bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPARC ‐ Anatomical Analysis and Optogenetic Stimulation of TRPV1+ Sensory Fibers in the Renal Cortex
Authors: Tyshynsky Roman , Van Helden Dusty , Larson Erin , Sensarma Sulagna , Schramm Lawrence P. , Vulchanova Lucy , Osborn John W. 
Published: April 2020

Hypertension is a major health concern throughout the world and is the leading contributor to cardiovascular‐related deaths. While drug‐based treatments exist, many patients are drug‐resistant while others do not adhere to their prescribed treatment. To combat these obstacles, clinical trials are currently underway investigating the efficacy of renal denervation (RDN) for the treatment of hypertension. While recent clinical trials support the concept that RDN is efficacious, it is nonspecifically destructive in nature, ablating both sympathetic (efferent) and sensory (afferent) renal nerves. Previous experiments from our group showed via afferent‐specific renal denervation that sensory nerves drive the development and maintenance of the DOCA‐Salt model of hypertension in rats. However, the roles that specific subtypes of sensory renal nerves play in regulating cardiovascular function in a non‐pathophysiological state remain to be elucidated. With this objective in mind, we use large volume tissue clearing and imaging techniques, as well as kidney‐targeted optogenetic modulation of TRPV1+ sensory fibers to better understand the anatomy and function of this subtype of sensory renal nerves.While previous anatomical studies of sensory renal nerves have focused on the innervation of the pelvic wall, here we report a close anatomical relationship between renal glomeruli and sensory fibers. To the best of our knowledge, this has not been quantified previously. Approximately half of the glomeruli analyzed are in close proximity to CGRP+ and/or TRPV1+ sensory fibers. These fibers occasionally appear to penetrate Bowman’s capsules, and they often follow a periglomerular path, contrasting the arteriolar interactions describing sympathetic fibers. Based on these observations and the expression profiles of these sensory fibers, our working hypothesis is that they sense changes in glomerular function, such as glomerular pressure. Further ongoing experiments will directly test this hypothesis.Furthermore, experiments investigating the roles of TRPV1+ renal sensory fibers in cardiovascular regulation and renal function are in progress. Using a custom‐designed optogenetic kidney cup, LED stimulation is applied to the renal cortex in transgenic mice that express channel rhodopsin in TRPV1+ nerve fibers. To define the functions of these fibers, we measure mean arterial pressure and cortical blood flow as physiological outputs of their optogenetic activation. Unilateral optogenetic stimulation applied to the cortex of the mouse kidney results in a decrease in renal cortical blood flow, no change in systemic arterial pressure, and therefore an increase in renal resistance. These results suggest that glomerular TRPV1+ renal sensory fibers may function in a novel sympathoexcitatory reflex.Support or Funding InformationNIH SPARC Award 1U01DK116320‐02, 2018‐2019 MnDRIVE Fellowship
Epigenetic Effects of Finasteride on Human Leydig Cells
Authors: Ihentuge Churchill , Csoka Antonei 
Published: April 2020

Finasteride is a synthetic 4‐azasteroid, used in the treatment of both androgenetic alopecia and benign prostatic hyperplasia. In some men, its use is associated with persistent erectile dysfunction, ejaculatory dysfunction, loss of libido, altered sperm counts and infertility ‐ even after cessation of the drug. This condition has been termed “Post‐finasteride Syndrome” (PFS). We want to understand the underlying biochemical mechanisms that govern the development of this condition. Therefore in this experiment we tested the effects of exposure of finasteride on human Leydig cells, the main hormone‐producing cell of the testis, to identify epigenetic changes in the cells that could be at least partially responsible for PFS. We cultured human Leydig cells in the presence of 0.5 μM finasteride for 14 days and performed whole‐genome DNA methylation analysis using the NimbleGen Human DNA Methylation 3×720K Promoter Plus CpG Island Array and Ingenuity Pathway Analysis. Here we describe initial identification of specific genes and pathways involved that may ultimately lead to treatments to reverse PFS.Support or Funding InformationNIH/NIA (IR25AG047843‐01) to ABC
Personalized determination of target training heart rates for all ages, including patients with heart disease
Authors: Traninger Heimo , Haidinger Manuela , Zemljic-Harpf Alice H. , Harpf Hanns H. 
Published: April 2020

BackgroundLack of physical exercise was recently accepted as a clinical diagnosis (ICD‐10‐CM Z72.3). The prescription of exercise requires a personalized training plan. Currently the Karvonen formula is used to calculate a target training heart rate (HR) by subtracting the age from 220. Because of individual differences in aerobic exercise capacities, resting parasympathetic tone, cardiac disease state, co‐morbidities, and medications (especially beta blocker), we suggest applying treadmill exercise tolerance testing to determine a personalized training HR zone, including patients with heart disease.Methods and study protocolIn 1999, the Austrian ambulatory cardiac rehabilitation was established and currently includes 12 centers. The cardiac rehabilitation program consists of three phases; phase I begins during the hospital stay, while phase II (6 weeks, 4 times/week) and phase III (up to 13 months, 2 times/week) are conducted in ambulatory cardiac rehabilitation centers under physician supervision. Additional home‐based training is recommended every day of the week. Male and female subjects participating in phase II and phase III rehabilitation underwent initial screening, and subjects with aortic stenosis, low systolic output (EF% < 15), and dyspnea at rest (NYHA Class IV) were excluded. Bicycle ergometer exercise protocols used were 10W/10W/min (~90% of subjects) or 20W/20W/min (~10% of subjects) and HR was monitored continuously to generate a continuous HR curve to show a clear HR deflection point.ResultsWe retrospectively analyzed 9042 ECG treadmill test results (male = 7053, female = 1989) conducted at the Center for Ambulatory Rehabilitation Graz between 1‐1‐1999 and 10‐31‐2019. No significant difference in maximal training capacities was found between male and female subjects. Under physician supervision treadmill exercise tolerance testing was safe and well tolerated by maximally challenged male and female subjects of all ages, and no cardiac or cerebral events occurred during or after treadmill testing. The HR deflection point was assessed for each subject. The personalized training HR zone was compiled of 80–95% of the HR deflection point (not 220‐age), and training initiated during phase II and continued during phase III. Subjects were encouraged to achieve optimal training HR for 30 minutes daily and advised to perform muscle strengthening exercises twice per week.ConclusionOur study shows that optimal training heart rates can be determined by treadmill exercise testing, when patients are maximally challenged. Once “true” exhaustion is tested (which is often not achieved) a personalized target training HR zone can be calculated utilizing the individual HR deflection point. This approach will offer two advantages: 1) evaluation of underlying cardiovascular disease (cardiac ischemia), and 2) determination of an individualized and recommended target training heart rates for the “medical prescription of exercise”.
Involvement of ER stress‐mediated sEH Activation in Myocardial Ischemia‐Reperfusion Injury
Authors: Xue Hong-Mei , Sun Wen-Tao , Chen Huan-Xin , Wang Jun , He Guo-Wei , Yang Qin 
Published: April 2020

ObjectivesPrevious studies have suggested the role of endoplasmic reticulum (ER) stress in myocardial ischemia/reperfusion (I/R) injury and inhibition of soluble epoxide hydrolase (sEH) was found to be protective against I/R‐induced injury. Whether ER stress mediates myocardial I/R injury via regulating sEH remains uninvestigated. The present study aimed to understand the role of ER stress‐sEH signaling in cardiac and coronary function in an in vitro rat model of myocardial I/R.MethodsIsolated rat hearts were randomly divided into four groups including control, I/R, and I/R groups pretreated with either the IRE1α inhibitor GSK2850163 or the sEH inhibitor dicyclohexylurea (DCU). The hearts were mounted on a Langendorff apparatus and I/R groups were subjected to 30‐min global ischemia followed by 60‐min reperfusion. GSK2850163 and DCU were perfused for 15 min prior to the onset of ischemia. Left ventricular function was monitored during the experiment. Branches of the left anterior descending artery were isolated after I/R for study of endothelium‐dependent vasorelaxation in a myograph. The protein expression of IRE1, phosphorylated IRE1 (p‐IRE1), and sEH was determined by western blotting.ResultsLeft ventricular end diastolic pressure (LVEDP) was increased and the maximum velocity of contraction (+dp/dtmax) and relaxation (‐dp/dtmax) of the left ventricle was decreased during I/R, which could be partially reversed by GSK2850163 or DCU pretreatment. Relaxant response of coronary artery to acetylcholine was also improved by GSK2850163 or DCU. Inhibition of IRE1 phosphorylation by GSK2850163 significantly downregulated the protein expression of sEH.ConclusionsActivation of sEH induced by the IRE1 branch of ER stress is involved in I/R‐induced cardiac dysfunction, in which impairment of coronary dilator function is an important contributing factor.Support or Funding InformationSupported by NSFC 81870227 & 81870288, Tianjin Science and Technology Commission (18PTZWHZ00060) & Binhai New Area Health Bureau (2018BWKZ005), and Non‐profit Central Research Institute Fund of Chinese Academy of Medical Sciences 2018TX31002 & 2019XK310001.
Do Changes in the Composition of Bone Marrow Adipose Tissue Affect the Development of Osteoarthritis?
Authors: Shepherd Rebecca F , Allison Kathryn , Rhodes Bryan , Kerns Jemma G , Taylor Adam M 
Published: April 2020

There are three types of adipocytes in the human body, classified as white, brown and beige. Bone marrow adipose tissue (BMAT) is often described as having a heterogeneous appearance and has been suggested to be a distinct class of ‘yellow’ adipocytes. However, recent studies have also identified beige‐like adipocytes present in the bone marrow cavity, and they appear to have a relationship with the formation of bone like structures found in patients with osteoarthropathies, termed trabecular excrescences. The BMAT in osteoarthritic (OA) patients has an increased number of adipocytes compared to healthy and osteoporotic bone marrow. The objective of this study was to identify changes in BMAT composition between non‐osteoarthritic and osteoarthritic (OA) bone samples.Human joint samples from 28 patients (14 non‐OA, 14 OA) were obtained with informed consent from patients undergoing joint surgery at University Hospitals of Morecambe Bay NHS Trust (Lancaster, UK). North of Scotland NHS Research Ethics Committee (UK) approved this research. Samples were prepared for routine histological analysis and flow cytometry. Flow cytometric analysis gated for adipocytes by size and lipid content. Markers for adiponectin (Acrp30), uncoupling protein 1 (UCP1) and myogenic factor 5 (Myf5), were used to distinguish between white, beige and brown adipocytes. To corroborate the results, sections of joint tissues underwent immunohistochemical analysis. The anatomical location of the adipocytes within the bone marrow cavity was also studied.The data analysis showed an approximate 9:1 ratio of white to beige adipocytes found within BMAT, with only trace amounts of brown adipocytes identified. Statistical analysis to account for disease, age and biological sex demonstrated no significant difference in the adipocytes present between control and OA samples. However, male sex and ageing were shown to be factors for an increase in beige adipocytes. The histological study confirmed the presence of beige adipocytes and showed that, when present the beige adipocytes were found closer to the bone surface than the centre of the bone marrow adipose tissue.Previous studies have argued that BMAT is a distinct class of adipocyte. This study has demonstrated the presence of beige adipocytes within the BMAT of patients with and without OA. The methods used give a quantitative method of identifying different types of bone marrow adipocytes. Understanding changes in the anatomical composition of BMAT and the role of adipocytes in skeletal health may prove important in understanding the progression of age associated bone disorders.Support or Funding InformationThis work was funded by the Anatomical Society and sponsored by the American Association for Anatomy.
Mathematical Modeling of In Vitro‐In Vivo Atypical Kinetics of Diazepam
Authors: Wang Zeyuan , Nagar Swati , Korzekwa Ken 
Published: April 2020

Cytochrome P450 (CYP) and uridine 5'‐diphospho‐glucuronosyltransferase (UGT) enzymes are responsible for metabolism of most marketed drugs. Due to the large binding sites of certain CYPs and UGTs, CYP and UGT substrates tend to show non ‐ Michaelis‐Menten kinetics (atypical kinetics). Although several in vitro data provide evidence for the existence of atypical kinetics, this characteristic is seldom observed with in vivo data. The purpose of this project is to characterize the atypical kinetics of diazepam and its sequential metabolism in in vitro and in vivo systems. Numerical methods will be used to obtain kinetic parameters, which will be used for in vitro‐in vivo correlations (IVIVC).Diazepam, which exhibits atypical kinetics in vitro, and its primary metabolites (temazepam, nordiazepam), and secondary metabolite (oxazepam) were characterized with in vitro studies with pooled male Sprague Dawley rat liver microsome (MRLM), pooled female Sprague Dawley (FRLM), and purified rat cyp isoforms (cyp3a1, cyp3a2, and cyp2c11) separately. Rat microsomal partition and rat plasma protein binding assays were conducted via equilibrium dialysis to determine the free fraction of the drug. Two substrate binding (ESS) models provided better fits than one substrate (ES) models, as determined from the resulting AICc values. Preliminary in vitro data from MRLM and cyp3a1 showed obvious sigmoidal saturation curves for temazepam formation. Only cyp3a1 show significant sigmoidal curves for nordiazepam formation. For cyp3a1, Km and Vmax values for temazepam and nordiazepam calculated with the EES model are significantly different from those with the ES model. The intrinsic clearance (CLint) values calculated from the MRLM and cyp3a1 ESS models is not constant within the observed range of diazepam plasma levels of rats. No obvious sigmoidicity of diazepam saturation curves was observed for cyp3a2 (male‐specific) and cyp2c11 (male‐specific) isoforms, which are other cyp isoforms responsible for diazepam metabolism in male rats. In order to characterize in vitro‐in vivo correlations for diazepam, in vivo PK studies with female and male rats are currently underway.Support or Funding InformationThis research was supported by NIGMS grants: R01GM114369 and R01GM104178.
Agreement between ACSM’s equation and cardiopulmonary exercise test in determine maximal oxygen uptake in individuals with metabolic syndrome
Authors: Ceolin-Nascimento Reginaldo , Cepeda Felipe Xerez , DeMoura José Roberto , Camargo Fernanda Cristina Ferreira , Fortes-Queiroz Lucas , Ferreira Fabiana Gonçalves , Hussid Maria Fernanda , Consolim-Colombo Fernanda M. , Correia Marilia Almeida , Trombetta Ivani Credidio 
Published: April 2020

PurposeLow functional capacity is associated with cardiovascular risk factors. Cardiopulmonary exercise test (CPET) is the gold standard evaluation to determine functional capacity through maximal oxygen uptake (VO2max) measurement. However, the high financial cost, the material and the time spent on this method difficult its use in a large number of clinicals. In this sense, it is possible to determine VO2max via the equivalence formulas. The aim of this study was to verify the agreement between indirect calculation of VO2max using American College of Sports Medicine (ACSM) equation and the directly measure of maximal oxygen uptake in metabolic syndrome (MetS) patients.MethodsSixty non‐diabetic and without medication patients with MetS (ATP‐III) were divided in 2 groups, according to gender: Male (n=32; 46±9 y; 31.2±3.0 kg/m2); and Female (n=28; 49±9 y; 32.7±3.1 kg/m2). VO2max was measured during CPET in a cycle ergometer with ramp protocol and estimated by ACSM’s equation [VO2= 7.0+ (1.8 x work rate)/body mass].ResultsAll patients included achieved respiratory exchange rate (RER=VCO2/VO2) >1.10 at maximal exercise. In Male group, despite correlation between methods (R=0.78; P=0.0001), VO2max estimated by ACSM’s equation was higher than the VO2max of the direct measurement (28.7±3.1 vs. 26.9±6.0 ml/kg/min; P=0.049). Similarly, in Female group there was correlation (R=0.79; P=0.0001), however VO2max estimated by ACSM’s equation was higher than direct measured VO2max (20.3±3.3 vs. 18.8±3.3 ml/kg/min; P=0.0008). In both genders, Bland‐Altman plot analysis suggested a lack of agreement between predicted and direct VO2max.ConclusionIn bout groups, Male and Female, the ACSM’s equation overestimates the VO2max. It seems that ACSM’s equation is not capable of accurately predicting VO2max in men and women with MetS.
Anatomy Tour at the Mall; an Outreacha Activity for the Public by Nursing and Physical Therapy Students
Authors: Sola Maryvi Gonzalez , George Michael , Woodson Cassandra , Junious Victoria , Jose Aleena , Rosario Martin G. 
Published: April 2020

IntroductionAnatomical kinesthetic education is one of the best active learning techniques to educate clinicians to avoid having limited exposure to clinical training. An outreach entitled ‘Anatomy Tour at the Mall’ allows students to practice while interacting with the public who could benefit from these anatomical educational activities.Aims1. Have the nursing and physical therapy (PT) students give participants a pre‐test, 2. engage with the public by teaching them anatomy and execute non‐invasive free tests including vital signs, balance and visual tests, and 3. giving them a post‐test and survey. The hypothesis is this activity will allow the students to assimilate knowledge by practicing their skills while edifying the public, which will likewise learn significantly by participating.MethodsA 10‐question pre‐test (1 point each) was given at the beginning to the public after signing a consent form (IRB approved). Then, participants will pass by 6 stations about the following systems: respiratory, nervous, special senses, musculoskeletal, cardiovascular and human organs, managed by both nursing and PT students. Finally, a 10‐question post‐test (1 point each) and a survey were given to the participants and students.ResultsA total of 77 male and female individuals participated and completed the pre‐test (average 5.42), but only 57 completed the post‐test (average 7.24, 0.00 t‐test, 1.28
st.dev) achieving higher scores in all the stations except for the musculoskeletal. Also, 64 participants rated the Anatomy tour with A, 6 B, and 1 C. Finally, a 1–5 Likert scale of the Anatomy tour being ‘worthy of their time’ and ‘completely beneficial activity’ (both 1 being ‘strongly disagree’ and 5 being ‘completely agree’), the median was 5. The student’s survey revealed that out of 28 students, 15 rated the activity with A, 11 B, and 2 C, 24 students said this activity was beneficial for their future careers and 25 would consider participating again. Additional data is currently being collected and yet to be analyzed.Discussion and ConclusionBoth the students and the public agreed on this activity is beneficial and constructive for their education. The overall post‐test indicates the public learned about the aforementioned anatomical stations.Support or Funding InformationFaculty Scholarship Award by West Coast University
Chronic Kidney Disease Impact on Total Joint Arthroplasty Outcomes: A National Inpatient Sample Based Study
Authors: DiMagno Allyson N , Hussein Inaya Hajj , Sayeed Zain , El-Othmani Mouhanad M 
Published: April 2020

INTRODUCTIONIn the United States, chronic kidney disease (CKD) affects roughly 11% of the population or 19.2 million people. As the prevalence of CKD and demand for total joint arthroplasty (TJA) continue to rise, it is critical to assess the impact of CKD on post‐operative clinical and economic outcomes.METHODSDischarge data from 2006–2011 National Inpatient Sample (NIS) was used for this study. A total of 851,150 TJA patients were divided into 3 cohorts: Group 1 included no CKD, CKD Stage I, and CKD Stage II; Group 2 included CKD Stage III and Stage IV; Group 3 included CKD Stage V. Inverse Probability of Treatment Weighting (IPTW)/Propensity Score Weighting was used to predict outcome variables as a function of age, sex, and Elixhauser comorbidities. Patients were compared against group I for in‐hospital postoperative outcomes.RESULTSStage III/IV CKD patients undergoing primary TJA had higher odds of any complication (odds ratio [OR], 2.63; P<0.0001), longer length of stay, and higher total charge (length of stay [LOS], 4.34 vs 3.48 days; total charge, $56,003 vs $46,115; P<0.0001) when compared to patients with no CKD/Stage I or II. Similarly, Stage V CKD patients undergoing primary TJA had higher odds of any complication (OR, 1.64, P<0.0001), longer LOS, and higher total charges (LOS, 5.81 vs 3.48 days; total charge, $59,869 vs $46,115) than their counterparts with no CKD/Stage I or II CKD.DISCUSSIONOur results indicate that Stage III, IV, or V CKD, compared with those with no CKD, Stage I or II patients are at a greater risk for postoperative complications and consume more resources following TJA.
Crosstalk between brown adipocytes and macrophages
Authors: Zurkovic Jelena , Sanyal Abhishek , Mass Elvira , Schlitzer Andreas , Pfeifer Alexander 
Published: April 2020

There are two types of adipose tissue (AT): white adipose tissue (WAT), which is involved in energy storage, and brown adipose tissue (BAT) that dissipates energy in the form of heat (non‐shivering‐thermogenesis). AT acts as an endocrine organ that secretes hormones or cytokines known as adipokines. Dysregulation of secretion of adipokines, caused by adipocyte hypertrophy and dysfunction, is directly linked to chronic inflammation. Inflammation of WAT during obesity leads to increased expression and secretion of pro‐inflammatory cytokines such as TNF‐α, IL‐6, MCP‐1 (Villarroya et al., 2018). This increase in adipocyte‐derived pro‐inflammatory cytokines causes a dramatic shift in the immune cell population, especially in macrophages, and leads to metaflammation. On the other hand, adipose tissue‐resident macrophages (ATMs) play a very important role in innervation and energy expenditure of BAT (Wolf et al., 2017). All these facts are the reason why we investigate signal pathways as well as secreted molecules that play a role in the communication between brown adipocytes and ATM. We are focusing on the crosstalk between brown adipocytes and macrophages. We used three in vitro models: direct co‐cultivation, transwell system and conditioned medium. In our experiments, we used two different types of macrophages: fetal liver derived macrophages (FLDMs) and bone marrow derived macrophages (BMDMs). We found that macrophages regulate expression of adipogenic (e.g. PPARg) as well as thermogenic (e.g. UCP1) markers. Interestingly, we observed that brown adipocytes produce different factors that regulate macrophages and their pro‐ versus anti‐inflammatory phenotype. These data indicate a crosstalk between macrophages and adipocytes in BAT.Support or Funding InformationInstitute of Pharmacology and Toxicology, University of Bonn, 53127 Bonn, Germany Research Training Group 1873, University of Bonn, 53127 Bonn, Germany