Transplantation elicits a clonally diverse CD8+ T cell response that is comprised of potent CD43+ effectors.

CD8+ T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. Using MHC class I tetramers, we find that allogeneic CD8+ T cells are present at an elevated naive precursor frequency relative to other epitopes, only modestly increase in number after grafting, and maintain high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8+ T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defines potent effectors after transplantation. Activated CD43+ effector T cells maintain high expression of the coreceptor induced T cell costimulator (ICOS) in the presence of CTLA-4 immunoglobulin (Ig), and dual CTLA-4 Ig/anti-ICOS treatment prolongs graft survival. These data demonstrate that graft-specific CD8+ T cells have a distinct response profile relative to anti-pathogen CD8+ T cells and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ T cell populations that form after transplantation.

TIGIT agonism alleviates costimulation blockade-resistant rejection in a regulatory T cell-dependent manner.

Belatacept-based immunosuppression in kidney transplantation confers fewer off-target toxicities than calcineurin inhibitors but comes at a cost of increased incidence and severity of acute rejection, potentially due to its deleterious effect on both the number and function of Foxp3+ regulatory T cells (Tregs). TIGIT is a CD28 family coinhibitory receptor expressed on several subsets of immune cells including Tregs. We hypothesized that coinhibition through TIGIT signaling could function to ameliorate costimulation blockade-resistant rejection. The results demonstrate that treatment with an agonistic anti-TIGIT antibody, when combined with costimulation blockade by CTLA-4Ig, can prolong allograft survival in a murine skin graft model compared with CTLA-4Ig alone. Further, this prolongation of graft survival is accompanied by an increase in the frequency and number of graft-infiltrating Tregs and a concomitant reduction in the number of CD8+ T cells in the graft. Through the use of Treg-specific TIGIT conditional knockout animals, we demonstrated that the TIGIT-mediated reduction in the graft-infiltrating CD8+ T cell response is dependent on signaling of TIGIT on Foxp3+ Tregs. Our results highlight both the key functional role of TIGIT on Foxp3+ Tregs under conditions in which CTLA-4 is blocked and the therapeutic potential of TIGIT agonism to optimize costimulation blockade-based immunosuppression.

Validation of the Short-Test of Functional Health Literacy in Adults for the Samoan Population.

BACKGROUND: Health literacy encompasses various levels of communication for an individual, provider, and an organization. Validated and reliable tools have been developed to assess health literacy; however, there is a paucity of tools available to assess health literacy in native languages for indigenous and racial/ethnic minority populations. OBJECTIVE: This article shares the process taken to translate and evaluate validation and reliability of the Short Test of Functional Health Literacy in Adults for use with the Samoan population. METHODS: Respondent-driven sampling was used to collect data from 1,543 adults age 45 years and older in American Samoa. A confirmatory factor analysis using a two-factor model for validation was conducted. KEY RESULTS: The validation results indicated a "good fit" in multiple indices and Cronbach's alpha indicated high internal consistency in both the English and Samoan languages. CONCLUSIONS: Developing culturally validated and reliable health literacy assessment tools is important to help health care professionals decrease health disparities and address inadequate health literacy in all cultures. [HLRP: Health Literacy Research and Practice. 2022;6(4):e247-e256.] Plain Language Summary: The INSPIRE project studied the Short Test of Functional Health Literacy in Adults (STOFHLA) tested on the American Samoan population age 50 years and older. The results would show if the STOFHLA is a valid tool to measure functional health literacy in American Samoa adults.

Building Support for Place-Based Solutions to Childhood Obesity: Findings From Missouri.

BACKGROUND: Place-based efforts offer promise in reducing childhood obesity. Yet, lack of public demand and support may hinder implementation. AIMS: This study aimed to assess whether the emphasis on place-based solutions, community-wide strategies, and multisector engagement in the Healthy Schools Healthy Communities (HSHC) initiative would shift public views on obesity including the need for greater public involvement and an increase in awareness and support for strategies. METHOD: As part of the evaluation, two surveys were conducted-in 2014 and 2016-to examine the relationship between HSHC strategies and changes in public perception, support, and awareness of obesity. Both surveys were cross-sectional and conducted with a randomized sample of households. RESULTS: Most respondents indicated that parents/family (84.3% in 2014; 87.8% in 2016) and children (70.9% in 2014; 74.8% in 2016) had a large/very large responsibility for addressing childhood obesity. A higher percentage of 2016 respondents indicated willingness to work with others to increase availability of healthy foods (71.3% vs. 64.2%, respectively; p = .0280) and increase the number of places to be physically active in their community (71.1% vs. 60.7%, respectively; p = .0015). DISCUSSION: Findings suggest awareness and support of place-based efforts and willingness to engage may help garner ongoing support. However, individuals and families are still perceived as primarily responsible for addressing childhood obesity. Countering this mindset remains an ongoing challenge. CONCLUSION: Streamlined messaging regarding the issue and associated solutions, enhanced skills and capacity to implement these efforts, and citizen engagement to garner support for place-based initiatives are important.

Research Capacity Strengthening in American Samoa: Fa'avaeina le Fa'atelega o le Tomai Sa'ili'ili i Amerika Samoa.

Capacity-building partnerships are central to the sustainable development goals (SDGs), the UN's blueprint for achieving global health equity. The UN Permanent Forum on Indigenous Issues endorses the SDG and underscores the need for global partnerships that respect local leadership and culture. Innovations that weave or integrate Indigenous and Western knowledges are emphasised. These recommendations guided the INdigenous Samoan Partnership to Initiate Research Excellence (INSPIRE). INSPIRE is led by investigators from American Samoa and supported by US co-investigators. In project year one, INSPIRE queried: What weaving approaches are feasible for promoting community access to INSPIRE's research hub and for training Indigenous researchers? Weaving procedures involved interlacing Samoan and Western knowledges. Cultural tailoring strategies were used to customise communications. Formative evaluation suggests the feasibility of INSPIRE's efforts. Evidential tailoring provided information on American Samoa (A.S.) social determinants of health; trainees indicated increased research commitment. Linguistic and sociocultural relevance tailoring were positively received; trainees reported increased interest in research praxis and initiated an A.S. research capacity-strengthening model. Social work assured knowledge parity in development/delivery of the training curriculum and culturally safe discussions on social determinants of health, territorial status and Samoan survivance. Findings are context-specific yet offer considerations for capacity-strengthening partnerships seeking to advance health equity.

CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence.

The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8+ T pool is unexpectedly comprised of both CD45RBhi and CD45RBlo populations. Relative to CD45RBlo memory T cells, CD45RBhi memory T cells have lower affinity and display greater clonal diversity, as well as a persistent CD27hi phenotype. The CD45RBhi memory population displays a homeostatic survival advantage in vivo relative to CD45RBlo memory, and long-lived high-affinity cells that persisted long term convert from CD45RBlo to CD45RBhi. Human CD45RO+ memory is comprised of both CD45RBhi and CD45RBlo populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RBhi. These data demonstrate that CD45RB status is distinct from the conventional central/effector T cell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8+ T cell responses.

Factors associated with telemonitoring use among patients with chronic heart failure.

Background In adults with chronic heart failure (HF; defined as people with previously diagnosed left ventricular dysfunction) telemonitoring randomized controlled trials (RCTs) failed to consistently demonstrate improved clinical outcomes. We aimed to examine if patient and HF characteristics are associated with device preferences and use. Methods Using a cross-sectional, multicenter, international design, ambulatory and hospitalized adults with HF in Ohio, California, and Denmark viewed a six-minute video of telemonitoring configurations (tablet, smart phone, and key fob) and completed questionnaires. Comparative analyses were performed and when significant, pairwise comparisons were performed using Bonferroni-adjusted significance levels. Results Of 206 participants, 48.2% preferred smart phones for telemonitoring, especially when traveling (54.8%), with new/worsening symptoms (50%), for everyday use (50%), and connecting with doctors (48.5%). Participants preferred two-way communication and a screen with words over voice or number pads. Of device purposes, allowing for nurse communication ranked highest, followed by maintaining overall health. Very few patient and HF factors were associated with device preferences. Patients with higher health literacy ( p = 0.007), previous/current device use history ( p = 0.008), higher education level ( p = 0.035), and married/cohabitating status ( p = 0.023) had higher perceptions of ease of using devices. Those who were asymptomatic or had mild HF had higher self-confidence for health devices ( p = 0.024) and non-white patients perceived devices as more useful ( p = 0.033). Conclusion Telemonitoring use may be enhanced by simple plug-and-play type devices, two-way communication, and features that meet patients' personal learning and use needs.

Nitrate and nitrite levels in commonly consumed vegetables in Hong Kong.

Levels of nitrate and nitrite in 73 different vegetables, a total of 708 individual samples grouped into leafy, legumes, root and tuber, and fruiting vegetables, which are traded mainly in Hong Kong, were measured. Where available, five samples of each vegetable type were purchased from different commercial outlets during the winter of 2008 and summer of 2009. Levels of nitrate and nitrite were determined by ion chromatography and flow injection analysis, respectively. Nitrate and nitrite levels of all samples ranged <4-6300 and <0.8-9.0 mg kg⁻¹, respectively. Nitrate concentrations for the different groups, in descending order, were leafy > root and tuber > fruiting and legume vegetables. More than 80% of vegetables had mean nitrate concentrations less than 2000 mg kg⁻¹, but mean nitrate concentrations of three types of leafy vegetables, namely Chinese spinach, Shanghai cabbage and Chinese white cabbage, were >3500 mg kg⁻¹. On the other hand, nitrite concentrations were generally low - <1 mg kg⁻¹ on average. Nitrate in vegetables (i.e. Chinese flowering cabbage, Chinese spinach and celery) can be reduced significantly (12-31%) after blanching for 1-3 min, but not after soaking.

Dietary exposure of Hong Kong adults to nitrate and nitrite from vegetable intake.

The aim of this study was to assess the dietary exposure of adults in Hong Kong to nitrate and nitrite from vegetables. If all vegetables consumed were raw, the dietary exposure to nitrate for average consumers was estimated to be 4.4 mg kg(-1) body weight (bw) day(-1) and, for high consumers, was estimated to be 13 mg kg(-1) bw day(-1), which is about 120 and 350% of acceptable daily intake (ADI), respectively. If all vegetables consumed were cooked, the dietary exposure to nitrate from vegetables for the average adult consumer was estimated to be 3.5 mg kg(-1) bw day(-1) and, for high consumer, was estimated to be 10 mg kg(-1) bw day(-1), which is about 95 and 270% of ADI, respectively. On the other hand, the dietary exposure to nitrite from vegetables for average and high consumers were well below the ADI.