bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Cardiac Glucose Transport Corrects Diabetic Cardiomyopathy Even Without Alleviation of Hyperglycemia
Authors: Mia Sobuj , Kyriazis Ioannis D. , Sidiropoulou Rafailia , Hill Daniel , Mantalaris Athanasios , Drosatos Konstantinos 
Published: May 2022

Healthy hearts rely more on fatty acid (FA) rather than glucose utilization. It remains unclear whether diabetic cardiomyopathy (DbCM) is accounted for by glucotoxicity or lipotoxicity. Previously, we discovered that either insulin deficiency or insulin resistance causes FOXO1‐KLF5 activation in human and murine hearts, which drives cardiac lipotoxicity and oxidative stress. Now, we investigate how glucose activates cardiac KLF5 and causes DbCM. We hypothesized that higher cardiac glucose content in diabetes potentiates FOXO1‐KLF5 activation and causes glucolipotoxicity.We mimicked Type‐1 diabetes (T1D) in C57BL/6 mice via 5 daily intraperitoneal injections of streptozotocin (STZ). In contrast to late T1D (12 Wks post‐STZ), cardiac KLF5 expression levels are not increased in the early T1D (4 Wks post‐STZ). However, mice developed cardiac dysfunction in early T1D. Seahorse analysis in adult cardiomyocytes isolated from mice with early T1D showed suppression of FA dependence in the expense of higher glucose dependence compared to non‐diabetic mice. To confirm whether hyperglycemia or higher cardiac glucose content accounts for cardiac dysfunction in early T1D, we applied anti‐hyperglycemia treatment (Dapagliflozin, DAPA, SGLT2 inhibitor) or GLUT1 inhibition (STF‐31). Either of the two treatments restored cardiac FA dependence and prevented both glucose preference and cardiac dysfunction in early T1D. GC‐MS analysis in hearts of mice with late T1D, which have shifted back to increased FA dependence, showed increased cardiac glucose content ‐presumably unused glucose‐ and subsequent increase of cardiac KLF5, as previously shown, which exacerbates cardiac dysfunction. New data revealed that GLUT1 levels were increased in late T1D compared to early T1D, as well as that this is driven by KLF5 activation. The lack of activation of KLF5 expression in early T1D, which reverses in late T1D, is mirrored by FOXO1 transcriptional activity as shown by expression of FOXO1 targets and lower FOXO1 acetylation in late T1D, which is controlled by Sirtuin‐1. Analysis of hearts from mice with late T1D and a human cardiomyocyte cell line (AC16) that was treated with high glucose indicated higher Sirtuin‐1 expression and Sirtuin‐1 binding on FOXO1. Accordingly, prevention of glucose transport to hearts of diabetic mice via treatment with either DAPA or STF‐31 for 12 Wks lowered cardiac expression of KLF5 and its targets and improved cardiac function.Conclusively, DbCM begins in early T1D with lower mitochondrial FA utilization that is compensated by higher glucose utilization and is exacerbated in late T1D with activation of SIRT1‐FOXO1‐KLF5 axis that causes combined lipotoxicity and glucotoxicity. Inhibition of GLUT1 alleviates DbCM via prevention of both early glucose dependence and late KLF5 activation.
Liver Fatty Acid‐Binding Protein (LFABP) Ablation Drives Hyperplastic Expansion of Subcutaneous Adipose Tissue in Male Mice Fed High‐Fat Diet
Authors: Diolintzi Anastasia , Zhou YinXiu , Fried Susan K. , Polunas Marianne , Sidossis Labros S. , Storch Judith 
Published: May 2022

Liver fatty acid‐binding protein (LFABP) functions both in intracellular lipid trafficking in liver and small intestine, and in systemic energy homeostasis regulation. We found that despite the marked obesity of high fat‐fed LFABP null (LFABP‐/‐) mice compared to their wild‐type (WT) counterparts, they display a ‘metabolically healthy obese’ (MHO) phenotype characterized by normoglycemia and normoinsulinemia, increased spontaneous physical activity, and a resistance to high‐fat diet (HFD)‐induced decline in exercise capacity. They also display increased muscle fatty acid oxidation suggesting that adipose tissue lipolysis is enhanced. To gain insight into the effects of Lfabp ablation on the quality of adipose tissue, we determined the mass and cellularity of the inguinal (iWAT) and epididymal (eWAT) white adipose tissues.LFABP‐/‐ mice fed HFD for 12 weeks weighed 23.7% more (BW, g: 41.7 LFABP‐/‐ vs 33.7 WT, p=0.006, n=5) and their fat pads tended to be heavier (iWAT, g: 1.1 LFABP‐/‐ vs 0.8 WT, p=0.060, n=5; eWAT, g: 1.4 LFABP‐/‐ vs 1.8 WT, p=0.065, n=5). Intriguingly, as shown in Figure 1, adipocyte size of iWAT adipocytes is smaller than that of the WT mice (44.6pL LFABP‐/‐ vs 188.1pL WT per cell, p=0.009, n=5). Adipocyte number was substantially increased in the iWAT of LFABP‐/‐ (23.6 LFABP‐/‐ vs 4.6 WT x 106, p=0.001, n=5). In contrast, the eWAT adipocyte size in the LFABP‐/‐ is comparable to WT (210pL LFABP‐/‐ vs 268 pL WT per cell, p=0.293, n=5), and eWAT fat cell number was highly variable and trended higher in the LFABP‐/‐ mice (9.8 LFABP‐/‐ vs 4.7 WT x 106, p=0.059, n=5).Because LFABP is not expressed in adipose tissue, our data suggest that its ablation promotes interorgan signaling that may limit hypertrophy and drive hyperplasia in expansion of potentially metabolically beneficial subcutaneous iWAT. More studies are warranted to elucidate the marked differences in cell size and the apparent depot‐dependent effects of LFABP‐/‐ deficiency, as well as the mechanisms by which it modulates adipocyte growth and function.
Modeling Surgical Management of Uterine Atony Induced Postpartum Hemorrhage using Cadaver Dissection
Authors: Richter Emily , Fogarthy Tannice , Ravikumaran Nair Rakesh 
Published: May 2022

IntroductionThere is a well‐documented disconnect that medical students experience when applying preclinical anatomical knowledge to clinical applications.1 According to the United States National Inpatient Sample, postpartum hemorrhage (PPH) carries an overall incidence of up to 3% of all U.S. deliveries; this study designates uterine atony as the most common etiology of PPH, causing at least 80% of PPH cases.2Thus, fourth year medical students preparing to enter into the specialty of obstetrics and gynecology should have in vivo exposure to the surgical management of uterine atony induced PPH prior to beginning residency. Modeling arterial ligation of the anterior division of the internal iliac artery using a cadaver model is a practical approach that most resembles an in vivo illustration of PPH surgical management while also maintaining a safe, controlled environment.ObjectiveIn efforts to provide fourth year medical students with exposure to PPH management, create a guide for ligation of the internal iliac artery’s anterior division using a cadaver model.Material and MethodsDissection was completed by two fourth year HWCOM medical students anticipating entry into the specialty of obstetrics and gynecology. After completion of anterior abdominal wall dissection and peritoneal entry, GI organ were retracted for full visualization of genitourinary structures. The following arteries were identified and skeletonized in the following fashion: common iliac artery, internal iliac artery, anterior division of the internal iliac artery, umbilical artery, obturator artery, and uterine artery. The anterior division of the internal iliac artery was identified and ligated 2 cm below the bifurcation of the common iliac artery to avoid unintentional ligation of the superior gluteal artery. A picture of the arterial ligation site was captured.Results/ImagesProper arterial ligation site of the internal iliac artery’s anterior division can be visualized in the appendix.Conclusion and Significance/ImplicationSurgical management of PPH requires both anatomical knowledge of arterial and pelvic anatomy but also spatial familiarity of structures in vivo. Performing the surgical management of PPH on a cadaver model could provide fourth year medical students an opportunity to learn the appropriate sites and steps and surgical arterial ligation in a less pressured environment before entering residency. Future implications of this study could combine virtual learning tools, such as anatomy mobile applications, to further aid in medical education’s exposure to PPH management and associated anatomy.
GARLAQs vs. Multiple Choice Questions: Do First‐Year Medical Students Perform Similarly on their Anatomy Examinations?
Authors: Thom Mitchell L. , O'Neill Steven , Crofton Andrew , Wish‐Baratz Susanne 
Published: May 2022

PURPOSEMedical students at the Case Western Reserve University School of Medicine are assessed on their knowledge of anatomy using an essay exam that tests clinically relevant anatomy/radiology concepts (Gross Anatomy, Radiology, and Living Anatomy Questions, or GARLAQ). GARLAQs are uniquely designed to facilitate student collaboration, as such these essay questions are given to students months prior to examination. This format has raised concerns about student memorization and a lack of in‐depth understanding of GARLAQ answers. The purpose of the present study is threefold: 1) to examine whether students perform similarly on GARLAQs and Multiple Choice Question (MCQ) examinations, 2) to assess whether students perform similarly to the GARLAQs on MCQs throughout the hierarchy of Bloom’s Taxonomy, 3) to collect qualitative data on student opinions of both assessment formats.METHODSFirst‐year medical students will be assessed during the gastrointestinal unit of their clinical anatomy curriculum. Volunteers will be recruited from a class of 184 students. A crossover study design will be employed, wherein participants will be randomly placed into one of two cohorts: 1) first complete the required GARLAQ exam, second the MCQ exam, or 2) first complete the MCQ exam, second the required GARLAQ exam. A paired t‐test will determine if there is a difference in overall examination performance for each respective student. Each MCQ will be categorized using Bloom’s Taxonomy. A paired t‐test will compare each student’s mean scores by Bloom’s category to their GARLAQ performance. Participants will also complete a post‐test survey in which they will be asked to rate their opinions about contrasting exam modalities on a 5‐point Likert scale.RESULTSData collection is currently ongoing and will be completed in February, 2022CONCLUSIONInformation gained through review of student assessment scores and responses can guide future curricular changes at our institution in a cycle of continuous improvement.
The Polysaccharide of Ligustrum Lucidum Ait. Protected from Renal Fibrosis by Interfering with Angiotensin II Signaling
Authors: Zhang Jia‐li , Wang Na‐ni , Zhang Yan 
Published: May 2022

BackgroundA number of preclinical advances have indicated the cellular and molecular mechanisms underlying renal fibrosis, such as the signaling of angiotensin II (Ang II), which is a bioactive peptide in renin‐angiotensin system. As one of kidney‐tonifying herbs, Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae) recorded as a tonic and dietary supplement, is a commonly prescribed component in traditional kidney‐tonifying herbal formula. This study aimed to clarify the polysaccharide component in FLL and investigate its potential role in preservation against renal fibrosis.MethodsThe crude polysaccharide of FLL was prepared and deproteinized by Sevag reagent. After lyophilization, the DEAE‐cellulose DE52 column and the Sephacryl S‐200 HR column were used for further isolation and purification of homogenous polysaccharide. The mice with unilateral ureteral obstruction (UUO) underwent daily intraperitoneal injection with FLL polysaccharide starting 7 days before UUO surgery until day 7 after surgery. The murine mesangial SV40‐MES13 cells were treated with vehicle, Ang II (10‐7 M) either with the absence and presence of angiotensin type I receptor blocker (ARB) (10‐6M), or with low dose (50 μg/mL, Poly‐L) and high dose (200 μg/mL, Poly‐H) of FLL polysaccharide.ResultsThe purified homogenous polysaccharide (Poly) was explored from FLL and the carbohydrate content was 97.45%. A hypothetical structure for Poly was proposed considering the comprehensive data of methylation, monosaccharides, and NMR analyses. Treatment of UUO mice with Poly decreased kidney index and ameliorated glomerular sclerosis and interstitial fibrosis, as well as down‐regulated the expression of profibrogenic factor VEGF and matrix fibrotic protein fibronectin (FN). Furthermore, as the same effect to ARB, the pre‐incubation with Poly alleviated the Ang II‐induced up‐regulation of FN in mesangial cells by immunofluoresence staining. The protein expressions of FN and proinflammatory factors like MCP‐1 and Rantes were significantly lower in Poly‐treated cell group than those in Ang II treatment group.ConclusionThe polysaccharide of Ligustrum lucidum Ait. was accurately explored with structure clarification. This polysaccharide component repressed angiotensin II‐induced fibrotic phenotype of renal mesangial cells and exerted beneficial effects on kidney of UUO mice.
Abnormal Relationship with the Styloglossus and Medial Pterygoid Muscles: A Description of Two Cases
Authors: Kim Pil‐Woo 
Published: May 2022

IntroductionLateral pharyngeal space is of great interest to dentists and surgeons. The pre‐styloid space is located in a portion of the lateral pharyngeal space. The pre‐styloid space has stylohyoid muscle, styloglossus muscle, stylopharyngeus muscle, and external carotid artery. Medial and lateral pterygoid muscles are located anterior to the pre‐styloid space. This study describes the relationship of the structures in the cases.HypothesisThe muscular attachment from the medial pterygoid muscle to the styloglossus muscle is unique. Morphological understanding with the external carotid artery of the cases will be helpful to prevent surgical mistakes.MethodsThe two cadavers were found to have a rare medial pterygoid and styloglossus during the dissection in 2020. It had been assessed in the adjacent structures.ResultsBoth cases showed that the medial pterygoid muscle has a tendinous attachment from the inside to the styloglossus muscle. The first case’s tendon and muscle were 5mm wide, 3mm thick, and 10mm long and attached to 15mm proximal area of the styloglossus muscle (Fig. 1). The second case’s tendon was 5mm wide, 1mm thick, and 7mm long and attached to a 12mm proximal area of the styloglossus muscle (Fig. 2). Both styloglossus muscles were attached to the tip of the styloid process. Both styloid processes were more than 25mm long from the temporal bone (Fig. 2).Both external carotid arteries passed through between stylohyoid and styloglossus muscles and ran behind the tendon and up to the head of the mandible (Fig. 1.C).ConclusionThe medial pterygoid muscle attaches to the ramus of the mandible. The ramus has an accessory fascicle that attaches to the styloglossus muscle in the fetus. It may not entirely disappear after being born. The length of the styloid process may be a contributing factor in the development of eagle syndrome.The styloglossus muscle plays an essential role in swallowing, mastication, and speech. The attachment involves the function of the motion of the mandible. The external carotid artery travels along with the accessory muscle‐tendon and needs to be considered during surgery.
Resistance Training Enhances Muscle Function and Hemorheological Properties in Middle‐aged Obese Women
Authors: Seo Jisu , Jung Won‐Sang , Kim Sung‐Woo , Kim Jisu , Park Hun‐Young , Lim Kiwon 
Published: May 2022

PurposeThe present study investigated the effects of resistance training for 12‐week on body composition, blood pressure, blood lipid level, cross sectional area (CSA) of muscles, isokinetic muscle function, and hemorheological properties in middle‐aged obese women.MethodsThirty obese women (50.79 ± 5.80 years), with no history of any injuries to the musculoskeletal system and no participating any regular exercise program, were included in the present study. All participants were randomly assigned to a control group (CON, n = 15) or an experimental group (EXP, n = 15); but two participants in the CON voluntarily withdrew because of personal reasons, and thirteen participants in the CON finally participated. The EXP underwent resistance training program composed of warm‐up, main resistance exercise (bench press, preacher bench biceps curl, barbell rowing, dumbbell shoulder press, dead lift, barbell squat, seated leg extension, and lying leg curl), and cool‐down. Main resistance exercise was consisted of three sets of 8–10 repetitions (reps) performed with 80% of 1‐RM. The training frequency was 80 min, 3 days per week for 12 weeks. The CON maintained their daily lifestyle without training. All participants underwent body composition (weight, body mass index, lean body mass, fat mass, and %body fat), blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure), blood lipid level (triglyceride, total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol), cross sectional area (CSA) of muscles (quadriceps CSA, hamstring CSA, and total thigh muscle CSA), isokinetic muscle function (peak torque, relative peak torque, mean power, and total work in quadriceps femoris and hamstrings), and hemorheological properties (erythrocyte deformability and erythrocyte aggregation) were measured before and after 12‐week of training.ResultsThe EXP showed a significant decrease in fat mass (p = .018) via 12‐week of resistance training. Also, the EXP yielded more significant improved muscle function including peak torque (p < .001), relative peak torque (p < .001), and total work (p = .001) in quadriceps femoris and total work (p = .018) in hamstrings. Regarding hemorheological properties, the EXP showed a significant increase in erythrocyte deformability (p = .001) via 12‐week of resistance training. However, there was no significant change in blood pressure and muscle CSA parameters via 12‐weeks of resistance training.ConclusionThe present study verified our resistance training program shows greater muscle strength and endurance, decreasing fat mass, and improving hemorheological properties such as erythrocyte deformability.
Dexamethasone ameliorates arthritis through epigenetic and transcriptional regulation of CCL17 production
Authors: Achuthan Adrian 
Published: May 2022

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which leads to poor quality of life due to the debilitating effect of inflammation. Clinical trials in rheumatoid arthritis targeting the cytokine, granulocyte macrophage‐colony stimulating factor (GM‐CSF) are showing promise although its mode of action remains largely unknown. We have previously shown that that GM‐CSF drives CCL17 production via a new interferon regulatory factor 4 (IRF4)‐dependent pathway in human monocytes and mouse macrophages, as well as in vivo. Importantly, in arthritis and pain models IRF4‐regulated CCL17 formation mediates the proinflammatory and algesic actions of GM‐CSF.Glucocorticoids (GCs) are potent anti‐inflammatory and immunosuppressive agents broadly used in anti‐inflammatory therapy, albeit with adverse side effects associated with long‐term usage. The negative consequences of GC therapy provide an impetus for research into gaining insights into the molecular mechanisms of GC action on immune cells.We report here that GM‐CSF‐induced CCL17 expression is inhibited by dexamethasone, a synthetic GC, in human monocytes and mouse macrophages. Moreover, we provide evidence for the first time that dexamethasone suppresses GM‐CSF‐induced IRF4 expression via regulating the expression and activity of JMJD3, which demethylates trimethylated‐H3K27. Further, we demonstrate that dexamethasone suppresses the expression of JMJD3, via the recruitment of GC receptor‐alpha to the negative GC response element in the upstream region of JMJD3 gene. Significantly, we measured elevated levels of CCL17 in synovial fluid from patients with RA compared to healthy controls. Using synovial fluid mononuclear cells from RA patients, we provide molecular evidence for the anti‐inflammatory actions of GCs through epigenetic regulation of IRF4 expression and downstream inhibition of CCL17 production. The delineated pathway potentially provides new therapeutic options for the treatment of inflammatory diseases and their associated pain.
Long‐term neuroprosthetic hemotherapy treats autonomic dysreflexia after spinal cord injury
Authors: Soriano Jan Elaine , Hudelle Rémi , Squair Jordan W. , Anderson Mark A. , Gautier Matthieu , Mahe Löis , Tso Marcus , Amir Suje , Courtine Gregoire , Phillips Aaron A. 
Published: May 2022

Disrupted descending supraspinal control results in a hyper‐excitable sympathetic nervous system connectome after spinal cord injury (SCI). A condition termed “autonomic dysreflexia” (AD) results, which is characterized by severe elevations in blood pressure that are life‐threatening. There are no effective therapies for AD. Long‐term epidural stimulation below the level of the SCI can promote functionally‐relevant plasticity of volitional motor circuits, and this paradigm may prevent the hyper‐excitable sympathetic connectome after SCI.Here we studied the potential rehabilitative effect of long‐term epidural stimulation, as well as the mechanisms that are responsible for the development of AD. For this experiment, we compared SCI rats that underwent 30 minutes of epidural stimulation 5x/week for 6 weeks to SCI rats receiving normal care. Long‐term epidural stimulation abrogated AD induced by colorectal distension (p<0.0001; Figure 1). Viral tracing of ascending propriospinal neurons was also performed in these groups. Long‐term epidural stimulation normalized the sympathetic connectome as the axons and synapses were significantly reduced compared to SCI rats (p=0.0021; p=0.0127). We next performed chemogenetic silencing of excitatory and inhibitory interneurons, as well as sympathetic preganglionic neurons, in the lower thoracic spinal segments while experimentally inducing AD. Preliminary data indicate that AD is, at least in part, mediated by excitatory interneuronal connections to sympathetic preganglionic neurons.Long‐term epidural stimulation may be an effective hemotherapy for preventing AD after SCI. This project may provide direction for basic and clinical research to develop treatments for sympathetic nervous system dysfunction after SCI, and thereby improve health and patient quality of life over the long term.