bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐Tech Gamification and TBL Strategies to Teach Physiolgy
Authors: Tejada-Simon Maria Victoria , Silverthorn Dee 
Published: April 2020

The concept of gamification in education refers to the process of adding active game elements into a course to encourage participation. Games help develop skills and confidence in healthcare professionals. Herein, we are aiming to engage the students in a game experience that will uncover the topic in question in a scaffolding manner. Specifically, we assisted first year Pharmacy students in understanding the autonomic nervous system’s (ANS) structure and function using an interactive game coupled to a team‐based learning session, devoid of any technology. We used a flipped/TBL classroom design in a 2‐hour interactive problem‐solving supplemental instruction session (SI). Prior to class, the students completed pre‐class activities in form of diagrams, crossword puzzles and fill‐in the blank to engage them with anatomical terminology. During the SI, 8 students/group (128 students total) worked collaboratively. The class met in an active learning designed room to facilitate small group interaction. The organization of the SI followed a constructive alignment: (1) Pre‐class activities: self‐paced interactive learning and reading; (2) Assessment of foundational learning before SI session with group activity, pair‐share/team‐based learning (TBL), 1–3 minutes microlecture; (3) Student group activity with discussion: game, diagram, fill in the blanks, match activities; (4) Group share: white board sharing “quiz” among the groups. To evaluate the success of this approach we used a grading rubric for pre‐class activities, post‐lecture assessments, measure classroom activity using GORP, student evaluation/survey, faculty peer evaluation.Support or Funding InformationPromoting Active Learning and Mentoring Network (PALM); College of Pharmacy Faculty Development ‐ University of Houston
Overexpression of SIRT3FL Improves Cardiac SERCA2a Function Following High Fat‐High Sucrose Feeding in Mice
Authors: Oldfield Christopher J. , Moffatt Teri L. , O'Hara Kimberley A. , Xiang Bo , Dolinsky Vernon W. , Duhamel Todd A. 
Published: April 2020

BackgroundDiabetes induces a distinct form of cardiomyopathy, termed diabetic cardiomyopathy (DCM). A key pathophysiological mechanism of DCM is reduced level and activity of sarco(endo)plasmic reticulum Ca2+ ATPase 2a (SERCA2a). Recently, it has been discovered that the function of SERCA2a is negatively regulated by the post‐translational modification, acetylation. The sirtuin (SIRT) isoform, SIRT3 full‐length (SIRT3FL), deacetylates protein substrates, though it is unknown if SIRT3FL deacetylates SERCA2a. Therefore, the objective of this study was to determine if the overexpression of SIRT3FL alters cardiac SERCA2a acetylation and function in a mouse model of diabetes, induced by high fat‐high sucrose (HFHS) feeding.Methods and ResultsAdult (12 weeks of age) male C57BL/6J Wild Type (WT) mice and adult male MCK‐mSIRT3‐M1‐Flag transgenic (SIRT3FLTG) mice on a C57BL/6J background, who overexpress the SIRT3FL isoform in skeletal and cardiac muscle, were randomized into groups fed either a standard lab diet (Control) or a HFHS diet for 4‐months. After 4‐months, HFHS‐fed mice exhibited increased body weight, left ventricle (LV) weight, LV weight relative to body weight, and liver weight, compared to control fed‐mice. LV systolic parameters were unchanged by HFHS feeding, while the A and E wave forms of HFHS‐fed mice were slowed, compared to control‐fed mice. HFHS‐fed mice exhibited LV thickening, compared to control‐fed mice. Glucose tolerance was impaired in HFHS‐fed mice, compared to control‐fed mice. Diet did not alter SIRT3 protein content. Likewise, HFHS feeding did not alter the level or function of cardiac SERCA2a. LV SERCA2a protein content was not altered by genotype. However, SIRT3FLTG mice, regardless of diet, had 21% greater maximal SERCA activity (Vmax) and an 11% greater Hill coefficient, compared to WT mice. The Ca50, which is the Ca2+concentration that elicits 50% of Vmax, was 24% lower in SIRT3FLTG‐HFHS‐fed mice, compared to WT‐HFHS‐fed mice, indicating an increase in Ca2+ sensitivity.ConclusionHFHS feeding induced a diabetic phenotype in WT and SIRT3FLTG mice but level and function of cardiac SERCA2a was unchanged. However, overexpression of the SIRT3FL isoform improved cardiac SERCA2a function, regardless of HFHS feeding.Support or Funding InformationThis work was supported by a grant‐in‐aid from the Heart and Stroke Foundation of Canada
Testosterone Reverses the Urethra Hypercontractility in Ovariectomized Rat: Role of Voltage‐Operated Calcium Channel
Authors: Bonilla Sandra Milena , Antunes Edson 
Published: April 2020

Introduction and AimPostmenopausal women exhibit overactive bladder (OAB), as evidenced by urgency, frequency and noctúria (1). Ovariectomized (OVX) rats display OAB and urethral hypercontractility that is normalized by in vivo testosterone replacement (2). Androgen receptors (AR) have been found in urinary bladder, suggesting they play an important role in the urinary continence (3,4). However, the mechanism of action of testosterone in urethra of female rats has not been elucidated. L‐type voltage‐operated calcium channels (VOCC) are implicated in urinary contraction during the voiding phase (4). We hypothesized here that testosterone via VOCC activation regulates the female urethra. This study aimed therefore to evaluate the effects of testosterone and its modulation by VOCC on urethra contractility in OVX rats.Materials and methodsTwo‐month old female Sprague Dawley rats were submitted to bilateral ovariectomy, whereas Sham‐operated rat were manipulated but the ovaries were left intact. After 4‐month OVX, the urethra was removed, and concentration‐response curves to calcium chloride (CaCl2; 10 μM – 300 mM) were performed in the presence of testosterone (100 nM; 30 min), vehicle (alcohol; 0.5 μL) and/or the VOCC inhibitor nifedipine (3 nM; 30 min).ResultsBilateral OVX significantly increased the urethra contraction to compared with Sham group (P < 0.05). Testosterone (100 nM prevented CaCl2‐induced urethral hypercontractility in OVX group. Pre‐incubation with nifedipine (3 nM) also reduced the contractile response to extracellular calcium in OVX group. In Sham group, testosterone and/or nifedipine had no effects.ConclusionOur data suggests that testosterone via non‐classical genomic pathway acts to inhibit VOCC to normalize the urethral hypercontractility in OVX rats.All animal procedures were approved by the Ethical Committee on Animals Use CEUA/UNICAMP (CEUA; No. 4421‐1, 5250‐1).Support or Funding InformationFINANCIAL SUPPORT: FAPESP (2017/26564‐9).
Inhibition of actin‐related protein (Arp) 2/3 complex blocks vasopressin‐induced AQP2 membrane accumulation
Authors: Liu Chen-Chung Steven , Cheung Pui Wen , Bouley Richard , Brown Dennis 
Published: April 2020

Aquaporin 2 (AQP2) is a water channel protein located primarily on principal cells of kidney collecting ducts, and is crucial for regulating body water homeostasis. Regulation of AQP2 trafficking is subject to hormonal control, mainly via the canonical vasopressin (VP) signaling pathway which stimulates AQP2 membrane accumulation. Active actin cytoskeleton remodeling also plays an important role in AQP2 trafficking, but the mechanism is incompletely understood. Using immunohistochemistry and confocal microscopy, we discovered that actin‐related protein (Arp) 2/3 complex, an actin nucleator, was highly expressed in inner medullary principal cells where it colocalized with AQP2. Using an Arp2/3 complex inhibitor, CK‐666, we found that VP‐induced AQP2 membrane accumulation was inhibited both in rat kidneys and LLC‐AQP2 cells in vitro. Instead of distributing throughout the cytoplasm, AQP2 in cells treated with CK‐666 was concentrated in vesicles forming a perinuclear patch, which was also positive for Rab‐11 (a recycling endosome marker) and clathrin (a trans Golgi Network (TGN) marker). Similar perinuclear AQP2 patches appear in cells incubated at 20°C (cold block), which allows endocytosis to continue, but prevents protein exit from the TGN. By rewarming the cells to 37°C, these perinuclear patches dissipate, and AQP2 quickly redistributes throughout the cytoplasm (cold block release). However, we found that in cells exposed to a 20°C cold block and treated with CK‐666, AQP2 patches failed to dissipate upon rewarming, suggesting that CK‐666 blocked release of AQP2 from the TGN in the exocytotic pathway. This effect of CK‐666 was independent of VP signaling, and did not alter the VP‐induced phosphorylation state of AQP2 at residues serine‐256, S269 and S261. In conclusion, inhibition of the Arp2/3 complex blocks VP‐induced AQP2 plasma membrane accumulation by blocking AQP2 exocytosis at the level of the TGN and the recycling endosome, but did not affect VP signaling pathway. This result suggests that actin filament nucleation and growth via Arp2/3 activity is essential for AQP2 recycling and trafficking.Support or Funding InformationCCL is supported by NIH training grant 5T32DK007540. PWC is supported by NIH grant DK115901. DB is supported by NIH grant DK096586
Occupational Stress Among Doctors ‐ Role of Duty Schedule and De‐Stressing Techniques.
Authors: Khan Mohammed Moizuddin 
Published: April 2020

IntroductionJob or occupational stress is something we all face as employees or employers and we all handle it differently. It is a mismatch between the individual capabilities and organizational demands. Presently various challenges are faced by doctors making medical profession a tough job leading to occupational stress. Doctors are involved in long and irregular working hours which is resulting in varying levels of exhaustion and ultimately occupational stress. Emergencies or night duties are an inseparable part of medical profession so its desirable to find best possible ways to manage occupational stress.Aim & ObjectivesTo evaluate the role of emergencies and night duties in causing occupational stress among doctors. To study the effect of de‐stressing techniques used by doctors to cope up with occupational stress.Material & MethodsThis is a cross sectional Observational study conducted in Indian doctors. Structured pro‐forma was used to collect demographic data, professional work pattern, exercising habits etc. To assess the psychological occupational stress a standardized professional psychological stress test questioner was used.ResultsIt was seen that the doctors who attended more than 6 calls/week the percentage of occupational stress was found to be on higher than who attended less numbers. 28.89% had moderate stress while 13.33% and 6.67% were having stress or major stress. There was statistically significant association between emergency call/week and psychological occupational stress score. Physical exercise, plying sports, de‐stressing techniques like listening to music, net surfing were significant in coping with psychological occupational stress.ConclusionOccupational stress among doctors can be managed effectively by adopting a combination of measures which include modification in working schedules, regular psychological stress monitoring at institutional level and incorporating healthy lifestyle practices like physical exercise, sports etc. at personal level.Support or Funding InformationCollege of Medicine, Dar Al uloom University, Riyadh
TMED2 is Required for Trophoblast Migration, Differentiation, and Proliferation
Authors: Aber Rachel , Kaiser Caroline , Yuan Libin , Jerome-Majewska Loydie 
Published: April 2020

Essential cargo receptors, specifically members of the Transmembrane emp24 domain (TMED) protein family, are implicated in numerous cellular morphogenesis. The localization and levels of TMED proteins are tightly controlled to regulate cell survival, migration, and proliferation. TMED proteins have an N‐terminal coiled‐coil region essential for interactions with TMED partners and a Golgi dynamics (GOLD) domain required for heterodimerization and cargo recognition. Although the structure of TMED2 is known, the function of TMED2 in placental development remains poorly understood. Mouse embryos homozygous for a null mutation in the signal sequence of TMED2 died at midgestation from failure to form a placental labyrinth layer. Moreover, ex vivo cultures of pre‐attachment chorion and allantois suggest that cell‐type‐specific transport of fibronectin and VCAM1, by TMED2, is required for chorionic‐allantoic cell communication and for trophoblast differentiation. Thus, we hypothesize that events necessary for labyrinth layer formation such as trophoblast migration and syncytiotrophoblast fusion, require functional TMED2. To test the role of TMED2 in cell migration and survival, we conducted scratch and viability assays in HEK293 cells overexpressing wild‐type and mutant TMED2. We also tested the effects of mutating residues in the GOLD domain of TMED2, E48 and K91, that are predicted to be involved in heterodimerization with TMED10. We found that HEK293 cells overexpressing wild‐type TMED2 displayed reduced cell migration and increased ER stress. Similarly, overexpression of mutant TMED2‐E48Q, resulted in a comparable reduction in cell migration. However, cells overexpressing TMED2‐K91R, showed increased cell migration and viability compared to TMED2 and TMED2‐E48Q cells. To more precisely investigate the absence of a labyrinth layer in TMED2 deficient embryos, we conducted proliferation and fusion studies in two human choriocarcinoma cell lines: JEG‐3 and BeWo. Overexpression of wild type TMED2 in JEG‐3 cells was sufficient for syncytiotrophoblast fusion; however, knockdown of TMED2 in BeWo cells inhibited fusion, supporting a requirement for TMED2 in this process. Moreover, proliferation and metabolic activity assays revealed that knockdown of TMED2 in BeWo cells increased cell proliferation and decreased cell migration. Overall, our data suggest that levels of TMED2 must be tightly regulated for cell proliferation and viability. In addition, we found that the K91 residue of TMED2, which is predicted to help mediate heterodimerization with TMED10 is important for TMED2 function. We propose that the abnormalities displayed by embryos and cells deficient in or overexpressing TMED2 reflect the inadequate transport and localization of fibronectin and likely more unidentified proteins critical for regulating proliferation and migration of trophoblast cells.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada
Assessment of Novel Rexinoids for Therapeutic Potential in Combating Alzheimer's Disease
Authors: Pedroza Morgan Arielle , Mallick Sanchita , Marshall Pamella , Wagner Carl , Jurutka Peter 
Published: April 2020

Bexarotene is an FDA approved anti‐cancer agent, but more recently this drug has been assessed for its potential as a therapeutic for dementia. Bexarotene may reduce amyloid beta (α□) plaques that are thought to play a role in Alzheimer’s disease pathophysiology, although clinical use of bexarotene causes unwanted side‐effects including hyperlipidemia and hypothyroidism. Bexarotene drives retinoid‐X‐receptor (RXR) homodimerization on the retinoid‐X‐response element (RXRE), as well as facilitating heterodimers with liver‐X‐receptors (LXR) and peroxisome proliferator activated receptor gamma (PPARγ). These RXR‐containing dimers are hypothesized to induce apolipoprotein (ApoE) in glial cells to control lipid and cholesterol homeostasis in the brain. We tested the ability of bexarotene and a panel of novel rexinoids to drive RXR dimerization using dual luciferase reporter assays to assess transcriptional efficiency of these compounds. We employed both RXRE‐mediated reporter assays, as well as a mammalian 2 hybrid system (M2H) to probe the ability of our novel rexinoids to activate RXR signaling. These compounds were also tested as activators of LXRE‐directed transcription, and as inducers of ApoE mRNA in U87 glial cells. Results from these multiple assay systems reveal that our panel of RXR analogs contain compounds with diverse activities, some of which bind to RXR with greater affinity than others, and in some cases can stimulate ApoE expression to a greater extent than bexarotene. These results suggest that chemical modifications to the parent bexarotene chemical scaffold may yield novel analogs with an amplified ability to activate RXR and possibly combat Alzheimer’s disease via a reduction in amyloid beta (α□) plaques.Support or Funding InformationCoins For Alzheimer’s Research Trust
Advanced Activity‐Based Probes to Monitor the Proteasome in Live Cells
Authors: Trader Darci Jones , Zerfas Breanna 
Published: April 2020

The probes currently available to monitor the activity of the proteasome need to be used at high micromolar concentrations to obtain significant signal and can be hydrolyzed non‐specifically by other cellular proteases. We have been using an LC/MS‐based screening method to discover peptide scaffolds that are cleaved more efficiently by the proteasome than other enzymes in human serum. Our new probes incorporate a Rhodamine 110 fluorophore and a peptoid moiety to enhance cell permeability. These new probes can be used in live cells to detect real‐time activity of various isoforms of the proteasome.Support or Funding InformationNIH R21GM131206
Hyperhomocysteinemia: Instigating the Mechanism of Periodontal Disease
Authors: Stanisic Dragana , George Akash K. , Molnar Jack , Mallonee Carissa Jo , Homme Rubens P. , Smolenkova Irina , Tyagi Suresh C. , Singh Mahavir 
Published: April 2020

Periodontal disease is one of the most common conditions resulting from poor oral hygiene and is characterized by a destructive process in the periodontium which essentially include gingiva, alveolar mucosa, cementum, periodontal ligament, and the alveolar bone. Notably, the destructive event in the alveolar bone has been linked to homocysteine (Hcy) metabolism however; it has not yet been fully investigated. Therefore; the implication of Hcy towards initiation, progression, and maintenance of the periodontal disease remains incompletely understood. Our research has led to the discovery that hyperhomocysteinemia (HHcy) causes changes in the periodontal tissues as well as it leads to an increase in the angiogenesis‐related proteins, potentially indicating a faster onset of periodontal disease in the susceptible individuals. To study periodontal tissue status and angiogenesis‐related protein levels, we compared wild‐type C57BL/6J (WT) and CBS+/− (HHcy) mice strains. The distance between cementoenamel junction, and the alveolar bone crest (CEJ‐BC) were measured histomorphometrically using histological preparations (Hematoxylin and Eosin; H&E, and the Masson’s Trichrome staining). Serum angiogenesis‐related levels namely the angiogenin, angiopoietin‐1, endostatin/collagen XVIII, FGF acid, IGFBP‐1, IGFBP‐2, MMP‐9 (pro and active forms), PDGF‐AA, PDGF‐AB/PDGF‐BB, pentraxin‐3 were measured using the Proteome ProfilerTM Array Kit specific for the mouse. The data suggest an increase in the distance between cementoenamel junction, and the alveolar bone crest. Levels of the angiogenesis‐related proteins in CBS+/− mouse strain were also significantly increased in comparison to the WT control mice. Interestingly, some of these angiogenesis‐related proteins have been shown to be upregulated during the periodontal disease. Our findings thus underscore the importance of Hcy metabolism towards the loss of periodontal tissue homeostasis, and the causation of the periodontal disease indicating that regulating Hcy metabolism can help prevent periodontal tissue damage, and the periodontal disease in people who suffer from chronic metabolic disorders such as hyperhomocysteinemia.Support or Funding InformationFunding from the National Institutes of Health (NIH): HL139047, AR071789, HL74815, HL107640, HL139047, and DK116591.
The Effect of Teaching Methodology and Course Duration on Student Performance at Different Assessment Types across Different Cognitive Levels as defined by Bloom’s Taxonomy
Authors: Sunba Khaleel , Rogers Kem 
Published: April 2020

The University of Western Ontario currently offers a third year systemic human anatomy course (ANATCELL 3319) in face to face (F2F) and online sections during the fall/winter intake (F/W). While F/W sections share the same lecture and assessment materials, F2F students attend weekly one‐hour cadaveric labs while online students attend weekly interactive video conference labs. During the summer intake, the course is offered in the online section only, with labs given twice a week. The assessments consist of multichoice (MCQ) and short answer questions. Our previous publication
Sunba & Rogers (2018) showed that F/W F2F scored higher in their MCQ assessments than F/W online students at different Bloom’s Taxonomy levels. In addition, F/W online students scored higher than summer online students in the shared MCQ.In the current study, we further compared the performance of students in MCQ against their performance in short answer questions, in total and at different Bloom’s Taxonomy levels within/against the assessment type(s). For F/W sections (F2F students n=142; online students n=172), there were 300 MCQ (knowledge (n= 149), comprehension (n= 120), application (n= 21), and analysis (n= 10)) and 118 short answer questions (knowledge (n= 88), comprehension (n= 18.5), application (n= 10.5), and analysis (n= 1)). Both groups scored higher in their MCQ than short answer questions, in total and at most cognitive levels (p ≤ 0.05). F/W F2F students scored higher than F/W online in both assessment types and at most levels. The variance across levels differed based on the assessment type. For example, All F/W students scored the highest in comprehension MCQ but the lowest in short answer comprehension questions. This indicates that a change of assessment type influences the way in which students answer.With summer online students (n=44), we compared 169 MCQ (knowledge (n=79), comprehension (n=74), application (n=9) and analysis (n=7)) with 59 short answer questions (knowledge (n= 34), comprehension (n=12), application (10) and analysis (n=3)). Students scored higher (p ≤ 0.05) in their MCQ total, comprehension MCQ, and application MCQ than the adjacent levels of the short answers. Unlike their F/W counterparts, students scored lowest in their MCQ comprehension (p<0.001) in relation to the other levels.Our findings indicate that teaching F2F is likely to improve student performance in terms of both overall grades and cognitive ability. In addition, students are likely to score higher in MCQ than short answer questions which is indicative of a reliance on cues within MCQ (especially comprehension) to help them overcome their lack of information. Finally, the performance of summer students, particularly in relation to comprehension‐type questions which rely on memorisation, indicates that the spacing of course material may help in achieving higher grades.Support or Funding InformationDr. Kem Roger