Beyond opioid prescribing:Evaluation of a substance use disorder curriculum for OBGYN residents

Objective Amidst the current opioid crisis, there is a need for better integration of substance use disorder screening and treatment across specialties. However, there is no consensus regarding how to best instruct OBGYN trainees in the clinical skills related to opioid and other substance use disorders (SUD). Study objectives were (1) to assess the effectiveness a SUD curriculum to improve self-reported competence among OBGYN residents and (2) to explore its effectiveness to improve attending evaluations of residents clinical skills as well as its feasibility and acceptability from the resident perspective. Methods A pilot 3-session curriculum was developed and adapted to SUD screening and treatment which included readings, didactics, and supervised outpatient clinical experiences for OBGYN post-graduate year 1 (PGY-1) residents rotating through an integrated OBGYNSUD clinic. Eighteen residents completed pre and post clinical skills self-Assessments (SUD screening, counseling, referring, Motivational Interviewing) using an adapted Zwisch Rating Scale (range 1 5). Scores were compared between time points using paired t-Tests. Subsamples also (a) were evaluated by the attending on three relevant Accreditation Council for Graduate Medical Education Milestones (ACGME) milestone sets using the web-based feedback program, myTIPreport (n = 10) and (b) completed a qualitative interview (n = 4). Results All PGY-1s (18/18) across three academic years completed the 3-session SUD curriculum. Clinical skill self-Assessments improved significantly in all areas [SUD Screening (2.44 (0.98) vs 3.56 (0.62), p = 0.01); Counseling (1.81 (0.71) vs 3.56 (0.51), p = .01; Referring (2.03 (0.74) vs 3.17 (0.71), p = .01; Motivational Interviewing (1.94 (1.06) vs 3.33 (0.69), p = .01)]. Milestone set levels assigned by attending evaluations (n = 10) also improved. Qualitative data (n = 4) revealed high acceptability; all curriculum components were viewed positively, and feedback was provided (e.g., desire for more patient exposures). Conclusion A pilot SUD curriculum tailored for OBGYN PGY-1 residents that goes beyond opioid prescribing to encompass SUD management is feasible, acceptable and likely effective at improving SUD core clinical skills.</p

Beyond opioid prescribing:Evaluation of a substance use disorder curriculum for OBGYN residents

Objective Amidst the current opioid crisis, there is a need for better integration of substance use disorder screening and treatment across specialties. However, there is no consensus regarding how to best instruct OBGYN trainees in the clinical skills related to opioid and other substance use disorders (SUD). Study objectives were (1) to assess the effectiveness a SUD curriculum to improve self-reported competence among OBGYN residents and (2) to explore its effectiveness to improve attending evaluations of residents clinical skills as well as its feasibility and acceptability from the resident perspective. Methods A pilot 3-session curriculum was developed and adapted to SUD screening and treatment which included readings, didactics, and supervised outpatient clinical experiences for OBGYN post-graduate year 1 (PGY-1) residents rotating through an integrated OBGYNSUD clinic. Eighteen residents completed pre and post clinical skills self-Assessments (SUD screening, counseling, referring, Motivational Interviewing) using an adapted Zwisch Rating Scale (range 1 5). Scores were compared between time points using paired t-Tests. Subsamples also (a) were evaluated by the attending on three relevant Accreditation Council for Graduate Medical Education Milestones (ACGME) milestone sets using the web-based feedback program, myTIPreport (n = 10) and (b) completed a qualitative interview (n = 4). Results All PGY-1s (18/18) across three academic years completed the 3-session SUD curriculum. Clinical skill self-Assessments improved significantly in all areas [SUD Screening (2.44 (0.98) vs 3.56 (0.62), p = 0.01); Counseling (1.81 (0.71) vs 3.56 (0.51), p = .01; Referring (2.03 (0.74) vs 3.17 (0.71), p = .01; Motivational Interviewing (1.94 (1.06) vs 3.33 (0.69), p = .01)]. Milestone set levels assigned by attending evaluations (n = 10) also improved. Qualitative data (n = 4) revealed high acceptability; all curriculum components were viewed positively, and feedback was provided (e.g., desire for more patient exposures). Conclusion A pilot SUD curriculum tailored for OBGYN PGY-1 residents that goes beyond opioid prescribing to encompass SUD management is feasible, acceptable and likely effective at improving SUD core clinical skills.</p

Assessment of the Validity of Reported Antibiotic Allergic Reactions in Pediatric Patients

Study Objective. To determine whether a reported antibiotic allergy was likely to have been immunologically mediated. Design. Questionnaire-based study. Setting. Tertiary care, freestanding children\u27s hospital. Patients. One hundred patients aged 1 month-18 years for whom guardians reported an allergy to an antibiotic at the time of hospital admission between October 2009 and March 2010. Intervention. Guardians of the patients were interviewed by using a standardized allergy assessment questionnaire. Measurements and Main Results. Based on answers to the questionnaire, the reported allergic reactions were categorized to determine if they were true allergies or adverse reactions. Among the 100 patients, reported allergies were categorized as immunologically mediated reactions in 58%, non-immunologically mediated adverse drug reactions in 27%, no reaction in 3%, and unknown in 12%. Reactions to penicillins, cephalosporins, or sulfonamides were reported most frequently and were attributed to immunologically mediated reactions in 68% (26/38), 74% (17/23), and 67% (10/15) of instances, respectively. Conclusion. Use of the allergy assessment questionnaire determined that 58% of the 100 reported antibiotic allergies fulfilled criteria for an immunologically mediated reaction. These findings underscore the utility of an allergy assessment questionnaire, versus a simple drug history, in improving the accuracy of reported antibiotic reactions

The effect of metabolic phenotype on sociability and social group size preference in a coral reef fish

Although individuals within social groups experience reduced predation risk and find food patches more consistently, there can be competition for food among groupmates. Individuals with a higher standard metabolic rate (SMR) may be less social, to prioritize food acquisition over defense, while a greater maximum metabolic rate (MMR) may modulate sociability through increased competitive ability. Therefore, in theory, individuals with a higher SMR may prefer smaller groups and those with greater MMR may prefer larger groups. We examined links among metabolic phenotype, sociability, and choice of group size in the redbelly yellowtail fusilier Caesio cuning. Individuals were exposed to three association tests: (a) a choice between two fish or zero fish; (b) a choice between five fish or zero fish; and (c) a choice between two fish and five fish. The first two tests quantified sociability while the third measured relative group size choice. Although there was no link between SMR and sociability, fish with a higher MMR were more social than those individuals with a lower MMR. While no correlation was found between MMR and group size choice, there was weak evidence that, if anything, individuals with a higher SMR preferred larger groups, contrary to our hypothesis. As C. cuning is an active fish that spends a large proportion of time operating above SMR, this result could suggest that the links between sociability and SMR may shift depending on a species’ routine behavior. Links between sociability and MMR may arise if competitive ability allows individuals to obtain resources within groups. Although metabolic traits had no significant influence on group size choice, variation in food availability or predation risk could alter the effects of metabolism on group size choice

The Circadian Clock Protein BMAL1 Acts as a Metabolic Sensor In Macrophages to Control the Production of Pro IL-1β

The transcription factor BMAL1 is a clock protein that generates daily or circadian rhythms in physiological functions including the inflammatory response of macrophages. Intracellular metabolic pathways direct the macrophage inflammatory response, however whether the clock is impacting intracellular metabolism to direct this response is unclear. Specific metabolic reprogramming of macrophages controls the production of the potent pro-inflammatory cytokine IL-1β. We now describe that the macrophage molecular clock, through Bmal1, regulates the uptake of glucose, its flux through glycolysis and the Krebs cycle, including the production of the metabolite succinate to drive Il-1β production. We further demonstrate that BMAL1 modulates the level and localisation of the glycolytic enzyme PKM2, which in turn activates STAT3 to further drive Il-1β mRNA expression. Overall, this work demonstrates that BMAL1 is a key metabolic sensor in macrophages, and its deficiency leads to a metabolic shift of enhanced glycolysis and mitochondrial respiration, leading to a heightened pro-inflammatory state. These data provide insight into the control of macrophage driven inflammation by the molecular clock, and the potential for time-based therapeutics against a range of chronic inflammatory diseases

Inhalation of Ultrafine Particles Alters Blood Leukocyte Expression of Adhesion Molecules in Humans

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter ~ 25 nm, geometric standard deviation ~ 1.6), for 2 hr, in three separate protocols: 10 μg/m(3) at rest, 10 and 25 μg/m(3) with exercise, and 50 μg/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 μg/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 μg/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed

Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading of the Failing Human Heart: Implications for Cardiac Reloading and Conditioning

This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF) in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD) implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The increased pyruvate was not directed toward the mitochondria and the TCA cycle for complete oxidation, but instead, was mainly converted to cytosolic lactate. Increased nucleotide concentrations were present, potentially indicating increased flux through the pentose phosphate pathway. Evaluation of mitochondrial function and structure revealed a lack of post-LVAD improvement in mitochondrial oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic acid content. Finally, post-LVAD unloading, amino acid levels were found to be increased and could represent a compensatory mechanism and an alternative energy source that could fuel the TCA cycle by anaplerosis. In summary, the authors report evidence that LVAD unloading induces glycolysis in concert with pyruvate mitochondrial oxidation mismatch, most likely as a result of persistent mitochondrial dysfunction. These findings suggest that interventions known to improve mitochondrial biogenesis, structure, and function, such as controlled cardiac reloading and conditioning, warrant further investigation to enhance unloading-induced reverse remodeling and cardiac recovery

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG):Protocol for an exposure-based cohort study in the UK

INTRODUCTION: Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP. METHODS AND ANALYSIS: PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother-infant dyads comprising 200 preterm births (gestational age, GA &lt;32 weeks, exposed) and 100 term births (GA &gt;37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database. ETHICS AND DISSEMINATION: A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog)

Redox regulation of Rac1 by thiol oxidation

The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange. Herein, we show that Rac1 contains a redox-sensitive cysteine (Cys18) that can be selectively oxidized at physiological pH because of its lowered pKa. Consistent with these observations, we show that Rac1 is glutathiolated in primary chondrocytes. Oxidation of Cys18 by glutathione greatly perturbs Rac1 guanine nucleotide binding and promotes nucleotide exchange. As aspartate substitutions have been previously used to mimic cysteine oxidation, we characterized the biochemical properties of Rac1C18D. We also evaluated Rac1C18S as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1WT but is resistant to thiol oxidation. In addition, Rac1C18D, but not Rac1C18S, shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1C18D in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1C18D in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1WT and the redox-insensitive Rac1C18S variant. Moreover, expression of Rac1C18D in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys18 is a novel posttranslational modification that upregulates Rac1 activity

MFA12 (MFA 2012)

Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum May 4-Aug. 6, 2012. Contents include Introduction / Buzz Spector -- Think, make, show and tell / Patricia Olynyk -- Ifeoma Ugonnwa Anyaeji -- J.E. Baker / Elissa Yukiko Weichbrodt -- Natalie Baldeon / Emily Hanson -- As in a turning gear : E. Thurston Belmer / Rickey Laurentiis -- Lauren Cardenas / Nicholas Tamarkin -- Megan Sue Collins / Catherine Chiodo -- Adrian Cox -- Maya Durham / Dolly Laninga -- Erin Falker / Melissa Olson -- St. Louis dreamscape : Jieun Kim / Caitlin Tyler -- Howard Krohn -- Scape : Robert Long / Robert Whitehead -- Marie Bannerot McInerney / Elissa Yukiko Weichbrodt -- Ghost : Nikki McMahan / Rickey Laurentiis -- Michael T. Meier -- Katie Millitzer -- Reid G. Norris / Ross Rader -- Kathleen Perniciaro / Melissa Olson -- Emily Squires / Nicholas Tamarkin -- Jamie Presson Wells -- Whitney Lorene Wood / Reid G. Norris -- Andrew Woodard -- Kelly K. Wright -- Contributors -- About the Sam Fox School.https://openscholarship.wustl.edu/books/1003/thumbnail.jp