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.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

One in six nursing home residents and staff with positive SARS-CoV-2 tests ≥90 days after initial infection had specimen cycle thresholds (Ct) <30. Individuals with specimen Ct<30 were more likely to report symptoms but were not different from individuals with high Ct value specimens by other clinical and testing data.

The main objective of this study was to investigate the relationships between motivation and readiness levels for physical activity and exercise behaviour among persons with chronic musculoskeletal pain. Participants were 211 U.S. adults with chronic musculoskeletal pain from online support groups as well as specialty and primary care clinics (females = 86.7%; mean age = 43.4 years, SD = 14.4 years). The participants completed an online survey on their engagement in physical activity and exercise behaviour. Multiple one-way analyses of variance with post-hoc comparisons using the Tukey HSD test revealed significant differences between the readiness stages of change groups of preintenders, intenders, and actors in their motivation for physical activity and exercise behaviour. Specifically, the actor group of behavioural change reported higher levels of motivation beliefs for physical activity and exercise behaviour compared to preintenders and intenders. These findings suggest that people with chronic musculoskeletal pain experiencing increased motivation for physical activity and exercise behaviour are more engaged in desired behaviours than the persons with chronic pain reporting varying degrees of behavioural intentions.

Finch trichomonosis, caused by Trichomonas gallinae, emerged in the Canadian Maritime provinces in 2007 and has since caused ongoing mortality in regional purple finch (Carpodacus purpureus) and American goldfinch (Carduelis tristis) populations. Trichomonas gallinae was isolated from (1) finches and rock pigeons (Columbia livia) submitted for post-mortem or live-captured at bird feeding sites experiencing trichomonosis mortality; (2) bird seed at these same sites; and (3) rock pigeons live-captured at known roosts or humanely killed. Isolates were characterized using internal transcribed spacer (ITS) region and iron hydrogenase (Fe-hyd) gene sequences. Two distinct ITS types were found. Type A was identical to the UK finch epidemic strain and was isolated from finches and a rock pigeon with trichomonosis; apparently healthy rock pigeons and finches; and bird seed at an outbreak site. Type B was obtained from apparently healthy rock pigeons. Fe-hyd sequencing revealed six distinct subtypes. The predominant subtype in both finches and the rock pigeon with trichomonosis was identical to the UK finch epidemic strain A1. Single nucleotide polymorphisms in Fe-hyd sequences suggest there is fine-scale variation amongst isolates and that finch trichomonosis emergence in this region may not have been caused by a single spill-over event.

The present study used a systematic review approach to identify relevant randomised control trials (RCT) with vitamin D and then apply meta-regression to explore the most appropriate model of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) relationship to underpin setting reference intake values. Methods included an updated structured search on Ovid MEDLINE; rigorous inclusion/exclusion criteria; data extraction; and meta-regression (using different model constructs). In particular, priority was given to data from winter-based RCT performed at latitudes >49·5°N (n 12). A combined weighted linear model meta-regression analyses of natural log (Ln) total vitamin D intake (i.e. diet and supplemental vitamin D) v. achieved serum 25(OH)D in winter (that used by the North American Dietary Reference Intake Committee) produced a curvilinear relationship (mean (95 % lower CI) serum 25(OH)D (nmol/l) = 9·2 (8·5) Ln (total vitamin D)). Use of non-transformed total vitamin D intake data (maximum 1400 IU/d; 35 μg/d) provided for a more linear relationship (mean serum 25(OH)D (nmol/l) = 0·044 × (total vitamin D)+33·035). Although inputting an intake of 600 IU/d (i.e. the RDA) into the 95 % lower CI curvilinear and linear models predicted a serum 25(OH)D of 54·4 and 55·2 nmol/l, respectively, the total vitamin D intake that would achieve 50 (and 40) nmol/l serum 25(OH)D was 359 (111) and 480 (260) IU/d, respectively. Inclusion of 95 % range in the model to account for inter-individual variability increased the predicted intake of vitamin D needed to maintain serum 25(OH)D ≥ 50 nmol/l to 930 IU/d. The model used to describe the vitamin D intake–status relationship needs to be considered carefully when setting new reference intake values in the Europe.

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experience in utero growth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19–50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (−0·53mmol/l per kg (95% CI −0·97, −0·09), P=0·02 and −0·39mmol/l per kg (95% CI −0·76, −0·02), P=0·04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that the in utero growth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.

Why photoreceptors turn over a portion of their photoreceptive membrane daily is not clear; however, failure to do so properly leads to retinal degeneration in vertebrates and invertebrates. Little is known about the molecular mechanisms that regulate shedding and renewal of photoreceptive membrane. Photoreceptor cells in the lateral eye of the horseshoe crab Limulus turn over their photoreceptive membrane (rhabdom) in a brief, synchronous burst in response to dawn each morning. Transient rhabdom shedding (TRS), the first phase of rhabdom turnover in Limulus, is triggered by dawn, but requires a minimum of 3–5 h of overnight priming from the central circadian clock (Chamberlain & Barlow, 1984). We determined previously that the clock primes the lateral eye for TRS using the neurotransmitter octopamine (OA) (Khadilkar et al., 2002), and report here that OA primes the eye for TRS through a Gs-coupled, adenylate cyclase (AC)/cyclic adenosine 3′,5′-monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) signaling cascade. Long-term intraretinal injections (6–7 h @ 1.4 μl/min) of the AC activator forskolin, or the cAMP analogs Sp-cAMP[S] and 8-Br-cAMP primed the retina for TRS in eyes disconnected from the circadian clock, and/or in intact eyes during the day when the clock is quiescent. This suggests that OA primes the eye for TRS by stimulating an AC-mediated rise in intracellular cAMP concentration ([cAMP]i). Co-injection of SQ 22,536, an AC inhibitor, or the PKA inhibitors H-89 and PKI (14-22) with OA effectively antagonized octopaminergic priming by reducing the number of photoreceptors primed for TRS and the amount of rhabdom shed by those photoreceptors compared with eyes treated with OA alone. Our data suggest that OA primes the lateral eye for TRS in part through long-term phosphorylation of a PKA substrate.