bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing Standardized Patient Encounter in Pharmacology Education of Undergraduate Medical Students
Authors: Athauda Gagani , Ottolenghi Joseph , Lupi Carla , Kashan Sanaz , Gray Elizabeth , Stumbar Sarah 
Published: June 2021

Noting a gap in the curriculum, students and faculty at Florida International University (FIU) Herbert Wertheim College of Medicine (HWCOM) created a pre‐recorded lecture and in‐class, interactive Standardized Patient (SP) case on contraceptive pharmacology and risk communication. The lecture focused on mechanisms of action, bioavailability, drug‐drug interaction, effectiveness, and major vascular risks of combined hormonal and progestin‐only contraceptives. The in‐class session integrated knowledge of risks and effectiveness of contraception and basic clinical skills with risk communication surrounding contraceptive counseling.Students watched a 20 minute pre‐recorded lecture before attending a 50‐minute intermediate‐sized group session led by an instructor and involving a SP. Students anonymously and voluntarily completed a 5 question session evaluation, rating their perceived learning impact of module and class session. Students learning was assessed with 5 multiple‐choice questions on the students' pharmacology final exam, taken a week later.Overall, students agreed that the recording helped to prepare them for the session, and that the standardized patient exercise allowed them to apply and solidify their learning. The class average performance on the relevant final exam questions was 77.6%, with better performance on lower order questions derived from the online module. All questions had robust discrimination indices.The lecture and in‐class SP case addressed gaps in the curriculum and provided students the opportunity to integrate multiple domains of learning. Students' perception of the materials was positive and students demonstrated adequate learning. Further work to improve performance at this level and build on learning is underway.Support or Funding InformationThis study was not supported by a grant and has been approved by FIU IRB.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Medical Pharmacology Board Scores Increase With Flipped Classroom and Video Lectures
Authors: Prancan Arthur , Ali Kamilah 
Published: June 2021

Medical Pharmacology, in the second year at Touro College of Osteopathic Medicine in Harlem, New York, beginning in Fall 2008, was offered as a didactic lecture and examination program using a syllabus with course expectations, topics, class schedule and learning objectives as a guide for students. Content was offered in class with PowerPoint presentations, 50 minutes at a time. Attendance varied between 20% and 60% of the class. COMLEX‐USA Level 1 discipline mean scores in pharmacology ranged from 462.22 to 506.95 as reported by NBOME in the period 2010 through 2012. The National Mean covering this period was 515.74. The First Pass rate averaged 82.82% against the National rate which averaged 89.69%In Fall 2012, the course content delivery and access was changed to video recordings of the lectures by faculty. Students accessed course content via a server which housed a library of course topics on video, still according to the syllabus. No classroom lectures were offered, but students were invited to participate in quiz and discussion sessions in the classroom, one hour per week per course. Classroom time was decreased to one‐third. Students now preview the videos and actively participate in the quiz sessions, often covering 2–3 topics in one hour. Discussion of topics among students is encouraged and often becomes very animated and dynamic. Students come to class prepared for quiz and discussion, receive minor credit for the quiz and leave aligned in their understanding of topics. Class attendance is typically 85% and may reach 100%. COMLEX‐USA Level 1 mean discipline scores in pharmacology have improved from 517.56 in 2013 to 600.02 in 2018 against an average National score in Pharmacology of 542.21 over the same period. The First Pass rate has increased from 87.29% in 2013 to a rate of 97.73% in 2018. The mean National First Pass rate for this period is 92.91%The faculty at this medical college are able to provide consistent and regularly improved content presentations via the video lectures while freeing time for scholarly activities. Students manage their study efficiently during time which is free of scheduled lectures and they achieve board scores in the top half of the national scale.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Predicting Impulsivity and Compulsivity in Mice Using a Rapid Drug Abuse Liability Battery (RDALB) Assessing Hyperneophagia, Locomotor Reactivity, and Novelty Preference
Authors: Hyatt William , Berquist Michael , Russell Lauren , Fantegrossi William 
Published: June 2021

Impulsivity and compulsivity are two major biobehavioral contributors to addiction in human and animal models. In preclinical research, assays typically used to measure these variables are often labor intensive and require an extensive training history, so developing inexpensive, high‐throughput procedures that are predictive of drug abuse vulnerability would be a significant advancement. The data presented here will describe a combined battery that concurrently measures baseline hyperneophagia, locomotor reactivity, and novelty preference in a 1‐hour session. All experiments took place in a 3‐compartment spatial conditioning chamber, comprised of two large chambers and a connecting hallway. Video was collected via a cell phone camera and analyzed using Behavior Cloud software that quantified locomotor activity, with each compartment analyzed separately as discrete zones. In the present experiments, 48 drug‐naïve mice were examined using the rapid drug abuse liability battery (RDALB) to profile animals into high‐ and low‐ impulsivity and compulsivity groups, which is hypothesized to inform abuse liability risk. Animals were initially placed in one compartment with the door closed for a 30 minute habituation period. This habituation period was also interpreted as ‘inescapable novelty’ and any locomotor activity observed was classified as locomotor reactivity, which is believed to predict impulsivity. After the habituation period the chamber door was raised, and animals were free to explore all three sections for a second 30 minute period. The time spent in the novel compartment, versus the time spent in the initial compartment, was calculated as novelty preference, which is believed to predict compulsive behaviors. Hyperneophagia was measured as the latency to drink a novel milk solution after emergence from the first chamber. Large individual differences were found between animals within each assay, allowing for separation into discrete phenotypes ‐‐ for instance, the latency for animals to drink milk ranged from 7 seconds to over 21 minutes. No correlations were observed between different behavioral outcomes, indicating that the RDALB is likely measuring distinct impulsive and compulsive phenotypes. Future oral self‐administration experiments are planned to validate the predictive validity of the RDALB.Support or Funding InformationThese studies are supported by DA039195, DA022981 and the UAMS Center for Translational Neuroscience.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dopamine Cell Loss within the Nigrostriatal Pathway Due to Oxidative Stress from Chronic Methylphenidate
Authors: Oakes Hannah Virginia , Hall Alexis , Ensley Tucker , Medlock Kristen , Ketchem Shannon , Pond Brooks 
Published: June 2021

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects 11% of children in the U.S. alone. Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD. MPH acts by blocking dopamine (DA) transporters and norepinephrine (NE) transporters, preventing the reuptake of these catecholamines following release. Many children receive MPH from childhood to early adulthood; yet, most of the scientific literature focuses on understanding short‐term consequences of MPH. As such, it is extremely important to examine the long‐term consequences of MPH exposure. Previous research has shown that long‐term exposure to MPH causes dopaminergic neurons within the nigrostriatal pathway to be more sensitive to the Parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). We hypothesize that oxidative stress caused by the spontaneous oxidation of the excess DA in the synaptic cleft renders dopaminergic neurons within the nigrostriatal pathway to be more sensitive to MPTP.To investigate this, adolescent male Swiss‐Webster mice received intraperitoneal (IP) injections of saline, 1, or 10 mg/kg MPH for 12 weeks. After 12 weeks, all animals received a drug washout period of 7 days and then half of each group was treated with MPTP (4 × 20mg/kg, every 2 hours), while the other half was administered 4 injections of sterile saline. Seven days after the MPTP injection, mice were sacrificed and the striatum (STR), substantia nigra (SN) and the occipital cortex (OCtx) were microdissected and flash‐frozen. Oxidative stress related to increased dopamine levels was examined using a glutathione assay to measure glutathione content and near‐infrared fluorescence to measure free and protein‐bound ortho‐quinones.It appears that long‐term exposure to MPH sensitizes dopaminergic neurons within the nigrostriatal pathway to oxidative stress, rendering them vulnerable to further insults, such as MPTP exposure. As such, these studies provide insight into the risks of long‐term psychostimulant exposure.Support or Funding InformationAmerican Foundation of Pharmaceutical EducationEast Tennessee State UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Correlation between neuroanatomical and respiratory functional changes in a Parkinson's disease model.
Authors: de Araujo Fernandes Silvio , Carvalho Karin , Moreira Thiago Santos , Takakura Ana Carolina 
Published: June 2021

Parkinson's disease (PD) is a disorder characterized by motor and non‐motor symptoms associated with loss of dopaminergic neurons in the compact part of the substantia nigra (SNc). However, other brainstem structures may also be degenerated, contributing to the appearance of non‐motor abnormalities, as breathing disorders that have a negative impact on the life's quality of those individuals. The aim of this study was to perform a temporal correlation between respiratory and neuroanatomical changes in an experimental model of PD. Adult male Wistar rats, with bilateral injections of 6‐hydroxy‐dopamine (6‐OHDA, 24 μg/μl) or vehicle into the striatum were used. At 30, 40 and 60 days after PD induction, the animals had functional and neuroanatomical parameters assessed by whole body plethysmography and immunohistochemical analysis. The results showed that in this model there are more than 70% of reduction in the dopaminergic neurons of the SNc and a reduction in the resting respiratory frequency (40 days: 88 ± 2 and 60 days: 81 ± 2, vs. vehicle 113 ± 2, bpm) and ventilation (40 days: 643 ± 29 and 60 days: 377 ± 21, vs. vehicle 877 ± 48 ml/kg/min) from 40 days after PD‐induction. A reduction in the hypercapnia‐induced respiratory frequency (fR: 40 days: 115 ± 4 and 60 days: 120 ± 3, vs. vehicle 131 ± 2 bpm) and ventilation (VE: 40 days: 1138 ± 96 and 60 days: 701 ± 66, vs. vehicle 1414 ± 102 ml/kg/min) was also observed in the same period. The neuroanatomical results showed that there was a reduction in the number of Phox2b neurons from 30 days after the injury in the nucleus of the solitary tract (NTS: 46%) and retrotrapezoid nucleus (RTN: 55%) and a reduction in the density of glial fibrillary acidic protein (GFAP) in the region of the rostral ventral respiratory group (rVRG: 39.3%). At 40 days, a reduction in the density of receptors for neurokinin‐1 (NK1R) was also observed in the pre‐Botzinger Complex (preBotC: 25%) and in the rVRG (38%) and in the density of GFAP in the RTN region (40.7%). At 60 days, the reduction in the densitity of GFAP was also present in the regions of preBotC (51.9%) and NTS (47.4%). The present results show that the neuroanatomical changes start before functional respiratory deficits and can be a cause for respiratory problems observed in PD.Support or Funding InformationFAPESP, CNPq and CAPES.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Involvement of CRF1 receptors in bed nucleus of stria terminalis (BNST) on baroreflex responses in chronically stressed rats
Authors: de Oliveira Leandro Augusto , de Souza Lucas Gomes , Benini Ricardo , Crestani Carlos Cesar 
Published: June 2021

INTRODUCTIONStudies suggest the involvement of CRF receptors in bed nucleus of the stria terminalis (BNST) on cardiovascular responses in acute stress. Data from our group had demonstrated that the expression of CRF1 receptors within the BNST is decreased in animals exposed to chronic variable stress (CVS). Nevertheless, an involvement of BNST CRF neurotransmission on cardiovascular changes evoked by CVS has never been investigated.AIMTo evaluate the involvement of CRF1 receptor in the BNST on baroreflex changes evoked by CVS in rats.METHODOLOGYMale Wistar rats (250g) were submitted to stereotaxic surgery for implantation of cannulas into the BNST. After 4 days of recovery, the animals were exposed to a CVS protocol for 10 days. After the last session, the rats had the femoral artery and vein cannulated for cardiovascular record and drug infusion, respectively. Twenty‐four hours later, the experiments were performed. Baroreflex function was assessed by evoking changes on arterial pressure throughout intravenous infusions of phenylephrine and sodium nitroprusside, which evoke pressor and depressor effects, respectively. Baroreflex activity was evaluated in both control rats and animals subjected to ECV protocol before and after bilateral microinjection of the selective CRF1 antagonist CP376395 (5nmol/100nL) into the BNST.RESULTSComparison of values before BNST treatment revealed that ECV decreased the bradycardiac response evoked by blood pressure increase (−48±10 vs −114±23 bpm, P<0.03). Moreover, bilateral microinjection of CP376395 into the BNST decreased reflex bradycardia in control group (−51±13 vs −114±23 bpm, P<0.02), but not in animals subjected to ECV (−51±10 vs −48±10 bpm, P>0.05). The tachycardia evoked by blood pressure decrease was also decreased following ECV (57±5 vs 97±11 bpm, P<0.05). The BNST treatment with CP376395 decreased the tachycardiac response in control animals (50±9 vs 97±11 bpm, P<0.001), but without affecting this response in CVS rats (52±5 vs 57±5 bpm, P>0.05).CONCLUSIONThe impairment of baroreflex function evoked by CVS is related to decreased control of this reflex cardiovascular by CRF1 receptor in the BNST.Support or Funding InformationFINANCIAL SUPPORT: FAPESPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelial GPCRs Activate p38 MAPK Inflammatory Signaling Via Non‐canonical TAB1, 2 and 3‐dependent Pathways
Authors: Lin Ying , Narala Rachan , Grimsey Neil , Trejo JoAnn 
Published: June 2021

Vasculature disease is a leading cause of morbidity and mortality worldwide. A hallmark of vascular inflammation is endothelial cell dysfunction, which is induced by vascular inflammatory mediators, many of which act through G protein‐coupled receptors (GPCRs). We previously showed that thrombin stimulation of endothelial protease‐activated receptor‐1 (PAR1) activates p38 MAPK through a non‐canonical pathway mediated by TAB1 (transforming growth factor‐β‐activated kinase binding protein‐1). TAB1 binds directly to p38α inducing a conformational change resulting in autophosphorylation and activation bypassing the requirement for upstream MAP2Ks. We also found that non‐canonical p38 activation induced by thrombin/PAR1 promotes endothelial barrier permeability in vitro and further showed that p38 is required for PAR1‐stimulated vascular leakage in vivo. While non‐canonical p38 activation induced by PAR1 is established, it remains unclear if other endothelial GPCRs also promote p38 activation through a TAB1‐dependent pathway and was examined. Here we report that multiple GPCRs agonists including histamine, PGE2, ADP and thrombin induce p38 activation via the non‐canonical TAB‐dependent pathway to promote cytokine production. We assessed GPCR‐induced p38 activation in macrovascular and microvascular endothelial cell lines including HUVEC, EA.hy926 and HDMECs. Using immunoblotting and qPCR, the expression of p38, TAB1, 2, 3 and MKK3,6 were quantified and appear to be comparable across the endothelial cell lines. To determine if p38 activation induced by GPCRs is mediated by autophosphorylation, we used the p38α/β SB203580 inhibitor which blocks p38 autophosphorylation but not phosphorylation mediated by upstream MAP2Ks. In HUVEC, EA.hy926 and HDMEC pretreated with SB203580, all four agonists including histamine, PGE2, ADP and thrombin failed to promote p38 phosphorylation, suggesting that endothelial GPCR‐induced p38 activation occurs through autophosphorylation. Next, we used combinations of TAB1, 2 and 3‐specific siRNAs to deplete endothelial cells of TAB proteins and found that all GPCR agonists require TAB expression to induce maximal p38 activation in endothelial cells. In addition, endothelial GPCR‐induced cytokine production was also dependent on p38 signaling and TAB expression. Taken together, these data support a critical role for TAB1‐dependent activation of p38 MAPK induced by endothelial GPCRs in inflammatory signaling.Support or Funding InformationThis work is funded by NIH/NIGMS R01 GM090689, R01 GM116597 and UC Tobacco‐related Disease Research Program High Impact Pilot Award 26IP‐0050This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ellagic Acid exerts anti‐inflammatory actions via disruption of store‐operated Ca entry (SOCE) pathway activators and coupling mediators[Office1]
Authors: Murphy Matthew , Quin Xia , Mathias Clinton , Thomas David , Bose Diptiman 
Published: June 2021

Pharmacological agents that can modulate Ca2+ homeostasis are being extensively explored as potential anti‐inflammatory agents. Ellagic acid (EA), a polyphenolic compound found in many fruits and plant extracts, has been known to possess anti‐inflammatory properties. However, the mechanism of action behind its anti‐inflammatory action is unclear. We studied the effects of EA on Ca2+ handling, in particular, store‐operated Ca2+ entry (SOCE), a process critical to proper T cell function. EA is thought to modulate Ca2+ homeostasis by enhancing sarcoplasmic endoplasmic reticulum ATPase pump (SERCA) activity, however effects of EA on Ca2+ signaling is not clearly understood. We demonstrate that acute addition of EA induced Ca2+ release (EC50= 63 μM). A 12 h incubation of Jurkat T cells with EA decreased the ATP‐induced Ca2+ release and diminished the SOCE‐mediated Ca2+ influx in a dose dependent manner (IC50= 23 μM). The inhibition of SOCE was also confirmed by reduced Mn2+ entry rates in the EA‐treated cells. The two important components of SOCE are the endoplasmic reticulum (ER)‐Ca2+ sensor Stromal Interaction Molecule (STIM), and highly‐Ca2+ selective plasma membrane (PM) Orai channels. EA treatment attenuated the ATP‐induced Ca2+ influx in EA‐treated HEK293 cells transiently transfected with SOCE channel Orai1‐myc and ER‐sensor stromal interaction molecule (STIM1) (HEKSTIM/Orai). Furthermore, EA treatment interfered with the Orai1 and STIM1 coupling by disrupting STIM1 puncta formation in the HEKSTIM/Orai cells. Since expression of certain cytokines is directly dependent on Ca2+ influx, we measured the levels of IL‐2 and INFγ in EA‐treated Jurkat cells. Indeed, EA‐treated resulted in a significant decrease in IL‐2 and INFγ expression. The activity of nuclear factor of activated T‐cell (NFAT), a transcriptional factor has been shown to be dependent on SOCE mediated Ca2+ influx. Prolong exposure to EA decreased the translocation of nuclear factor of activated T‐cell in stimulated T cells. Hence, by inhibiting SOCE mediated Ca2+ influx, EA decreased downstream activation of pro‐inflammatory mediators. These observations suggest a novel target to EA‐mediated effects and provide insight into the mechanisms underlying EA mediated anti‐inflammatory effects.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulation of Synaptic transmission: Quantitative analysis of Gβγ specificity to adrenergic α2a receptor and SNARE.
Authors: Yim Yun Young , Betke Katherine , McDonald W. Hayes , Gilsbach Ralf , Chen Yunjia , Hyde Karren , Wang Qin , Hein Lutz , Schey Kevin , Hamm Heidi 
Published: June 2021

Modulation of neurotransmitter exocytosis by activated Gi/o coupled G‐protein coupled receptors (GPCRs) is a universal regulatory mechanism used both to avoid overstimulation and to influence circuitry. One of the known modulation mechanisms is Gβγ interaction with soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE). There are 5 Gβ and 12 Gγ subunits, but specific Gβγs activated by a given GPCR and the specificity to effectors in vivo are not known. Presynaptic α2a‐adrenergic receptors (α2aARs) in both adrenergic (auto α2aARs) and non‐adrenergic neurons (hetero α2aARs) inhibit neurotransmitter release and affect various physiological functions such as anesthetic sparing and working memory enhancement. With a quantitative MRM proteomic analysis of neuronal Gβ and Gγ subunits to detect neuronal Gβ and Gγ subunits, several mouse models including transgenic Flag‐α2aARs, knock‐in HA‐α2aARs, and other biochemical techniques such as co‐immunoprecipitation, we investigate the specificity of Gβ and Gγ subunits to α2aARs in both adrenergic(auto α2aARs) and non‐adrenergic neurons (hetero α2aARs), and SNARE in presence of epinephrine. Gβ2, Gγ2, Gγ3, and Gγ4 preferentially interact with activated auto α2aARs while Gβ4 and Gγ12 preferentially interact with activated hetero α2aARs. We also detect a subset of Gβ and Gγ subunits interacting with SNARE upon α2aARs activation. Further understanding of Gβγ specificity on its downstream signaling, especially Gβγ‐SNARE interaction, offers new insights into the normal functioning of the brain and lead to an identification of potential pathophysiological states in which the Gβγ‐SNARE interaction may be dysregulated. These studies yield additional insights into Gi/o‐coupled GPCR‐mediated regulation of exocytosis.Support or Funding InformationThis work was supported by the National Institutes of Health (EY10291, MH101679, DK109204, and T32 GM07628).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.