Functional, Motivational And Emotional Support: A Qualitative Study Of Social Influences On Diabetes Management Among Low-Income Adults

Objective To understand how low-income adults living with type 2 diabetes conceptualize and utilize social support in their diabetes management. Methods The data for this paper came from a larger qualitative study, conducted by the advisor and last author, exploring the intersection of housing access and diabetes management among 40 low-income adults diagnosed with type 2 diabetes in New Haven, Connecticut. This qualitative study utilized 58 of the previously collected semi-structured interviews (some participants were interviewed more than once). Excerpts from two broad parent codes from the original study were analyzed using a flexible and iterative coding process. Results Participants conceptualized diabetes management as a “battle” that is taxing mentally, emotionally and physically. Understanding the magnitude of diabetes management, participants often relied on their social networks for assistance. Social influences greatly aided but, in some instances, hindered diabetes management through three main domains of influence: functional, motivational and emotional. Conclusion and Implications Diabetes self-management is a lifelong process with life or death implications. The nature of diabetes management can be taxing and burdensome for individuals as it requires both behavioral and medical interventions. Participants detailed how their social support networks mitigated many stressors associated with their chronic disease management via functional, motivational and emotional support. Future research should explore how social support networks can be more routinely incorporated into diabetes management and effectively utilized to promote health and well-being especially for low-income populations

Understanding Risk Perception and Xenophobic Attitudes during the Coronavirus Disease 2019 (COVID-19) Pandemic in the United States

Introduction: There have been over 87 million cases of Coronavirus Disease 2019 (COVID-19) in the United States (US). Objective: The objective of this study was to develop a novel questionnaire to assess risk perception of COVID-19 and xenophobic attitudes among adults in the US at the beginning of the pandemic. Methods: An anonymous self-report questionnaire was developed for this study in February 2020, and was distributed using convenience sampling from March 10 to March 25, 2020. The questionnaire assessed knowledge and risk perceptions of COVID-19, as well as attitudes toward individuals of various races and ethnicities. Results: 662 US adults completed the questionnaire. On a scale from 1 (low) to 5 (high), the mean risk perception was 3.44. Those with knowledge of COVID-19 and higher education levels reported higher risk perception and higher feelings of warmth towards Asian people. Forty percent of the sample had recently witnessed or experienced anti-Asian attitudes at the time of the survey. The majority of participants reported having heard about COVID-19 from news media, social media, and family or friends. Conclusions: Our sample had a moderate level of risk perception, potentially due to the time period of data collection (i.e., early in the pandemic course). The results suggest that knowledge about COVID-19 informed perceived risk and affected willingness to engage in healthy protective behaviors. Our study provides historic context of how people perceived the virus at the beginning of the pandemic, and gives insight into the aftermaths regarding quarantine and attitudes towards Asian Americans

The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation

Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system

Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors

BACKGROUND Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. OBJECTIVES This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. METHODS We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (\u3c= 250 mg/m(2)), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin \u3e250 mg/m(2) were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell-derived cardiomyocytes, and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. RESULTS Thirty-one genes were differentially enriched for variants between case patients and control patients (p \u3c 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 x 10(-15)). A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical-only model. In vitro inhibition of gene-associated pathways (PI3KR2, ZNF827) provided protection from cardiotoxicity in cardiomyocytes. CONCLUSIONS Our study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (PPeer reviewe

Evidence of a Monoclonal Origin for Bilateral Serous Tubal Intraepithelial Neoplasia.

Serous tubal intraepithelial carcinoma (STIC) is found in 10% to 60% of cases of tuboovarian high-grade serous carcinoma (HGSC) and is presumed to be the site of origin, linking many HGSCs to the fallopian tube. Bilateral STIC is present in ∼20% of cases. Because clonal Tp53 mutations are a defining feature of HGSC, including their associated STICs, we analyzed 4 cases of bilateral serous tubal intraepithelial neoplasia (STIN), including STIC and Tp53-mutated serous tubal intraepithelial lesions (STILs), associated with HGSC to determine whether they contained the same or different p53 mutations. Extracted DNA from STINs, concurrent HGSCs and control tissues was analyzed for mutations in all exons of Tp53. Sequencing was successful in 3 of the 4 cases, and an identical Tp53 mutation was detected in the HGSC and bilateral STINs in 2 of these 3 cases. One STIN was morphologically a STIL. These findings confirm that a subset of bilateral STINs share the same Tp53 mutation, implying that at least one of the STINs is an intraepithelial metastasis from either the contralateral STIN or HGSC. This study complements others addressing the multiple origins of STIN in the setting of existing HGSC. It further underscores the fact that potential overlap in biologic behavior between STILs and STICs as well as timing and direction of metastatic spread has yet to be resolved

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention

The current theory of carcinogenesis for the deadliest of ‘ovarian’ cancers—high-grade serous carcinoma (HGSC)—holds that the malignancy develops first in the fallopian tube and spreads to the ovaries, peritoneum, and/or regional lymph nodes. This is based primarily on the observation of early forms of serous neoplasia (serous tubal intraepithelial lesions [STILs], and serous tubal intraepithelial carcinomas [STICS]) in the fimbria of women undergoing risk reduction surgery. However, these lesions are uncommon in the general population, confer a low risk (5%) of HGSC following their removal in at-risk women with germ-line BRCA1/2 mutations, and require 4 or more years to recur as intraperitoneal HGSC. These features suggest that isolated STILs and STICs behave as precursors, with uncertain cancer risk rather than carcinomas. Their evolution to HGSC within, or after, escape from the tube could proceed stepwise with multiple biologic events; however, it is unclear whether tubal or ovarian HGSCs encountered in the setting of advanced disease evolved in the same fashion. The latter scenario could also be explained by a ‘catastrophic’ model in which STICs suddenly develop with invasive and metastatic potential, overwhelming or obscuring the site of origin. Moreover, a similar model might explain the sudden emergence of HGSC in the peritoneal cavity following escape of precursor cells years before. Long-term follow-up data from opportunistic or prophylactic salpingectomy should shed light on where malignant transformation occurs, as well as the timeline from precursor to metastatic HGSC. © 2022 The Pathological Society of Great Britain and Ireland.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172948/1/path5891.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172948/2/path5891_am.pd