Health Information-Seeking Behaviors of Family Caregivers: Analysis of the Health Information National Trends Survey.

BACKGROUND: The growing population of aging adults relies on informal caregivers to help meet their health care needs, get help with decision making, and gather health information. OBJECTIVE: The objective of this study was to examine health information-seeking behaviors among caregivers and to identify caregiver characteristics that contribute to difficulty in seeking health information. METHODS: Data from the Health Information National Trends Survey 5, Cycle 1 (N=3181) were used to compare health information seeking of caregivers (n=391) with noncaregivers (n=2790). RESULTS: Caregivers sought health information for themselves and others using computers, smartphones, or other electronic means more frequently than noncaregivers. Caregivers born outside of the United States reported greater difficulty seeking health information (beta=.42; P=.02). Nonwhite caregivers (beta =-.33; P=.03), those with less education (beta =-.35; P=.02), those with private insurance (beta =-.37; P=.01), and those without a regular health care provider (beta =-.35; P=.01) had less confidence seeking health information. Caregivers with higher income had more confidence (beta =.12; P≤.001) seeking health information. CONCLUSIONS: This study highlights the prevalence of electronic means to find health information among caregivers. Notable differences in difficulty and confidence in health information seeking exist between caregivers, indicating the need for more attention to the socioeconomic status and caregivers born outside of the United States. Findings can guide efforts to optimize caregivers' health information-seeking experiences.

The Effects of Racism in Medical Education on Students' Decisions to Practice in Underserved or Minority Communities.

PURPOSE: The purpose of this study was to examine the relationship between manifestations of racism in medical school and subsequent changes in graduating medical students' intentions to practice in underserved or minority communities, compared with their attitudes and intentions at matriculation. METHOD: The authors used repeated-measures data from a longitudinal study of 3,756 students at 49 U.S. medical schools that were collected from 2010 to 2014. They conducted generalized linear mixed models to estimate whether manifestations of racism in school curricula/policies, school culture/climate, or student attitudes/behaviors predicted first- to fourth-year changes in students' intentions to practice in underserved communities or primarily with minority populations. Analyses were stratified by students' practice intentions (no/undecided/yes) at matriculation. RESULTS: Students' more negative explicit racial attitudes were associated with decreased intention to practice with underserved or minority populations at graduation. Service learning experiences and a curriculum focused on improving minority health were associated with increased intention to practice in underserved communities. A curriculum focused on minority health/disparities, students' perceived skill at developing relationships with minority patients, the proportion of minority students at the school, and the perception of a tense interracial environment were all associated with increased intention to care for minority patients. CONCLUSIONS: This study provides evidence that racism manifested at multiple levels in medical schools was associated with graduating students' decisions to provide care in high-need communities. Strategies to identify and eliminate structural racism and its manifestations in medical school are needed.

The Impact of Stigma on Community Reintegration of Veterans With Traumatic Brain Injury and the Well-Being of Their Caregivers.

OBJECTIVE: To assess the association between perceived stigma and discrimination and caregiver strain, caregiver well-being, and patient community reintegration. DESIGN: A cross-sectional survey study of 564 informal caregivers of U.S. military service veterans of wars in Iraq and Afghanistan who experienced traumatic brain injuries or polytrauma (TBI/PT). SETTING: Care settings of community-dwelling former inpatients of U.S. Department of Veterans Affairs Polytrauma Rehabilitation Centers. PARTICIPANTS: Caregivers of former inpatients (N=564), identified through next-of-kin records and subsequent nominations. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Caregiver strain, depression, anxiety, loneliness, and self-esteem; as well as care recipient community reintegration, a key aspect of TBI/PT rehabilitation. RESULTS: Family stigma was associated with strain, depression, anxiety, loneliness, lower self-esteem, and less community reintegration. Caregiver stigma-by-association was associated with strain, depression, anxiety, loneliness, and lower self-esteem. Care recipient stigma was associated with caregiver strain, depression, anxiety, loneliness, lower self-esteem, and less community reintegration. CONCLUSIONS: Perceived stigma may be a substantial source of stress for caregivers of U.S. military veterans with TBI/PT, and may contribute to poor outcomes for the health of caregivers and for the community reintegration of the veterans for whom they provide care.

Resurrection of a clinical antibody: template proteogenomic de novo proteomic sequencing and reverse engineering of an anti-lymphotoxin-α antibody.

A mouse hybridoma antibody directed against a member of the tumour necrosis factor (TNF)-superfamily, lymphotoxin-alpha (LT-α), was isolated from stored mouse ascites and purified to homogeneity. After more than a decade of storage the genetic material was not available for cloning; however, biochemical assays with the ascites showed this antibody against LT-α (LT-3F12) to be a preclinical candidate for the treatment of several inflammatory pathologies. We have successfully rescued the LT-3F12 antibody by performing MS analysis, primary amino acid sequence determination by template proteogenomics, and synthesis of the corresponding recombinant DNA by reverse engineering. The resurrected antibody was expressed, purified and shown to demonstrate the desired specificity and binding properties in a panel of immuno-biochemical tests. The work described herein demonstrates the powerful combination of high-throughput informatic proteomic de novo sequencing with reverse engineering to reestablish monoclonal antibody-expressing cells from archived protein sample, exemplifying the development of novel therapeutics from cryptic protein sources.

Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma: target and linker-drug selection.

Antibody-drug conjugates (ADC), potent cytotoxic drugs covalently linked to antibodies via chemical linkers, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells while reducing side effects. Here, we systematically examine the potential targets and linker-drug combinations that could provide an optimal ADC for the treatment for non-Hodgkin's lymphoma. We identified seven antigens (CD19, CD20, CD21, CD22, CD72, CD79b, and CD180) for potential treatment of non-Hodgkin's lymphoma with ADCs. ADCs with cleavable linkers mediated in vivo efficacy via all these targets; ADCs with uncleavable linkers were only effective when targeted to CD22 and CD79b. In target-independent safety studies in rats, the uncleavable linker ADCs showed reduced toxicity, presumably due to the reduced release of free drug or other toxic metabolites into the circulation. Thus, our data suggest that ADCs with cleavable linkers work on a broad range of targets, and for specific targets, ADCs with uncleavable linkers provide a promising opportunity to improve the therapeutic window for ADCs in humans.

The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells.

Here we have identified a surface protein, TIGIT, containing an immunoglobulin variable domain, a transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif that was expressed on regulatory, memory and activated T cells. Poliovirus receptor, which is expressed on dendritic cells, bound TIGIT with high affinity. A TIGIT-Fc fusion protein inhibited T cell activation in vitro, and this was dependent on the presence of dendritic cells. The binding of poliovirus receptor to TIGIT on human dendritic cells enhanced the production of interleukin 10 and diminished the production of interleukin 12p40. Knockdown of TIGIT with small interfering RNA in human memory T cells did not affect T cell responses. TIGIT-Fc inhibited delayed-type hypersensitivity reactions in wild-type but not interleukin 10-deficient mice. Our data suggest that TIGIT exerts immunosuppressive effects by binding to poliovirus receptor and modulating cytokine production by dendritic cells.

Evolution of NK receptors: a single Ly49 and multiple KIR genes in the cow.

Natural killer (NK) cell receptors for classical MHC class I molecules are encoded by the killer Ig-like receptor (KIR) multigene family in humans and other primates. Mouse NK cells, however, employ a completely different multigene family, the C-type lectin-like Ly49 genes, to perform the same function. This example of functional convergent evolution raises the question of what type of receptors are found in non-primate and non-rodent mammals. By screening a bovine spleen cDNA library, we isolated an Ly49 gene from the cow (Bos Taurus) and show by genomic Southern blotting that it is likely a single copy gene in this species. The coding region is intact and has an immunoreceptor tyrosine-based inhibition motif (ITIM) in the cytoplasmic domain, suggesting a role as an inhibitory receptor. We have also identified several bovine cDNA clones related to KIR and show that at least one has an intact open reading frame with two ITIM. Evidence for multiple KIR-like genes in the cow was obtained by Southern blotting and we found that at least two of these genes contain an ancient retro-element present in all human KIR genes. These results suggest that the cow and primate KIRgene families arose from a common ancestral gene but amplified independently. Furthermore, these findings indicate that the existence of multiple Ly49 genes may be a phenomenon unique to rodents.