Challenges and Opportunities: What Can We Learn from Patients Living with Chronic Musculoskeletal Conditions, Health Professionals and Carers about the Concept of Health Literacy Using Qualitative Methods of Inquiry?

The field of health literacy continues to evolve and concern public health researchers and yet remains a largely overlooked concept elsewhere in the healthcare system. We conducted focus group discussions in England UK, about the concept of health literacy with older patients with chronic musculoskeletal conditions (mean age = 73.4 years), carers and health professionals. Our research posed methodological, intellectual and practical challenges. Gaps in conceptualisation and expectations were revealed, reiterating deficiencies in predominant models for understanding health literacy and methodological shortcomings of using focus groups in qualitative research for this topic. Building on this unique insight into what the concept of health literacy meant to participants, we present analysis of our findings on factors perceived to foster and inhibit health literacy and on the issue of responsibility in health literacy. Patients saw health literacy as a result of an inconsistent interactive process and the implications as wide ranging; healthcare professionals had more heterogeneous views. All focus group discussants agreed that health literacy most benefited from good inter-personal communication and partnership. By proposing a needs-based approach to health literacy we offer an alternative way of conceptualising health literacy to help improve the health of older people with chronic conditions

The E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis

Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. By using single cell RNA sequencing analysis of immune cells in the same model, we establish the functional heterogeneity of macrophages and define an early pro-fibrogenic phase of NICM that is driven by Ccl5-expressing Ly6chigh monocytes. Among cardiac macrophage subtypes, WWP2 dysfunction primarily affects Ly6chigh monocytes via modulating Ccl5, and consequentially macrophage infiltration and activation, which contributes to reduced myofibroblast trans-differentiation. WWP2 interacts with transcription factor IRF7, promoting its non-degradative mono-ubiquitination, nuclear translocation and transcriptional activity, leading to upregulation of Ccl5 at transcriptional level. We identify a pro-fibrogenic macrophage subtype in non-ischemic cardiomyopathy, and demonstrate that WWP2 is a key regulator of IRF7-mediated Ccl5/Ly6chigh monocyte axis in heart fibrosis

Validation of Self-Reported Health Literacy Questions Among Diverse English and Spanish-Speaking Populations

BackgroundLimited health literacy (HL) contributes to poor health outcomes and disparities, and direct measurement is often time-intensive. Self-reported HL questions have not been validated among Spanish-speaking and diverse English-speaking populations.ObjectiveTo evaluate three self-reported questions: 1 "How confident are you filling out medical forms?"; 2 "How often do you have problems learning about your medical condition because of difficulty understanding written information?"; and 3 "How often do you have someone help you read hospital materials?" Answers were based on a 5-point Likert scale.DesignThis was a validation study nested within a trial of diabetes self-management support in the San Francisco Department of Public Health.ParticipantsEnglish and Spanish-speaking adults with type 2 diabetes receiving primary care.MethodsUsing the Test of Functional Health Literacy in Adults (s-TOFHLA) in English and Spanish as the reference, we classified HL as inadequate, marginal, or adequate. We calculated the C-index and test characteristics of the three questions and summative scale compared to the s-TOFHLA and assessed variations in performance by language, race/ethnicity, age, and education.Key resultsOf 296 participants, 48% were Spanish-speaking; 9% were White, non-Hispanic; 47% had inadequate HL and 12% had marginal HL. Overall, 57% reported being confident with forms "somewhat" or less. The "confident with forms" question performed best for detecting inadequate (C-index = 0.82, (0.77-0.87)) and inadequate plus marginal HL (C index = 0.81, (0.76-0.86); p<0.01 for differences from other questions), and performed comparably to the summative scale. The "confident with forms" question and scale also performed best across language, race/ethnicity, educational attainment, and age.ConclusionsA single self-reported HL question about confidence with forms and a summative scale of three questions discriminated between Spanish and English speakers with adequate HL and those with inadequate and/or inadequate plus marginal HL. The "confident with forms" question or the summative scale may be useful for estimating HL in clinical research involving Spanish-speaking and English-speaking, chronically-ill, diverse populations

A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

LIM and SH3 Protein -1 Modulates CXCR2-Mediated Cell Migration

BACKGROUND: The chemokine receptor CXCR2 plays a pivotal role in migration of neutrophils, macrophages and endothelial cells, modulating several biological responses such as angiogenesis, wound healing and acute inflammation. CXCR2 is also involved in pathogenesis of chronic inflammation, sepsis and atherosclerosis. The ability of CXCR2 to associate with a variety of proteins dynamically is responsible for its effects on directed cell migration or chemotaxis. The dynamic network of such CXCR2 binding proteins is termed as "CXCR2 chemosynapse". Proteomic analysis of proteins that co-immunoprecipitated with CXCR2 in neutrophil-like dHL-60 cells revealed a novel protein, LIM and SH3 protein 1 (LASP-1), binds CXCR2 under both basal and ligand activated conditions. LASP-1 is an actin binding cytoskeletal protein, involved in the cell migration. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CXCR2 and LASP-1 co-immunoprecipitate and co-localize at the leading edge of migrating cells. The LIM domain of LASP-1 directly binds to the carboxy-terminal domain (CTD) of CXCR2. Moreover, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4. Using a site-directed and deletion mutagenesis approach, Iso323-Leu324 of the conserved LKIL motif on CXCR2-CTD was identified as the binding site for LASP-1. Interruption of the interaction between CXCR2-CTD and LIM domain of LASP-1 by dominant negative and knock down approaches inhibited CXCR2-mediated chemotaxis. Analysis for the mechanism for inhibition of CXCR2-mediated chemotaxis indicated that LASP-1/CXCR2 interaction is essential for cell motility and focal adhesion turnover involving activation of Src, paxillin, PAK1, p130CAS and ERK1/2. CONCLUSIONS/SIGNIFICANCE: We demonstrate here for the first time that LASP-1 is a key component of the "CXCR2 chemosynapse" and LASP-1 interaction with CXCR2 is critical for CXCR2-mediated chemotaxis. Furthermore, LASP-1 also directly binds the CTD of CXCR1, CXCR3 and CXCR4, suggesting that LASP-1 is a general mediator of CXC chemokine mediated chemotaxis. Thus, LASP-1 may serve as a new link coordinating the flow of information between chemokine receptors and nascent focal adhesions, especially at the leading edge. Thus the association between the chemokine receptors and LASP-1 suggests to the presence of a CXC chemokine receptor-LASP-1 pro-migratory module in cells governing the cell migration

Health Literacy and Cardiovascular Disease: Fundamental Relevance to Primary and Secondary Prevention: A Scientific Statement From the American Heart Association

Health literacy is the degree to which individuals are able to access and process basic health information and services and thereby participate in health-related decisions. Limited health literacy is highly prevalent in the United States and is strongly associated with patient morbidity, mortality, healthcare use, and costs. The objectives of this American Heart Association scientific statement are (1) to summarize the relevance of health literacy to cardiovascular health; (2) to present the adverse associations of health literacy with cardiovascular risk factors, conditions, and treatments; (3) to suggest strategies that address barriers imposed by limited health literacy on the management and prevention of cardiovascular disease; (4) to demonstrate the contributions of health literacy to health disparities, given its association with social determinants of health; and (5) to propose future directions for how health literacy can be integrated into the American Heart Association's mandate to advance cardiovascular treatment and research, thereby improving patient care and public health. Inadequate health literacy is a barrier to the American Heart Association meeting its 2020 Impact Goals, and this statement articulates the rationale to anticipate and address the adverse cardiovascular effects associated with health literacy

When Does an Alien Become a Native Species? A Vulnerable Native Mammal Recognizes and Responds to Its Long-Term Alien Predator

The impact of alien predators on native prey populations is often attributed to prey naiveté towards a novel threat. Yet evolutionary theory predicts that alien predators cannot remain eternally novel; prey species must either become extinct or learn and adapt to the new threat. As local enemies lose their naiveté and coexistence becomes possible, an introduced species must eventually become ‘native’. But when exactly does an alien become a native species? The dingo (Canis lupus dingo) was introduced to Australia about 4000 years ago, yet its native status remains disputed. To determine whether a vulnerable native mammal (Perameles nasuta) recognizes the close relative of the dingo, the domestic dog (Canis lupus familiaris), we surveyed local residents to determine levels of bandicoot visitation to yards with and without resident dogs. Bandicoots in this area regularly emerge from bushland to forage in residential yards at night, leaving behind tell-tale deep, conical diggings in lawns and garden beds. These diggings were less likely to appear at all, and appeared less frequently and in smaller quantities in yards with dogs than in yards with either resident cats (Felis catus) or no pets. Most dogs were kept indoors at night, meaning that bandicoots were not simply chased out of the yards or killed before they could leave diggings, but rather they recognized the threat posed by dogs and avoided those yards. Native Australian mammals have had thousands of years experience with wild dingoes, which are very closely related to domestic dogs. Our study suggests that these bandicoots may no longer be naïve towards dogs. We argue that the logical criterion for determining native status of a long-term alien species must be once its native enemies are no longer naïve

Physicians' use of the 5As in counseling obese patients: is the quality of counseling associated with patients' motivation and intention to lose weight?

<p>Abstract</p> <p>Background</p> <p>Physicians are encouraged to counsel obese patients to lose weight, but studies measuring the quality of physicians' counseling are rare. We sought to describe the quality of physicians' obesity counseling and to determine associations between the quality of counseling and obese patients' motivation and intentions to lose weight, key predictors of behavior change.</p> <p>Methods</p> <p>We conducted post-visit surveys with obese patients to assess physician's use of 5As counseling techniques and the overall patient-centeredness of the physician.. Patients also reported on their motivation to lose weight and their intentions to eat healthier and exercise. One-way ANOVAs were used to describe mean differences in number of counseling practices across levels of self-rated intention and motivation. Logistic regression analyses were conducted to assess associations between number of 5As counseling practices used and patient intention and motivation.</p> <p>Results</p> <p>137 patients of 23 physicians were included in the analysis. While 85% of the patients were counseled about obesity, physicians used only a mean of 5.3 (SD = 4.6) of 18 possible 5As counseling practices. Patients with higher levels of motivation and intentions reported receiving more 5As counseling techniques than those with lower levels. Each additional counseling practice was associated with higher odds of being motivated to lose weight (OR 1.31, CI 1.11-1.55), intending to eat better (OR 1.23, CI 1.06-1.44), and intending to exercise regularly (OR 1.14, CI 1.00-1.31). Patient centeredness of the physician was also positively associated with intentions to eat better (OR 2.96, CI 1.03-8.47) and exercise (OR 26.07, CI 3.70-83.93).</p> <p>Conclusions</p> <p>Quality of physician counseling (as measured using the 5As counseling framework and patient-centeredness scales) was associated with motivation to lose weight and intentions to change behavior. Future studies should determine whether higher quality obesity counseling leads to improved behavioral and weight outcomes.</p