Investigating Risk Factors for Pediatric Opioid Morbidity and Mortality

Young children are sometimes prescribed opioids and may be exposed to opioids in utero and through breast milk. Clinical and genetic factors create large inter- individual variability in opioid response and have been associated with life threatening and often fatal adverse drug reactions in young children. Genetic factors have been studied in adults but there is little clinical evidence in young children. The focus of this thesis is on three commonly prescribed opioids: codeine, morphine and methadone. The objective of this work was to investigate risk factors associated with opioid related morbidity and mortality in young children. Risk factors were examined in three populations of children including neonates exposed to opioids in utero, infants exposed to codeine in breast milk as well as young children receiving codeine and morphine for post-surgical pain relief. We hypothesize that genetics and clinical factors will affect opioid response in young children. As the prevalence of opioid use increases it is important to investigate clinical and genetic risk factors as well as cost-effective treatment options. Neonates exposed to opioids in utero do not show an increased risk for mortality. Genetics may play a role in the development of neonatal withdrawal symptoms following in utero methadone exposure. Further work is necessary in order to corroborate the role of genetic and clinical factors in predicting neonatal abstinence syndrome. Codeine use during lactation has been shown to result in a significant neonatal sedation, much of which was associated with maternal genotype and dose. Guidelines based on predetermined clinical risk factors were able to mitigate the previously identified increased genetic risk. Several fatalities have been reported following codeine use in children post-tonsillectomy. In a randomized clinical trial we found that standard morphine doses (0.2-0.5mg/kg) may not be a safe alternative in children with obstructive sleep apnea. The safety and effectiveness of lower morphine doses should be investigated. Genetic variability in drug metabolizing enzymes, drug transporters and receptors, influence opioid response and create risks for adverse effects in young children. Standard doses of opioids are not safe in all children, and should be dosed on an individual basis

Peer Mentoring in an Entry-Level Occupational Therapy Program: Student Experiences During the COVID-19 Pandemic

Background: The COVID-19 pandemic has had significant impacts on education. During this time, educators were tasked to develop creative and new ways to engage and teach students. Mentoring has been shown to positively impact academic and psychosocial outcomes and can enhance clinical skills in both in-person and e-learning environments. However, there is need for further research on peer mentoring programs in occupational therapy curriculum. Method: This retrospective qualitative study investigates the effects of peer mentoring on student perceptions of learning and professional development. Experiences were tracked for three semesters during the pandemic at an accredited entry-level occupational therapy program in the US. The students answered two to three questions at the end of each semester; qualitative analysis followed. Results: Twenty-six to 28 students consented each semester. Positive experiences, improved communication, and professional skills were reported. Most of the students felt peer mentoring enhanced learning, reduced stress, and fostered comradery. Collaborative partnership was preferred, and the students often asked for more structured faculty support. Discussion: The results are consistent with current evidence and confirm use of mentoring in entry-level occupational therapy programs may be beneficial even in adapted learning environments. This study gives insight to learning during a global pandemic and provides guidance for post pandemic pedagogical design

Peer Mentoring in an Entry-Level Occupational Therapy Program: Student Experiences During the COVID-19 Pandemic

Background: The COVID-19 pandemic has had significant impacts on education. During this time, educators were tasked to develop creative and new ways to engage and teach students. Mentoring has been shown to positively impact academic and psychosocial outcomes and can enhance clinical skills in both in-person and e-learning environments. However, there is need for further research on peer mentoring programs in occupational therapy curriculum. Method: This retrospective qualitative study investigates the effects of peer mentoring on student perceptions of learning and professional development. Experiences were tracked for three semesters during the pandemic at an accredited entry-level occupational therapy program in the US. The students answered two to three questions at the end of each semester; qualitative analysis followed. Results: Twenty-six to 28 students consented each semester. Positive experiences, improved communication, and professional skills were reported. Most of the students felt peer mentoring enhanced learning, reduced stress, and fostered comradery. Collaborative partnership was preferred, and the students often asked for more structured faculty support. Discussion: The results are consistent with current evidence and confirm use of mentoring in entry-level occupational therapy programs may be beneficial even in adapted learning environments. This study gives insight to learning during a global pandemic and provides guidance for post pandemic pedagogical design

Hypervelocity Star Candidates in the SEGUE G & K Dwarf Sample

We present 20 candidate hypervelocity stars from the Sloan Extension for Galactic Understanding and Exploration (SEGUE) G and K dwarf samples. Previous searches for hypervelocity stars have only focused on large radial velocities; in this study we also use proper motions to select the candidates. We determine the hypervelocity likelihood of each candidate by means of Monte Carlo simulations, considering the significant errors often associated with high proper motion stars. We find that nearly half of the candidates exceed their escape velocities with at least 98% probability. Every candidate also has less than a 25% chance of being a high-velocity fluke within the SEGUE sample. Based on orbits calculated using the observed six-dimensional positions and velocities, few, if any, of these candidates originate from the Galactic center. If these candidates are truly hypervelocity stars, they were not ejected by interactions with the Milky Way's supermassive black hole. This calls for a more serious examination of alternative hypervelocity-star ejection scenarios.Comment: 8 pages, 5 figures, published in ApJ, this version includes all figures as intende

ADAD1 and ADAD2, testis-specific adenosine deaminase domain-containing proteins, are required for male fertility.

Adenosine-to-inosine RNA editing, a fundamental RNA modification, is regulated by adenosine deaminase (AD) domain containing proteins. Within the testis, RNA editing is catalyzed by ADARB1 and is regulated in a cell-type dependent manner. This study examined the role of two testis-specific AD domain proteins, ADAD1 and ADAD2, on testis RNA editing and male germ cell differentiation. ADAD1, previously shown to localize to round spermatids, and ADAD2 had distinct localization patterns with ADAD2 expressed predominantly in mid- to late-pachytene spermatocytes suggesting a role for both in meiotic and post-meiotic germ cell RNA editing. AD domain analysis showed the AD domain of both ADADs was likely catalytically inactive, similar to known negative regulators of RNA editing. To assess the impact of Adad mutation on male germ cell RNA editing, CRISPR-induced alleles of each were generated in mouse. Mutation of either Adad resulted in complete male sterility with Adad1 mutants displaying severe teratospermia and Adad2 mutant germ cells unable to progress beyond round spermatid. However, mutation of neither Adad1 nor Adad2 impacted RNA editing efficiency or site selection. Taken together, these results demonstrate ADAD1 and ADAD2 are essential regulators of male germ cell differentiation with molecular functions unrelated to A-to-I RNA editing

The biological reducing agent Oxyrase improves the resuscitation of dormant Mycobacterium smegmatis and Mycobacterium avium subsp. paratuberculosis

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s disease, a chronic intestinal disease of cattle and other ruminants. Diagnostic culture for MAP is typically unrewarding until latter stages of the disease. This may be a consequence of oxidative damage to dormant organisms, which results from culture. The purpose of this investigation was to determine the effect of the commercial reducing agent Oxyrase® for Broth (OB) on the recovery of dormant Mycobacterium smegmatis (MS) and MAP. Dormant organisms were inoculated into medium only or that supplemented with media containing serial dilutions of OB. Growth was monitored by optical density for up to 21 days. Treatment of MAP and MS with OB led to significant increases in recovery and growth yield. However, the concentration of OB necessary to promote recovery was dependent on the number of viable organisms present in seed cultures. Mitigating oxidative damage by using OB can facilitate the recovery of dormant mycobacteria. Whether this is a direct or indirect effect has yet to be be established

A Comparison of Homemade Phantoms for Ultrasound Guided Peripheral Intravenous Catheter Insertion

Purpose: Ultrasound (U/S) guided peripheral intravenous catheter (PIV) placement is implemented in clinical settings across the medical field, with evidence supporting the use of point-of-care U/S as a procedural tool to improve patient outcomes. Non-commercial vascular access phantoms made of various materials have been described in published literature and online tutorials; however, there has been no comparison of the models. The primary objective of this study is to determine if non-commercial phantoms are useful for the education of U/S guided PIV placement. Methods: This prospective observational study trialed six unique phantom models: 1) the Amini ballistics gel model, 2) the Morrow ballistics gel model, 3) the University of California San Diego (UCSD) gelatin model, 4) the Rippey chicken model, 5) the Nolting spam model, 6) and the Johnson tofu model. Selected phantoms were assembled through instructions from the source reference. Six U/S fellowship trained Emergency Medicine physicians performed U/S guided PIV placement on each model to evaluate their effectiveness pertaining to phantom haptics, echogenicity properties, and utility for PIV practice. Results/ Conclusion: The Rippey model outperformed other models in this study, doing so with a mid-level cost and minimal preparation time. The Rippey model scored highest on aggregate scores pertaining to haptics, echogenicity, and utility for U/S guided PIV placement and comparability to commercial products. Non-commercial U/S phantoms may represent cost-effective and useful PIV insertion educational tools. Future studies should investigate the utility of these phantoms in teaching USIV to novice learners and direct comparison of non-commercial to commercial phantoms