Changes in Capacity Building and Sustained Implementation Among a Statewide Coalition to Address Racial/Ethnic COVID-19 Disparities.

This article describes Arkansas Community Engagement Alliance Against COVID-19 Disparities (CEAL) Coalition initiatives and changes in measures of organizational capacity and sustainability via two waves of surveys. The Arkansas CEAL Coalition used several initiatives to address racial/ethnic COVID-19 disparities by building the capacity of community-based organizations and businesses to increase COVID-19 protective behaviors among their clients. Our study can inform future strategies that use a community-engaged coalition structure to reduce disparities among communities that suffer disproportionately from COVID-19. (Am J Public Health. (Am J Public Health. 2024;114(S1):S59-S64. https://doi.org/10.2105/AJPH.2023.307470).

Tuberculosis and Risk of Emphysema among US Adults in the NHANES I Epidemiologic Follow-Up Study Cohort, 1971-1992.

(1) Background: History of TB is a known risk factor for long-term respiratory impairment affecting lung functions in both restrictive and obstructive lung disease. (2) Methods: We analyzed data from the NHANES I Epidemiologic Follow-up Study (NHEFS), a longitudinal study conducted on a noninstitutionalized adult US population aged 25-74 years. Approximately 93 percent of the original NHANES I cohort was successfully traced by the end of the survey period and was available for analysis. The final adjusted model included age groups, gender, family income, lifetime smoking, body mass index (BMI), and frequency of alcohol consumption as potential confounders. (3) Results: The estimated hazards ratio of developing emphysema during follow-up for individuals with a past diagnosis of TB was 54% lower (95% CI = 0.35, 0.61) that that in individuals with no past TB, after controlling for potential confounders and using proportional hazards regression appropriate to the complex sample design. The association, however, was not statistically significant (HR = 0.86, p-value = 0.38) when only a self-reported history of TB was considered as the exposure in an unadjusted model. (4) Conclusions: Tuberculosis (self-reported or LTBI) was strongly (but inversely) associated with emphysema incidence. The association was not statistically significant with only a self-reported history of TB as exposure.

Factors associated with smokefree rules in the homes of Black/African American women smokers residing in low-resource rural communities.

Little is known about the implementation of voluntary policies in the homes of Black/African American women smokers who live in rural areas where health care access is limited. This paper examines 1) the sample's prevalence of comprehensive smoke-free rules; 2) sociodemographic, social, and smoking characteristics of women by home rule type; and 3) the association of social indicators with the outcome complete ban on smoked tobacco use in the home (n = 191). Families Rising to Enforce Smokefree Homes collected baseline data from 2019 to 2021 prior to randomization to an intervention that aimed to increase comprehensive smokefree policies in the homes African American women living in the rural Delta region of Arkansas. The primary outcome was implementation of a complete ban on all smoked tobacco products anywhere inside the home. Results showed that 26% of women had a rule that completely banned all smoked tobacco products in the home. Women who reported having no ban were more likely to be employed part-time (50.0%), while women with a partial (66.9%) or complete ban (60.0%) were more likely to not currently work for pay. Women who indicated that they just meet basic expenses and meet needs with little left had significantly lower odds of having a complete ban on smoked tobacco in the home than women who indicated that they live comfortably. Perceived financial security may be a motivating factor that helps women keep their homes free from all smoked tobacco products (# NCT03476837).

Temporal dynamics of SARS-CoV-2 genome and detection of variants of concern in wastewater influent from two metropolitan areas in Arkansas.

Although SARS-CoV-2 can cause severe illness and death, a percentage of the infected population is asymptomatic. This, along with other factors, such as insufficient diagnostic testing and underreporting due to self-testing, contributes to the silent transmission of SARS-CoV-2 and highlights the importance of implementing additional surveillance tools. The fecal shedding of the virus from infected individuals enables its detection in community wastewater, and this has become a valuable public health tool worldwide as it allows the monitoring of the disease on a populational scale. Here, we monitored the presence of SARS-CoV-2 and its dynamic genomic changes in wastewater sampled from two metropolitan areas in Arkansas during major surges of COVID-19 cases and assessed how the viral titers in these samples related to the clinical case counts between late April 2020 and January 2022. The levels of SARS-CoV-2 RNA were quantified by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) using a set of TaqMan assays targeting three different viral genes (encoding ORF1ab polyprotein, surface glycoprotein, and nucleocapsid phosphoprotein). An allele-specific RT-qPCR approach was used to screen the samples for SARS-CoV-2 mutations. The identity and genetic diversity of the virus were further investigated through amplicon-based RNA sequencing, and SARS-CoV-2 variants of concern were detected in wastewater samples throughout the duration of this study. Our data show how changes in the virus genome can affect the sensitivity of specific RT-qPCR assays used in COVID-19 testing with the surge of new variants. A significant association was observed between viral titers in wastewater and recorded number of COVID-19 cases in the areas studied, except when assays failed to detect targets due to the presence of particular variants. These findings support the use of wastewater surveillance as a reliable complementary tool for monitoring SARS-CoV-2 and its genetic variants at the community level.

Erratum: Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers.

[This corrects the article DOI: 10.18332/tid/142579.].

Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers.

INTRODUCTION: Although smoking is a strong risk factor for lung diseases including asthma, COPD, and asthma-COPD overlap syndrome (ACOS), studies are needed to examine the association between e-cigarettes and asthma, COPD, and ACOS. This study evaluated the association between e-cigarette use and self-reported diagnosis of asthma, COPD, and ACOS using a large nationally representative sample of adults aged ≥18 years in the United States. METHODS: Cross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2016 to 2018 were used to examine self-reported information on current e-cigarette use, demographic variables, and asthma and COPD status among never cigarette smokers (n=8736). Asthma and COPD were measured by self-reported diagnosis, and respondents who reported having both diagnoses were then classified as having ACOS. Of the 469077 never cigarette smokers, 4368 non-e-cigarette users were 1:1 propensity score-matched to e-cigarette users on age, sex, race/ethnicity and education level. We used multinomial logistic regression to examine association between current e-cigarette use and self-report asthma, COPD, and ACOS while controlling for marital status and employment in addition to matching variables. RESULTS: Compared with never e-cigarette users, e-cigarette users had increased odds of self-reported ACOS (OR=2.27; 95% CI: 2.23-2.31), asthma (OR=1.26; 95% CI: 1.25-1.27) and COPD (OR=1.44; 95% CI: 1.42-1.46). CONCLUSIONS: Our findings suggest that e-cigarette use is associated with an increased odds of self-reported asthma, COPD, and ACOS among never combustible cigarette smokers. BRFSS provides cross-sectional survey data, therefore a causal relationship between e-cigarette use and the three lung diseases cannot be evaluated. Future longitudinal studies are needed to validate these findings.

Electronic cigarette use and its association with asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome among never cigarette smokers.

INTRODUCTION: Although smoking is a strong risk factor for lung diseases including asthma, COPD, and asthma-COPD overlap syndrome (ACOS), studies are needed to examine the association between e-cigarettes and asthma, COPD, and ACOS. This study evaluated the association between e-cigarette use and self-reported diagnosis of asthma, COPD, and ACOS using a large nationally representative sample of adults aged ≥18 years in the United States. METHODS: Cross-sectional data from the Behavioral Risk Factor Surveillance System (BRFSS) from 2016 to 2018 was used to examine self-reported information on current e-cigarette use, demographic variables, and asthma and COPD status among never cigarette smokers (n=8736). Asthma and COPD were measured by self-reported diagnosis, and respondents who reported having both diagnoses were then classified as having ACOS. Of the 46079 never cigarette smokers, 4368 non-e-cigarette smokers were 1:1 propensity score-matched to e-cigarette smokers on age, sex, race/ethnicity and education level. We used multinomial logistic regression to examine association between current e-cigarette use and self-report asthma, COPD, and ACOS while controlling for marital status and employment in addition to matching variables. RESULTS: Compared with never e-cigarette smokers, e-cigarette smokers had increased odds of self-reported ACOS (OR=2.27; 95% CI: 2.23-2.31), asthma (OR=1.26; 95% CI: 1.25-1.27) and COPD (OR=1.44; 95% CI: 1.42-1.46). CONCLUSIONS: Data from this large nationally representative sample suggest that e-cigarette use is associated with increased odds of self-reported asthma, COPD, and ACOS among never combustible cigarette smokers. The odds of ACOS were twice as high among e-cigarette users compared with never smokers of conventional cigarettes. The findings from this study suggest the need to further investigate the long-term and short-term health effects of e-cigarette use, since the age of those at risk in our study was 18-24 years.

Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach.

Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.

DNA methylation inhibition in myeloma: Experience from a phase 1b study of low-dose continuous azacitidine in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma.

The DNA methyltransferase inhibitor azacytidine (aza) may reactivate pathways associated with plasma cell differentiation, cell cycle control, apoptosis, and immune recognition and thereby restore sensitivity to lenalidomide (len) and dexamethasone (dex) in relapsed and/or refractory multiple myeloma (RRMM). We aimed to develop an aza regimen that reaches epigenetically active levels 8 times in 28 days with less bone marrow toxicity than the myeloid malignancy standard of 7 consecutive doses to enable safe combination with len. Aza was escalated from 30 mg/m2 once a week up to a predefined maximum of 50 mg/m2 twice a week in combination with GFR-adjusted len (≥ 60 mL/min: 25 mg, 3059 mL/min: 10 mg) day 1 to 21 every 28 days and dex 40 mg once a week followed by a limited expansion study to a total N of 23 at the highest tolerated dose. Fifty-one patients (pts) with RRMM were screened, 42 were treated and 41 were evaluable for response based on at least 1 response assessment or progression after treatment start. The median number of prior lines of therapy was 5 (1-11) and 81% (34) were refractory to len and/or pomalidomide (pom). Two DLTs occurred in different cohorts, 1 neutropenic fever in 1/6 pts on the aza 40 mg/m2 twice a week GFR ≥ 60 mL/min cohort and 1 GGT elevation in 1/6 pts on the aza 50 mg/m2 GFR 30-59 mL/min cohort. An MTD was not reached and aza 50 mg/m2 SC twice a week was chosen for the expansion study. At least possibly related Grade 3/4 AEs occurred in 28 pts (67%) with the following in > 1 pt: neutropenia (N = 16, 38%), anemia (N = 6, 14%), lymphopenia (N = 5, 12%), thrombocytopenia (N = 4, 10%), leukopenia (N = 4, 10%), febrile neutropenia (N = 4, 10%), fatigue (N = 3, 7%), fever (N = 2, 5%), and infection (N = 2, 5%). At a median follow up time for alive pts of 60.2 months (range: 36.1-82.5 months), the overall response rate (≥ partial response) and clinical benefit response rate (≥ minor response) was 22 and 32%, respectively, with 4 very good partial responses (10%), 5 partial responses (12%), and 4 minor responses (10%). The median PFS was 3.1 months (95% confidence interval [CI]: 2.1-5.1 months), median TTP 2.7 months (95% CI: 2.1-7.5 months), and median OS 18.6 months (95% CI: 12.9-33.0 months). Achieving at least minor response and reaching TTP > 6 months was associated with approximately 35% lower median plasma levels of the enzyme that inactivates aza, plasma cytidine deaminase (CDA, P< .0001). Two of the len refractory pts achieved longer disease control than with any prior regimen and 1 responded immediately after progression on len, bortezomib, and prednisone. Analyses of the methylation state of over 480,000 CpG sites in purified myeloma cells at screening were possible in 11 pts and on day 28 in 8 of them. As in other studies, the majority of differentially methylated CpGs compared to normal plasma cells were hypomethylated in myeloma. Treatment decreased the number of CpGs that were differentially methylated in normal plasma cells by > 0.5% in 6 and by > 5% in 3 of the 8 pts, most pronounced in 2 pts with clinically convincing aza contribution who achieved a reduction in overall differentially methylated CpGs by 23 and 68%, respectively, associated with increased expression of immunoglobulin genes. The study demonstrated tolerability of twice a week SC aza at 50 mg/m2 with len and dex in RRMM and suggested aza may help overcome the len/pom refractory state, possibly by activating differentiation pathways. Relatively low response rates and association of clinical benefit with low plasma levels of the aza inactivating enzyme CDA suggest the aza regimen will need to be optimized further and pt selection may be required to maximize benefit.

Characterization of Electronic Cigarette Warning Statements Portrayed in YouTube Videos.

INTRODUCTION: In 2018, the United States Food and Drug Administration (FDA) required that electronic cigarette (e-cigarette) manufacturers, packagers, importers, distributors, and retailers display an addictive or alternate warning statement on e-cigarette visual advertisements. Few studies have investigated the FDA-mandated and other warnings on social media. This study examined the prevalence and content of warning statements in e-cigarette-related YouTube videos. METHODS: In 2019, The Virginia Commonwealth University Center for the Study of Tobacco Products conducted bi-monthly (February-June) YouTube searches by relevance and view count to identify e-cigarette-related videos. Overall, 178 videos met the inclusion criteria. Staff coded each video for the presence of a visual/verbal warning statement, warning statement type (eg, FDA-mandated, addiction/tobacco, safety/toxic exposure, health effects), sponsorship, and tobacco product characteristics. A data extraction tool collected the video URL, title, upload date, and number of views, likes/dislikes, and comments. RESULTS: Only 5.1% of videos contained FDA-mandated and 21.9% contained non-mandated warnings. All videos with FDA-mandated and 46.2% of non-mandated warnings were represented visually. Only 13.1% of industry-sponsored videos uploaded after the mandate effective date had an FDA-mandated warning statement and videos with FDA-mandated and non-mandated (v. no) warnings had significantly fewer views, likes, dislikes, and comments. Among all non-mandated warnings, 31.3% featured an addiction/tobacco, 18.8% a safety/toxic exposure, and 37.5% a health effects warning. CONCLUSIONS: The prevalence of FDA-mandated warning statements in e-cigarette related YouTube videos was low. FDA enforcement of the warning statement mandate on YouTube could increase the public's understanding of the addictive nature of nicotine in e-cigarettes. IMPLICATIONS: The FDA has the authority to regulate the advertisement and promotion of e-cigarettes on the Internet. These data can inform future FDA requirements related to the language content and visual representation of addiction/tobacco, safety/exposure, and health effects warning statements that appear in YouTube videos and other visual social media popular among young people. Such data would help consumers make informed decisions about purchasing e-cigarette products, using e-cigarettes, and avoiding unintentional harm related to e-cigarettes. In addition, these data may help social media platforms make decisions on whether they will prohibit advertisements that promote or facilitate the sale of tobacco products.

The difference between hypertension determined by self-report versus examination in the adult population of the USA: Continuous NHANES 1999-2016.

BACKGROUND: Studies have considered the validity of self-reported hypertension relative to hypertension detected by examination; no study has explored trends in the difference between these two measures. Our objective was to calculate these differences overtime within subpopulations of the USA. METHODS: We included non-Hispanic white, non-Hispanic black and Hispanic adults who participated in the National Health and Nutrition Examination Surveys from 1999 to 2016, in the analysis (N = 44 333). We subtracted self-reported hypertension from hypertension detected by examination to calculate blood pressure difference (BPD). We fit weighted linear regression models that included important covariates along with all combination of two- and three-way interactions to predict the BPD. We used the fitted lines of the models to depict the patterns of differences in the different subpopulations. RESULTS: Age ≥ 45 years, lack of annual clinical visit, body mass index (BMI) < 25 and time were important factors associated with increased BPD. CONCLUSIONS: People who are ≥ 45 years, have normal BMI, or do not have annual medical visits are more likely to have a bigger BPD. We can use the calculated BPD, to adjust estimates of the prevalence of self-reported hypertension.

Crop burning and the prevalence of asthma and COPD emergency department treatments in a rural Arkansas county.

OBJECTIVE: To evaluate the impact of crop burning on the prevalence of asthma and COPD emergency department (ED) treatments in a rural Arkansas county. METHODS: Administrative datasets listing ED treatments for asthma and COPD obtained from the Arkansas Hospital Discharge Dataset System for the calendar years 2014-2016 were used in this semi-ecological study. Primary diagnosis codes (ICD-9: 490-496 and ICD-10: J40-J47) were used to identify patients who were diagnosed with asthma and COPD. Patients with a reported county of residence in Craighead County were determined as case county residents and those in Sebastian County were control county residents. Month of visit was used to determine seasonal variation. PM 2.5 air quality data were obtained from the EPA AQS Data Mart. RESULTS: Between 2014 through 2016, there were a combined total of 2,536 ED treatments due to asthma and 8,530 due to COPD in Craighead and Sebastian counties. The odds of being treated in the ED during the fall months for asthma and COPD are associated with a 20.9% increase and 16.9% increase respectively in Craighead County as compared to Sebastian Country after adjusting for potential confounders (p = 0.04, p = 0.003). PM 2.5 concentrations were higher in Craighead County than Sebastian County during the fall season (p = 0.005). CONCLUSION: Fall ED treatments for asthma and COPD were higher in Craighead County, Arkansas compared to Sebastian County, Arkansas for the years 2014-2016. PM 2.5 levels were also higher in Craighead County in the fall during these years. These differences may be attributable to crop burning.​.

Association of PARP1-specific polymorphisms and haplotypes with non-small cell lung cancer subtypes.

OBJECTIVE: The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer. MATERIALS AND METHODS: DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed. RESULTS: SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12-3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19-6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61-6.75; 95%CI from 1.82 to 19.9; P-value<0.001. CONCLUSION: PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.

Document Oriented Graphical Analysis and Prediction.

In general, small-mid size research laboratories struggle with managing clinical and secondary datasets. In addition, faster dissemination, correlation and prediction of information from available datasets is always a bottleneck. To address these challenges, we have developed a novel approach, Document Oriented Graphical Analysis and Prediction (DO-GAP), a hybrid tool, merging strengths of Not only SQL (NoSQL) document oriented and graph databases. DO-GAP provides flexible and simple data integration mechanism using document database, data visualization and knowledge discovery with graph database. We demonstrate how the proposed tool (DO-GAP) can integrate data from heterogeneous sources such as Genomic lab findings, clinical data from Electronic Health Record (EHR) systems and provide simple querying mechanism. Application of DO-GAP can be extended to other diverse clinical studies such as supporting or identifying weakness of clinical diagnosis in comparison to molecular genetic analysis.

Consumption of Vitamin K and Vitamin A Are Associated With Reduced Risk of Developing Emphysema: NHANES 2007-2016.

Chronic obstructive pulmonary disease (COPD) comprising of emphysema and chronic bronchitis are the most common chronic respiratory diseases that impart a huge economic and clinical burden. Factors other than smoking and air pollutants can cause inflammation and emphysematous changes in the lung airspaces or alveoli have been understudied. Using a cross-sectional study design, we assessed the association of dark green vegetables, vitamin K and Vitamin A with emphysema status among adults at U.S. These nutrients have a role in lung biology. A complete case NHANES data (n = 17,681) was used. After adjusting for modifiable and non-modifiable confounders, consumption of recommended amounts of vitamin K was associated with 39% decrease in odds (Odds Ratio: 0.61; 95% CI: 0.40-0.92, P-val: 0.02) of emphysema. Similarly consumption of recommended amounts vitamin A dose was associated with 33% decrease in odds (Odds Ratio: 0.67; 95% CI: 0.44-1.00, P-val: 0.05) of emphysema. Vitamin K shows an inverse association suggesting that it may be important in slowing the emphysematous process. Vitamin A is important in maintaining the anti-inflammatory process. Together vitamin K and vitamin A are important in the lung health.

Using Machine Learning to Predict Progression in the Gastric Precancerous Process in a Population from a Developing Country Who Underwent a Gastroscopy for Dyspeptic Symptoms.

BACKGROUND: Gastric cancer is the fourth most common cancer and the third most common cause of cancer deaths worldwide. Morbidity and mortality from gastric cancer may be decreased by identification of those that are at high risk for progression in the gastric precancerous process so that they can be monitored over time for early detection and implementation of preventive strategies. METHOD: Using machine learning, we developed prediction models for gastric precancerous progression in a population from a developing country with a high rate of gastric cancer who underwent gastroscopies for dyspeptic symptoms. In the data imputed for completeness, we divided the data into a training and a validation test set. Using the training set, we used the random forest method to rank potential predictors based on their predictive importance. Using predictors identified by the random forest method, we conducted best subset linear regressions with the leave-one-out cross-validation approach to select predictors for overall progression and progression to dysplasia or cancer. We validated the models in the test set using leave-one-out cross-validation. RESULTS: We observed for all models that complete intestinal metaplasia and incomplete intestinal metaplasia were the strongest predictors for further progression in the precancerous process. We also observed that a diagnosis of no gastritis, superficial gastritis, or antral diffuse gastritis at baseline was a predictor of no progression in the gastric precancerous process. The sensitivities and specificities were 86% and 79% for the general model and 100% and 82% for the location-specific model, respectively. CONCLUSION: We developed prediction models to identify gastroscopy patients that are more likely to progress in the gastric precancerous process, among whom routine follow-up gastroscopies can be targeted to prevent gastric cancer. Future external validation is needed.

The Association between Salt and Potential Mediators of the Gastric Precancerous Process.

BACKGROUND: The process by which salt affects the gastric precancerous process has not been adequately studied in humans. METHODS: We investigated the effects of salt on gastric inflammation, epithelial damage, the density of Helicobacter pylori infection, and gastric epithelial cell proliferation, all of which may be mediators between salt and gastric precancerous/cancerous lesions. These potential mediators were measured using gastric biopsies as: (a) the density of polymorphonuclear and mononuclear cells (gastric inflammation), (b) mucus depletion (gastric epithelial damage), and (c) the severity of H. pylori infection. Salt intake was measured with spot urine samples (using urinary sodium/creatinine ratios), self-reported frequency of adding salt to food, and as total added salt. RESULTS: The average sodium/creatinine ratio (at baseline and post-treatment at five months) was associated with increased epithelial damage over the 12-year follow-up period among those with a greater severity of chronic inflammation and among those with continued H. pylori infection after treatment at five months. This association was stronger when both severe gastric inflammation and H. pylori infection were present at five months (ß: 1.112, 95% CI: 0.377, 1.848). CONCLUSION: In humans, salt was associated with an increase in epithelial damage in stomachs with more severe previous H. pylori-induced chronic inflammation.

Association between Dietary Salt Intake and Progression in the Gastric Precancerous Process.

Gastric cancer is the third leading cause of cancer mortality worldwide. Studies investigating the effect of salt on gastric cancer have mainly used self-reported measures, which are not as accurate as sodium/creatinine ratios because individuals may not know the amount of salt in their food. Using data from a prospective cohort study, we investigated the effect of salt intake on progression to gastric precancerous lesions. Salt intake was estimated by urinary sodium/creatinine ratios, self-reported frequencies of adding salt to food, and total added table salt. We repeated the analyses among groups with and without Helicobacter pylori infection. We did not observe a positive association between salt intake, measured by urinary sodium/creatinine ratio, and overall progression in the gastric precancerous process (adjusted risk ratio (RR): 0.94; 95% confidence interval (CI) 0.76-1.15). We did observe an association between salt intake and increased risk for progression to dysplasia or gastric cancer overall (adjusted risk ratio (RR): 1.32; 95% confidence interval (CI): 0.96-1.81), especially among those who continued to have H. pylori infection at the five-month follow-up (adjusted RR: 1.53; 95% CI: 1.12-2.09), and among those who had persistent H. pylori infection over 12 years (adjusted RR: 1.49; 95% CI: 1.09-2.05). Salt intake may increase the risk of gastric dysplasia or gastric cancer in individuals with H. pylori infection.

Genome-wide tracts of homozygosity and exome analyses reveal repetitive elements with Barrets esophagus/esophageal adenocarcinoma risk.

BACKGROUND: Barrett's esophagus (BE) is most commonly seen as the condition in which the normal squamous epithelium lining of the esophagus is replaced by goblet cells. Many studies show that BE is a predisposing factor for the development of esophageal adenocarcinoma (EAC), a particularly lethal cancer. The use of single nucleotide polymorphisms (SNPs) to map BE/EAC genes has previously provided insufficient genetic information to fully characterize the heterogeneous nature of the disease. We therefore hypothesize that rigorous interrogation of other types of genomic changes, e.g. tracts of homozygosity (TOH), repetitive elements, and insertion/deletions, may provide a comprehensive understanding of the development of BE/EAC. RESULTS: First, we used a case-control framework to identify TOHs by using SNPs and tested for association with BE/EAC. Second, we used a case only approach on a validation series of eight samples subjected to exome sequencing to identify repeat elements and insertion/deletions. Third, insertion/deletions and repeat elements identified in the exomes were then mapped onto genes in the significant TOH regions. Overall, 24 TOH regions were significantly differentially represented among cases, as compared to controls (adjusted-P = 0.002-0.039). Interestingly, four BE/EAC-associated genes within the TOH regions consistently showed insertions and deletions that overlapped across eight exomes. Predictive functional analysis identified NOTCH, WNT, and G-protein inflammation pathways that affect BE and EAC. CONCLUSIONS: The integration of common TOHs (cTOHs) with repetitive elements, insertions, and deletions within exomes can help functionally prioritize factors contributing to low to moderate penetrance predisposition to BE/EAC.

PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin.

Non-small cell lung cancer (NSCLC) is the major form of lung cancer, with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being its major subtypes. Smoking alone cannot completely explain the lung cancer etiology. We hypothesize that altered lung microbiome and chronic inflammatory insults in lung tissues contribute to carcinogenesis. Here we explore the microbiome composition of LUAD samples, compared to LUSC and normal samples. Extraction of microbiome DNA in formalin-fixed, paraffin-embedded (FFPE) lung tumor and normal adjacent tissues was meticulously performed. The 16S rRNA product from extracted microbiota was subjected to microbiome amplicon sequencing. To assess the contribution of the host genome, CD36 expression levels were analyzed then integrated with altered NSCLC subtype-specific microbe sequence data. Surprisingly phylum Cyanobacteria was consistently observed in LUAD samples. Across the NSCLC subtypes, differential abundance across four phyla (Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes) was identified based on the univariate analysis (p-value < 6.4e-4 to 3.2e-2). In silico metagenomic and pathway analyses show that presence of microcystin correlates with reduced CD36 and increased PARP1 levels. This was confirmed in microcystin challenged NSCLC (A427) cell lines and Cyanobacteria positive LUAD tissues. Controlling the influx of Cyanobacteria-like particles or microcystin and the inhibition of PARP1 can provide a potential targeted therapy and prevention of inflammation-associated lung carcinogenesis.