bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological Characterizations of the Brain Vascular Hyalinosis in Patients with Systemic Hypertension‐Induced Ischemic Stroke
Authors: Gychka Sergiy G. , Shults Nataliia V. , Sariipek Nurefsan E. , Rybka Vladyslava , Malysheva Tatiana , Dibrova Vyacheslav A. , Gavrish Alexander S. , Suzuki Yuichiro J. 
Published: April 2020

BackgroundIschemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the brain vascular lumen increases the incidence of stroke and the formation of hyalinosis lesion is an irreversible process that occurs in the late stage of the disease and contributes to the vascular narrowing and stroke. Understanding pathologic mechanisms of brain vascular hyalinosis, thus, should contribute to the development of new therapeutic agents that inhibits and/or reverse the formation of hyalinosis, thereby reducing the incidence of ischemic stroke. Despite the clinical importance of this lesion, properties of brain vascular hyalinosis have not been well investigated. Thus, the present study performed detailed histological examinations of the hyalinosis lesions of postmortem brain vascular tissues of human patients who died of ischemic stroke due to systemic hypertension.Methods & ResultsHematoxylin and eosin staining, as well as periodic acid‐Schiff staining, showed the presence of vascular hyalinosis in patient brain tissues. In these lesions, the protein organization of the extracellular matrix was changed, the number and size of smooth muscle cells were altered, and plasma proteins, such as apolipoprotein E and fibrin, infiltrated into the vessel wall. Signs of oxidative stress and lipid peroxidation were also found. These changes are pronounced at the loci of the infiltration of the vessel walls by ApoE. We found increased number of vasa vasorum in adventitia of the small arteries. The formation and deposition of hyaline occur both from the side of the lumen of the artery and from the side of the vase vasorum. Transmission electron microscopy showed that with the development of hyalinosis, the number of smooth muscle cells that undergo atrophy. The deposition of proteins in the arterial wall is also associated with the degree of damage to endothelial cells in the lumen of the vessel and in the vasa vasorum.ConclusionsThese results demonstrate that, at the beginning of the development of hyalinosis, smooth muscle cells and vasa vasorum are increased. This process seem to involve oxidative stress, which damages endothelial cells both in the lumen of the arteries and in the vasorum vase and contributes to the infiltration of blood plasma proteins into the vascular wall. The resulting hyalinosis decreases the lumen of the arteries and increases the incidence of stroke.Support or Funding InformationSupported by NIH
Low‐dose Lithium is Associated with Left Ventricular Ejection Fraction in Healthy Young Men but not Women
Authors: Dempster Kylie S. , Fajardo Val A. , Baranowski Ryan W. , Hamstra Sophie I. , Wade Terrance J. , O'Leary Deborah D. 
Published: April 2020

The impact of lithium (Li) exposure on the cardiovascular system is perplexing, as beneficial, negative, and null effects have been identified. Li is an inhibitor of glycogen‐synthase kinase 3β (GSK3‐β) which has been identified as a possible therapeutic target for cardiovascular disease (CVD) and mental health disorders. While earlier ecological studies suggest that trace amounts of Li may protect against CVD, no study to date has investigated the effects of low‐dose Li exposure on cardiac structure and function in healthy young adults without CVD and whether these associations are sex dependent. The purpose of the present investigation was to examine the association between Li exposure and left ventricular mass (LVM) and function in healthy young adults. This investigation represents a cross‐sectional analysis of the Niagara Longitudinal Heart Study (NLHS) at the midpoint of data collection for 156 participants aged 19 – 25 years. A final sample size of 117 had both valid Li and left ventricular data upon analyses. LVM was indexed to height2.7 (LVMi), ejection fraction (EF), fractional shortening (FS), and stroke volume (SV) were assessed following echocardiography in the parasternal long‐axis view of the left ventricle. Serum Li levels were measured using inductively‐coupled plasma mass spectrometry. Li concentration was significantly associated with EF (r = −0.183, p = 0.05) and ESV (r = 0.197, p = 0.03) among the total sample. Li concentration did not differ when examined by sex (p > 0.05), however LVMi, ESV, EDV, SV, and EF were all significantly higher in males than females (p < 0.05). Li was only significantly correlated with EF in men (r = −0.320, p = 0.02) however no correlation was observed among women (p > 0.05). The novel result of our investigation was naturally occurring concentration of Li is associated with decreased EF in men, but not women, although, there was no significant difference in SV. Further, there was no effect of low‐dose Li on LVMi. This is in contrast to some animal studies which demonstrate long‐term exposure to Li has potent hypertrophic effect on the left ventricle, although, Li concentrations in our sample were considerably lower and fall within a normal physiological range. These findings may result from differential sensitivities of the GSK‐3β receptor to Li in the left ventricle in men and women, although further investigation is required.Support or Funding InformationThis research project is funded by the Canadian Institutes of Health Research (CIHR #s 363774, 399332). KSD is funded by a CIHR Doctoral Research Award – Frederick Banting and Charles Best Canada Graduate Scholarship (RFN#167014). VAF is supported by a Brock Explore Grant and an NSERC Discovery Grant (2019‐05833).
Autonomic Dysfunction in Women with Androgen Excess PCOS
Authors: Stone Tori , Leone Cheryl , Ayers Thomas , Stachenfeld Nina 
Published: April 2020

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrinopathy, affecting approximately 10% of reproductive age women. Further, 75% of women with PCOS have the more severe phenotype, Androgen Excess‐PCOS (AE‐PCOS), that is dominated by clinical and biochemical manifestations of hyperandrogenism. AE‐PCOS is also associated with elevated blood pressure (BP), which we hypothesized is the result of androgen‐associated impairments in autonomic function. Thus, we tested the hypothesis that androgen excess is associated with impaired baroreflex sensitivity (BRS) in women with AE‐PCOS. We tested four obese women with AE‐PCOS (age 30±3 y; BMI 39±11 kg/m2) at 0, HDT, ‐20, ‐30 lower body negative pressure (LBNP) under three conditions: Baseline (BL), during hormone suppression with a GnRH antagonist (GnRH ant, 7 days, 250 μg/day), and with GnRH ant+testosterone (T, 4 days, 5 mg/day). Women were mildly hypertensive at rest at BL, but BP increased following hormone suppression with the GnRH ant and remained elevated with T (93±7, 105±5, 105±9 mm Hg for BL, GnRH ant, and T, respectively, P=0.02). Blood pressure was well maintained during LBNP under the three hormone conditions. Forearm vascular resistance (FVR) increased during LBNP under each condition, but the increase was greatest during GnRH ant and T (Δ54±19, Δ235±145, Δ104±64 units for BL, GnRH ant, and T, respectively, P=0.04). The resulting BRS slopes were greater in GnRH ant (−5.2 units/mm Hg) compared to BL (−1.6 units/mm Hg), demonstrating concomitant testosterone and estrogen suppression improved BRS in women with AE‐PCOS. When we restored androgens, the BRS slope was again attenuated (T= −1.7 units/mm Hg), suggesting an important role for androgens in autonomic function in AE‐PCOS. GnRH ant increased resting BP independent of T in AE‐PCOS, which is likely a function of the continued estrogen suppression. Thus, hypertension associated with AE‐PCOS appears closely associated with estrogen suppression and independent of testosterone‐induced changes in BRS. In summary, both estrogens and androgens contribute to BP regulation in women with AE‐PCOS. Women with AE‐PCOS frequently present with mild hypertension that is driven by altered estrogen and testosterone exposures. Treating hypertension is crucial for preventing cardiovascular disease in this vulnerable population.Support or Funding InformationR01 HL135089
The Role of Mental and Motor Processes in Conceiving, Developing and Validating 3D Interactive Human Anatomy Learning Tools
Authors: Hoyek Nady , Rienzo Franck Di , Guillot Aymeric , Collet Christian 
Published: April 2020

Understanding human anatomy requires several mental and motor processes: i) mental imagery: the ability to mentally represent a physical object, a concept or a situation; ii) mental rotation: the ability to mentally turn the image of an object in the three space planes; iii) motor imagery: the ability to imagine a human movement without any real movement execution. These mental and motor processes have been used in Lyon 1 university to conceive and develop hundreds of 3D animations that are used to teach anatomy for undergraduate allied health sciences students, especially kinesiology students. All our animations are available in our YouTube Chanel “Anatomie 3D Lyon”. Our approach is experimentally validated through several paradigms. For instance, we found a significant correlation between anatomy examination results and visuo‐spatial ability tests (Guillot et al., 2007). We also showed that mental rotation training enhanced the acquisition of anatomical information requiring visuo‐spatial ability (Hoyek et al., 2009). Our 3D animations, when used in real learning condition, enhance the acquisition of anatomy knowledge requiring spatial ability as compared to 2D images (Hoyek et al., 2014). We further showed the efficiency of 3D animations compared to static 3D images in the mental representation and description of the scapula (Berney et al. 2015). In sum, 3D animations are efficient in teaching and learning anatomy, however their passive visualization lacks interaction, which is essential for anatomy learning. In our actual funded projects (Antepulsio and An@tomy 2020) we are developing new interactive tools that allow both personal body experience and good spatial representation of anatomical structures. This approach is based on evidences that body movements could improve learning of different knowledge by augmenting or enriching traces in long‐term memory. This embodied perspective is particularly relevant for functional anatomy learning as the knowledge to acquire could be specifically related to the learner’s body in motion. Our new prototypes as well as our related preliminary results will be presented during the conference. All our experiments were approved by our local ethic board. They were conducted on our kinesiology students with their understanding and consent.Support or Funding Information1) Agence Nationale de la Recherche: project An@tomy20202) Fond Unique Interministériel: project ANTEPULSIO
Colonic mucosae is affected by experimental gastric restriction
Authors: Akamatsu Flávia Emi , Fontes Luiz Gustavo , Itezerote Ana , Saleh Samir , Hojaij Flávio , Andrade Mauro , Pereira José Aires , Martinez Carlos , Jacomo Alfredo Luiz 
Published: April 2020

BackgroundObesity‐related comorbidity is defined as a condition caused by overweight/obesity or known to contribute to the presence or severity of the condition. These comorbid conditions are expected to improve or go into remission in the presence of effective and sustained weight loss. World Health Organization reports obesity as a rising chronic condition with many devastating health consequences. Gastric reduction procedures are currently employed to treat morbid obesity and there are few reports concerning the consequent effects in large intestine.MethodsExperimental model of gastric restriction was devised using rats. The animals were submitted to surgical gastrostomy and a cylindrical loofah was inserted into the stomach. We studied 30 adult male Wistar rats divided in three groups: the stomach reduction group (R20), the sham group (SH20), which underwent the same procedure except for the loofah insertion and the control group (C20). Animals were fed and kept in separate cages. Sections of the colon were obtained and stained with hematoxylin‐eosin and analyzed for the length of the crypts, mucous cells and inflammatory cells.Goblet cells and inflammatory cells were obtained in all groups as mean, median, minimum and maximum and were compared between groups using generalized estimation equations (GEE) with normal distribution and identity link function supposing exchangeable correlation matrix between fields. Bonferroni’s multiple comparison was applied to identify differences between groups. The results are described by the mean value with respective standard deviation.ResultsThe analysis of Goblet cells count on R20 group indicated a statistically significant reduction and shallower crypts as compared to the C20. There was a significant difference regarding inflammatory cells on R20 compared to C20 and SH20. Polymorphonuclear inflammatory cells were increased in all groups when compared to lymphomononuclear cell but with no significant difference among groups.ConclusionThese findings might be a result of colonic mucosae atrophy secondary to the effects of gastric restriction in this model. The increase in neutrophil infiltrate may be related to the presence of bezoar, as well as the greater aggression to the colic epithelium due to lack of short chain fatty acids (CCFA), oxidative stress epithelial damage due to lack of CCFA.
Natural Saponin Formosanin C‐induced Ferroptosis in Human Hepatocellular Carcinoma Cells Involved Ferritinophagy
Authors: Su Chun-Li , Lin Pin-Lun 
Published: April 2020

Formosanin C (FC) is an anti‐tumor diosgenin saponin isolated from Paris formosana Hayata (Liliaceae) which is a perennial herb grown in the humid and dark forests of Taiwan at about the level of 1000 m. The plat has been used as a folk remedy for snake‐bite inflammation and tumors. FC is also a component of “Yunnan Bai Yao”, a traditional Chinese hemostatic medicine. Ferroptosis is a new form of iron‐dependent cell death, which occurs via an increased labile iron pool and lipid reactive oxygen species (ROS). Ferritinophagy is a ferritin (an iron storage protein) degradation pathway, depending on a selective autophagic cargo receptor nuclear coactivator 4 (NCOA4). Increased labile iron pool by ferritinophagy has been recognized as an upstream regulator of ferroptosis. Thus, ferroptosis has been reported to be a form of autophagic cell death. Although iron is an essential nutrient that facilitates cell proliferation and growth, overexpression of ferritin and down‐regulation of ferroportin (an iron export protein) has recently been observed in human hepatocellular carcinoma (HCC), indicating the increased dependence of iron in the cancer cells. In the present study, FC caused a significant dosage‐related population growth inhibition in HCC HepG2 and Hep3B cells using SRB assay, which can be partially blocked by co‐administration of ferroptosis inhibitor ferrostatin‐1 (a scavenger of lipid ROS). FC induced elevation in lipid ROS formation can also be partially reversed by addition of either ferrostatin‐1, or the presence of antioxidant vitamin C and/or vitamin E using flow cytometry, confirming FC‐induced ferroptosis. Flow cytometric analysis also revealed that FC elevated the percentage of acidic vesicular organelles‐positive cells, representing the formation of autolysosomes and induction of autophagic flux in both cell lines. The FC‐induced autophagy was confirmed using Western blotting, characterized by the production of LC3‐II and a further elevation of LC3‐II expression by addition of autophagy inhibitor bafilomycin A1 to prevent the fusion of autophagosomes and lysosomes for cargo degradation. In the present of bafilomycin A1, accumulation of NCOA4 and ferritin was observed in both FC‐treated cell lines using Western blotting. Concurrently, increase in co‐localization of LC3 puncta with NCOA4 or ferritin was exhibited using confocal microscopy, suggesting FC‐induced ferritinophagy. It is noteworthy that HepG2 cells with a higher NCOA4 expression were more sensitive to FC‐induced ferroptosis and autophagy compared to Hep3B cells with a higher ferritin expression. Overall, our data suggest chemotherapeutic potential of phytochemical FC for treatment of HCC with higher expression of NCOA4 via ferritinophagy and ferroptosis.Support or Funding InformationSupported in part by the Ministry of Science and Technology, Taiwan, No. MOST 106‐2320‐B‐003‐006‐MY3 and 107‐2320‐B‐003‐002‐MY2
Sympathetic Activation to Limb Venous Distension is Preserved during Muscle Metaboreceptor Stimulation
Authors: Cui Jian , Blaha Cheryl , Leuenberger Urs A. , Sinoway Lawrence I. 
Published: April 2020

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). Animal studies suggest that venous distension increases the discharge of Group III and IV afferent nerve endings in peripheral veins. Exercise also activates the Group III and IV afferent nerves in exercising muscles. It is unclear if the venous distension reflex contributes to BP regulation during exercise. We hypothesized that muscle metaboreceptor stimulation might alter the venous distension reflex response. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects (13 M, 5 F, 26 ± 1 yrs). In trial 1, saline (5% forearm volume) was infused into veins of an arterially occluded arm (non‐handgrip trial). In the second experiment, subjects performed 2 min static handgrip followed by post exercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into veins of the arm (handgrip trial). In trial 1, infusion increased MSNA (18.5 ± 1.6 to 29.1 ± 2.4 bursts/min, P < 0.001) and BP (P <0.001) as expected. Handgrip significantly raised MSNA (19.8 ± 1.6 to 28.0 ± 1.8 bursts/min, P < 0.001), BP (P < 0.001) and venous lactic acid (1.0 ± 0.1 to 3.1 ± 0.4, mmol/L, P < 0.001). Venous saline infusion during PECO further raised MSNA (prior infusion vs. end of infusion, 29.0 ± 2.4 to 37.7±2.7 bursts/min, P= 0.001) and BP (P < 0.001). The changes in MSNA evoked by infusion during PECO were not significantly different from the rises in the non‐handgrip trial (delta 8.6 ± 1.5 to delta 10.6 ± 1.8 bursts/min, P = 0.258). The BP responses to the infusion were not different in the two trials. These observations indicate that venous distension reflex responses are preserved during the sympathetic activation mediated by the muscle metaboreceptor stimulation. These data may suggest that venous distension reflex contributes to the BP regulation during exercise.Support or Funding InformationSupported by NIH R01 HL144781 (Cui and Sinoway) and UL1 TR002014 (Sinoway), and Pennsylvania Department of Health Tobacco CURE Funds SAP#4100079742 (Cui).
Assessment of Pulsatile Load During Lower Body Aerobic Exercise in Young and Older Adults
Authors: Stock Joseph Michael , Chouraminis Nicholas V. , Shenouda Ninette , Patik Jordan C. , Martens Christopher R. , Farquhar William B. , Chirinos Julio A. , Edwards David 
Published: April 2020

Increased wave reflection magnitude (RM) and early return of reflected pressure waves augment pulsatile load, waste left ventricular effort, and are associated with cardiovascular events. Acute lower body aerobic exercise (AE) decreases RM and reflected wave transit time (RWTT) in young adults (YA). Due to age‐related changes in arterial structure and function, older adults (OA) experience an elevated RM and earlier RWTT at rest compared to YA. However, it is unknown how AE influences RM and RWTT in OA, and whether OA respond differently than YA.PURPOSEThe purpose of this study was to test the hypotheses that 1) RM and RWTT would be reduced during AE and 2) the reduction in RM would be attenuated in OA while the reduction in RWTT would be augmented in OA compared to YA.METHODSRadial artery pressure waveforms and aortic blood flow velocities were acquired at baseline and during light, moderate, and vigorous intensity AE on a supine cycle via applanation tonometry and echocardiography, respectively, in 20 YA (25±5 yrs) and 20 OA (66±4 yrs). Central pressure waveforms were synthesized from radial waves using a generalized transfer function. Pressure‐flow relations were analyzed offline to perform wave separation analysis. This provided a comprehensive assessment of ventricular‐arterial interactions for the determination of the relative amplitude and timing of forward (Pf) and backward (Pb) pressure waves, yielding RM (Pb/Pf) and RWTT.RESULTSAs expected, baseline RM was greater in OA (YA: 40±6 vs. OA: 49±6%, p<0.05) and RWTT was shorter in OA compared to YA (YA: 191±20 vs. OA: 140±18 ms, p<0.05). RM was decreased during all intensities of AE. However, the reduction in RM from baseline was different between YA and OA during light intensity AE (ΔYA: −12±8 vs. ΔOA: −17±7, p<0.05), trended toward being different during moderate AE (ΔYA: −12±10 vs. ΔOA: −18±7%, p=0.06), and was not different during vigorous AE (ΔYA: −15±6 vs. ΔOA: −18±6%, p>0.05). RWTT decreased during all intensities of AE. The reduction in RWTT from baseline was attenuated in OA compared to YA during light (ΔYA: −39±18 vs. ΔOA: −9±13ms, p<0.05), moderate (ΔYA: −51±18 vs. ΔOA: −11±17ms, p<0.05), and vigorous intensity AE (ΔYA: −57±25 vs. ΔOA: −19±17ms, p<0.05).CONCLUSIONRM decreased during AE, however, differences in ΔRM between YA and OA were exercise intensity dependent. Our results suggest a greater decrease in RM in OA compared to YA during light‐moderate intensity AE. Contrary to our hypothesis, there was an attenuated reduction in RWTT in OA compared to YA during all intensities of AE, which may be due to the OA reaching the floor in RWTT.Support or Funding InformationACSM Foundation Doctoral Student Research Grant and NIH grant P20 GM 113125