Challenges and Successes in Health Communication Messaging With Asian Americans.

Asians are the fastest growing racial and ethnic group in the United States, and in Michigan, Asians represent 3.4% of the state's population. Asians have long been aggregated as a homogeneous group and stereotyped as a "model minority." Asians, however, are very diverse, and each subgroup has different values, histories, beliefs, and dialects. The diversity among populations and variations in chronic disease risks demonstrate the importance of disaggregating Asian American ethnicities with respect to health promotion, which must be culturally and linguistically tailored to make the biggest impact. This article describes our challenges and successes in health communication messaging with Asian Americans during the 4 years of our Racial and Ethnic Approaches to Community Health (REACH) Cooperative Agreement.

Perceptions of COVID-19 Vaccine, Racism, and Social Vulnerability: An Examination among East Asian Americans, Southeast Asian Americans, South Asian Americans, and Others.

As COVID-19 vaccines are readily available and most U.S. adults who are enthusiastic about the vaccine have received it, motivating those who have not been vaccinated to accept it has become a challenge. The purpose of this study was to understand the mechanisms behind COVID-19 vaccine acceptance in Asian American ethnic groups, including how sociodemographic characteristics and racism predict COVID-19 and vaccine perceptions. The study also examined associations between social vulnerability and COVID-19 and vaccine perceptions. Social vulnerability is defined as the degree to which a community is able to prepare and respond to a natural or man-made disaster. This cross-sectional study used community-based survey data collected from April to September 2021. Study measures included demographics, perceptions of COVID-19 and COVID-19 vaccines, and racism-related experiences. The results showed that, compared to Non-Asians, East Asians reported that they had significantly more challenges accessing COVID-19 vaccines, and South Asians reported significantly higher safety concerns about COVID-19 vaccines. Our study also found that racism experience mediates the association between race/ethnicity and safety concerns about COVID-19 vaccines. Three Asian subgroups (East Asians, South Asians, and Southeast Asians) experienced more racism (compared to Non-Asians), and more experience of racism was related to greater safety concerns. Geographical Information System (GIS) maps revealed that residents of lower social vulnerability index (SVI) areas reported fewer unfairness perceptions and that higher SVI areas had lower vaccine accessibility and trust in public health agencies. Our study advances the understanding of racism, social vulnerability, and COVID-19 vaccine-related perceptions among Asian Americans. The findings have implications for policymakers and community leaders with respect to tailoring COVID-19 program efforts for socially vulnerable populations and Asian American groups that experience greater challenges regarding vaccine safety concerns and accessibility.

Using Community Engagement and Geographic Information Systems to Address COVID-19 Vaccination Disparities.

The COVID-19 pandemic has exacerbated existing health disparities and had a disproportionate impact on racial and ethnic minority groups in the United States. Limited COVID-19 data for Asian Americans have led to less attention for this population; nevertheless, available statistics have revealed lesser known impacts of COVID-19 on this population. Even with significant increases in vaccine supply and recent increases in COVID-19 vaccination rates, racial and ethnic disparities in vaccine uptake still persist. These disparities are amplified for individuals with limited English proficiency (LEP). The purpose of this paper is to apply community-engaged and geographic information system (GIS) strategies to increase equitable access to COVID-19 vaccination uptake by decreasing the structural barriers to COVID-19 vaccine uptake, with a particular focus on Asian Americans with LEP. Building upon existing community-academic partnerships between the academic unit and community-based organizations, the project team established community-led mobile and pop-up COVID-19 vaccination clinics to reach underserved individuals in their communities, worked with commercial pharmacies and reserved appointments for community-based organizations, used GIS to establish COVID-19 vaccination sites close to communities with the greatest need, and deployed trusted messengers to deliver linguistically and culturally relevant COVID-19 vaccine messages which built vaccine confidence among the community members. The implementation of mobile clinics expanded COVID-19 vaccine access and community-driven, multi-sector partnerships can increase the capacity to enhance efforts and facilitate access to COVID-19 vaccination for hard-to-reach populations.

Growth Factor-Independent 1 Is a Tumor Suppressor Gene in Colorectal Cancer.

Colorectal cancer is the third most common cancer and the third leading cause of cancer death in the United States. Growth factor-independent 1 (GFI1) is a zinc finger transcriptional repressor responsible for controlling secretory cell differentiation in the small intestine and colon. GFI1 plays a significant role in the development of human malignancies, including leukemia, lung cancer, and prostate cancer. However, the role of GFI1 in colorectal cancer progression is largely unknown. Our results demonstrate that RNA and protein expression of GFI1 are reduced in advanced-stage nonmucinous colorectal cancer. Subcutaneous tumor xenograft models demonstrated that the reexpression of GFI1 in 4 different human colorectal cancer cell lines inhibits tumor growth. To further investigate the role of Gfi1 in de novo colorectal tumorigenesis, we developed transgenic mice harboring a deletion of Gfi1 in the colon driven by CDX2-cre (Gfi1F/F; CDX2-cre) and crossed them with ApcMin/+ mice (ApcMin/+; Gfi1F/F; CDX2-cre). Loss of Gfi1 significantly increased the total number of colorectal adenomas compared with littermate controls with an APC mutation alone. Furthermore, we found that compound (ApcMin/+; Gfi1F/F; CDX2-cre) mice develop larger adenomas, invasive carcinoma, as well as hyperplastic lesions expressing the neuroendocrine marker chromogranin A, a feature that has not been previously described in APC-mutant tumors in mice. Collectively, these results demonstrate that GFI1 acts as a tumor suppressor gene in colorectal cancer, where deficiency of Gfi1 promotes malignancy in the colon. IMPLICATIONS: These findings reveal that GFI1 functions as a tumor suppressor gene in colorectal tumorigenesis.

Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach.

Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSC(vect)) or short hairpin RNA (shRNA) targeting the Shh gene (stMSC(ShhKO)). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSC(Shh)), stMSC(vect), or stMSC(ShhKO) cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSC(Shh) and stMSC(vect) cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSC(ShhKO) cells. Compared with stMSC(ShhKO)-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSC(vect)- and wtMSC(Shh)-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation.

Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) promote gastric cancer in response to gastritis. In culture, BM-MSCs are prone to mutation with continued passage but it is unknown whether a similar process occurs in vivo in response to gastritis. AIM: The purpose of this study was to identify the role of chronic gastritis in the transformation of BM-MSCs leading to an activated cancer-promoting phenotype. METHODS: Age matched C57BL/6 (BL/6) and gastrin deficient (GKO) mice were used for isolation of stomach, serum and mesenchymal stem cells (MSCs) at 3 and 6 months of age. MSC activation was assessed by growth curve analysis, fluorescence-activated cell sorting and xenograft assays. To allow for the isolation of bone marrow-derived stromal cells and assay in response to chronic gastritis, IRG/Vav-1(Cre) mice that expressed both enhanced green fluorescent protein-expressing hematopoietic cells and red fluorescent protein-expressing stromal cells were generated. In a parabiosis experiment, IRG/Vav-1(Cre) mice were paired to either an uninfected Vav-1(Cre) littermate or a BL/6 mouse inoculated with Helicobacter pylori. RESULTS: GKO mice displayed severe atrophic gastritis accompanied by elevated gastric tissue and circulating transforming growth factor beta (TGFß) by 3 months of age. Compared to BM-MSCs isolated from uninflamed BL/6 mice, BM-MSCs isolated from GKO mice displayed an increased proliferative rate and elevated phosphorylated-Smad3 suggesting active TGFß signaling. In xenograft assays, mice injected with BM-MSCs from 6-month-old GKO animals displayed tumor growth. RFP+ stromal cells were rapidly recruited to the gastric mucosa of H. pylori parabionts and exhibited changes in gene expression. CONCLUSIONS: Gastritis promotes the in vivo activation of BM-MSCs to a phenotype reminiscent of a cancer-promoting cell.

Sonic hedgehog mediates the proliferation and recruitment of transformed mesenchymal stem cells to the stomach.

Studies using Helicobacter-infected mice show that bone marrow-derived mesenchymal stem cells (MSCs) can repopulate the gastric epithelium and promote gastric cancer progression. Within the tumor microenvironment of the stomach, pro-inflammatory cytokine interferon-gamma (IFNγ) and Sonic hedgehog (Shh) are elevated. IFNγ is implicated in tumor proliferation via activation of the Shh signaling pathway in various tissues but whether a similar mechanism exists in the stomach is unknown. We tested the hypothesis that IFNγ drives MSC proliferation and recruitment, a response mediated by Shh signaling. The current study uses transplantation of an in vitro transformed mesenchymal stem cell line (stMSC(vect)), that over-expresses hedgehog signaling, in comparison to non-transformed wild-type MSCs (wtMSCs), wtMSCs transfected to over-express Shh (wtMSC(Shh)), and stMSCs transduced with lentiviral constructs containing shRNA targeting the Shh gene (stMSC(ShhKO)). The effect of IFNγ on MSC proliferation was assessed by cell cycle analysis in vitro using cells treated with recombinant IFNγ (rmIFNγ) alone, or in combination with anti-Shh 5E1 antibody, and in vivo using mice transplanted with MSCs treated with PBS or rmIFNγ. In vitro, IFNγ significantly increased MSC proliferation, a response mediated by Shh that was blocked by 5E1 antibody. The MSC population collected from bone marrow of PBS- or IFNγ-treated mice showed that IFNγ significantly increased the percentage of all MSC cell lines in S phase, with the exception of the stMSCs(ShhKO) cells. While the MSC cell lines with intact Shh expression were recruited to the gastric mucosa in response to IFNγ, stMSCs(ShhKO) were not. Hedgehog signaling is required for MSC proliferation and recruitment to the stomach in response to IFNγ.

Gastric Sonic Hedgehog acts as a macrophage chemoattractant during the immune response to Helicobacter pylori.

BACKGROUND & AIMS: Macrophages mediate the epithelial response to Helicobacter pylori and are involved in the development of gastritis. Sonic Hedgehog (Shh) regulates gastric epithelial differentiation and function, but little is known about its immunoregulatory role in the stomach. We investigated whether gastric Shh acts as a macrophage chemoattractant during the innate immune response to H pylori infection. METHODS: Mice with parietal cell-specific deletion of Shh (PC-Shh(KO)) and control mice were infected with H pylori. Levels of gastric Shh, cytokines, and chemokines were assayed by quantitative reverse-transcriptase polymerase chain reaction or by a Luminex-based multiplex assay 2, 7, or 180 days after infection. Circulating concentrations of Shh were measured by enzyme-linked immunosorbent assay. Bone marrow chimera experiments were performed with mice that have myeloid cell-specific deletion of the Hedgehog signal transduction protein Smoothened (LysMCre/Smo(KO)). Macrophage recruitment was measured in gastric tissue and peripheral blood by fluorescence-activated cell sorting analysis. RESULTS: Control mice infected with H pylori for 6 months developed an inflammatory response characterized by infiltration of CD4(+) T cells and increased levels of interferon gamma and interleukin 1ß in the stomach. PC-Shh(KO) mice did not develop gastritis, even after 6 months of infection with H pylori. Control mice had increased concentrations of Shh, accompanied by the recruitment of CD11b(+)F4/80(+)Ly6C(high) macrophages 2 days after infection. Control mice that received bone marrow transplants from control mice had an influx of macrophages to the gastric mucosa in response to H pylori infection; this was not observed in H pylori-infected control mice that received bone marrow transplants from LysMCre/Smo(KO) mice. CONCLUSIONS: H pylori induces release of Shh from the stomach; Shh acts as a macrophage chemoattractant during initiation of gastritis.

The role of sonic hedgehog reemergence during gastric cancer.

Sonic Hedgehog (Shh) signaling has been extensively studied for its role in developmental biology and cancer biology. The association between Shh and cancer development in general is well established but the functional role of Shh in the development and progression of gastric cancer specifically is largely unknown. Bone marrow-derived stem cells, specifically mesenchymal stem cells (MSCs) infiltrate and engraft into the gastric mucosa in response to the chronic inflammatory environment of Helicobacter infection. In this review, MSC infiltration and changes in the cytokine and cellular profiles of later-stage chronic environments will be tied into their interactions with the Shh pathway. We will discuss how these changes shape tumorigenesis and tumor progression in the gastric mucosa. The current review focuses on the Shh signaling pathway and its role in the development of gastric cancer, specifically in response to Helicobacter pylori infection. We follow with an in-depth discussion of the regulation of the Hedgehog pathway during acute and chronic gastric inflammation with a focus on signaling within the MSC compartment.

Increasing eye contact toward learning materials in a toddler with autism.

Individuals with Autism Spectrum Disorder often display deficits in eye contact that limit communicating with others, completing tasks, and attending to relevant stimuli. The participant in this study was a two-and-a-half-year-old boy with autism who seldom looked at materials while attempting three different tasks-assembling the pieces of a puzzle, stacking objects, and looking at pictures. This study compared rates of eye contact toward three target materials under two conditions: when food reinforcers were provided when he made eye contact with task materials and when they were withheld. An initial baseline phase was followed by a continuous reinforcement schedule in the first experimental phase that subsequently was thinned to an intermittent reinforcement schedule in the final phase. Results demonstrated an increase in eye contact toward target materials under both continuous and intermittent reinforcement conditions.