Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase ß.

The catalytic function of DNA polymerase ß (pol ß) fulfills the gap-filling requirement of the base excision DNA repair pathway by incorporating a single nucleotide into a gapped DNA substrate resulting from the removal of damaged DNA bases. Most importantly, pol ß can select the correct nucleotide from a pool of similarly structured nucleotides to incorporate into DNA in order to prevent the accumulation of mutations in the genome. Pol ß is likely to employ various mechanisms for substrate selection. Here, we use dCTP analogues that have been modified at the ß,γ-bridging group of the triphosphate moiety to monitor the effect of leaving group basicity of the incoming nucleotide on precatalytic conformational changes, which are important for catalysis and selectivity. It has been previously shown that there is a linear free energy relationship between leaving group pKa and the chemical transition state. Our results indicate that there is a similar relationship with the rate of a precatalytic conformational change, specifically, the closing of the fingers subdomain of pol ß. In addition, by utilizing analogue ß,γ-CHX stereoisomers, we identified that the orientation of the ß,γ-bridging group relative to R183 is important for the rate of fingers closing, which directly influences chemistry.

Correlates of supportive care needs among Asian Americans with colorectal, liver, or lung cancer from a web-based patient navigation portal intervention: The Patient COUNTS study.

BACKGROUND: Cancer is the leading cause of death among Asian Americans, who often face barriers to cancer care. Cancer supportive care needs among Asian Americans remain understudied. AIMS: We examined cancer supportive care needs and participant factors correlated with these needs, identified profiles of supportive care needs, and examined whether needs profiles are associated with quality of life among Asian American adults. METHODS AND RESULTS: We recruited 47 Asian American adults with colorectal, liver, or lung cancer who spoke Chinese, English, or Vietnamese, and were starting or undergoing cancer treatment. We assessed cancer supportive care needs in four domains: cancer information, daily living, behavioral health, and language assistance. Hierarchical cluster analysis was used to identify clusters of participants based on their supportive need profiles to further examine the association between need profiles and quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy. Participants (mean age = 57.6) included 72% males and 62% spoke English less than very well. Older participants (age ≥ 65) and those with annual income <$50K reported higher daily living needs. Men and younger participants (age < 50) reported higher behavioral health needs. We found three clusters displaying distinct cancer supportive need profiles: Cluster 1 (28% of the sample) displayed high needs across all domains; Cluster 2 (51%) had low needs across all domains; and Cluster 3 (21%) had high needs for cancer information and daily living. Cluster 1 participants reported the lowest QoL. CONCLUSION: Cancer supportive care needs among Asian American patients with colorectal, liver, and lung cancer were associated with patient characteristics and QoL. Understanding cancer supportive care needs will inform future interventions to improve care and QoL for Asian American patients with cancer. CLINICALTRIALS: gov Identifier: NCT03867916.

Asian American Women's Experiences of Discrimination and Health Behaviors during the COVID-19 Pandemic.

The COVID-19 pandemic exacerbated racism experienced by Asian Americans, especially women and older individuals. Little is known about how discriminatory experiences during the pandemic have influenced health behaviors among Asian Americans. Between 10/2021 and 6/2022, we surveyed 193 Asian American women in the San Francisco area. Participants were asked to report types of discrimination they experienced since March 2020. We explored bivariable associations of discrimination and changes in health behaviors and healthcare utilization. Most women were Chinese American (75%) and over 45-years-old (87%). The top three discriminatory experiences reported were being treated with less respect (60%), being treated unfairly at restaurants/stores (49%), and people acting as if they are better (47%). Chinese American women (vs. non-Chinese Asian American women) reported higher frequencies of being threatened/harassed (40% vs. 22%). Women who reported any discriminatory experience (vs. none) were more likely to report less physical exercise (42.7% vs. 26.3%) and canceling/rescheduling medical appointments (65.0% vs. 45.1%). Our findings begin to elucidate Asian American women's experiences of discrimination since the pandemic and provide evidence of the harmful impacts of anti-Asian racism on health behaviors.

Chemotherapy-related symptoms and exercise adherence in older patients with myeloid neoplasms.

PURPOSE: Exercise may ameliorate treatment-related symptoms, but older adults have lower exercise adherence compared to their younger counterparts due to treatment-related symptoms. METHODS: We recruited older patients with myeloid neoplasms receiving chemotherapy to a pilot study of a mobile health exercise intervention. Participants entered their steps and resistance data into the app daily, and symptom data twice a week, over an 8-12 week period. In this proof-of-concept analysis, we used a linear mixed-effects model to assess the association of symptoms from the previous week with exercise adherence in the current week among older adults with myeloid neoplasms. RESULTS: Mean age was 74.3 (SD = 5.0) years (N = 7). At baseline, patients on average walked 2564 daily steps (SD = 1816), which increased to 2967 (SD = 3448) post-intervention. Patients on average performed 3.5 (SD = 2.6) days of resistance training weekly, with mean duration of 21.5 min (SD = 11.6) and rated perceived exertion of 3.68 (SD = 1.78) on a 0-10 scale. Lower average steps in the current week was associated with greater interference with daily activities from pain (ß = - 203.13, p = 0.05), memory (ß = - 492.29, p = 0.09), numbness (ß = - 353.57, p = 0.07), and sadness (ß = - 403.03, p = 0.09) in the previous week. Similarly, lower average resistance minutes in the current week were associated with greater pain, sadness, and anxiety in the previous week. CONCLUSIONS: We found that greater pain, sadness, and anxiety were associated with lower exercise adherence. Symptom monitoring and management in older adults with myeloid neoplasms receiving chemotherapy can promote exercise adherence and in turn improve symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04035499. Registered 7/29/2019.

Disparities in cancer incidence by rurality in California.

BACKGROUND: Cancer rates in rural areas across the United States have different patterns than in urban areas. This study examines associations between rurality and incidence for the top 5 cancers in California and evaluates whether these associations vary jointly by sex, race, and ethnicity. METHODS: We used 2015-2019 California Cancer Registry data to compare incidence rate ratios (IRRs) and trends for breast, prostate, lung, colorectal, and skin (melanoma) cancers. We leveraged census tract aggregation zones and 7 levels of percentage rural population (0%, >0% to <10%, 10% to <20%, 20% to <30%, 30% to <40%, 40% to <50%, and 50+%). RESULTS: Zones with higher proportions of rural population were significantly associated with lower incidence of female breast cancer and prostate cancer, though the trends were not statistically significant overall. Zones with higher proportions of rural population were significantly associated with higher incidence of lung cancer and melanoma. There were no statistically significant trends for colorectal cancer overall. Comparing areas with 50% and over rural population with areas with 0% rural population, the IRR for lung cancer in Hispanic females was higher (IRR = 1.43, 95% confidence interval [CI] = 1.17 to 1.74) than in Hispanic males (IRR = 0.90, 95% CI = 0.72 to 1.11). Also, in areas with 50% or more rural population, the IRR for melanoma was higher in Hispanic females (IRR = 1.75, 95% CI = 1.23 to 2.45) than non-Hispanic White females (IRR = 0.87, 95% CI = 0.80 to 0.95). CONCLUSIONS: Our findings show that rurality is associated with cancer incidence and underscore the importance of jointly examining rural disparities with sex, race, and ethnicity by cancer site.

Neighborhood Factors Associated with COVID-19 Cases in California.

BACKGROUND: There is a need to assess neighborhood-level factors driving COVID-19 disparities across racial and ethnic groups. OBJECTIVE: To use census tract-level data to investigate neighborhood-level factors contributing to racial and ethnic group-specific COVID-19 case rates in California. DESIGN: Quasi-Poisson generalized linear models were used to identify neighborhood-level factors associated with COVID-19 cases. In separate sequential models for Hispanic, Black, and Asian, we characterized the associations between neighborhood factors on neighborhood COVID-19 cases. Subanalyses were conducted on neighborhoods with majority Hispanic, Black, and Asian residents to identify factors that might be unique to these neighborhoods. Geographically weighted regression using a quasi-Poisson model was conducted to identify regional differences. MAIN MEASURES: All COVID-19 cases and tests reported through January 31, 2021, to the California Department of Public Health. Neighborhood-level data from census tracts were obtained from American Community Survey 5-year estimates (2015-2019), United States Census (2010), and United States Department of Housing and Urban Development. KEY RESULTS: The neighborhood factors associated with COVID-19 case rate were racial and ethnic composition, age, limited English proficiency (LEP), income, household size, and population density. LEP had the largest influence on the positive association between proportion of Hispanic residents and COVID-19 cases (- 2.1% change). This was also true for proportion of Asian residents (- 1.8% change), but not for the proportion of Black residents (- 0.1% change). The influence of LEP was strongest in areas of the Bay Area, Los Angeles, and San Diego. CONCLUSION: Neighborhood-level contextual drivers of COVID-19 burden differ across racial and ethnic groups.

Patient-reported supportive care needs among Asian American cancer patients.

PURPOSE: Cancer is the leading cause of death for Asian Americans. However, few studies have documented supportive care needs from the perspective of Asian American cancer patients. This study describes the needs reported by Asian American patients with colorectal, liver, or lung cancer over a 6-month period during their treatment. METHODS: Participants were recruited through the Greater Bay Area Cancer Registry and from cancer care providers in San Francisco. Participants self-identified as Asian or Asian American; were age 21 or older; spoke English, Chinese, or Vietnamese; and had stage I-III colon, rectum, liver, or lung cancer. Participants were matched with a language concordant patient navigator who provided support during a 6-month period. Needs were assessed by surveys at baseline, 3, and 6 months. RESULTS: Among 24 participants, 58% were 65 years or older, 42% did not complete high school, and 75% had limited English proficiency (LEP). At baseline, the most prevalent needs were cancer information (79%), nutrition and physical activity (67%), language assistance (54%), and daily living (50%). At the 3- and 6-month follow-up surveys, there was a higher reported need for mental health resources and healthcare access among participants. CONCLUSION: In this pilot study of Asian American cancer patients who predominantly had LEP, participants reported many needs, with cancer information and language assistance as the most prominent. The findings highlight the importance of culturally and linguistically appropriate patient navigators in addressing supportive care needs among cancer patients with LEP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03867916.

Preferences and Perceptions of Medical Error Disclosure Among Marginalized Populations: A Narrative Review.

BACKGROUND: Disclosure of medical errors, in which a health care provider informs the patient/family of the error and takes responsibility, is an ethical imperative. Little is known about how medical error disclosure preferences or perceptions may vary for patients who are people of color, are older, or have lower educational attainment. METHODS: The researchers conducted a narrative review on medical errors and disclosure. Included were studies in high-income countries that included a predominantly marginalized population, defined by any one of the following: older age adults (mean age > 65 years); low educational attainment (> 55% of participants with less than a high school education); and/or racial/ethnic minority (< 55% of participants identifying as non-Hispanic white for US studies). RESULTS: The literature search yielded 3,050 articles, resulting in 6 studies included for analysis. Four studies used hypothetical vignettes; 1 used focus groups, and 1 used a survey. Three studies met the marginalized population criteria based on education; 3 met the criteria based on race/ethnicity. No study met the inclusion criteria for age. All 6 articles examined patient preferences for disclosure, and 2 studies also examined patient perceptions of disclosure. Overall, participants preferred that medical errors be disclosed to them. Most of the studies lacked multiple regression analysis to investigate differences in disclosure preferences by race/ethnicity, age, and education. CONCLUSION: Participants from marginalized populations may have similar disclosure preferences to white and highly educated participants. Future studies should aim to examine differences in error disclosure preferences among patients who have experienced adverse events across race/ethnicity, educational attainment, and age.

The role of cysteines in the structure and function of OGG1.

8-Oxoguanine glycosylase (OGG1) is a base excision repair enzyme responsible for the recognition and removal of 8-oxoguanine, a commonly occurring oxidized DNA modification. OGG1 prevents the accumulation of mutations and regulates the transcription of various oxidative stress-response genes. In addition to targeting DNA, oxidative stress can affect proteins like OGG1 itself, specifically at cysteine residues. Previous work has shown that the function of OGG1 is sensitive to oxidants, with the cysteine residues of OGG1 being the most likely site of oxidation. Due to the integral role of OGG1 in maintaining cellular homeostasis under oxidative stress, it is important to understand the effect of oxidants on OGG1 and the role of cysteines in its structure and function. In this study, we investigate the role of the cysteine residues in the function of OGG1 by mutating and characterizing each cysteine residue. Our results indicate that the cysteines in OGG1 fall into four functional categories: those that are necessary for (1) glycosylase activity (C146 and C255), (2) lyase activity (C140S, C163, C241, and C253), and (3) structural stability (C253) and (4) those with no known function (C28 and C75). These results suggest that under conditions of oxidative stress, cysteine can be targeted for modifications, thus altering the response of OGG1 and affecting its downstream cellular functions.