Stress and diabetes coexist in a vicious cycle. Different types of stress lead to diabetes, while diabetes itself is a major life stressor. This was the focus of the Chicago Biomedical Consortium’s 19th annual symposium, “Stress and Human Health: Diabetes,” in November 2022. There, researchers primarily from the Chicago area met to explore how different sources of stress – from the cells to the community – impact diabetes outcomes. Presenters discussed the consequences of stress arising from mutant proteins, obesity, sleep disturbances, environmental pollutants, COVID-19, and racial and socioeconomic disparities. This symposium showcased the latest diabetes research and highlighted promising new treatment approaches for mitigating stress in diabetes.

OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.

Stratigraphic records extending to Marine Oxygen Isotope Stage (MIS) 3 (57,000–29,000 cal yr BP) or older in Beringia are extremely rare. Three stratigraphic sections in interior western Alaska show near continuous sedimentological and environmental progressions extending from at least MIS 3, if not older, through MIS 1 (14,000 cal yr BP–present). The Kolmakof, Sue Creek, and VABM (vertical angle bench mark) Kuskokwim sections along the central Kuskokwim River, once a highland landscape at the fringe of central and eastern Beringia, contain aeolian deposition and soil sequences dating beyond 50,000 14C yr BP. Thick peaty soil, shallow lacustrine, and tephra deposits represent the MIS 3 interstade (or older). Sand sheet and loess deposits, wedge cast development, and very thin soil development mark the later MIS 3 period and the transition into the MIS 2 stade (29,000–14,000 cal yr BP). Loess accumulation with thicker soil development occurred between ~16,000–13,500 cal yr BP at the MIS 2 and MIS 1 transition. After ~13,500 cal yr BP, loess accumulation waned and peat development increased throughout MIS 1. These stratigraphic sequences represent transitions between a warm and moist period during MIS 3, to a cooler and more arid period during MIS 2, then a return to warmer and moister climates in MIS 1.

In this paper, we ask whether or not we can afford to realize the potential benefits of genetic testing as a screening tool for adoptees. Our method is to provide reasonable cost and savings estimates. We argue that the prospect of cost neutrality should be sufficient to explore the targeted screening for a population who will otherwise suffer an avoidable health disparity in access to inherited disease information. Our goal here is to establish that the investment needed to attain these benefits is not beyond our means.

Traditional ambulatory rhythm monitoring in children can have limitations, including cumbersome leads and limited monitoring duration. The ZioTM patch ambulatory monitor is a small, adhesive, single-channel rhythm monitor that can be worn up to 2 weeks. In this study, we present a retrospective cross-sectional analysis of the ZioTM monitor’s impact in clinical practice. Patients aged 0–18 years were included in the study. A total of 373 studies were reviewed in 332 patients. In all, 28.4% had structural heart disease, and 16.9% had a prior surgical, catheterisation, or electrophysiology procedure. The most common indication for monitoring was tachypalpitations (41%); 93.5% of these patients had their symptoms captured during the study window. The median duration of monitoring was 5 days. Overall, 5.1% of ZioTM monitoring identified arrhythmias requiring new intervention or increased medical management; 4.0% identified arrhythmias requiring increased clinical surveillance. The remainder had either normal-variant rhythm or minor rhythm findings requiring no change in management. For patients with tachypalpitations and no structural heart disease, 13.2% had pathological arrhythmias, but 72.9% had normal-variant rhythm during symptoms, allowing discharge from cardiology care. Notably, for patients with findings requiring intervention or increased surveillance, 56% had findings first identified beyond 24 hours, and only 62% were patient-triggered findings. Seven studies (1.9%) were associated with complications or patient intolerance. The ZioTM is a well-tolerated device that may improve what traditional Holter and event monitoring would detect in paediatric cardiology patients. This study shows a positive clinical impact on the management of patients within a paediatric cardiology practice.

Late prehistoric archaeological research in Myanmar is in a phase of rapid expansion. Recent work by the Mission Archéologique Française au Myanmar aims to establish a reliable Neolithic to Iron Age culture-historical sequence, which can then be compared to surrounding regions of Southeast Asia. Excavations at Nyaung'gan and Oakaie in central Myanmar have provided 52 new AMS dates, which allow the creation of Myanmar's first reliable prehistoric radiometric chronology. They have also identified the Neolithic to Bronze Age transition in central Myanmar, which is of critical importance in understanding long-range interactions at the national, regional and inter-regional level. This research provides the first significant step towards placing late prehistoric Myanmar in its global context.

We previously demonstrated an abnormally high right ventricular systolic pressure response to exercise in 50% of adolescents operated on for isolated ventricular septal defect. The present study investigated the prevalence of abnormal right ventricular systolic pressure response in 20 adult (age 30–45 years) patients who underwent surgery for early ventricular septal defect closure and its association with impaired ventricular function, pulmonary function, or exercise capacity. The patients underwent cardiopulmonary tests, including exercise stress echocardiography. Five of 19 patients (26%) presented an abnormal right ventricular systolic pressure response to exercise ⩾ 52 mmHg. Right ventricular systolic function was mixed, with normal tricuspid annular plane systolic excursion and fractional area change, but abnormal tricuspid annular systolic motion velocity (median 6.7 cm/second) and isovolumetric acceleration (median 0.8 m/second2). Left ventricular systolic and diastolic function was normal at rest as measured by the peak systolic velocity of the lateral wall and isovolumic acceleration, early diastolic velocity, and ratio of early diastolic flow to tissue velocity, except for ejection fraction (median 53%). The myocardial performance index was abnormal for both the left and right ventricle. Peak oxygen uptake was normal (mean z score −0.4, 95% CI −2.8–0.3). There was no association between an abnormal right ventricular systolic pressure response during exercise and right or left ventricular function, pulmonary function, or exercise capacity. Abnormal right ventricular pressure response is not more frequent in adult patients compared with adolescents. This does not support the theory of progressive pulmonary vascular disease following closure of left-to-right shunts.

Field plot experiments were conducted to examine the interactions between tall fescue grass (Festuca arundinacea Schreb.), musk thistle (Carduus nutans L. = thoermeri Weinmann # CRUNU), and two thistle weevils Trichosirocalus horridus (Panzer) and Rhinocyllus conicus Froelich. Restriction of musk thistle growth was greatest when the weevils were allowed to feed on the musk thistles competing with tall fescue. Significant reductions were found in total musk thistle seeds per plant, root weight, flower buds per plant, stem dry weight, seeds per head, root crown diameter, stem height, rosette diameter, and head diameter. Seed weight and viability were not reduced. Of the three stress factors (tall fescue and the two Carduus thistle weevils), tall fescue had the greatest impact. When musk thistle seeds were planted in 1-yr-old tall fescue, germination was low. Seeds that germinated did not grow more than four Leaves and none of the thistles developed to the reproductive stage. A 1-year-old tall fescue stand effectively prevented musk thistle reproduction. Thus, tall fescue helped suppress musk thistle growth more quickly than the use of Carduus thistle weevils alone without competitive vegetation. Dry weight of tall fescue grass was lower in musk thistle-infested plots than in the thistle-free plots.

In spring 2013 the American College of Medical Genetics and Genomics (ACMG) Working Group on Incidental Findings in Clinical Exome and Genome Sequencing (hereafter “Working Group”) released a report of “Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” the culmination of a three-year long consensus project. The Working Group recommended that a number of incidental findings, which they define as “the results of a deliberate search for pathogenic or likely pathogenic alterations in genes that are not apparently relevant to a diagnostic indication for which the sequencing test was ordered,” be returned to clinicians (and patients) independent of patient preferences. The Working Group recognized that their recommendations may violate existing ethical norms, but believe this is justified by a fiduciary duty on the part of clinicians and laboratory personnel to prevent harm by warning patients about certain findings, a duty they claim “supersedes concerns about autonomy.”