Comprehensive Genomic Profiling of Androgen-Receptor-Negative Canine Prostate Cancer.

Canine carcinomas have been considered natural models for human diseases; however, the genomic profile of canine prostate cancers (PCs) has not been explored. In this study, 14 PC androgen-receptor-negative cases, 4 proliferative inflammatory atrophies (PIA), and 5 normal prostate tissues were investigated by array-based comparative genomic hybridization (aCGH). Copy number alterations (CNAs) were assessed using the Canine Genome CGH Microarray 4 × 44K (Agilent Technologies). Genes covered by recurrent CNAs were submitted to enrichment and cross-validation analysis. In addition, the expression levels of TP53, MDM2 and ZBTB4 were evaluated in an independent set of cases by qPCR. PC cases presented genomic complexity, while PIA samples had a small number of CNAs. Recurrent losses covering well-known tumor suppressor genes, such as ATM, BRCA1, CDH1, MEN1 and TP53, were found in PC. The in silico functional analysis showed several cancer-related genes associated with canonical pathways and interaction networks previously described in human PC. The MDM2, TP53, and ZBTB4 copy number alterations were translated into altered expression levels. A cross-validation analysis using The Cancer Genome Atlas (TCGA) database for human PC uncovered similarities between canine and human PCs. Androgen-receptor-negative canine PC is a complex disease characterized by high genomic instability, showing a set of genes with similar alterations to human cancer.

Food availability and food access in rural agricultural communities: use of mixed methods.

BACKGROUND: Hispanics bear some of the highest burden of the obesity epidemic and the disparities gap is bigger among Hispanics in rural communities. This mixed methods study examined the objective and subjective assessment of food availability and food access in four rural, agricultural, and predominantly Hispanic communities. METHODS: In this convergent parallel mixed methods study, we used the Nutrition Environment Measures Survey (NEMS) of Food Stores and Restaurants to objectively assess 57 food stores and 69 restaurants in four rural agricultural communities in Washington State. To complement the objective assessment findings, we conducted semi-structured interviews with 32 community residents. The data were collected from 2013 to 2014. Frequencies and means were calculated for quantitative data and content analysis conducted for interview data. RESULTS: Participants (n = 32) had a mean age of 35.6 (SD 6.2) years, were mostly women, uninsured, low income, and had less than a high school education. Grocery and convenience stores had low NEMS composite scores indicating low overall availability of food items, low quality, and high food prices. Composite scores for sit-down restaurants, fast casual restaurants, and fast-food restaurants were similarly low in all four towns indicating limited availability of healthier options. Semi-structured interviews revealed participants perceived high availability and accessibility of quality fresh produce. Most participants reported eating out regularly several times a week, frequenting restaurant chains that serve buffets or fast foods, and allowing children to make decisions regarding their own food choices. CONCLUSIONS: Community members' perception of food availability and food access may be different from the objective assessment of food environment. This information can be used to inform community-wide interventions to address food environment in these rural communities.

IGF-1 Attenuates Hypoxia-Induced Atrophy but Inhibits Myoglobin Expression in C2C12 Skeletal Muscle Myotubes.

Chronic hypoxia is associated with muscle wasting and decreased oxidative capacity. By contrast, training under hypoxia may enhance hypertrophy and increase oxidative capacity as well as oxygen transport to the mitochondria, by increasing myoglobin (Mb) expression. The latter may be a feasible strategy to prevent atrophy under hypoxia and enhance an eventual hypertrophic response to anabolic stimulation. Mb expression may be further enhanced by lipid supplementation. We investigated individual and combined effects of hypoxia, insulin-like growth factor (IGF)-1 and lipids, in mouse skeletal muscle C2C12 myotubes. Differentiated C2C12 myotubes were cultured for 24 h under 20%, 5% and 2% oxygen with or without IGF-1 and/or lipid treatment. In culture under 20% oxygen, IGF-1 induced 51% hypertrophy. Hypertrophy was only 32% under 5% and abrogated under 2% oxygen. This was not explained by changes in expression of genes involved in contractile protein synthesis or degradation, suggesting a reduced rate of translation rather than of transcription. Myoglobin mRNA expression increased by 75% under 5% O2 but decreased by 50% upon IGF-1 treatment under 20% O2, compared to control. Inhibition of mammalian target of rapamycin (mTOR) activation using rapamycin restored Mb mRNA expression to control levels. Lipid supplementation had no effect on Mb gene expression. Thus, IGF-1-induced anabolic signaling can be a strategy to improve muscle size under mild hypoxia, but lowers Mb gene expression.

Ciclovia in a Rural Latino Community: Results and Lessons Learned.

CONTEXT: Ciclovias involve the temporary closure of roads to motorized vehicles, allowing for use by bicyclists, walkers, and runners and for other physical activity. Ciclovias have been held in urban and suburban communities in the United States and Latin America. OBJECTIVE: We evaluated the first ciclovia held in a rural, predominantly Latino community in Washington State. SETTING: Three blocks within a downtown area in a rural community were closed for 5 hours on a Saturday in July 2015. OUTCOME MEASURES: The evaluation included observation counts and participant intercept surveys. RESULTS: On average, 200 participants were present each hour. Fourteen percent of youth (younger than 18 years) were observed riding bikes. No adults were observed riding bikes. A total of 38 surveys were completed. Respondents reported spending on average 2 hours at the ciclovia. Seventy-nine percent reported that they would have been indoors at home involved in sedentary activities (such as watching TV, working on computer) if they had not been at the ciclovia. CONCLUSION: Regularly held ciclovias, which are free and open to anyone, could play an important role in creating safe, accessible, and affordable places for physical activity in rural areas. Broad community input is important for the success of a ciclovia.

An innovative strategy to reach the underserved for colorectal cancer screening.

Hispanics are an underserved population in terms of colorectal cancer (CRC). CRC is the second leading cause of cancer incidence among Hispanic men and women, and Hispanics have lower screening rates than non-Hispanic whites. The overall purpose of this project was to provide CRC information, education, and fecal occult blood test (FOBT) kits to Hispanics in a rural three-county region of Washington State. We held a series of 47 community health fair events that incorporated the use of a giant inflatable, walk-through colon model with physical depictions of healthy tissue, polyps, and CRC. We used a pre/post-design to look for changes in familiarity with CRC before and after walking through the colon among adults aged 18 and older (n = 947). McNemar's test analysis indicated significant differences in the distribution of the percentage of correct participant responses to CRC-related questions from pre- to post-test after an educational tour of the colon. Results from logistic regression analysis identified multiple participant characteristics associated with self-reported likelihood of being screened for CRC in 3 months following post-test. We distributed 300 free FOBT kits to be analyzed at no charge to the end user and to attendees aged 50 and older who toured the inflatable colon; 226 FOBT kits (75.3%) were returned for analysis. The use of the inflatable colon was an innovative way to attract people to learn about CRC and CRC screening modalities. Furthermore, the response to our distribution of FOBT kits indicates that if given the opportunity for education and access to services, this underserved population will comply with CRC screening.

Diabetes prevention in Hispanics: report from a randomized controlled trial.

INTRODUCTION: Hispanics are at increased risk of developing type 2 diabetes. Lifestyle interventions are effective in preventing diabetes and restoring glucose regulation. METHODS: We recruited Hispanic men and women (N = 320) who were residents of the Lower Yakima Valley, Washington, aged 18 years or older with hemoglobin A1c (HbA1c) levels higher than 6% to a parallel 2-arm randomized-controlled trial conducted from 2008 through 2012. The trial compared participants in the intervention arm, who received an immediate educational curriculum (n = 166), to participants in the control arm, who received a delayed educational curriculum (n = 154). The home-based curriculum consisted of 5 sessions led by community health workers and was designed to inform participants about diabetes, diabetes treatment, and healthy dietary and physical activity behaviors. Participants were randomly assigned to the intervention and control arms, and analysts were blinded as to participant arm. We evaluated intervention effects on HbA1c levels; frequency (times per week) of fruit and vegetable consumption; and frequency (times per week) of mild, moderate, and strenuous leisure-time physical activity. At baseline, 3 months, and 6 months after randomization, participants completed a questionnaire and provided a blood sample. Analysts were blinded to intervention arm. RESULTS: The immediate intervention group (-0.64% [standard error (SE) 0.10]) showed a significant improvement in HbA1c scores (-37.5%, P = .04) compared with the delayed intervention group (-0.44%, P = .14). No significant changes were seen for dietary end points or changes in physical activity. We did observe a trend of greater increases in frequency of moderate and vigorous physical activity and a smaller increase in mild physical activity in the immediate intervention group than in the delayed intervention group. CONCLUSION: This home-based intervention delivered by CHWs was associated with a clinically and statistically significant reduction in HbA1c levels in Hispanic adults with HbA1c levels higher than 6%.

Reopening schools safely and educating youth (ROSSEY) study: Protocol for a community-based, cluster randomized controlled trial.

INTRODUCTION: ROSSEY is a community-academic partnership aiming to develop and test a COVID-19 risk communication intervention for elementary school students and families in Yakima County, Washington. We describe the ROSSEY study protocol that will be implemented in the Yakima School District. METHODS: Aim 1 is to identify the community's social, ethical, and behavioral needs and resources for students to return to school and maintain onsite learning. We will conduct semi-structured interviews with students and school employees and focus groups with parents. Aim 2 is to evaluate the effectiveness of risk communication on students' school attendance. We will conduct a cluster randomized control trial. We will enroll 14 Yakima School District elementary schools with 900 student participants and randomize the schools into the COVID-19 risk communication intervention or control group. Aim 3 will assess implementation of the risk communication intervention and schools' COVID-19 mitigation strategies. We will use the RE-AIM framework to guide this work, which will entail conducting semi-structured interviews with students and school employees and focus groups with parents. DISCUSSION: Implementation of science-based risk communication can educate the community on the benefits and safety of COVID-19 testing and vaccination. Risk communication may also inform families about the role of COVID-19 testing and vaccines as part of mitigation strategies to allow for safe in-person learning. Schools have extraordinary influence to promote children's health through policy and practice change. Study findings will provide evidence to facilitate policy decisions and best practices at schools that facilitate adoption of COVID-19 risk communication. TRIAL REGISTRATION: ClinicalTrials.govNCT04859699. Registered on April 26, 2021.

An agricultural community's perspectives on COVID-19 testing to support safe school reopening.

Introduction: School-based COVID-19 testing may be an effective strategy for reducing transmission in schools and keeping schools open. The study objective was to examine community perspectives on school-based COVID-19 testing as a mitigation strategy to support safe school reopening. Methods: We conducted a qualitative study in Yakima County, an agricultural region of Washington state, where over half of residents are Hispanic/Latino. From June to July 2021, we interviewed 18 students (13 years old, on average) and 19 school employees, and conducted four focus groups (2 in Spanish, 2 in English) with 26 parents. We audio-recorded the semi-structured interviews and focus group discussions which were then transcribed. We used an inductive, constant comparison approach to code the transcripts and conducted a thematic analysis to generate themes. Results: We identified four main themes. Students, parents, and school employees desired a return to in-person learning (Theme 1). Schools implemented numerous COVID-19 mitigation strategies (e.g., masking) to facilitate a safe return to school but felt that adding testing would not be feasible due to a lack of resources and overworked staff (Theme 2). Parents and school employees' familiarity with COVID-19 testing procedures influenced their support for testing (Theme 3). Parents and school employees felt there were inadequate resources for individuals who test positive for COVID-19 (Theme 4). Discussion: Schools require adequate resources and medical personnel to implement COVID-19 testing. Individuals also need resources after testing positive, including physical space to isolate, financial resources for those without paid time off, and delivery of food and other necessities to households in rural communities.

School-Academic Partnerships in Support of Safe Return to Schools During the COVID-19 Pandemic.

Safely returning underserved youth to school during the coronavirus disease 2019 (COVID-19) pandemic through diagnostic testing and health education is imperative to mitigate the ongoing negative impact of COVID-19 and reduce health inequalities in underserved communities. The Rapid Acceleration of Diagnostics-Underserved Populations program is a consortium of research projects across the United States funded by the National Institutes of Health to understand the factors associated with the disproportionate burden of the pandemic among underserved populations and to leverage mitigation strategies, including diagnostic testing, with a focus on reducing health disparities. In this article, we provide an overview and introduce the articles from 8 Rapid Acceleration of Diagnostics-Underserved Populations projects featured in the supplement "Navigating a Pandemic in the K-12 Setting: Keeping Our School Communities Safe" published in Pediatrics. These projects funded in the program's first phase focus on COVID-19 diagnostic testing approaches for youth and employees at schools in underserved communities to support safe in-person learning. In the articles comprising the supplement, researchers present barriers and facilitators of the community engagement process necessary to establish school-academic partnerships. These efforts showcase school-based implementation testing strategies during the COVID-19 pandemic but are translatable to tackling other challenges related to reducing health disparities.

Active living environment assessments in four rural Latino communities.

OBJECTIVE: Latinos and rural residents are less active and have a greater prevalence of overweight/obesity compared with their non-Latino white and urban counterparts. The objective of this study was to assess the active living environment in four rural, predominantly Latino communities. METHODS: Assessments were taken using the Rural Active Living Assessment (RALA) in four rural predominantly Latino communities in Central Washington from September-November 2013. Street Segment Assessments of town center, thoroughfare, neighborhood and school zones were assessed for features related to walkability. Physical activity amenities, programs and policies in each town were assessed. Scores were generated for amenities, programs and policies. Data were analyzed with descriptive statistics and logistic regression. RESULTS: A total of 103 segments were assessed. Sidewalks in good condition were present in 32% of segments and shoulders in 44% of segments. Half of street segments were rated as walkable. Parks and playgrounds were available; however, half of these were rated in poor condition. All four districts offered after school physical activity programming but only two had a late bus option. CONCLUSIONS: These four rural towns have some policies, programming and infrastructure in place that support active living. The information from the RALA can be used to inform program and policy development to enhance physical activity in these rural communities.

PSEN1 and PSEN2 gene expression in Alzheimer's disease brain: a new approach.

Presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes encode the major component of y-secretase, which is responsible for sequential proteolytic cleavages of amyloid precursor proteins and the subsequent formation of amyloid-ß peptides. 150 RNA samples from the entorhinal cortex, auditory cortex and hippocampal regions of individuals with Alzheimer's disease (AD) and controls elderly subjects were analyzed with using real-time rtPCR. There were no differences between groups for PSEN1 expression. PSEN2 was significantly downregulated in the auditory cortex of AD patients when compared to controls and when compared to other brain regions of the patients. Alteration in PSEN2 expression may be a risk factor for AD.

Reevaluation of the critical-care pain observation tool in intubated adults after cardiac surgery.

BACKGROUND: Pain assessment in critically ill patients who are intubated, sedated, and unable to verbalize their needs remains a challenge. No universally accepted pain assessment tool is used in all intensive care units. OBJECTIVES: To examine concurrent validation of scores on the Critical-Care Pain Observation Tool for a painful and a non-painful procedure and to examine interrater reliability of the scores between 2 nurse raters. METHODS: A prospective, repeated-measures within-subject design was used. A convenience sample of 35 patients was recruited to achieve enrollment of 30 patients during a 5-month period. Observational data were collected on patients intubated after cardiac surgery during routine turning and during dressing changes for central catheters. RESULTS: Raters' mean scores did not increase significantly during dressing changes (increase, +0.25; 95% CI, -0.07 to 0.57; P = .12) but did increase significantly during turning (increase, +3.04; 95% CI 2.11-3.98; P < .001). The degree to which mean scores increased was significantly greater during turning than during dressing changes (increase, +2.80; 95% CI, 1.84-3.75; P < .001). The Fleiss-Cohen weighted κ for the inter-rater reliability of the ratings of research nurses was 0.87 (95% CI, 0.79-0.94). CONCLUSION: The results support previous research investigations on validity and reliability of the Critical-Care Pain Observation Tool for evaluating pain in intubated, critically ill adults.