bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of cardiomyocytes in right ventricle viscoelasticity with pulmonary hypertension development
Authors: LeBar Kristen , Liu Wenqiang , Roth Kellan , Ahern Matt , Evans Erith , Pang Jassia , Ayers Jessica , Chicco Adam , Wang Zhijie 
Published: May 2022

BackgroundThe myocardium is viscoelastic, which means there exists elastic and viscous resistant forces during cardiac motion. It has been shown that cardiomyocyte (CM) or muscle fiber has significant viscoelasticity, and microtubule depolymerization via colchicine treatment reduces the CM’s viscoelasticity. However, most prior study is focused on the left ventricle, and the role of CM in right ventricle (RV) viscoelasticity in healthy and pulmonary hypertensive (PH) states is poorly understood. Our goal is to evaluate the contribution of CM to RV viscoelasticity in healthy and PH rats. We hypothesize that CM contributes to both healthy and PH RV viscoelasticity.MethodsAll procedures were approved by Colorado State University IACUC. 6‐week‐old male rats were treated with 3‐week monocrotaline (MCT) (60 mg/kg) to induce PH, and intact healthy rats served as control. RV function was quantified by echocardiography and in vivo pressure‐volume (PV) measurements. After euthanasia, RV free wall underwent equibiaxial stress relaxation in a relaxant bath to obtain passive, biaxial viscoelasticity pre and post colchicine treatment (0.3mM). The tissue was stretched at 20% of strain and with physiological ramp speed (5Hz). Relaxation modulus and normalized stress at 0.01 s were used to quantify elasticity and viscosity. Student t test was performed.ResultsIn vivo RV function measurements showed the development of PH and RV failure in MCT rats (Table 1). Marked RV dilation and decreased fractional shortening confirmed the RV failure establishment. PV loop data with fewer samples (n=3) also implies declines in cardiac output, contractility (Ees) and ventricular‐vascular coupling (Ees/Ea). At the baseline, PH development led to increased viscoelasticity in the RV (Fig. 1). Mechanical data before and after colchicine treatment showed reduced elasticity in both healthy and MCT RVs (Fig. 1A&B). The percentage reduction in elasticity was similar between groups, indicating a similar contribution of CM to RV elasticity. Unexpectedly, we did not observe significant change in viscosity after colchicine treatment in both groups (Fig. 1C&D). Moreover, the control RVs were isotropic, whereas the MCT RVs showed marked anisotropy in elasticity (Fig. 1B).ConclusionOur results demonstrated similar impact of CM on RV viscoelasticity before and after PH development, despite the CM hypertrophy. Colchicine reduced elasticity in healthy and MCT RVs, but minimally changed RV viscosity. These findings will deepen the understanding of biomechanical mechanism of RV failure associated with viscoelastic changes.
Increased Integration in Mutant Mice: An Analysis of the Patterns of Covariance through Ontogeny in Fgfr2 Mice
Authors: Ogg Miette L. , Pennings Amanda N. , McNulty Margaret A. , Holmes Megan A. , Mussell Jason C. , DeLeon Valerie B. 
Published: May 2022

Mutations in the FGF/FGFR2 gene result in the premature fusion of fibrous and cartilaginous joints in the skull. This results in profound morphological changes in the skulls of both humans and mice with these mutations. Previous studies have indicated that morphological integration of the skull is expected to become more pronounced in dysmorphic syndromes, including FGFR2 syndromes which result in craniosynostosis. In this study, our objective was to test two hypotheses: 1) that the magnitude of morphological integration was greater in Fgfr2C342Y/+ mutant mice relative to wild‐type littermates; and 2) that the magnitude of morphological integration would increase through ontogeny.Our sample included Fgfr2C342Y/+ mutants and wild‐type littermates at postnatal day 14 (P14) and adult stages. We used micro‐computed tomography (microCT) scans to create image volumes of the skull. Virtual reconstructions of the cranium were produced in 3DSlicer software, using volume renders based on tissue densities to define the surface of the bone. We collected coordinate data for 38 biologically homologous landmarks with approximately equal distribution across face and neurocranium. All morphometric analyses were conducted using the geomorph package in R. The sample was subdivided by Age and Genotype. Landmark coordinates were divided into face and neurocranium modules. Coordinate data for each subset were superimposed with object symmetry using the bilat.symmetry() function. Covariance across modules was tested using the two.b.pls() function for each sample subset.Results confirmed our expectation that the magnitude of covariation between face and neurocranium increased in the mutant sample relative to the wild‐type sample at both timepoints. Surprisingly, within the mutant sample, integration between face and neurocranium was greater in the younger P14 mice than the older adults. Results of this study can be used to inform researchers about patterns of covariance that can be applied to better understand craniosynostosis syndromes that affect humans.
Effect of acetaminophen treatment on endocrine pathways in placenta: Proteomics investigation in JEG‐3 cell model
Authors: Naji‐Talakar Siavosh , Kruger Laken , Prasad Bhagwat 
Published: May 2022

Acetaminophen (APAP) is the most used medication for pain and fever in pregnancy, but recent studies have elucidated in uteroAPAP as an endocrine disruptor associated with neurocognitive disorders. The placenta is a vital endocrine organ and disruption in metabolic pathways have been associated with adverse fetal neurodevelopment such as attention deficit hyperactivity disorder (ADHD) and autism. The aim of this study was to investigate the effect of APAP treatment on androgen pathways in JEG‐3 placental cells.JEG‐3 cells were seeded in 6 well plates at 100,000 cells per well and treated with the vehicle control (DMSO) and 0.1, 0.3, and 0.9 mM APAP for 72 hours, in triplicate. Cells were harvested and samples were digested with trypsin. Global proteomics data were acquired using a Q‐Exactive HF Quadrupole‐Orbitrap mass spectrometer (Thermo Fisher Scientific, Waltham, MA) followed by data processing by MaxQuant (version 1.6.8.0) using the Andromeda search engine. Unique and significantly different (upregulated or downregulated) proteins were identified. Label‐free quantification (LFQ) intensities of sex‐steroid pathway proteins were compared across control and treatment groups.Proteomics data analysis detected 2338 – 2560 total proteins with 1953 proteins in common between all treatments. The vehicle control group had 88 unique proteins and APAP treatment groups ranging from 0.1, 0.3, and 0.9 mM resulted 62, 55, and 157 unique proteins, respectively. Treatment with APAP upregulated ~200 proteins and downregulated ~40 proteins representing critical metabolic processes. APAP treatment elevated the level of AKR1B1 by at least 63% across all treatment groups. There was no change in the levels of SOAT1, CYP19A1, and STS in any treatment group. Interestingly, ABCG2 was uniquely detected in the lower APAP treatments.Sex steroid metabolism plays a significant in utero role in brain and reproductive development of a fetus. Determining how APAP disrupts endocrine pathways is critical in managing pain treatment guidelines in pregnant women. This is the first study investigating the effect the APAP on sex steroid related proteome in placental cells, which when validated by our metabolic and activity assays, will provide a critical mechanistic information towards mitigating adverse effects of APAP.
Perception of Pharmacology Instruction and Confidence in Independent Prescription Among Osteopathic Medical Graduating Seniors
Authors: Eldeeb Khalil 
Published: May 2022

The prescription of medicines is one of the most critical acts performed by physicians. With millions of drugs prescribed every year, poor prescribing may potentially impact patient safety and healthcare costs. Pharmacology curriculum varies in length, content, instruction methods, and assessment even within similar health‐related programs. Doctor of Osteopathic Medicine (DO) students' perceptions of these variations and their effects on their confidence to independently prescribe is not thoroughly studied.MethodsThis study reviewed the DO graduating seniors' evaluation of time devoted to clinical pharmacology and therapeutic management instruction and how confident they are to write safe and indicated orders and prescribe therapies or interventions in various settings without direct supervision. This study reviewed and analyzed a secondary database of the graduating seniors' survey published by the American Association of Colleges of Osteopathic Medicine from 2012‐2013 to 2020‐2021.ResultsThe graduating seniors reported that the time devoted to clinical pharmacology instruction as appropriate increased from 78% in 2012/2013 to 87% in 2020/2021. On the other hand, no change in the percentage of graduating seniors who reported that the time devoted to therapeutic management instruction was appropriate in 2012/2013 and 2020/2021. The percentage of graduating seniors who feel very confident and somewhat confident to prescribe therapies or interventions in various settings without direct supervision was below 70% between 2012/213 and 2018/2019. Over the last two academic years, 2019/2020 and 2020/201, the percentage increased to 93% and 77%, respectively.ConclusionWhile most of the DO graduating seniors reported that the time devoted to clinical pharmacology and therapeutic management instructions as appropriate, their current confidence level to prescribe independently might highlight the need to update the pharmacology curriculum to emphasize the development of prescription skills.
Cortisol Receptor Sensitivity as a Risk Factor for Depression
Authors: Michielli Michela , Cohen Brian 
Published: May 2022

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic‐Anterior‐Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).Our research has examined mutations known as single‐nucleotide‐polymorphisms (SNPs) relating to cortisol‐receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and depression. The relationship between SNPs relating to receptor sensitivity and depression in patients will be established by analysis of SNPs in coordination with data from psychological inventory assessments collected for each patient. Patient samples and clinical information was collected from adult patients diagnosed with depression by collaborating physicians. Quantitative polymerase chain reaction (qPCR) was used for genotyping. Analysis of the data yielded no significant correlation between SNPs relating to GR or MR and depression as scored by the Beck Depression Inventory (BDI). However one SNP in GR (rs33389) and one SNP on the 11β‐hydroxysteroid dehydrogenase type 1 gene (rs12086634) correlated with scores on the Mindful Attention Awareness Scale and State Trait Anxiety scale, respectively.Current studies focus on SNPs involved in the regulation of GR and MR activity that are not directly found in those receptors such as the FKBP5 GR co‐regulator protein. Investigating other non‐GR and MR SNPs could provide alternate explanations for cortisol sensitivity beyond the receptors themselves. In analyzing genetic differences relating to cortisol sensitivity in patients clinically diagnosed with depression, we aim to determine if an imbalance in an individual’s response to cortisol is linked to depression. If such a relationship can be established, this can provide physicians with a screening tool to better inform them of a patient’s risk factors for depression.
Uncovering the Perceptions of Grades in Dentistry Students – How Grades are Impacting Learning & Clinical Development
Authors: Yuen Jenna J. , Horne Andrew , Beveridge Tyler S. , McLean Sarah 
Published: May 2022

IntroductionGrades in healthcare professional schools may be doing more harm than good. In fact, educators and researchers suggest grades have lasting negative impacts on professional development and the ability to navigate clinical settings (i.e., impairs self‐regulated learning, interferes with developing patient‐care competencies, and decreases levels of empathy). Although some studies have incorporated grade perceptions into their investigations, we lack research dedicated to primarily understanding the student’s perception of grades, and whether they think grades help or hinder the quality of their clinical learning.AimsThe first aim of this study is to identify the most prevalent grade perceptions among dentistry students. The second aim is to explore the underlying contributing factors and to determine how dentistry students’ grade perceptions are influencing their learning and clinical development.MethodsTo address the first aim, we distributed an online survey to dentistry students at the Schulich School of Medicine & Dentistry. To address our second aim, we conducted virtual semi‐structured interviews and a focus group on the same population of dentistry students. Survey results guided and informed interview/focus group discussions. Qualitative data was analyzed through an inductive thematic process.ResultsFourteen grade perception themes were identified. The three most frequent perceptions were grades as a tool for ranking students, an evaluation tool to test knowledge and comprehension, and a feedback tool on comprehension. Seventy students participated in the survey; 70% agreed that grades guided their learning/studying strategies; 91% agreed grades reflected their ability to memorize content; 85% did not think grades accurately represented their practical skills; and 89% agreed that grades determined their acceptance into specialty/residency programs.Nine students participated in the interviews/focus group. Emerging topics included the importance of grades during specialty/residency applications, the disconnect between grades on a 0‐100% scale and clinical development, and mixed opinions about grades facilitating learning. Characterization of dentistry students’ perceptions towards grades in a clinical learning environment is ongoing.ConclusionDentistry students commonly perceive grades as a ranking tool because of its central role in specialty/residency applications. While some note that grades help their learning, the majority of students agree that grades reflect memorization of content. Our data also suggest students do not find grades on the 0‐100% scale helpful in their clinical development because it does not indicate whether professionally acceptable standards are met. Findings obtained from our study brings students’ voices to the forefront of the ongoing discussion about grades, and may provide important considerations for future healthcare professional curricula.
Preservation of Right Ventricular Contractility After Transient Phenylephrine‐Induced Pressure Overload in Swine
Authors: Konecny Filip , Weil Brian R. 
Published: May 2022

ObjectiveWe have previously demonstrated that a transient phenylephrine (PE)‐induced rise in systemic arterial blood pressure leads to reversible left ventricular (LV) systolic dysfunction in the absence of ischemia (i.e., “stretch‐induced stunning”). However, the extent to which this phenomenon occurs in the right ventricle (RV) is unclear. Accordingly, the present study was designed to assess changes in pulmonary artery (PA) pressure and RV function during and after systemic administration of PE in swine.MethodsClosed‐chest propofol‐anesthetized swine (n=5) were instrumented with a Swan‐Ganz catheter and an admittance catheter for continuous measurement of PA pressure, RV pressure, and RV volume (ADV500; Transonic SciSense, Inc.). Ventricular end‐diastolic and end‐systolic volumes were assessed by multi‐detector computed tomography with iodinated contrast (1 mL/kg at 4 mL/s) before, during, and 30‐minutes after transient pressure overload elicited by a 1‐hour intravenous infusion of PE (18 mg/hour). Load‐independent RV systolic function was derived from RV pressure‐volume loops collected during inferior vena cava occlusion at baseline and 30 min after PE.ResultsPE elicited a significant rise in PA pressure (27±1/14±1 to 43±1/23±31mmHg; p<0.05) and RV pressure (25±2/3±1 to 44±2/8±2 mmHg; p<0.05) that normalized 30‐minutes after the end of the infusion period (PA: 28±1/11±1 mmHg; RV: 29±5/4±2 mmHg). This was accompanied by a significant increase in RV end‐diastolic and end‐systolic volumes and decrease in RV ejection fraction that tended to persist 30‐minutes after cessation of PE (Table; top panel). However, load‐dependent (dP/dtmax) and load‐independent (ESPVR and PRSW) parameters of RV systolic function were preserved after PE‐induced TPO (Table; bottom panel).ConclusionsDespite causing a significant rise in RV preload volume and pressure, transient PE‐induced pressure overload is not associated with RV contractile dysfunction during the post‐infusion period. The absence of stretch‐induced stunning in the RV may be linked to inherent differences in compliance relative to the LV as well as a diminished pressor response to PE in the pulmonary vs. systemic circulation.
Quantitative analysis of straight length of the external ear
Authors: Mokhtar Abd‐Elmagid Ahmed Elsir , Elfaki Amani A. , Şahin Bünyamin , Medani Khalid , Ali Qurashi M. , Babikir Haydar E. , Nahir Mert , Demir Osman , Elmustafa Shamail D. A. , Mohammed Noor Abdulrahman 
Published: May 2022

IntroductionClinical anatomy of the external ear canal (EEC) has a significant role in the diagnosis of Otitis Media (OM) and other auditory system diseases. OM is one of the most common infections and major causes of morbidity in adults if the complications of the OM take place. In the developing and low‐income countries, the OM has a direct and indirect role in their life, because it’s one of the causes leading to doctors’ visits, and the indirect costs may affect the families and economy. EC measurements are needed in daily life, as an example; in the ears plugs manufacturing.MethodThis study was conducted by the Declaration of Helsinki, and approved by the research ethics committee at the Faculty of Medicine, University of Gezira, Sudan, this observational case‐control study. Informed consent was obtained from all‐volunteer participants enrolled in the study. From January 2015‐2018, temporal bone computed tomography (CT) images of volunteer patients and healthy subjects, were collected from Khartoum State. ImageJ software (V 1.52a), used in the measurement of EC; OsiriX image processing application for Mac (OsiriX Lite) to display images for the external ear area of the skull’s temporal bone, statistical analysis was performed by Statistical Package for the Social Sciences SPSS V.22, and statistical software suite developed by SAS Institute (The SAS System V.9). The level of significance was set at P‐value <0.05. Chi‐Square test was used and Receiver Operating Characteristic (ROC) analysis was applied to determine the power of straight length (SL) in predicting patient.ResultsIn the cases the total number is 140 (patient 70 and healthy 70), with a range of 18–40 years, 52.9 % (n=74) of the patients were females and 47.1% (n=66) are males. The distribution of quantitative variables shows that the mean of the straight length (SL) is ±34.13, Standard Deviation (SD) ± 5.83, and the minimum and maximum SL are 11.33 and 47.00, respectively. Distribution of quantitative variables by a case in SL, shown that the patients mean ±32.69, SD ±6.58; and the healthy mean ±35.58 SD ±4.66, t ±3.106 and the P‐value <0.003. Distribution of SL by Gender shown that in male mean ±34.89, SD ±6.22, female mean ±33.45, SD ±5.42. Distribution of SL by Side shown that left side means ±34.14, and SD ±5.66, right side mean ± 34.12, and SD ±6.04.ConclusionIf the straight length (SL) value is equal to 31.33 or less, the case sample is classified as an otitis media patient. There is a highly significant difference in the SL between male patients and healthy a p‐value <0.061 and between females’ patients and healthy as a p‐value<0.016. and significance differences comparing the patients and healthy groups with the gender, result shown that t =2.909 in males and females t=2,456.
The activation of C1 neurons during REM sleep is dependent on the arterial baroreflex
Authors: Souza George M. , Stornetta Daniel S. , Abbott Stephen B. 
Published: May 2022

IntroductionNatural sleep‐wake patterns are associated with changes in sympathetic nerve activity (SNA) controlling cardiovascular function. The mechanisms underlying the effects of sleep‐wake state on SNA are not well understood. C1 neurons in the rostral ventrolateral medulla regulate cardiovascular function through SNA and mediate the sympathetic arterial baroreflex. In this study we determine the effect of sleep‐wake transitions on the activity of C1 neurons and investigate the contribution of the arterial baroreflex to these effects.MethodsThe activity of C1 neurons was measured using fiber photometry (calcium imaging) in freely behaving adult rats while monitoring the vigilance states. C1 neurons were targeted with GCaMP7s by microinjection of AAV1‐syn‐FLEX‐jGCaMP7s in the RVLM of Tyrosine Hydroxylase‐Cre transgenic rats, an optical fiber was implanted above the injection site, rats were fitted with a EEG/EMG head stage to monitor sleep‐wake state, and a radio telemetry probe to record BP. One month after the surgery, C1 neuron activity was recorded before and 7 days after sino‐aortic denervation to eliminate inputs from arterial baroreflex. Normalized fluorescence changes are expressed as Z‐score (mean ± SD) and t‐test was used to determine statistically significant differences.ResultsC1 activity was increased by acute hypotension induced by sodium nitroprusside (2.1 ± 0.5 vs. ‐0.92 ± 0.4, p<0.0001, n=5), indicating the barosensitive nature of the recorded cells. C1 activity increased during transitions from NREM to wake (‐0.60 ± 0.1 vs. 0.59 ± 0.2, p<0.0001, n=6) and decreased during transitions from wake to NREM (0.34 ± 0.2 vs. ‐0.32 ± 0.2, p<0.0001, n=6). C1 activity increased during transitions from NREM to REM sleep (‐0.74 ± 0.1 vs. 0.77 ± 0.1, p<0.0001, n=6) and decreased in transitions from REM to wake (0.58 ± 0.2 vs. ‐0.59 ± 0.2, p<0.0001, n=5). Baroreceptor denervation attenuates the increase in C1 neuron activity during REM sleep (0.4 ± 0.7 vs1.8 ± 0.4 Δ Z‐score, p=0.0054, n=4) and during wakefulness (0.59 ±0.6 vs 1.6 ± 0.4, p=0.0210, n=4) when compared to the increase before sino‐aortic denervation.ConclusionC1 neuron activity during sleep‐wake transitions mirrors the pattern of SNA. This observation indicates that C1 neurons contribute to changes in SNA associated with natural sleep‐wake patterns. Baroreceptor denervation attenuates the change in C1 activity observed during transitions to REM, indicating that the feedback from the arterial baroreflex contributes to the elevation in C1 activity in this sleep state.