bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Teaching Up‐to‐Date Medical Pharmacology Material. Who Wins? The Board Preparation Resources!!
Authors: Hernandez Mark J. , Parker R Wayne , MacGregor Gordon G. 
Published: April 2020

IntroductionPharmacology faculty are faced with the challenge of preparing medical students to become doctors but are also challenged with preparing the students to successfully complete the USMLE Step‐1, and or COMLEX Level‐1 (for osteopathic medical schools). Faculty student evaluations can help highlight the student perspective on this high‐stakes exam and the pressure it brings. But what is a pharmacology faculty to do when traditional resources such as textbooks and even some board preparation resources are not in agreement with the most current therapeutic guidelines.MethodsMost recently in 2017 and 2018 there were updates in the management of hypertension (2017) and hyperlipidemias (2018), and even the classification of antiarrhythmic drugs (2018). Those updates, amongst others, were most recently addressed in a second‐year cardiovascular system pharmacology course in our institution. Revisions required updating the pharmacology content of the course and sharing the updates on the scope of pharmacology with the physician faculty who also teach about the drugs. We then compared the student feedback in the course from the previous five years using a thematic analysis approach.ResultsThe number of times words such as: “clinical”, “integration”, and/or “boards” appeared in course‐evaluation surveys was two to three‐fold higher in 2019 compared to that of previous 5 years. Presenting updated content caused more frustration and discontent among some medical students. When the content did not necessarily match that found in the popular board preparation resources it led to a distrust in the instructor.ConclusionsThe latest pharmacology information may not necessarily support the information found in board preparation resources. In addition, clinical faculty may present therapeutic information based on their own clinical experience. Often it is the case that the pharmacology faculty is solely responsible for the overall content in the curriculum even when it may be presented at different levels from different sources. Students need to succeed on the boards and in our pharmacology courses but what are the faculty to do when the AMSPC knowledge objectives, which have traditionally been used as the standard of what to teach in pharmacology, become outdated. There is a need for updated pharmacology knowledge objectives.Support or Funding InformationNAComparison of the Cardiovascular System End‐of‐Course Evaluations as it pertains to PharmacologyFigure 1
Waist‐to‐height Ratio as an Indicator to Determinate Obesity and Central Obesity in Pediatric Population
Authors: Mendoza-Hernandez Alma Nubia , Flores-Rojas Lupitha Elizabeth , de Lourdes Silva-Fernandez María 
Published: April 2020

IntroductionIn school‐age children and adolescents, the obesity is a public health alarm that particularly has been increasing. The highest prevalence rates of childhood obesity have been observed in developed countries; still, its prevalence is increasing in developing countries as well. The best evidence to date suggests that measures of central adiposity should be used in order to best identify individuals at increased risk of obesity‐related ill health. In the clinical environment, techniques such as Body Mass Index (BMI), waist circumference (WC) have been used extensively, but the waist‐to‐height ratio (WHtR) could be a better tool to detect central obesity.ObjectiveThe objective was to evaluate the association of body mass index (BMI) and waist to height ratio in overweight and obese paediatric age group.MethodsIs a cross‐sectional study, schoolchildren in a Mexican population, ages from 9 to 18 years. The anthropometric variables measured were waist circumference, body mass index, waist‐to‐height ratio, Waist circumference at the midpoint between the last rib and the iliac crest. The use of The Center for Disease Control and Prevention growth tables classified overweight as at or above 85th percentile and obesity as at or above 95th percentile of BMI. The relationship between waist‐to‐height ratio (WHtR) and body mass index (BMI) was analyzed by X2, t‐test and ANOVA.ResultsA cross‐sectional study of 594 children and adolescents from 9 to 18 years of age. In the analysis the population was grouped by aged group of 9 to 11(23%), 12 to 14 (33%) and 15 to 18 years(44%). The body mass index (BMI) for age showed 18% for overweight and 13% for obesity. The waist to height ratio was 24% for higher cardiometabolic risk with a mean of 0.47 and a waist circumference of 73.9cm. A cardiometabolic risk by WtHR was 4% in normal BMI/age, in overweight 8% and in Obesity was 12% (p=0.01).ConclusionThe prevalence of overweigh and obesity was 31%. It is important to recognize the capacity of anthropometric measurements on identifying overweight and obesity diagnosis. A combined diet and physical activity intervention conducted in the community with a school component should be applied preventing obesity or overweight. The waist to height ratio was 24% for cardiometabolic risk. Anthropometric measurements such as weight, height and waist circumference are simple and effective as global indicator for health risks.Support or Funding InformationUPAEP UNIVERSITY

Anthropometric measurements in the paediatric group

AGE (yrs)

Weight (kg)

Height (cm)

Waist circumference (cm)

BMI (kg/m2)

WHtR

Mean

13.6

55.6

158.6

73.9

21.9

0.47

SD

2.34

14.4

11.6

10.3

4.1

0.06

Min

9.0

23.0

127.0

50.0

13.6

0.34

Max

18.0

115.0

195.0

125.0

40.5

0.74

Range

9.0

92.0

68.0

75.0

26.9

0.4

*Standard DeviationProportion categorized by WHtR Risk and BMITable 2
Analysis of FAM19A2/TAFA‐2 function
Authors: Okada Shuichi , Okada Junichi , Yamada Masanobu 
Published: April 2020

FAM19A2/TAFA‐2, a member of the chemokine CC family, shares 31% sequence identity with MIP‐1α, which is known to elevate body temperature and reduce food intake. A single administration of 250 pM of FAM19A2/TAFA‐2 to the third ventricle of mice just before the initiation of dark period increased food intake and meal number significantly, but reduced meal size during the dark period. The respiratory exchange rate and energy expenditure were increased significantly during the dark period, while the ambulatory count and vertical activity were not affected. These data suggest that FAM19A2/TAFA‐2 participates in the regulation of food intake and metabolic activities.Effect of FAM19A2 on Food intake, Meal number, and Meal sizeFigure 1Effect of FAM19A2 onRER and EEFigure 2
Platelet extravasation across inflamed venules depends on CD18, mast cells and neutrophils
Authors: Bray Monica A. , De La Cruz Angie , Courson Justin , Magadi Sri , Landry Paul T. , Lam Fong W. , Hanlon Samuel D. , Smith C. Wayne , Burns Alan R. , Rumbaut Rolando E. 
Published: April 2020

Platelets and neutrophils are often recruited at sites of microvascular inflammation. While neutrophil extravasation in inflammation is well characterized, platelet extravasation in inflammation is poorly understood and has only been documented in a small number of studies. We showed previously that mice expressing low levels of the leukocyte integrin CD18 (CD18hypo) had reduced total recruitment of platelets (intravascular and extravascular) in the corneal limbus following corneal epithelial wound injury. In this study we sought to determine the role of CD18 in platelet extravasation. Following corneal wound injury, wild‐type (WT) mice had evidence of platelet extravasation across limbal venules; however, CD18hypo mice had markedly reduced platelet extravasation. In view of isolated reports that platelets express CD18, we compared blood platelet counts and ex vivo platelet function under shear stress between CD18hypo and WT mice. Blood platelet counts were measured with a Scil Vet ABC hematology analyzer (Scil animal care company). Flow chamber assays were conducted using a microfluidic BioFlux System (Fluxion Biosciences) with plates coated with type I collagen (25 μg/ml; Helena) and blocked with 5% Bovine serum albumin. The labeled blood was perfused over the collagen‐coated surfaces at two values of fixed shear stress (16 dyne/cm2 and 30 dyne/cm2). Platelet counts and platelet adhesion to collagen at both levels of shear stress were comparable between CD18hypo and WT mice. Since a variety of leukocytes express CD18, including mast cells and neutrophils, we performed experiments to assess the role of these leukocytes in platelet extravasation. We found that CD18hypo mice had a small but statistically significant decrease in mast cell number and a marked decrease in degranulated mast cells as compared to WT mice following wound injury. Further, corneal epithelial wound injury in mice deficient in mast cells (KitW‐sh/W‐sh) resulted in a marked decrease in platelet extravasation as compared to WT mice. Finally, antibody‐induced depletion of circulating neutrophils resulted in a marked decrease in platelet extravasation relative to control mice. Overall, these studies demonstrate that platelet extravasation in a corneal wound injury model of inflammation depends on CD18, mast cells, and neutrophils.Support or Funding InformationSupported by: NIH EY018239, EY17120, HL079368 and VA BLR&D Merit Review Award I01 BX002551. M.A.B. was supported by NHLBI T32 HL139425Extravascular platelets (green) are evident surrounding venules 24 hours postwounding in wild type mice.Figure 1Platelets from CD18 hypomorphic mice had similar adhesion under shear as those from Wild‐type mice; blood platelet counts were similar in both strainsFigure 2
Explaining the impact of environmental risk factors on cardiovascular health by the “exposome” concept
Authors: Daiber Andreas , Münzel Thomas 
Published: April 2020

There is growing evidence that environmental risk factors (pollution and non‐chemical stressors) contribute to the global burden of cardiovascular, metabolic and mental disease. Clinical and epidemiological studies support that traffic‐associated environmental risk factors, air pollution and noise exposure, are associated with a higher risk for cardiovascular disease and significantly contribute to overall mortality. According to the results of the Lancet Commission on pollution and health, up to 9 Mio global annual deaths can be attributed to environmental pollution [Landrigan et al., Lancet 2018]. The numbers will rather increase in the future, because of increasing urbanization and continuous refinement of global exposure‐mortality models, which is supported by the recently reported global all‐cause mortality rate attributable to ambient air pollution by PM2.5 and O3 of 8.79 Mio [Lelieveld et al. and Münzel, Eur Heart J 2019]. Air pollution is obviously the leading health risk factor in the physical environment, followed by water and soil pollution with heavy metals, pesticides, other chemicals and occupational exposures. However, non‐chemical environmental health risk factors such as mental stress, light exposure, climatic changes and traffic noise are so far ignored by global health action plans. Especially for traffic noise‐related health effects there are numerous clinical and epidemiological studies reporting significant impact on cardiovascular disease. In this respect, the “exposome” concept represents a comprehensive description of lifelong exposure history and a rather novel scientific field that is now investigated more systematically. We here provide an in‐depth overview on the health effects of the external exposome, with emphasis on air pollution and traffic noise, and briefly present the actual studies on this topic. In addition, we summarize our previously published experimental research investigating effects of aircraft noise exposure in mice and men providing mechanistic insights on how noise contributes to non‐communicable disease.Support or Funding InformationThe present work was supported by the Boehringer Ingelheim Foundation “Novel and neglected risk factors” (to A.D. and T.M.).The exposome concept. The external exposome represents the sum of all environmental exposures including behavioral/ lifestyle factors. The external exposome (e.g. mental stress and environmental pollution) confer changes of the internal exposome (e.g. altered circadian clock by forward/backward shift, stress hormones, inflammation and oxidative stress) leading to health risks and disease conditions (e.g. atherosclerosis, vascular stenosis and myocardial infarction). BJP, submitted.Figure 1
Regulation of vascular function and inflammation via crosstalk of reactive oxygen and nitrogen species from mitochondria or NADPH oxidase
Authors: Daiber Andreas 
Published: April 2020

Oxidative stress plays a key role for the development of cardiovascular, metabolic and neurodegenerative disease. This concept has been proven by using the approach of genetic deletion of reactive species producing (pro‐oxidant) enzymes as well as by the overexpression of reactive species detoxifying (antioxidant) enzymes leading to a marked reduction of reactive oxygen and nitrogen species (RONS) and in parallel to an amelioration of the severity of diseases. Vice versa, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of antioxidant RONS detoxifying enzymes. We have previously identified crosstalk mechanisms between different sources of RONS, which can amplify the oxidative stress signal. Pathways and potential mechanisms leading to this crosstalk will be analysed in detail and highlighted by selected examples from the current literature and own data including hypoxia, angiotensin II‐induced hypertension, nitrate tolerance, aging and others. The general concept of redox‐based activation of RONS sources via “kindling radicals” and enzyme‐specific “redox switches” as well as the interaction with redox‐sensitive inflammatory pathways will be discussed. An outlook will be provided with preliminary data on the existence of such crosstalk in the setting of diabetes but also mouse models of cardiovascular dysfunction triggered by environmental noise exposure.Support or Funding InformationThe present work was supported by the European Cooperation in Science and Technology (COST Action BM1203/EU‐ROS), by generous financial support by the “Stiftung Mainzer Herz”, by the Centre of Translational Vascular Biology (CTVB), by “NMFZ” and “Stufe 1” funds from the Johannes Gutenberg University Mainz.Crosstalk between different sources of ROS and RNS (mitochondria, NADPH oxidases, xanthine oxidase and NO synthase). Superoxide/hydrogen peroxide formation by any source may be triggered by oxidative stress from all other ROS sources via redox‐activation of multiple mechanisms. From Daiber et al. BJP 2017.Figure 1
Role of PP2A in Racial Differences in Endothelial Dysfunction
Authors: Gomez Dulce Hiraci , Aldokhayyil Maitha Hiraci , Kavazis Andreas N. , Brown Michael 
Published: April 2020

BackgroundAfrican Americans (AA) exhibit a higher prevalence of endothelial dysfunction and an exaggerated response to inflammatory cytokines compared to Caucasian Americans (CA). Endothelial dysfunction is characterized by a reduction in endothelial nitric oxide synthase (eNOS) activity and ultimately a lower nitric oxide production. Data obtained from bovine endothelial cells show that a reduction in eNOS activity in response to an inflammatory stimulus is mediated by protein phosphatase 2A (PP2A). Additionally, higher PP2A activity is associated with a decrease in the phosphorylation of PP2A at the Tyrosine 307 residue (p‐PP2AY307). Therefore, the purpose of this study was to investigate the role of PP2A in racial differences seen in endothelial dysfunction in response to an inflammatory stimulus.MethodsHuman umbilical vein endothelial cells (HUVECs) (n=6 cell lines; 3 CA & 3 AA) were cultured under two conditions: control or tumor necrosis factor‐α (TNF‐α) (10 ng/mL, 4 hours). Western blotting was used to measure protein expression of p‐PP2AY307, PP2A, p‐eNOSS1177 and eNOS. A two‐way ANOVA was used to assess the effects of race and conditions.ResultsNo racial differences were found in the protein expression of PP2A (Fig.
) and eNOS (Fig.
) at baseline or with TNF‐α stimulation. However, AA had a lower p‐PP2AY307 expression (p=0.021; Fig.
) compared to CA HUVECs under both conditions. Additionally, AA had a lower p‐eNOSS1177 expression (p=0.008; Fig.
) compared to CA HUVECs under both condition.ConclusionLower p‐PP2AY307 and p‐eNOSS1177 levels in AA endothelial cells could be attributed to an increase in PP2A activity that can ultimately inhibit eNOS phosphorylation and decrease nitic oxide production. Therefore, PP2A activity can explain, in part, racial differences observed in endothelial dysfunction and consequently cardiovascular diseases.Support or Funding InformationRacial differences in p‐PP2AY307 and PP2A protein expression in HUVECs after 4 hours of incubation with TNF‐α (10ng/ml).A) Densiometric quantification and representative Western blot of p‐PP2AY307 and B) Densiometric quantification and representative Western blot of PP2A. (# p= .02 in AA compared to CA HUVECs, n= 4 independent experiments. Data are shown as mean ± SEM).Figure 1Racial differences in p‐eNOSS1177 and eNOS protein expression in HUVECs after 4 hours of incubation with TNF‐α (10ng/ml).A) Densiometric quantification and representative Western blot of p‐eNOSS1177 and B) Densiometric quantification and representative Western blot of eNOS. (# p= .008 in AA compared to CA HUVECs, n= 4 independent experiments. Data are shown as mean ± SEM).Figure 2AcknowledgementsFunded partially by AU PGOP Fellowship.
Effect of Ethanol Extract of Tetrapleura tetraptera (Schum and Thonn) Taub Leaves on Oral Glucose Tolerance in Normal, Glucose‐induced and Normotensive Female Wistar Rats
Authors: Kareem Oluwatosin Feyikemi , Ishola Ismail , Aderibigbe Olaide Ruth , Ayoola Gloria Abiodun 
Published: April 2020

Traditional Medicine is reported the oldest, widely practiced healthcare system in Africa. This practice has further gained momentum in recent years due to its accessibility, affordability and extensive scientific validation. Leaves of Tetrapleura tetraptera are being used in treatment of diabetes, oxidative stress, hyperlipidemia and managing dysfunctional lipid metabolism (a side effect of the use of sulphonylureas as antidiabetics). However, there has been paucity of information on therapeutic synergy. The present study aimed to evaluate the hypoglycemic effect of Tetrapleura tetraptera ethanol leaf extract on blood glucose levels (BGL) in glucose‐induced hyperglycemic and normotensive rats. Mature female Wistar rats with average weight of 120 g were fasted for 12 h then placed into six groups of five rats each. The following treatment schedules were applied accordingly: no treatment (vehicle); glucose (2 g/kg, control); three groups of glucose‐induced hyperglycemia treated with 100 (TT100GLU), 200 (TT200GLU) and 400 (TT400GLU) mg/kg ethanol extract doses of Tetrapleura tetraptera leaves (EtTT) respectively; and 400 mg/kg extract dose of EtTT (TT400, normotensive). Blood glucose concentration through femoral vein was evaluated at 0, 30, 60, 90, 120 and 150 minutes after oral treatment in all cases. Average fasting blood glucose level in all groups at 0 min was 90± 3.71 mg/dL. All treatment groups showed an elevation in BGL at 30 min with values ranging from 86.20 ± 2.22 in vehicle to 107.4 mg/dL in TT400GLU before a progressive decrease in BGL with increase in time. The decline in BGL of treatment groups was generally not significantly different at p<0.05 from control, however, the extract significantly (p< 0.05) reduced blood glucose in normotensive group (TT400GLU) such that at 150 min, BGL dropped to 59.8 mg/dL and animals were showing symptoms of hypoglycemia. Ethanol extract of T. tetraptera leaves possesses the capacity to lower blood glucose levels thus reducing the tendency for hyperglycemic complications. These results further validate its traditional use and it can be proposed that the leaf extract dose should not be administered singly in fasting conditions as it could lead to hypoglycemia.Support or Funding InformationI am a member of American Society for Pharmacology and Experimental Therapeutics (ASPET) with membership ID 0057705Comparison of fasting blood glucose level of various groups. Data are expressed mean ± SEM for 6 groups of 5 rats each with significant difference tested at p<0.05Figure 1
The Monitoring of Neurochemical Dynamics in Zebrafish Retina using Fast Scan Cyclic Voltammetry
Authors: Zestos Alexander George , Wonnenberg Pauline , Cho Whirang , Connaughton Victoria P. 
Published: April 2020

Dopamine is a crucial neurotransmitter important for several behavioral, pharmacological, and disease states. Cocaine, amphetamine, and other psychostimulants elicit their effects by increasing dopamine in the extracellular space, while Parkinson’s disease is caused by the lack of extracellular dopamine due to the death of dopaminergic neurons. Techniques such as fast scan cyclic voltammetry (FSCV) have been utilized to measure extracellular dopamine and other neurotransmitters through the application of a triangle waveform, which can oxidize and, subsequently, reduce neurotransmitters at the surface of the electrode, producing a cyclic voltammogram where peak oxidative current is proportional to concentration. Utilizing FSCV with carbon fiber microelectrodes (CFMEs) is useful because the carbon electrodes are biocompatible and have both high temporal and spatial resolution. This makes the electrode amenable for the detection of neurotransmitters on a fast subsecond timescale comparable to the fast, phasic firing of dopaminergic neurons.Preliminary studies have illustrated the utility of CFMEs with FSCV for neurochemical detection in zebrafish
(Danio rerio). CFMEs were implanted into zebrafish brain preserved in oxygenated buffer ex vivo with a micromanipulator. The electrodes were also inserted into zebrafish retina for the measurement of neurotransmitter release. The release of neurotransmitters was stimulated by the application of potassium chloride (KCl), amphetamine and cocaine, or electrical stimulation. Significant differences in dopamine levels were observed between wildtype control animals and hyperglycemic (diabetic) zebrafish. Moreover, behavioral assays such locomotor measurement displayed cognitive defects in hyperglycemic animals in addition to the thinning of the retina, which correlated to significant increases in extracellular dopamine in comparison to wildtype animals. Further work includes the examination of raclopride to increase extracellular dopamine, selective serotonin reuptake inhibitors to monitor serotonin, and desipramine to measure norepinephrine dynamics. This study allows for the further investigation of the neurochemical and behavioral effects of hyperglycemia in zebrafish. Future work will extend to the analysis of other monoamines such as serotonin and other dopamine metabolites.Support or Funding InformationNIH STTR: 1R41NS113702‐01Raw for the detection of dopamine in zebrafish retina after potassium chloride stimulation.Figure 1