bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment by Multi‐Distance Hyperspectral NIRS of Changes in the Oxidation State of Cytochrome C Oxidase (oxCCO) to Carotid Artery Compressions
Authors: Shoemaker Leena , Suwalski Marianne , Milej Daniel , Shoemaker J. K. , Chui Jason , St. Lawrence Keith 
Published: May 2022

IntroductionThe occlusion of the common carotid artery (CCA) during carotid endarterectomy (CEA) is associated with a risk of cerebral ischemia due to inadequate collateral blood flow1. By monitoring tissue oxygen saturation (StO2), near‐infrared spectroscopy (NIRS) is frequently employed during CEA2 to determine sufficient oxygen delivery. However, StO2 is only a proxy of oxygen metabolism and an unreliable marker of ischemic injury. In contrast, cytochrome c oxidase (oxCCO) is an enzyme in the mitochondrial electron transport chain and therefore a specific marker of aerobic metabolism3. Thus, the aim of this study was to assess the ability of a multi‐distance hyperspectral (hs) NIRS to monitor changes in StO2 and oxCCO during CCA compressions in healthy participants. We hypothesized that changes in oxCCO concentration would be greater in the brain (i.e., long source‐detector distance, SDD) than in the extracerebral tissue (i.e., short SDD), and this difference would be larger than that of StO2.MethodsWe modified an in‐house built hsNIRS4 to include a second channel for acquiring data at two SDD (1 and 3 cm) to detect potential changes in the extracerebral tissue. Data from 10 young, healthy participants was acquired continuously during one 30‐second unilateral digital CCA compression, performed ipsilateral to the location of the optic probes. In addition, cerebral blood flow index was determined using diffuse correlation spectroscopy and mean arterial blood pressure by finger photoplethysmography.ResultsDuring CCA compression, the change in oxCCO at 3 cm vs. 1 cm (0.4 ± 0.3 µM vs. 0.06 ± 0.1 µM, p = 0.027) was approximately 50% greater than the change in StO2 at 3 cm vs. 1cm (‐4.0 ± 2.2% vs. 1.2 ± 0.7% p = 0.007). The corresponding decrease in cerebral blood flow was 57 ± 14% (p < 0.001 vs. baseline). Mean arterial blood pressure increased 4 ± 1 mmHg (p < 0.001 vs. baseline).DiscussionA larger difference between the two distances was observed for oxCCO than StO2, likely due to the greater concentration of mitochondria in the brain compared to extracerebral tissues. Collecting multi‐distance hsNIRS demonstrated the enhanced sensitivity of oxCCO to the brain. Lastly, this study demonstrates the utility of momentary unilateral CCA compressions as a fast, easy, and strong perturbation for transiently altering cerebral inflow and metabolism.References(1) Aceto, Eur. J. Anestesiol.(2020); (2) Yu, Cochrane Database Syst. Rev.(2014); (3) Bale, J. Biomed. Opt. (2020); (4) Rajaram, Brain Sci (2020).
Leave it to the Learners … Student Perspectives on the Effectiveness of Prosection and Dissection
Authors: Dyre Lillian , Langley Natalie , Quillen Jaxon , Zhang Nan 
Published: May 2022

Studies have shown that prosection and dissection facilitate similar academic outcomes and promote meaningful learning in anatomy laboratory courses. While dissection is the mainstay of many graduate level anatomy curricula, financial and other constraints have increased the use of prosection. This research evaluates student preference for studying different body regions and accomplishing learning outcomes related to content knowledge, teamwork, career preparation, humanistic learning, and wellness.First‐year medical students (n=51) who completed a hybrid prosection and dissection course completed a post‐course survey about their perceptions of the effectiveness of each lab learning modality. Response options included prosection, dissection, no preference (equally effective), and no preference (equally ineffective). A one‐way ANOVA was used to evaluate performance differences on course assessments between students in the hybrid course and students in past years who participated in a dissection based course.The response rate was 51%. Respondents preferred dissection for learning the back (62%), thorax (68%), abdomen (54%), shoulder, axilla, and arm (61.5%), and hip, thigh, and leg (46%). Prosection was favored for the pelvis (perineum 81%, cavity 69%), foot (58%), hand (46%), and head/neck (64%). Students favored dissection for gaining hands‐on skills relevant to surgical practice, appreciating anatomical variation, becoming more comfortable handling the human body, engaging in self‐directed learning, and fostering teamwork. Respondents felt prosection provided more time for independent study and wellness activities. Prosection and dissection were rated equally effective for developing a medical vocabulary, applying anatomical knowledge to clinical conditions, and gaining a 3D appreciation of the body. A hybrid prosection and dissection course was preferred by 73% of respondents, compared to 4% who ranked prosection alone as their preference; no students ranked dissection alone as their first choice. There were no statistically significant differences in academic performance related to teaching methods (F(3,195) = 2.65, p=0.34) between students in the hybrid course and students in previous dissection only courses.Students prefer prosection for learning more spatially complex and intricate regions requiring time‐consuming and skilled dissection. However, learners recognize distinct benefits of dissection for acquiring various technical and non‐technical skills. Hybrid courses should capitalize on the strengths of each method, aligning instructional methods with outcomes and incorporating learner preferences to achieve meaningful, lasting learning.
The Role of Vitamin D and Platelet Aggregation in Patients with Hypertension
Authors: Vuthaluru Ashita R. , Goyal Manjeet K. 
Published: May 2022

IntroductionPlatelet aggregation is seen in many inflammatory conditions and in the pathogenesis of chronic conditions like hypertension,atherosclerosis, diabetes mellitus. It is seen to be associated with complications of these diseases and also has a considerable influence on the morbidity and mortality. Vitamin D improves endothelial function and causes reduction of platelet aggregation. This study aims to determine the role of Vitamin D in platelet aggregation and its effects in reducing the morbidity and mortality in patients with hypertension.Materials and MethodsThe study was conducted at a tertiary healthcare centre in 50 primary hypertensives. All subjects completed physical and cardiovascular system examination. Blood pressure recordings were done. A blood sample was taken from each patient. Platelet aggregation was estimated using chronologaggregometer after extracting platelet rich plasma using principle of light transmission. ADP and epinephrine were added to PRP to induce platelet aggregation. Serum Vitamin D levels were also measured. The values of platelet aggregation were correlated with serum Vitamin D levels in each subject.ResultsPlatelet aggregation and Vitamin D levels were correlated and a negative correlation was found. Correlation coefficient of platelet aggregation to ADP with Vitamin D was ‐0.992 (p value<0.0001) and of platelet aggregation to epinephrine with Vitamin D was ‐0.838 (p value<0.0001).ConclusionThe study determines that platelet aggregation is one of the physiological events that occurs in hypertension and may be one of the causative factors of complications like cerebrovascular accidents, ischemic heart diseases etc. Cases with lower serum Vitamin D levels showed increased platelet aggregation showing an inversely proportional relationship between platelet aggregation and serum Vitamin D levels. Hence, it can be concluded that supplementation of Vitamin D can be considered in patients with hypertension as a primary prophylactic measure for reducing thrombotic complications of hypertension and helps improve the morbidity and mortality.
Endothelial Sensitivity to Exercise‐Induced Shear Rate in Pre‐ and Post‐Menopausal Females and in Males
Authors: Debray Amélie , Ravanelli Nicholas , Gravel Hugo , Bartlett Audrey‐Ann , Usselman Charlotte W. , Bherer Louis , Gagnon Daniel 
Published: May 2022

BACKGROUNDPost‐menopausal females appear resistant to the beneficial effects of exercise on endothelial function. Repeated increases in shear stress are considered important mediators of exercise‐induced improvements in endothelial function. It is therefore possible that endothelial sensitivity to shear stress is reduced in post‐menopausal females, thereby blunting endothelial adaptations to exercise training. The objective of this retrospective analysis was to test the hypothesis that post‐menopausal females exhibit a lower endothelial sensitivity to exercise‐induced shear rate relative to pre‐menopausal females and age‐matched males.METHODSFive pre‐ (48 ± 1 yrs) and fifteen post‐ (65 ± 10 yrs) menopausal females, and five males (67 ± 5 yrs) performed 4‐min rhythmic handgrip exercise bouts. Ten participants (6 post and 6 males) exercised at 20%, 40%, 60% and 80% of maximal voluntary contraction, and 15 participants (5 pre, 9 post and 2 males) exercised at 3 kg, 6 kg and 9 kg. The contraction/relaxation cycle was 2‐sec/3‐sec and each bout was separated by 10 min of rest. Brachial artery diameter and blood velocity were measured using high‐resolution ultrasound and analyzed using edge‐detection software. Endothelial sensitivity to exercise‐induced shear rate was quantified as the slope of the relationship between brachial artery dilation (% change from baseline) and shear rate (in s‐1).RESULTSBaseline diameter was greater in males (4.68 ± 0.55 mm) compared with post‐ (3.24 ± 0.53 mm, p<0.01) and pre‐ (3.55 ± 0.19 mm, p<0.01) menopausal females. The rhythmic handgrip protocols elicited net shear rates that ranged between 38 s‐1 and 392 s‐1. A positive correlation was observed between brachial artery dilation and net shear rate in males (r=0.66, p<0.01), and post‐menopausal females (r=0.38; p<0.01), but not in pre‐menopausal females (r=‐0.25, p=0.36). Endothelial sensitivity to exercise‐induced shear rate did not differ between pre‐ (0.037 ± 0.120 %/s‐1)and post‐ (0.069 ± 0.081 %/s‐1, p>0.99) menopausal females, between pre‐menopausal females (0.037 ± 0.120 %/s‐1)and males (0.027 ± 0.055 %/s‐1, p>0.99), or between post‐menopausal females (0.069 ± 0.081 %/s‐1) and males (0.027 ± 0.055 %/s‐1, p>0.99).CONCLUSIONThese results suggest that post‐menopausal females do not demonstrate a reduced endothelial sensitivity to exercise‐induced shear rate compared with pre‐menopausal females as well as with males of similar age.
Downregulation of BCRP (ABCG2) in Placenta of Rat Model of Preeclampsia
Authors: Dai Wanying , Piquette‐Miller Micheline 
Published: May 2022

BACKGROUNDRecent studies in our laboratory demonstrated downregulation of breast cancer resistance protein (BCRP/ABCG2) in placenta obtained from women with preeclampsia (PE). Pregnant women with PE are often prescribed medications to manage disease progression and prevent adverse outcomes. Many of these drugs, as well as other clinically relevant therapeutics are substrates for BCRP. BCRP is highly expressed in placenta and plays an important role in preventing xenobiotics from crossing the placenta and entering the fetal compartment. Thus, the impact of PE and BCRP downregulation on fetal drug exposure needs to be examined. As studies in pregnant women are often not feasible, use of preclinical models is an important approach. Thus, our objective was to characterize transporter changes in an endotoxin rat model of PE to determine its utility and predictive value for future drug disposition studies. This frequently utilized PE model is associated with maternal immune activation and induction of PE‐like symptoms including high blood pressure, proteinuria and pathology which are characteristic of human disease.METHODSPregnant rats were injected intraperitoneally with 10 μg/kg of bacterial endotoxin (LPS) on GD13, followed by 40 μg/kg LPS daily until GD 16. Controls were injected with sterile saline. Urine was collected daily. Dams were sacrificed on GD17 or GD18 for collection of maternal plasma, placentas, and fetuses (n=7‐8/group/day). Plasma levels of TNF‐α and IL‐6 were quantified by ELISA Kit. Tissues were analyzed for the expression of transporters by using qPCR and western blot. Urine was analyzed using creatinine colorimetric and protein assays.RESULTSConsistent with previous reports, the urinary ratio of protein/creatinine was significantly elevated in PE dams on GDs 16‐18, demonstrating proteinuria. As compared to controls, maternal plasma concentrations and placental mRNA levels of the pro‐inflammatory cytokines, TNF‐α and IL‐6, were significantly higher in the PE group on GD17 and GD18. The mRNA levels of BCRP was significantly decreased by 40‐60 % in placenta of PE dams on GD17 and GD18 along with a corresponding decrease in protein expression on GD18. Significantly lower mRNA levels of Abcb1a, Abcb1b and Slco2b1 were observed in the PE group. PE was also associated with significantly decreased transcript levels of Bcrp, Abcb1a and Abc1b in fetal brains.CONCLUSIONOur data demonstrates that the endotoxin PE rat model exhibits proteinuria and immune activation consistent with human disease. Importantly, our observations of decreased placenta expression of BCRP in this PE model is consistent with findings in humans. This indicates that this preclinical model may serve as a useful translational tool to examine the impact of PE on the disposition and fetal exposure of BCRP drug substrates.
A Novel Technique to Reduce Kidney Injury by Maintaining Na/K Pump Functions Using Electric Energy
Authors: Wang Lei , Chen Wei , Liang Pengfei , Wei Jin , Zhang Jie , Buggs Jacentha , Liu Ruisheng 
Published: May 2022

Renal ischemia‐reperfusion injury is an important contributor to the development of delayed graft function, which is associated with higher rejection rates and worse long‐term outcomes of the allografts. One of the earliest impairments during ischemia is insufficient ATP supply‐induced Na/K pump dysfunction, which results in subsequent cellular damage. Consequently, strategies that preserve ATP levels or Na/K pump function may limit the extent of renal injury during ischemia‐reperfusion.In this study, we developed a novel technique that applies an oscillating electrical field to first synchronize the pump molecules, and then modulate their pumping rates. We dubbed this technique as the synchronization modulation electric field. We present this novel technique of using electric energy to substitute ATPs in fueling and activating the pumps, thereby efficiently maintaining cellular functions under ATP insufficient conditions. We tested the effectiveness of this technique in two kinds of models of ischemic renal injury: an in situ renal ischemia‐reperfusion injury model (predominantly warm ischemia) and kidney transplantation rodent and swine models (predominantly cold ischemia).Our results show that application of the specially designed electric field effectively delayed ATP depletion during ischemia and preserves Na/K pump activity, thereby alleviating kidney injury by about 45% (plasma creatinine of 1.17±0.04 and 1.97±0.06 mg/dL for electric field treated and untreated groups, respectively) and improving renal allograft function by over 50% compared with the controls.This novel technique for preserving Na/K pump function may have therapeutic potential not only for ischemic kidney injury, but also for other diseases associated with dysfunction of Na/K pumps.
microRNA‐34a modulates the senescence of activated hepatic stellate cells in alcohol‐associated liver injury
Authors: Slevin Elise , Wan Ying , Harrison Kelly , Zhang Yudian , Li Xuedong , Li Tian , Lorenzo Sugeily R. , Xu Wenjuan , Klaunig James E. , Shetty Ashok K. , Meng Fanyin 
Published: May 2022

BackgroundReversion of activated hepatic stellate cells (HSCs) to quiescence is likely to be a promising pathway in liver fibrosis regression. The development of senescence in HSCs during alcoholic liver injury may lead to liver compensation against fibrosis. The current study aims to characterize the functional role of miR‐34a regulated cellular senescence during alcohol‐associated hepatitis.MethodsSenescence related gene and miR‐34a expression was assessed using a PCR Array and/or real‐time PCR analysis. Cellular senescence in cultured HSCs were measured by SA‐β‐gal staining. Senescence mediators were defined in LPS treated hepatic stellate cells in vitro, and in TLR‐4 knockout mice or morpholino antisense oligomer against miR‐34a (miR‐34a Morpho/AS) treated mice with chronic ethanol feeding in vivo.ResultsWe identified that 5 weeks of ethanol feeding significantly increased the total liver histopathology score and miR‐34a expression, along with the activation of hepatic stellate cells marked by enhanced α‐SMA staining. Treatment of HSCs with LPS (20 ng/ml) for 24 hr significantly increased miR‐34a expression, along with the enhanced SA‐β‐gal activity, up‐regulated α‐SMA/Collagen A1 expression and increased cellular viability. Silencing of miR‐34a decreased LPS‐induced activation in HSCs by downregulation of fibrosis markers α‐SMA, Col1a1 and TIMP‐1, and increased SA‐β‐gal activity as well as the cellular senescence marker CCl2, whereas silencing of the LPS receptor, TLR4, decreased this marker in the same group of HSCs, suggesting anti‐miR‐34a reversed LPS‐mediated HSC activation through inducing cellular senescence. Furthermore, the expression of miR‐34a and verified miR‐34a related senescence marker CCl2 were significantly altered in hepatic stellate cells from ethanol‐fed mouse liver specimens compared to controls. TLR4 knockout mice and miR‐34a Morpho/AS treated mice displayed less sensitivity to alcoholic injury, along with enhanced SA‐β‐gal activity and CCl2 level in HSCs, and recovered expressions of α‐SMA, Col1a1 and TIMP‐1. Summary andConclusionOur results show that miR‐34a mediated cellular senescence is essential for the potential reversion from activated to quiescent hepatic stellate cells during alcohol‐associated hepatitis. These findings provide new insight into the function of microRNA regulatedcellular senescence in human HSCs and increase opportunities for the development of novel treatment paradigms for the management of alcohol‐associated liver diseases.
Mitochondrial calcium retention capacity correlates with markers of muscle mass, strength, power and functional capacities in young and old adults
Authors: Cefis Marina , Marcangeli Vincent , Granet Jordan , Hammad Rami , Leduc‐Gaudet Jean‐Philippe , Gaudreau Pierrette , Robitaille Richard , Belanger Marc , Aubertin‐Leheudre Mylène , Morais José , Gouspillou Gilles 
Published: May 2022

RationaleThe aging‐related loss of muscle mass and function is a major risk factor for falls, fractures, frailty, loss of independence, institutionalization and even death. Although the underlying cellular and molecular mechanisms remain partly understood, impaired mitochondrial permeability transition pore (mPTP) function has been proposed as a potential mechanism. Indeed, altered mitochondrial calcium retention capacity (mCRC), a marker of mPTP function, has been documented with aging in both rodent and human skeletal muscles and mPTP opening was shown to cause muscle atrophy. However, studies on the impact of aging on mPTP function in humans remain scarce, and whether impaired mPTP function correlates with markers of muscle mass, performance and functional capacities remain unknown.ObjectiveThe present study aimed at investigating whether mCRC is associated with markers of muscle mass, muscle function and functional capacities in humans.MethodsTwelve young (29.4 ± 4.4y) and fourteen old (80 ± 7.4y) healthy men were enrolled in the present study. Leg lean mass (leg LM) was assessed using DEXA. Maximal isometric knee extension strength (iKES) and power were measured using a strain gauge system attached to a chair and the Nottingham Leg Extensor Power rig, respectively. To assess functional capacities, the performance at the 6‐min walk test and the step test (maximum number of steps in 20s) were evaluated. To assess mPTP function, mCRC was measured in permeabilized myofibers prepared from muscle biopsies obtained in the vastus lateralis.ResultsAs compared to young adults, old individuals displayed significantly lower leg LM (p<0.01), iKES (p<0.01), and power (p<0.01). The performance at the 6‐min walk test (p<0.01) and the step test (p<0.01) were also lower in old individuals. Old individuals also displayed a significantly lower mCRC (p<0.01). mCRC was significantly correlated with leg LM (r=0.34; p=0.045), iKES (r=0.35; p=0.04) and muscle power (r=0.41; p=0.02). In addition, mCRC was significantly correlated with the performance at the 6‐min walking test (r=0.42;p=0.01) and step test (r=0.46; p<0.01).ConclusionsThese results indicate that mPTP function is altered with aging in humans and highlight positive associations between mPTP, muscle mass, strength, power, and functional capacities. These findings therefore strengthen the emerging view that altered mPTP function contributes to the aging‐related loss of muscle mass and function in humans.
Pharmacological inhibition of ER stress mitigates testicular pathology in hind‐limb unloaded mice
Authors: Ranade Anu V. , Qaisar Rizwan , Khan Amir A. , Karim Asima , Gul Muhammed T. , Azeem Muhammad , Jose Josemin , Ramachandran Gopika , Ibrahim Zainab , Nair Vidhya , Elmoselhi Adel , Rahman Hassan Wael A. 
Published: May 2022

Reduced physical activity and cephalic fluid shift are common occurrences in prolonged bed rest and space flight, and can lead to testicular dysfunction. Experimental mouse model of hind‐limbs‐unloading (HU) mimics spaceflight and bed rest and recapitulates several features of testicular anomalies in such conditions including disruption of tubular architecture and associated histological changes that together contribute to male infertility. However, an effective pharmacological intervention to these changes remain elusive, partly because molecular mechanisms are poorly understood. Disruption of protein folding by endoplasmic reticulum (ER) or ER stress is a common etiology in several diseases but its contribution to testicular pathology is not known. We hypothesize that HU is associated with activation of ER stress and subsequent disruption of normal testicular histology in a time‐dependent manner, while treatment with 4‐Phenylburtyrate (4‐PBA; an ER‐stress inhibitor) will reverse these changes to normal levels. To test this hypothesis, 4‐months‐old male c57B16/j mice were subjected to 14 and 28‐days of HU. A significant reduction in thickness and organization of seminiferous tubular epithelium and discontinuation of germ cell layers was seen after 14 days of HU. We also observed a significant increase in the tubular and luminal diameter along with a reduction in the density of spermatozoa at 14 days. These changes were further intensified at 28 days of HU and were associated with signature alterations in the Raman spectroscopic analysis of the HU testis. Importantly, treatment with 4‐PBA for 3‐4 weeks (100mg/kg BW/d via intraperitoneal injections) partially reversed most of the pathological changes in mouse testis.Collectively, our findings reveal the pivotal role of ER stress in triggering testicular pathology in conditions mimicking spaceflight and present 4‐PBA as a potential therapeutic agent to prevent and/or reduce testicular disruption in such cases.Currently, we are characterizing the associated molecular phenotype in testicular disruption by mapping the global transcriptome and detailed Raman spectroscopic alterations in mouse testes under HU with and without 4‐PBA treatment.