Alternative end-joining (alt-EJ) repair of DNA double-strand breaks is associated with deletions, chromosome translocations, and genome instability. Alt-EJ frequently uses annealing of microhomologous sequences to tether broken ends. When accessible pre-existing microhomologies do not exist, we have postulated that new microhomologies can be created via limited DNA synthesis at secondary-structure forming sequences. This model, called synthesis-dependent microhomology-mediated end joining (SD-MMEJ), predicts that differences between DNA sequences near double-strand breaks should alter repair outcomes in predictable ways. To test this hypothesis, we injected plasmids with sequence variations flanking an I-SceI endonuclease recognition site into I-SceI expressing Drosophila embryos and used Illumina amplicon sequencing to compare repair junctions. As predicted by the model, we found that small changes in sequences near the I-SceI site had major impacts on the spectrum of repair junctions. Bioinformatic analyses suggest that these repair differences arise from transiently forming loops and hairpins within 30 nucleotides of the break. We also obtained evidence for ‘trans SD-MMEJ,’ involving at least two consecutive rounds of microhomology annealing and synthesis across the break site. These results highlight the importance of sequence context for alt-EJ repair and have important implications for genome editing and genome evolution.

Recent and comprehensive research of gout in the Pacific region and Hawai‘i is significantly lacking. This study was conducted to improve the understanding of the healthcare utilization of gout patients within a single health care system in Hawai‘i. The objective was to examine gout inpatient, outpatient and emergency department care within a single health care system in Hawai‘i. This study was a retrospective chart review of patients, ≥ 18 years admitted to three Hawai‘i Pacific Health facilities for a primary diagnosis of gout or rheumatoid arthritis (RA) from 2011 to 2017. Population data for the State of Hawai‘i was used to calculate visit rates per 1,000 Hawai‘i adults. Trend analysis was performed to compare changes over time. We studied gout health care utilization concurrently with RA to provide an internal comparison group for the healthcare utilization patterns of interest. Gout patients were primarily managed in the outpatient setting with high rates of emergency department visits. In contrast, RA patients were primarily managed in the outpatient setting, with low rates of emergency department visits. Both gout and RA patients had low rates of inpatient admissions. The cost of gout emergency department visits was approximately 3.4 times higher than gout outpatient visits. The rates for gout emergency department visits, outpatient visits, inpatients visits, and RA outpatient visits in 2017 were trending downward and significantly changed from 2011 (p <0.05). The rates for RA emergency department visits and inpatient visits were not significantly changed from 2011–2017. Gout care in Hawai‘i remains suboptimal with higher rates of emergency department visits, as compared to RA. Because emergency department visits are associated with higher cost, efforts should be made to reduce these emergency department visits to improve the quality of care.

No abstract

For the past three years, the Saint Louis University American Society for Biochemistry and Molecular Biology (SLU ASBMB) student chapter has planned and held “A Day in the Clinical Laboratory.” We selected 20 sophomore and junior students from local St. Louis high schools to learn about and perform different laboratory techniques in order to complete our designed case study. During the day, we had four lab stations that included hematology, urinalysis, blood bank, and chemistry. The laboratory techniques and case study were challenging in order to allow the students to think critically and to ensure interest in the study. The individual labs were all connected, and it showed how different clinical laboratories are done and how there is a need for collaboration between different departments in order to get a diagnosis for patients. Each group of students had 30 minutes at each station to ensure that they had enough time to complete the task and to ask any questions that they had. The students that came had an interest in science or medicine, and this program allowed them to get early exposure to research, science, technology, engineering, and mathematics fields. The event was free of charge and provided them the opportunity to see the importance in research and allowed them to network with different faculty mentors. Parents and teachers were also invited to attend, and student volunteers led a tour of the University campus facilities. High school students and their parents and teachers had the opportunity to speak with Saint Louis University Doisy College of Health Sciences Faculty on college application advising and additional opportunities available to local students interested in a scientific career. The event was run by SLU ASBMB students. At the end of the day, high school students were surveyed anonymously. All students gave positive feedback, and everyone expressed interest in attending another “A Day in the Clinical Laboratory” event.Support or Funding InformationFinancial support was received from the ASBMB Student Chapter Outreach Grant and the Saint Louis University Student Government Association.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Background: The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study. Methods: The MEC has been following over 215,000 residents of Hawai'i and Los Angeles for the development of cancer and other chronic diseases since 1993-1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity. Results: Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women. Conclusions: This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment. Funding: This research was partially supported by the Omidyar 'Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.

Background:The Coronavirus Disease of 2019 (COVID-19) has impacted the health and day-to-day life of individuals, especially the elderly and people with certain pre-existing medical conditions, including cancer. The purpose of this study was to investigate how COVID-19 impacted access to cancer screenings and treatment, by studying the participants in the Multiethnic Cohort (MEC) study. <br /><br />Methods:The MEC has been following over 215,000 residents of Hawai‘i and Los Angeles for the development of cancer and other chronic diseases since 1993-1996. It includes men and women of five racial and ethnic groups: African American, Japanese American, Latino, Native Hawaiian, and White. In 2020, surviving participants were sent an invitation to complete an online survey on the impact of COVID-19 on their daily life activities, including adherence to cancer screening and treatment. Approximately 7,000 MEC participants responded. A cross-sectional analysis was performed to investigate the relationships between the postponement of regular health care visits and cancer screening procedures or treatment with race and ethnicity, age, education, and comorbidity. <br /><br />Results: Women with more education, women with lung disease, COPD, or asthma, and women and men diagnosed with cancer in the past 5 years were more likely to postpone any cancer screening test/procedure due to the COVID-19 pandemic. Groups less likely to postpone cancer screening included older women compared to younger women and Japanese American men and women compared to White men and women. <br /><br />Conclusions:This study revealed specific associations of race/ethnicity, age, education level, and comorbidities with the cancer-related screening and healthcare of MEC participants during the COVID-19 pandemic. Increased monitoring of patients in high-risk groups for cancer and other diseases is of the utmost importance as the chance of undiagnosed cases or poor prognosis is increased as a result of delayed screening and treatment.<br /><br />Funding:This research was partially supported by the Omidyar 'Ohana Foundation and grant U01 CA164973 from the National Cancer Institute.

Given the current and emerging levels of bacterial resistance to existing antimicrobic agents, evaluative assessment of plant‐derived compounds for antibacterial potential was deemed important and timely. The focus of this research was to determine the effect of phytochemicals on Staphylococcus aureus using the Kirby‐Bauer susceptibility assay, a method widely used in clinical laboratories as standard operating procedure for determination of bacterial susceptibility to antibiotics. Whatman filter disks were saturated with phytochemical and placed onto a Mueller Hinton agar plate swabbed with bacteria using the standard 3‐way streak method. Bacterial plates were incubated and then susceptibility was determined by measurement of resultant zones of inhibition. Antibiotic disks were assessed in parallel with phytochemical‐impregnated disks. The hypothesis was that specific phytochemicals inhibit bacterial growth. S. aureus (n=4 ATCC strains) displayed large zones of inhibition for cinnamaldehyde (31±12 mm: mean±SD), epigallocatechin gallate (14±1 mm) and plumbagin (16±3 mm). Inclusion of cinnamaldehyde, epigallocatechin gallate or plumbagin as anti‐Staphylococcus agents as direct therapeutic agents or as combination treatment strategies with current antimicrobial drugs may offer treatment options for patients with multi‐drug resistant bacterial infections.Support or Funding InformationFinancial support for VPM was received from the DeNardo Education and Research Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

No abstract