 24 and 143 ؎ 11 fmol/mg cell protein by PDGF-BB and EGF, respectively, while the K D was unchanged. Northern and Western blot analyses demonstrated that neither PDGF-BB nor EGF increase LRP mRNA or protein levels. Instead, LRP was redistributed to the cell surface and remained localized primarily in coated pits, as determined by surface protein biotinylation, affinity labeling, and immunoelectron microscopy studies. The increase in cell-surface LRP was partially explained by a 50% decrease in receptor endocytosis rate; however, at 37°C, PDGF-BB-and EGF-treated VSMCs still bound/internalized increased amounts of activated ␣ 2 M and subsequently released increased amounts of trichloroacetic acid-soluble radioactivity. The cytokine-induced shifts in LRP subcellular distribution were stable when VSMCs were challenged with a saturating concentration of ligand and then incubated, in the absence of cytokine, for 2.5 h at 37°C. Regulation of LRP distribution and activity may be an important aspect of the VSMC response to the atherogenic cytokines, PDGF-BB and EGF. Low density lipoprotein receptor-related protein (LRP)1 is a receptor for diverse ligands, including apolipoprotein E (apoE)-enriched chylomicron and very low density lipoprotein remnants (-very low density lipoprotein), lipoprotein lipase, tissue-type and urokinase-type plasminogen activators, proteinase-Serpin complexes, thrombospondin I, secreted -amyloid precursor protein, and activated ␣ 2 -macroglobulin (␣ 2 M) (1-4). LRP is synthesized as a 600-kDa precursor and processed in the trans-Golgi to form the mature two-chain structure (5, 6). The 515-kDa heavy chain includes the ligand binding sites and is anchored to the cell surface by interaction with the 85-kDa light chain, which includes a transmembrane domain (1).Early studies showed that the ␣ 2 M receptor, which is identical to LRP (7), is recycled and reutilized (8, 9). Activated ␣ 2 M-LRP complexes undergo endocytosis and then dissociate in intracytoplasmic vesicles, as a result of acidification (10, 11). The receptor recycles to the cell surface while the ␣ 2 M is transferred to lysosomes. The sequence of LRP includes two copies of the NPXY motif, which functions as a signal for clustering and endocytosis of receptors in coated pits (1, 5). A monoclonal antibody which binds to the LRP heavy chain has been shown to follow the same cellular processing pathway as was originally described for activated ␣ 2 M (12).LRP is expressed by n...
Background Given the increasing prevalence of diabetes mellitus (DM) in the United States, estimating the effects of population‐level increases in obesity on incident DM has substantial implications for public health policy. Therefore, we determined the population attributable fraction, which accounts for the prevalence and excess risk of DM associated with obesity. Methods and Results We included non‐Hispanic White, non‐Hispanic Black, and Mexican American participants without DM at baseline from MESA (Multi‐Ethnic Study of Atherosclerosis) with available data on body mass index and key covariates from 2000 to 2017 to calculate unadjusted and adjusted (age, study site, physical activity, diet, income, and education level) hazard ratios (HR) for obesity‐attributable DM. We calculated national age‐adjusted prevalence estimates for obesity using data from NHANES (National Health and Nutrition Examination Survey) in 4 pooled cycles (2001–2016) among adults with similar characteristics to MESA participants. Last, we calculated unadjusted and adjusted population attributable fractions from the race/ethnic and sex‐specific HR and prevalence estimates. Of 4200 MESA participants, the median age was 61 years, 46.8% were men, 53.9% were non‐Hispanic White, 32.9% were non‐Hispanic Black, and 13.3% were Mexican. Among MESA participants, incident DM occurred in 11.6% over a median follow‐up of 9.2 years. The adjusted HR for obesity‐related DM was 2.7 (95% CI, 2.2–3.3). Adjusted population attributable fractions were 0.35 (95% CI, 0.29–0.40) in 2001 to 2004 and 0.41 (95% CI, 0.36–0.46) in 2013 to 2016, and greatest among non‐Hispanic White women. Conclusions The contribution of obesity towards DM in the population remains substantial and varies significantly by race/ethnicity and sex, highlighting the need for tailored public health interventions to reduce obesity. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NC00005487, NCT00005154.
A career in pediatrics can bring great joy and satisfaction. It can also be challenging and lead some providers to manifest burnout and depression. A curriculum designed to help pediatric health providers acquire resilience and adaptive skills may be a key element in transforming times of anxiety and grief into rewarding professional experiences. The need for this curriculum was identified by the American Academy of Pediatrics Section on Medical Students, Residents and Fellowship Trainees. A working group of educators developed this curriculum to address the professional attitudes, knowledge, and skills essential to thrive despite the many stressors inevitable in clinical care. Fourteen modules incorporating adult learning theory were developed. The first 2 sections of the curriculum address the knowledge and skills to approach disclosure of life-altering diagnoses, and the second 2 sections focus on the provider's responses to difficult patient care experiences and their needs to develop strategies to maintain their own well-being. This curriculum addresses the intellectual and emotional characteristics patient care medical professionals need to provide highquality, compassionate care while also addressing active and intentional ways to maintain personal wellness and resilience. Drs Serwint, Bostwick, Burke, Church, Gogo, Hofkosh, King, Linebarger, McCabe, Moon, Osta, Rana, Sahler, and Smith conceptualized the curriculum, wrote portions of the curriculum, reviewed and revised the curriculum, and reviewed and revised the manuscript; Ms Rivera served as the AAP staff member who assisted with the creation of the curriculum, provided feedback, uploaded the curriculum to the AAP Web site, and reviewed and revised the manuscript; Dr Baldwin served as a copy editor and assisted with the development of the curriculum, in review of the modules and categorizing content, and reviewed and revised the manuscript; and all authors approved the fi nal manuscript as submitted.
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