Pharmacogenetics, the study of how interindividual genetic differences affect drug response, does not explain all observed heritable variance in drug response. Epigenetic mechanisms, such as DNA methylation, and histone acetylation may account for some of the unexplained variances. Epigenetic mechanisms modulate gene expression and can be suitable drug targets and can impact the action of nonepigenetic drugs. Pharmacoepigenetics is the field that studies the relationship between epigenetic variability and drug response. Much of this research focuses on compounds targeting epigenetic mechanisms, called epigenetic drugs, which are used to treat cancers, immune disorders, and other diseases. Several studies also suggest an epigenetic role in classical drug response; however, we know little about this area. The amount of information correlating epigenetic biomarkers to molecular datasets has recently expanded due to technological advances, and novel computational approaches have emerged to better identify and predict epigenetic interactions. We propose that the relationship between epigenetics and classical drug response may be examined using data already available by (1) finding regions of epigenetic variance, (2) pinpointing key epigenetic biomarkers within these regions, and (3) mapping these biomarkers to a drug-response phenotype. This approach expands on existing knowledge to generate putative pharmacoepigenetic relationships, which can be tested experimentally. Epigenetic modifications are involved in disease and drug response. Therefore, understanding how epigenetic drivers impact the response to classical drugs is important for improving drug design and administration to better treat disease.

Children who have experienced maltreatment are more likely to have disrupted attachments, fewer psychosocial strengths, and poorer long-term psychosocial outcomes. However, few studies have examined the interplay between attachment security and psychosocial strengths among children involved in therapeutic services in the context of the child welfare system. The present longitudinal study examines the insecure attachment behaviors and psychosocial strengths of 555 children referred to the Therapeutic Family Care program (TFCP) in Cobourg, Ontario between 2000 and 2019. The children were assessed by their caregivers on a regular basis using the Assessment Checklist for Children (ACC) and the complementary strengths-focused ACC+ measure. Average age of children at baseline was 9.57 years (SD = 3.51) and 229 (41.26%) were female. We conducted growth curve and random intercepts cross-lagged panel models to test the longitudinal interplay between insecure attachment behaviors and strengths. Results suggest that females’ attachment security improved, males’ attachment security worsened, and both males and females developed strengths over time. Further, analyses revealed a directional effect, whereby fewer insecure attachment behaviors predicted more psychosocial strengths approximately 6 months later. Implications for attachment-oriented and strengths-based services in the context of child welfare are discussed.

The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention, 1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.

We describe 10 patients with severe coronavirus disease 2019 (COVID-19) who received tocilizumab and dexamethasone. We correlated isolation duration with cycle thresholds (Ct) values of nucleic acid amplification tests, clinical state and viral cultures. Isolation duration exceeded 21 days for 7 patients due to positive viral cultures or Ct values <30.

Dementia is a growing concern in Canada, affecting peoples’ health and raising the cost of care. Between June and October 2019, we conducted an environmental scan to identify primary care models, strategies, and resources for dementia care from 11 pre-selected countries and assess their impact on quality-of-life measures. Search strategies included a rapid scoping review, grey literature search, and discussions with stakeholders. Eighteen primary care-based models of dementia care were identified. Common factors include team-based care, centralized care/case coordination, individual treatment plans, a stepped-care approach, and support for care partners. Five provinces had released a dementia strategy. Evidence of positive outcomes supported primary care-based models for dementia care, although only one model demonstrated evidence of impact on quality of life. Although these findings are encouraging, further research is needed to identify primary care-based models of dementia care that demonstrably improve quality of life for people living with dementia and their care partners.

The objective of this paper was to review the reproductive biology, herbicide-resistant (HR) biotypes, pollen-mediated gene flow (PMGF), and potential for transfer of alleles from HR to herbicide-susceptible grass weeds including barnyardgrass, creeping bentgrass, Italian ryegrass, johnsongrass, rigid (annual) ryegrass, and wild oats. The widespread occurrence of HR grass weeds is at least partly due to PMGF, particularly in obligate outcrossing species such as rigid ryegrass. Creeping bentgrass, a wind-pollinated turfgrass species, can efficiently disseminate herbicide resistance alleles via PMGF and movement of seeds and stolons. The genus Agrostis contains about 200 species, many of which are sexually compatible and produce naturally occurring hybrids and hybrids with species in the genus Polypogon. The self-incompatibility, extremely high outcrossing rate, and wind pollination in Italian ryegrass clearly point to PMGF as a major mechanism by which herbicide resistance alleles can spread across agricultural landscapes, resulting in abundant genetic variation within populations and low genetic differentiation among populations. Italian ryegrass can readily hybridize with perennial ryegrass and rigid ryegrass due to their similarity in chromosome numbers (2n = 14), resulting in interspecific gene exchange. Johnsongrass, barnyardgrass, and wild oats are self-pollinated species, so the potential for PMGF is relatively low and limited to short distances; however, seeds can easily shatter upon maturity before crop harvest, leading to wider dispersal. The occurrence of PMGF in reviewed grass weed species, even at a low rate, is greater than that of spontaneous mutations conferring herbicide resistance in weeds and thus can contribute to the spread of herbicide resistance alleles. This review indicates that the transfer of herbicide resistance alleles occurs under field conditions at varying levels depending on the grass weed species.

ABSTRACT IMPACT: Correctly identifying and documenting patients’ primary care physicians in community hospital settings may improve clinical care and coordination for patients, potentially leading to a reduction in hospitalizations, while simultaneously increasing patient education and expanding the limits of electronic health record systems. OBJECTIVES/GOALS: Clinical research infrastructure can be leveraged to detect inaccuracies in primary care physician (PCP) identification and documentation in a community hospital. As a result, collaboration between clinical research and hospital clinical operations can produce long-term solutions required by patient-centered, learning health care systems. METHODS/STUDY POPULATION: Hospitalized patients at a community hospital were asked to verify the name of their PCP. The PCP name given by the patient was then compared to the PCP on file in the EHR system. A corrected list of PCP names for each patient was sent by a clinical research program to hospital management on a weekly basis and used to update the EHR. RESULTS/ANTICIPATED RESULTS: A total of 272 hospitalized patients were screened on the basis of eligibility and asked to verify their PCP name. Overall, 35.3% (N=96) of patients had incorrectly listed PCPs in the EHR system. DISCUSSION/SIGNIFICANCE OF FINDINGS: Accurate PCP identification processes may enable broader clinical communication and potentially reduce future hospitalizations by improving coordination of care. The benefits of collaboration between research and clinical activities may provide an opportunity to justify greater investment in clinical research in community settings.

In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1

Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta’s transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.

Background: In April 2019, the Georgia Department of Public Health (DPH) initiated whole-genome sequencing (WGS) on NDM-producing Enterobacteriaceae identified since January 2018. The WGS data analyzed at CDC identified related Klebsiella pneumoniae isolates with hypervirulence markers from 2 patients. Carbapenemase-producing hypervirulent K. pneumoniae (CP-hvKP) are rarely reported in the United States, but they can to cause serious, highly resistant, invasive infections. We conducted an investigation to identify cases and prevent spread. Methods: We defined a case as NDM-producing K. pneumoniae with ≥4 hypervirulence markers identified by WGS, isolated from any specimen source from a Georgia patient. We reviewed the case patient’s medical history to identify potentially affected facilities. We also performed PCR-based colonization screening and retrospective and prospective laboratory-based surveillance. Finally, we assessed facility infection control practices. Results: Overall, 7 cases from 3 case patients (A, B, and C) were identified (Fig. 1). The index case specimen was collected from case-patient A at ventilator-capable skilled nursing facility 1 (vSNF1) in May 2018. Case-patient A had been hospitalized for 1 month in India before transfer to the United States. Case-patient B’s initial isolate was collected in January 2019 on admission to vSNF2 from a critical access hospital (CAH). The CAH laboratory retrospectively identified case-patient C, who overlapped with case-patient B at the CAH in October 2018. The CAH and the vSNF2 are geographically distant from vSNF1. Case-patients B and C had no known epidemiologic links to case-patient A. Colonization screening occurred at vSNF1 in May 2018, following detection of NDM-producing K. pneumoniae from case-patient A ∼1 year before determining that the isolate carried hypervirulence markers. Among 30 residents screened, 1 had NDM and several had other carbapenemases. Subsequent screening did not identify additional NDM. Colonization screening of 112 vSNF2 residents and 13 CAH patients in 2019 did not reveal additional case patients; case-patient B resided at vSNF2 at the time of screening and remained colonized. At all 3 facilities, the DPH assessed infection control practices, issued recommendations to resolve lapses, and monitored implementation. The DPH sequenced all 27 Georgia NDM–K. pneumoniae isolates identified since January 2018; all were different multilocus sequence types from the CP-hvKP isolates, and none possessed hypervirulence markers. Conclusions: We hypothesize that CP-hvKP was imported by a patient hospitalized in India and spread to 3 Georgia facilities in 2 distinct geographic regions through indirect patient transfers. Although a response to contain NDM at vSNF1 in 2018 likely limited CP-hvKP transmission, WGS identified hvKP and established the relatedness of isolates from distinct regions, thereby directing the DPH’s additional containment activities to halt transmission.

Funding: None

Disclosures: None