bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrelationships Between Platelet Activity and the Immunoinflammatory Response to Severe Injury
Authors: Morris Rachel , Schaffer Beverly , Lundy John , Pidcoke Heather , Cap Andrew , Schwacha Martin 
Published: June 2021

BackgroundCritical injury causes alterations in coagulation and inflammation. Activation of these systems is critical to counteract the initial threats of hemorrhage and infection; however prolonged propagation is associated with poor outcomes. How coagulation and inflammation interact is an area of keen interest. The aim of this study is to correlate changes in circulating inflammatory mediators with coagulation in trauma (ISS>15) and burn patients.MethodsBlood samples were drawn from trauma (n=10) and burn (n=10) patients and healthy volunteers (HV; n‐10). Coagulation parameters (sCD40L, D‐Dimers), cytokines (IL‐6, IL‐10, IL‐17a, TNFα) and inflammatory markers (HSP‐72) were assessed.ResultsThe subjects were predominately male (85%) and ~44 years of age. A marked increase in IL‐6 and IL‐10 was observed in both injury groups, whereas only the trauma group showed an increase in IL‐17a and TNFα compared with HV. HSP‐72 levels were 3‐fold higher in the trauma group, but not elevated in the burn group compared with the HVs. In contrast, sCD40L, a marker of platelet activation, was elevated 10‐25 fold, and D‐Dimers were elevated 5‐8 fold in both injury groups. A strong correlation between IL‐17a and sCD40L was observed in the HVs and the burn group (R2 > 0.80), but not the trauma group (R2=0.02).ConclusionThese results show that the post‐injury inflammatory response is paralleled by activation of coagulation. However, in trauma patients, a critical interrelationship between platelet activation and the Th‐17 response appears to be lacking, which may contribute to coagulopathic complications and warrants further study.
Effects of Ageing on Gross and Cortical Cerebral Autoregulatory Upper Limits
Authors: Thompson Emma , Coney Andrew , Marshall Janice 
Published: June 2021

Ageing leads to impaired endothelium‐dependent vasodilatation and sympathetically‐mediated vasoconstriction in many tissues including brain. We hypothesised cerebral autoregulation is modulated by these influences and ageing is associated with impaired autoregulation at the upper limit (UL).In anaesthetised young (Y) male Wistar rats (6‐8 weeks, n=25), basal arterial blood pressure (ABP) was 127±2mmHg, whereas in old (O) rats (52‐58 weeks, n=12), ABP was 148±2mmHg* (*=P<0.05).Phenylephrine was infused (0.1–200µg/kg/min i.v.) to raise ABP and gross cerebral blood flow (CBF) was recorded from common carotid after external carotid ligation. Dual‐line linear regression of gross CBF vs ABP, gave an UL for Y rats of 168±2mmHg. In 8 Y rats, cortical red cell flux (cRCF) was simultaneously monitored by laser speckle imaging; in these, gross CBF UL was 166±4mmHg, but cCBF UL was higher at 170±5mmHg*. By contrast in O rats, gross CBF UL was 180±3mmHg* (vs Y rats), and cCBF UL was 179±1mmHg (NS vs gross CBF UL in O rats, or cCBF UL in Y rats).We suggest in Y rats, a higher UL for cCBF vs gross CBF reflects further capacity for autoregulatory constriction of smaller cerebral vessels even when larger, proximal vessels have reached their UL. This may protect cortical tissue circulation. Since O rats were hypertensive compared to Y rats and hypertension has been shown to increase the UL, this may explain the higher gross CBF UL in O rats. However, as the UL for cCBF and gross CBF were similar in O rats, it seems the extended autoregulatory range for smaller cerebral vessels is lost with ageing. This could result in fragile cortical vessels being exposed to increased pressure when ABP rises and increase the risk of haemorrhagic stroke.British Heart Foundation funding is gratefully acknowledged.
Paradigms of Cardiovascular Control in Response to Sympathetic Stimulation by Simulated Orthostatic Stress
Authors: Bronzwaer Anne‐Sophie , Verbree Jasper , Stok Wim , van Buchem Mark , Daemen Mat , van Osch Matthias , van Lieshout Johannes 
Published: June 2021

BackgroundSympathetic stimulation by lower body negative pressure (LBNP) as surrogate of orthostatic stress augments heart rate (HR) and total peripheral resistance (TPR) in maintaining blood pressure (BP). This study addressed the variation in cardiovascular response to LBNP within and between subjects.MethodsIn 10 healthy subjects (5 female), BP (Nexfin), HR, stroke volume (SV), cardiac output (CO), TPR, BP/HR variability, and frequency domain baroreflex HR control (BRS) were quantified during three consecutive 5 minute runs of ‐50 mmHg LBNP (repeated after one week) to determine reproducibility.ResultsIn response to repeated LBNP runs, SV and HR demonstrated excellent and CO and TPR good within‐subject reproducibility. The cardiovascular response between subjects differed. Subjects with a marked decrease in SV (ΔSV>31%) demonstrated a higher resting HF/Ptot ratio as surrogate of parasympathetic activity and a more HR mediated response to LBNP. Contrary, a small SV decrease (ΔSV蠄31%) paralleled a higher resting LF/HF ratio as surrogate of sympathetic activity and a predominant increase in TPR in response to LBNP. BRS did not differ between groups.ConclusionConsiderable between‐subject variation in cardiovascular responses to LBNP indicates differences in blood pressure regulation and suggests subject‐specific strategies of autonomic cardiovascular control in young healthy individuals.
Premature Ventricular Contractions Trigger Non‐Baroreceptor Mediated Sympathetic Bursting
Authors: Ratcliffe L , Nightingale A , Paton J , Hart E 
Published: June 2021

Premature ventricular contractions (PVC) trigger muscle sympathetic nerve activity (MSNA) of greater amplitude and duration compared to MSNA in normal sinus rhythm (NSR). The increase is usually attributed to a fall in diastolic blood pressure (DBP) that unloads arterial baroreceptors evoking a MSNA burst. We describe a case of spontaneous bigeminy where increased MSNA was not provoked by a fall in DBP (as most PVC caused systolic ejection) suggesting other pathways controlling MSNA during bigeminy.In a normotensive woman (53 years), MSNA (peroneal microneurography), blood pressure and electrocardiogram (ECG) were recorded. Data was analysed according to ECG rhythm: NSR, NSR with PVC, and bigeminy.Average DBP was highest in bigeminy (61 ± 0.4 mmHg, n=26 p<0.05) compared to NSR (57 ± 0.5 mmHg, n=35), and NSR with PVC (56 ± 0.6 mmHg, n=45). Total MSNA activity (arbitrary units per 10 heart beats, AU/10hb), was greatest in bigeminy (224.1 AU/10hb), and similar in both NSR (196.8 AU/10hb) and NSR with PVC (199.2 AU/10hb). Higher temporal resolution analysis demonstrated that MSNA burst area was highest in NSR with PVC (42.3 ± 1.7 AU). Interestingly, despite the DBP being highest in bigeminy the MSNA burst area was also higher in bigeminy (34.5 ± 0.1 AU) compared to NSR (12.7 ± 1.3 AU). PVC generating a systolic ejection were associated with a higher DBP compared to PVC not generating a systolic ejection (54.4 ± 0.4 vs. 48.8 ± 2.6 mmHg) but a trend suggests that the area of the post‐PVC MSNA burst was not different (51.5 ± 5 AU vs. 43 ± 1 AU p=0.07).Our data suggest that DBP during a PVC is not the only factor determining MSNA burst size. We propose that early systolic emptying and left ventricular &/or coronary artery mechanoreceptor reflexes may be important in regulating MSNA burst size during a PVC.BHF supported.
Proteomic Study Reveals Altered Carbamyl‐phosphate Synthetase I in Congenital Heart Disease‐associated Pulmonary Arterial Hypertension
Authors: Zhang Xi , Yang Qin , Wang Jun , Liu Zhi‐Gang , Liu Xiao‐Cheng , He Guo‐Wei 
Published: June 2021

Pulmonary arterial hypertension (PAH) associated with congenital heart disease and left‐to‐right shunt is characterized by increased pulmonary vascular resistance and remodeling. Endogenous nitric oxide (NO) derived from arginine supplied by the urea cycle is critical for the maintenance of normal pulmonary arterial pressure. The rate‐limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl‐phosphate synthetase I (CPSI). We examined the hypothesis that CPSI may be associated with PAH by an proteomic method using iTRAQ to compare protein profiles in pooled plasma samples of ventricular septal defect (VSD) patients with PAH (VSD‐PAH), VSD, and normal controls (n=20 for each). Among more than 150 differential plasma proteins, CPSI was 2‐fold down‐regulated in VSD‐PAH. We further validated CPSI in new VSD‐PAH and VSD patients as well as controls by ELISA. The plasma CPSI level in VSD‐PAH (109.2±7.718 pg/ml, N=40) was significantly lower (P<0.01) than that in VSD (196.5±35.68 pg/ml, N=21) and normal controls (431.8±41.42 pg/ml, N=37, p<0.0001). Thus we have for the first time identified alterations of the mitochondrial enzyme CPSI in the plasma of VSD‐PAH patients, suggesting important role of the urea cycle‐arginine‐NO pathway in PAH and providing important information for biomarkers in PAH and possible future interventional strategy.Supported by NSFC 81170148, China Postdoc Sci Foundation 2014M561181, National S & T Major Project 2013ZX09303004‐005.
Identification and Investigation of Mucin 1‐Mediated Kidney Disease
Authors: Schuler Bryce , Tsaih Shring‐Wern , Worthey Elizabeth , Kirby Andrew , Stevens Christine , Daly Mark , Jacob Howard 
Published: June 2021

Establishing a causal link between genomic variation and pathology is the foundation of the successful application of genomics to clinical medicine. Whole genome sequencing (WGS) increases the resolution with which we can investigate the genome, but this increased resolution leads to an increase in the number of potentially damaging or disease causing variants identified. Consequently, WGS in the analysis of disease requires both bioinformatics approaches for efficient prioritization of variants as well as experimental evidence that demonstrates that the variant alters the function of the protein which directly contributes to the development of the disease phenotype(s). We have identified a family with an autosomal dominant chronic tubulointerstitial nephritis that presents insidiously between 20 and 60 years of age, leads to end stage renal disease, and subsequently requires dialysis and transplantation. By utilizing a WGS approach in affected members of this family, literature queries, and targeted gene analyses, we were able to identify a single base insertion in mucin 1 (MUC1) that segregated with the disease in this family, was absent in the general population, and was bioinformatically interesting. We are utilizing a mutant Muc1 rat model in an effort to confirm that MUC1‐dysfunction is causative in this phenotype, to more completely characterize this disease process, and to investigate potential treatment strategies with the hope that subsequent findings can, at least in part, be directly applied to patient care.Funding was provided by the NIH (award 5T32HL007852‐17) and an extramural donation.
Klotho Deficiency Causes Kidney Fibrosis via Activation of the Notch2 Signaling pathway
Authors: Xu Yuechi , Sun Zhongjie 
Published: June 2021

BackgroundKlotho was originally identified as an aging‐suppressor gene. Mutation of Klotho gene causes severe kidney damage. In humans, chronic kidney disease is associated with diminished Klotho protein expression. The purpose of this study is to investigate molecular mechanism that mediates Klotho deficiency‐induced renal fibrosis.Methods & ResultsTrichrome staining showed that Klotho gene mutation enhanced tubular collagen deposition, indicating that Klotho deficiency caused kidney fibrosis. Interestingly, the Notch2 activity was increased significantly in kidneys of Klotho mutant mice, suggesting that Klotho may regulate Notch2 activity. Overexpression of Klotho suppressed Notch2 activity and decreased expression of fibrosis markers (smooth muscle actin and collagen I) in mouse kidney tubule cells. Knockdown of Notch2 also attenuated fibrosis markers. Therefore, Notch2 activation may mediate Klotho deficiency‐induced fibrosis formation. The functional interaction between Klotho and Notch2 was assessed by the lectin precipitate assay. Interestingly, the result showed that Klotho exhibited neuraminidase activity which inhibited Notch2 activity through removing α 2, 6 Neu5Ac from Notch2. A neuraminidase inhibitor (DANA) blocked the inhibitory effect Klotho on activation of Notch2.ConclusionKlotho deficiency‐induced renal fibrosis formation may be, at least in part, attributed to activation of Notch2. Klotho regulates Notch2 activity via its neuraminidase activity.
Breath‐Holding: Simple Demonstrations of Complex Physiology
Authors: Skow Rachel , Fuller Jonathan , Bruce Christina , Day Trevor , Steinback Craig 
Published: June 2021

The complex interaction of chemical (i.e. chemoreceptors) and mechanical (i.e. lung‐stretch receptors) factors influences breath‐holding (BH). The aim of this project was to develop a simple set of procedures to be used as class‐room demonstrations or laboratory exercises to differentiate the roles of chemical and mechanical mechanisms in regulating BH.The increase in ventilation during rebreathing (plastic bag) was initially used to demonstrate the progressive increase in drive to breathe due to chemical factors. BH time (stopwatch) was also used as a quantifiable and intuitive metric of drive to breathe. Maximal BH's were conducted under the following conditions: 1) end‐expiratory BH (lung stretch receptor unloading), 2) end‐inspiratory BH (lung stretch receptor loading), 3) BH following 30s of hyperventilation (reduces pCO2 & isolates the influence of decreased pO2), and 4) BH following 5 breaths of pure oxygen (elevates pO2 & isolates the influence of increased pCO2). Using the end‐expiratory BH as the standard, students observed the increase in BH time with each of the other 3 maneuvers. An advanced critical thinking procedure was also introduced whereby students rebreathed in and out of a bag twice at the end of a maximal BH before attempting to hold their breath again. This procedure highlights the powerful suppression of drive to breathe by lung‐stretch receptors despite elevated chemical drive to breathe.These procedures represent a simple method to highlight complex physiological mechanisms which contribute to the drive to breathe. Such simple activities are suitable and adaptable for use across a range of physiology curricula and teaching settings.
Using Deep Thought Processing for Better Learning Outcomes on Human Cadavers: A Pilot Study
Authors: Gribbin Mary 
Published: June 2021

IntroductionAccording to Chew (2014) applying deep thought processing questions as opposed to shallow learning strategy questions is more likely to lead to successful learning outcomes at the undergraduate level. Hypothesizing that the differences would be similar at the Masters level, a cohort of Human Gross Anatomy students was tested by using both cognitively active type questions and cognitively passive type questions.MethodsAdopting a quasi‐experimental approach with non‐equivalent groups, we took 22 students and split them into two tutorial groups. Group One attended Gross lab for six hours a week and attended a one hour tutorial involving both active and passive questions.Group Two followed the same regimen, and was given only shallow learning type questions. Both groups took a mid‐term Lab Practical exam. For the second four weeks, the procedure was reversed for each group, and then a final exam was administered. Both tests measured similar categories of knowledge.Results/ConclusionsThe results confirmed our expectations. Group 1(7 students), scored 19% higher than the students of Group 2 who received shallow type processing questions. Group 1 had a Final exam average of 81.20%, (2% lower) and Group 2 had a Final exam avg. of 70.15% ( 6% higher) on a one‐tailed Paired t‐Test, p<.05, results similar to those found by Stranger‐Hall (2014).In conclusion, the use of deep thought processing type questions as well as surface processing questions for the Study of Human Gross Anatomy seems to improve learning outcomes significantly and may be useful as a tool to increase long term memory and mastery of the subject..The outcomes and the limitations of our method indicate that further refinement would occur with the administration of pre‐and post‐testing and by using randomized groups in a similar experiment.
Using Echocardiography as a Promising Adjunctive Teaching Tool for Cardiac Anatomy and Physiology
Authors: Eladl Mohamed , Elmoselhi Adel , Seif Allah Mohamed 
Published: June 2021

A transformation in medical education is currently underway which prioritizes competency and clinical integration with basic sciences. Here we are exploring the feasibility of early echocardiography (Echo) experience as an adjunct tool for teaching heart anatomy and physiology to second year medical students.The study was conducted on 100 students in a problem‐based learning curriculum. Students were introduced to cardiac anatomy and physiology as well as the basic principles of ultrasonography before the Echo sessions. A pretest was conducted at the beginning of the Echo theoretical session, consisting of 10 questions on Echo images. The practical sessions included hands‐on experience on standardized patients with a checklist of structures that are commonly demonstrated in left parasternal and apical four chamber windows. A post‐test with the same questions was repeated after the clinical sessions.The post‐test outcome revealed a significant improvement in identifying the cardiac structures and function in comparison to the pre‐test (P value 蠄 0.0001)
imageAlthough the students were very accurate in identifying heart chambers and valves without assistance, the pulmonary artery and valve in the parasternal short axis were mostly able to be identified with assistance. Furthermore 95% of students admitted that prior basic knowledge is essential for Echo images identification and 86% stated that integrating this experience is helpful in consolidating different phases of the cardiac cycle.ConclusionSpatial orientation offered by Echo with prior basic knowledge seems to provide an effective tool in consolidating medical student's understanding of heart anatomical relations and cardiac physiology.
Is Carnivoran Skull Morphology Dependent on Predatory Style?
Authors: Dewar Eric , Kallamata Enian , Murray Brett , Hartnett Magen , Sood Ankit 
Published: June 2021

Living carnivorans are diverse both in skull morphologies and in feeding style. Because predation as a feeding style is highly reliant on vision, we wished to determine if carnivoran skull morphology—particularly the morphology of the orbit—were related to feeding style. We photographed the skulls of museum specimens of 48 extant carnivore species (n = 225) and three Eocene‐age carnivorans (n = 7). From this sample, we measured the relative size and completeness of the orbit as well as the relative proportions of the face, orbital region, and cranium. We compared these measurements with taxonomic affinity, diel activity pattern, and feeding style of these species.The longest orbital rims were found among the felids and the grey seal. The felids and phocids also had orbits with the largest relative diameter (measured from the postorbital process–dacryon). Diurnal hunters and more omnivorous species such as ursids and herpestids tended to have smaller orbital diameters. Nocturnal hunters such as felids and genets had the shortest faces and longest crania overall, in contrast to Canis and Ursus, which had the longest faces but shortest crania. Herpestids, hyaenids, and mustelids were intermediate in these proportions. Using these baseline data on Eocene carnivorans, we found that the small canid Hesperocyon overlapped with both canids and herpestids, while the Eocene felids Hoplophoneus and Dinictis demonstrated early establishment of the typical “cat‐like” skull proportions and feeding behaviors.
Phenotypic Analysis of Long Bones in Pannexin 3 Knockout Mice Using a Geometric Morphometric Approach
Authors: Caskenette Deidre , Laird Dale , Penuela Silvia , Wilson Tim , Willmore Katherine 
Published: June 2021

Pannexin 3 (Panx3) is a channel‐forming glycoprotein that is expressed in skin, mammary gland and skeletal tissues. In vitro studies have shown that Panx3 is induced at the growth plate where it is thought to promote cell differentiation, a key role in bone formation. However, whether or not the ablation of Panx3 in mice causes phenotypic anomalies is unknown.The study objective is to analyze the phenotype of long bones in a new Panx3 knockout (KO) mouse to assess the role of Panx3 in bone formation.Ten KO and 10 wild‐type (WT) adult mice were scanned using high resolution in vivo micro‐CT. Each long bone studied was digitized using homologous landmarks. Data analysis using geometric morphometrics (multivariate statistical methods) allowed for a quantitative comparison of shape, size and variation of long bones between KO and WT mice.KO mice demonstrated distinct long bone shape differences that were greatest at the joint surfaces. As well, long bones in KO mice were 5% smaller. A significant portion of the shape difference (20%) can be attributed to the size component of shape. KO mice demonstrated greater shape variation that also appeared to be driven by different patterns of growth.Our findings suggest that Panx3 affects long bone shape through its effect on size. Importantly, KO mice appear to have altered and less predictable patterns of long bone growth. Thus, Panx3 may have a role in maintaining optimum bone growth.
The Effects of Clinical, and Sub‐Clinical mTBI on Cognitive Function in Varsity Athletes
Authors: Brewer Danielle , Wilson Timothy , Owen Adrian 
Published: June 2021

Emerging research suggests that head trauma, causing clinical (medically diagnosed, ie. concussion), or sub‐clinical minor Traumatic Brain Injury (mTBI) is cumulative and correlates negatively with cognitive function. Given the high prevalence of head trauma in contact athletics, better understanding the relationship between contact‐athletic activity, mTBI, and independent aspects of cognitive function is imperative.Sixty‐eight varsity football athletes were recruited to examine how cumulative head trauma and self‐reported mTBI affect cognitive function. Participants completed a 12‐test online cognitive battery (www2.cbstrials.com) at time points prior to, bi‐weekly throughout, and after the season. With each cognitive test, participants also completed a personal history questionnaire to assess their ongoing athletic activity and mTBI status. Through assessing three distinct aspects of cognitive function (verbal ability, short‐term memory, and reasoning ability) via the cognitive battery in a longitudinal fashion, we will comprehensively examine the effects of contact athletic participation on independent aspects of cognitive function. Results look to better characterize the relationship between mTBI and cognitive function as well as inform sport decisions made by athletes, recreationalists and athletic governance councils to guide participation and safe play decisions.