bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐Term High‐Fat Feeding Reduces the Numbers of Satellite Cells and Myonuclei in the Adult Murine Skeletal Muscle Fibers
Authors: Allouh Mohammed Z. , Starling-Emerald Bright , Al Jailani Mohammed A.
Published: April 2020

High‐Fat Diet (HFD) affects the skeletal muscle fibers at both morphological and functional levels. At a functional level, it has been reported that HFD reduces the oxidative capacity and leads to insulin resistance in the skeletal muscle tissue. However, there are very limited and conflicting information about the effects of HFD on the morphology of skeletal muscle fibers. This study aimed to clarify the effects of long‐term feeding with HFD on murine skeletal muscle fibers. These effects include the size of skeletal muscle fibers, frequency of satellite cells, and number of myonuclei within the fibers. Adult male mice of the C57BL/6 strain were randomly divided into 2 groups; a control group, and a HFD group. Each group contained four mice. Food and water were provided ad libitum. At the end of a twenty‐week feeding period, the tibialis anterior (TA) muscle was dissected out from each animal and weighed. Immunocytochemical and morphometric image analyses techniques were applied to quantify the fiber diameter, satellite cell frequency, and number of myonuclei per fiber cross‐section. The HFD group showed a significant (P<0.01) decrease in TA muscle weight compared to control group. However, a significant (P<0.05) increase in the muscle fiber diameter was found in the HFD group compared to control one. In addition, significant reductions (P<0.01) in satellite cell frequency and number of myonuclei were detected in the HFD group compared to control group. This study showed that long‐term feeding with HFD increases the size of skeletal muscle fibers, which may be attributed to the accumulation of intramyocellular lipids. In addition, it reveals that HFD decreases the numbers of satellite cells and myonuclei within the murine skeletal muscle fibers.

Support or Funding Information

Funds for this study were provided by a seeding grant to MZA from the College of Medicine and Health Sciences at United Arab Emirates University.
Tribbles Homolog 3 (TRB3) Expression is Modulated During Skeletal Muscle Myogenesis and Regeneration
Authors: Sougey Wenddy Wyllie Damascena , Silvestre João Guilherme , Lós Deniele Bezerra , Moriscot Anselmo Sigari
Published: April 2020

Skeletal muscle mass and activity are primordial for homeostasis and are related to important functions such as breathing, locomotion and glucose metabolism. This tissue is susceptible to lesion from mechanical‐chemical injuries and also from the mechanical stress generated by contractions. Fortunately, skeletal muscle is highly capable of regeneration, although the cellular‐molecular mechanisms involved are still not properly understood. TRB3 is a gene that codes the homonymous protein often studied for its involvement in insulin resistance by inhibiting Akt2 activity. Because it has also been shown that TRB3 overexpression can decrease myotube formation, we decided to evaluate the TRB3 expression during skeletal muscle regeneration and also in myogenesis using C2C12‐derived myotubes as a model. We cultured C2C12 cells using DMEM 10% FBS with antibiotics as growth medium. Cells at ~80% confluence were induced to differentiation into myotubes with DMEM 2% for 2 and 4 days. Cells were then harvested and total RNA and protein were isolated for further analysis by using RT‐PCR and Western blot. Also, 16 adult male C57Bl mice (~8 weeks, ~30g) were housed in 12/12h light/dark regimen with food and water ad libitum and divided into Control and tibialis anterior‐injured by cardiotoxin (CTX, 10uM) for 1, 3 and 10 days. Statistical analyzes were conducted using t‐student test in comparison with Control Group (not injured mice) or one‐way ANOVA for nonparametric data with Dunns post‐hoc for C2C12 samples analysis, expressed in Mean +− SD and p≤0.05. All experiments were approved by the Institute of Biomedical Sciences Animal Experimentation Office Committee (6085260718). We observed elevated levels of TRB3 mRNA at 2 and 4 days of C2C12 differentiation (~2.5 fold for both time points, p<0.05). Interestingly, in spite of a clear rise in TRB3 mRNA, AKT2 (a target for TRB3) mRNA is also upregulated in differentiated C2C12 cells (~3.5 fold 4 days after differentiation, p<0.05). Likewise, GSK3b mRNA levels are elevated 4 days after differentiation (2.5 fold, p<0.05). In the regeneration model we also observed increased TRB3 mRNA levels in all time points evaluated (1 day~19 fold 3 days~9 fold and 10 days~5 fold, p<0.05). Accordingly, we preliminarily observed increased levels of TRB3 10 days after injury by Western blot. These results suggests that TRB3 might be involved in the early and late phases of the myogenic‐regenerative process and functional experiments involving manipulated TRB3 levels are ongoing.

Support or Funding Information

FAPESP, CAPES, CNPq
Board Relevance of an Osteopathic Medical Physiology Course Introductory, Cardiovascular and Respiratory Sections
Authors: Rhodes Spencer A. , Johnson Robert A. , Johnson Fruzsina K.
Published: April 2020

Physiology has been a foundational course in medical curriculums for several decades. As the discipline that integrates multiple other disciplines into a functional framework, medical physiology used to be a driving force of preclinical education complete with laboratory components. In recent years, medical education has begun to shift away from the traditional model. Organ system‐based curricula are becoming the standard and medical physiology is increasingly marginalized losing its laboratory component and receiving less and less contact time. As board scores remain a primary factor determining residency placement, students increasingly focus on board relevance in courses. Last year, our second‐year class identified Boards & Beyond as an exceptionally useful study tool not just for board preparation, but also to help prioritize course materials and revisit concepts with regularity. We at WCUCOM want to give our students every opportunity to succeed. Incoming first year students and teaching faculty were provided with Boards & Beyond access. Our overall goal was to map our Medical Physiology I and II courses to the Boards & Beyond review resources. We started with mapping the blocks in the fall semester Medical Physiology I course, namely: Introductory (general physiology concepts), Cardiovascular and Respiratory physiology blocks. We used topic key words established by Boards & Beyond for their physiology videos and added keywords of our own for topics not covered in Boards & Beyond videos. The first‐year (OMS‐1) Medical Physiology I course has 54 lectures. There are 19 introductory lectures which include membrane and muscle physiology, as well as an introduction to regulatory systems. The cardiovascular section has 26 basic physiology lectures and respiratory physiology is taught in 9 basic physiology lectures. We mapped the content of these 54 lectures to Boards & Beyond video contents. We found that except for the first 4 introductory lectures on homeostasis and the history and scope of physiology, even the introductory physiology lecture topics were at least 40% covered in Boards & Beyond videos. The overlap increased in the cardiovascular and respiratory physiology lecture topics, but never reached 100%. We conclude that our osteopathic medical physiology course introductory, cardiovascular and respiratory sections are highly board relevant. We also conclude that Boards & Beyond materials may be useful study tools to help prioritize topics is medical physiology, however they cannot replace the medical physiology course in our osteopathic medical curriculum.
Characterization of a Leucine‐Rich Repeat‐Containing G Protein‐Coupled Receptor
Authors: Erlandson Sarah C. , Rawson Shaun , Kruse Andrew C.
Published: April 2020

Leucine‐rich repeat‐containing GPCRs (LGRs) are a small group of Family A GPCRs consisting of glycoprotein hormone receptors, R‐spondin receptors, and relaxin receptors. All of these receptors have large N‐terminal ectodomains of leucine‐rich repeats (LRRs), however the mechanisms that couple ligand binding in the LRRs to signal transduction are poorly understood. We have been studying the relaxin receptor, RXFP1, which is a member of the LGR family with important roles in cardiovascular and reproductive biology. Activation of RXFP1 by its agonist, relaxin, induces pleiotropic cellular responses, including vasodilation, angiogenesis, and collagen degradation. These effects in various tissues, particularly the heart, liver, and kidneys, make RXFP1 a promising drug target to treat cardiovascular diseases and multiple diseases of organ fibrosis. Despite the biomedical relevance of RXFP1, there are few molecules available to modulate receptor signaling and relatively little is known about the receptor’s molecular mechanism of activation. We have created engineered versions of the relaxin hormone with the goal of generating a molecule that can target RXFP1 with a longer serum half‐life. To study the receptor’s molecular mechanism, we optimized an expression and purification strategy for RXFP1 in complex with relaxin and its intracellular effector, the heterotrimeric Gs protein, and have been studying the complex by cryo‐electron microscopy. These studies have revealed the shape of the receptor’s LRR ectodomain, which positions the binding site of relaxin away from the GPCR transmembrane domain. Details of the receptor’s interactions with G proteins were also investigated, showing that RXFP1’s helix 8 interacts with G proteins similarly to Class B GPCRs.

Support or Funding Information

Financial support for this work was provided by the Blavatnik Biomedical Accelerator at Harvard University and an NIH F31 Fellowship (5F31GM128233) (S.C.E.).
Facio‐genital dysplasia 5 (FGD5) regulates G‐protein coupled receptors (GPCRs) signaling to phosphatidylinositol 3 kinase (PI3K) pathway
Authors: Azad Abul Kalam , Farhan Maikel , Eitzen Gary , Murray Allan
Published: April 2020

Introduction

Drugs targeting the VEGF‐pathway have been approved to treat various cancers. However, tumors become resistant to this therapy due to the recruitment of alternative growth factors, acting via cognate endothelial cells (EC) receptor tyrosine kinases (RTK) or g‐protein coupled receptors (GPCR), to cue neo‐angiogenesis. Facio‐genital dysplasia 5 (FGD5) regulates vascular endothelial growth factor (VEGF)‐mediated angiogenesis, and VEGF receptor‐2 trafficking at the endosome. However, the role of FGD5 to regulate other pro‐angiogenic signaling pathways that co‐operate with VEGF has not been explored. Here, we identify a novel role of FGD5 to control G protein‐coupled receptor (GPCR) signaling.

Methods

Human umbilical vein endothelial cells (HUVEC) were mounted on microcarrier beads, suspended in fibrin gels, then co‐cultured with freshly harvested patient‐derived renal cell carcinoma (PD‐RCC) samples. The effect of FGD5 loss on sprouting angiogenesis was evaluated using RNAi against FGD5 in HUVEC. Stromal cell derived factor (SDF)‐1 was used as a model GPCR ligand to study the role of FGD5 in endothelial angiogenesis and PI3K signaling. Further, FDG5 domain‐deletant mutants were transiently overexpressed to rescue the effect of FGD5 knockdown on endothelial PI3K signaling. Western blot and confocal imaging were performed to readout the role of FGD5 in the GPCR/PI3K signaling pathway.

Results

Loss of FGD5 in HUVEC decreased sprouting angiogenesis stimulated by growth factors released from PD‐RCCs. The defect in angiogenesis was accompanied by downregulation of the expression of endothelial tip cell specific marker genes. Knockdown of endothelial FGD5 abolished the SDF‐1 angiogenic effect and SDF‐1 signaling to PI3K‐β and Akt. Inhibition of Rac1, a Rho GTP‐binding protein required for PI3K‐β activity, recapitulated the signaling defects of FGD5 deficiency, suggesting that FGD5 may control PI3K‐β activity through Rac1‐GTP. Overexpression of Dbl (Rho guanine nucleotide exchange factor) domain‐deleted FGD5 (FGD5ΔDbl) reduced SDF‐1‐stimulated Akt phosphorylation, and failed to rescue defective PI3K signalling in FGD5‐deficient cells, indicating that the Dbl domain of FGD5 regulates the activity of PI3K‐β. PI3K‐β and phosphorylated Akt localized to early endosomes after SDF‐1 stimulation, but loss of FGD5 decreased endosomal phosphorylated‐Akt. Failure of Akt activation at PI3K‐β‐positive endosomes suggests a defect in PI3K‐β activity after FGD5 loss.

Conclusions

We identify a novel role of FGD5 to regulate GPCR signaling to PI3K‐β. FGD5 acts at an endosomal convergence node regulating RTK and GPCR angiogenic pathways that may serve as a target for anti‐angiogenic therapy.

Support or Funding Information

University of Alberta Doctoral Recruitment Scholarship, Translational Medicine Research Award, Alberta Graduate Excellence Scholarship, Canadian Cancer Society, Division of Nephrology
RGS5 Deficiency Increases Blood Pressure and Causes Cerebral Vascular Oxidative Stress in Aged Male Mice
Authors: Luu Anh , Waldschmidt Ryan , Guisinger Trevor , Seeley Sarah , D’Souza Manoranjan , Chrissobolis Sophocles
Published: April 2020

Aging is associated with elevated blood pressure, vascular oxidative stress and emotional behavioral abnormalities, such as anxiety and depression. Angiotensin II (Ang II) is reportedly involved in both vascular and emotional behavioral abnormalities. The actions of Ang II are mediated by the Ang II type 1 receptor whose activity is modulated by regulator of G‐protein signaling 5 (RGS5) protein. We have previously reported that RGS5 deficiency exacerbates Ang II‐induced elevations in blood pressure, and emotional behaviors in the absence and presence of elevated Ang II levels in adult (~26 week old) male mice. In this study we assessed the role of RGS5 on blood pressure, vascular and emotional behavioral outcomes in aged male mice in the absence and presence of elevated Ang II levels (1 mg/kg/d for 21 days). Specifically, we used aged (16–20 month old) male mice lacking RGS5 and their wild type counterparts to assess effects of saline or Ang II on systolic blood pressure (SBP), vascular function and oxidative stress, locomotor activity, and anxiety‐ and depression‐like behavior. RGS5 deficiency increased SBP under normal conditions, and increased cerebral vascular superoxide levels in the absence and presence of elevated Ang II levels, suggesting that RGS5 deficiency leads to elevated blood pressure and cerebral vascular oxidative stress in aged mice. RGS5 deficiency did not impair relaxation responses to acetylcholine, or contraction to the nitric oxide synthase inhibitor l‐NAME in aorta, suggesting that RGS5 deficiency had no effect on endothelial function in aorta. Interestingly, elevated Ang II levels increased spontaneous locomotor activity in wild‐type mice, but not in mice lacking RGS5. These data suggest that RGS5 deficiency attenuated responsiveness to Ang II‐induced increases in spontaneous locomotor activity. RGS5 deficiency and Ang II treatment had no effect on anxiety‐ and depression‐like behavior. In summary, these data suggest that RGS5 protects against elevated blood pressure, and has protective effects in the cerebral circulation in the absence and presence of elevated Ang II levels in aged male mice. Clinically, these data suggest that inhibitors of the renin angiotensin system may reduce the risk of cerebrovascular disease in aged males lacking RGS5.

Support or Funding Information

This work was supported by funds from the College of Pharmacy, Ohio Northern University.
Enhancing Vascular Access Training with Ultrasonography
Authors: Canaan Ryan , Cross Evan , Pazdernik Vanessa , Batten Spencer , Kondrashova Tatyana
Published: April 2020

Background

Needle‐guided procedure training is important since ultrasound‐guided techniques may reduce risk of needle misplacement and complications. Vascular access training with ultrasound‐training models in preclinical education can enhance student confidence with vascular catheterization procedures and increase comfort with needle guidance in the clinical setting. The goal of our study was to assess medical student perception of ultrasound‐guided vascular access training, using training models and hands‐on venipuncture, and its importance for development of clinical skills for future practice.

Methods

Second‐year medical students participated in vascular access training by practicing an upper extremity vascular ultrasound exam on each other and on ultrasound phantoms (PICC line, central line, two‐vessel vein access) and by performing supervised venipuncture under ultrasound guidance. After training, students completed an anonymous paper survey about their perception of ultrasound‐guided vascular access laboratories using training models and hands‐on venipuncture and their importance for development of clinical skills.

Results

Students agreed training improved understanding of PICC line, central line, and venipuncture procedures (all P<.001). Training with ultrasound models improved skills (all P<.001) and boosted confidence for PICC line (P=.02), central line (P=.04), and ultrasound‐guided venipuncture (P<.001) in a clinical setting. The central line procedure was more challenging than venipuncture (t test P=.03). There was a strong positive correlation for feeling capable of performing the PICC line procedure on the model and in a clinical setting (r=0.68, P=.001). There was a positive, but less significant, correlation for the central line model and clinical practice (r=0.41, P=.08). Training improved image interpretation for all 3 procedures (all P ≤.04). All students agreed ultrasound‐training models improved clinical skills and models were useful for learning practical skills associated with vessel cannulation and access (both P<.001). Students felt prepared to use ultrasound for vascular access in clinical rotations, residency training, and professional practice (P<.001).

Conclusion

Vascular access training helped medical students build practical skills for PICC line, central line, and venipuncture procedures. It boosted confidence performing difficult procedures and introduced use of ultrasound technology for vascular access. Thus, vascular access training was beneficial to students in acquiring a skillset needed in future medical practice.
The Effects of Targeted Marine Phytoplankton Supplementation on Long Term Recovery During Intensified Training
Authors: Wilson Jacob , Sharp Matthew , Book Nicholous , Stefan Matthew , Reber Dallen , Gheith Raad , Ottinger Charlie , Lowery Ryan , Juturu Vijaya
Published: April 2020

Extended periods of intensified physical training results in decrements in physical and perceptual recovery. As a result, nutritional recovery methods are highly sought after.

Purpose

This study investigated targeted enriched marine phytoplankton supplementation (Microalgae Tetraselmis chuii, Oceanix™, OCX) on Perceived Recovery (PRS) and Explosive Strength recovery during long term intensive training.

Methods

Trained male and female subjects were divided into placebo (PLA) or Oceanix (OCX) (25 mg per day) conditions. The subjects were all placed on a 6‐week resistance‐training program interspersed with purposeful overreaching on Wk2 and Wk5, and low volume recovery training on Wk6. Recovery scale (PRS) changes (0–10) relative to initial maintenance training levels were taken on each successive week from baseline. Explosive Strength, measured as rate of force development, during a countermovement jump was assessed at pre‐test, and at weeks 2, 5 and 6.

Results

The relative increase in PRS during the recovery Wk6 of training was greater (+16%) for OCX compared to PLA (p<0.05), indicating greater recovery. Explosive Strength was reduced after overreaching at Wk2 and Wk5 for both conditions (p<0.05). However, explosive strength only recovered fully for OCX and not the PLA during the recovery Wk6.

Conclusions

Targeted marine phytoplankton supplementation (Oceanix™ supplementation) during extended periods of intensified training improves long‐term recovery in trained male and female subjects.

Support or Funding Information

Lonza
The Green Tea Catechin, EGCg, Preserves Both Muscle and Bone in Aging Sarcopenic Rats
Authors: Dvoretskiy Svyatoslav , Cole Todd , Skelding Mary-Beth , Reaves Lisa A. , Edens Neile K. , Pereira Suzette L.
Published: April 2020

Objectives

Sarcopenia is the progressive decline in muscle mass, strength and function that is exacerbated with age. It is well known that there is an overlap between sarcopenia and osteopenia/osteoporosis in the aging population. Thus, addressing both muscle and bone loss during aging is important. Epigallocatechin gallate (EGCg) is the most abundant green tea catechin and has well established anti‐inflammatory and antioxidant benefits. Green tea consumption has also been associated with bone health. In this study we examined the impact of chronic EGCg treatment on muscle mass and bone structure in aging rats.

Methods

Aged male Sprague‐Dawley rats (21 months) were fed the following diets ad libitum: Control group (n=9) fed AIN93M diet, and a treatment group (n=10) fed AIN93M diet +EGCg (200 mg/kg) for 8 weeks. At the end of study, gastrocnemius muscles were weighed, and histological analysis was performed to measure muscle fiber cross sectional area (CSA) using hematoxylin & eosin staining. Bones were analyzed by MicroCT imaging (Burker) of the tibia at ~22 μm resolution and images were processed using Inveon Research Workplace software. All bone samples were analyzed for trabecular bone volume, trabecular number, trabecular spacing, trabecular thickness, trabecular pattern factor and bone density.

Results

Gastrocnemius muscle wet weights were significantly higher (p<0.05) and fiber CSA tended to be higher (p<0.06) in the EGCg group compared to controls. Tibia bone volume/total volume density was significantly greater (p=0.03) in animals treated with EGCg compared to control. Significant differences were found in trabecular microstructure, with a significant increase in trabecular number per given volume (p=0.01) and a corresponding significant decrease in trabecular spacing (p=0.02) in EGCg‐treated rats compared to control. No significant group differences were found in overall bone density or trabecular thickness. Differences in mean values between control and EGCg groups were determined by student’s t‐test.

Conclusions

These data present novel findings on the osteoprotective mechanism of EGCg on the aging bone through an increase in trabecular bone volume, trabecular number and trabecular spacing. Furthermore, the preservation of muscle mass and muscle fiber CSA suggests that the use of green tea catechin, EGCg, could be a potential nutritional therapy to prevent the progression of muscle and bone loss during sarcopenia.

Support or Funding Information

Abbott Nutrition
Effect of Tibial Nerve Stimulation on Menopause‐associated Symptoms in Ovariectomized Rats
Authors: Xu Jiajie Jessica , Zimmerman Lauren , Soriano Vanessa , Mentzelopoulos Georgios , Kennedy Eric , Bottorff Elizabeth , Bruns Tim
Published: April 2020

Human menopause transition and post‐menopausal syndrome, driven by reduced ovarian activity which reduces estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, osteoporosis, and metabolic disease. Current treatments (both hormonal and non‐hormonal) are limited in efficacy and may have adverse consequences, so investigation for additional treatment options are necessary. Previous studies have demonstrated that tibial nerve stimulation or electro‐acupuncture are minimally invasive treatments that increase vaginal blood flow and serum estrogen in the rat model. In this study we examined the effects of biweekly tibial nerve stimulation (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine‐xylazine anesthesia in female ovariectomized (OVX) Sprague Dawley rats on various measurements that can change in association with menopause (serum estradiol, resting blood glucose, vaginal blood perfusion, uterine weight/histology, and bone density) either at weekly time‐points or during a terminal necropsy. Rats were split into three groups (n = 10 per group): 1) intact + no stimulation, 2) OVX + no stimulation, and 3) OVX + stimulation. Although preliminary data has not shown significant differences between treatment groups, data collection is ongoing and trends are expected after weeks of stimulation. The results of this study will examine the effects of tibial nerve stimulation on various menopause associated symptoms, and help guide recommendations for future studies and treatments.
Myeloid vitamin D receptor influences cell proliferation in small intestine
Authors: Ogbu Destiny , Bakke Danika , Sun Jun
Published: April 2020

The vitamin D receptor (VDR) is a ubiquitous nuclear receptor that acts as a transcription factor when vitamin D binds with VDR. Intestinal epithelial VDR has various physiological and anatomical benefits to intestine. Interactions between intestinal epithelial cells (IEC) and immune cells are critical for gut health. Cellular proliferation through Wnt/β‐catenin signaling is a result of immune and IEC crosstalk. Wnt proteins from macrophages bind to intestinal epithelial cells and activate the Wnt/β‐catenin pathway. This pathway is critical for cell proliferation which enables food and water absorption in the small intestine. However, the importance of myeloid VDR in regulating the Wnt/β‐catenin pathway in epithelial cells is not fully understood. The objective of this study is to assess how the presence of myeloid VDR in the intestinal epithelial cells influences cellular proliferation through the Wnt/β‐catenin pathway. We hypothesize that the low level of myeloid VDR will reduce expression of Wnt/β‐catenin signaling downstream and alleviate cell proliferation in the small intestine. This experiment utilized selective deletion of myeloid VDR in an ex‐vivo and in‐vivo set‐up. For the ex‐vivo, control mice (VDRLoxP) were crossed with lysozyme (M) ‐cre mice to create specific knockout of myeloid VDR (VDRrLyz) mice. Twelve mice (6 VDRLoxP mice and 6 VDRrLyz) were sacrificed and mucosal scrapings from the ileum (small intestine) were collected for westerns. For cell culture, small intestine organoids derived from the intestinal stem cells were cultured alone or co‐cultured with macrophages (VDR+/+ or VDR−/−). After 3 days, the organoids and organoid‐macrophage co‐cultures were collected for western blots. Western blots were used to measure and compare expression of Wnt/β‐catenin signaling proteins. The VDR−/− organoid macrophage co‐culture showed significantly decreased expression of β‐catenin and PCNA (a cell proliferation marker), compared to the VDR+/+ organoid macrophage co‐culture. Our results suggest that myeloid VDR influences the Wnt/β‐catenin signaling pathway. We present a novel role of myeloid VDR signaling in mediating immune/epithelial cell cross talk in intestine.
Alpha Lipoic Acid Attenuates ER Stress and Improves Glucose Uptake Through DNAJB3 Cochaperone
Authors: Dehbi Mohammed , Mahmoud Naela , Khattab Namat , Bensmail Ilham , Diane Abdoulaye
Published: April 2020

Persistent ER stress, mitochondrial dysfunction and failure of the heat shock response (HSR) are fundamental hallmarks of insulin resistance (IR); one of the early core metabolic aberrations that leads to type 2 diabetes (T2D). The antioxidant α‐lipoic acid (ALA) has been shown to attenuate metabolic stress and improve insulin sensitivity in part through activation of the heat shock response (HSR). However, these studies have been focused on a subset of heat shock proteins (HSPs). In the current investigation, we assessed whether ALA has an effect on modulating the expression of DNAJB3/HSP40 cochaperone; a potential therapeutic target with a novel role in mitigating metabolic stress and promoting insulin signaling. Treatment of C2C12 cells with 0.3 mM of ALA triggers a significant increase in the expression of DNAJB3 mRNA and protein. A similar increase in DNAJB3 mRNA was also observed in HepG2 cells. We next investigated the significance of such activation on endoplasmic reticulum (ER) stress and glucose uptake. ALA pre‐treatment significantly reduced the expression of ER stress markers namely, GRP78, XBP1, sXBP1 and ATF4 in response to both tunicamycin and glucolipotoxicity. In functional assays, ALA treatment abrogated significantly the tunicamycin‐mediated transcriptional activation of ATF6 while it enhanced the insulin‐stimulated glucose uptake. Silencing the expression of DNAJB3 but not HSP72 abolished the protective effect of ALA on tunicamycin‐induced ER stress, suggesting thus that DNAJB3 is a key mediator of ALA‐alleviated tunicamycin‐induced ER stress. Furthermore, the effect of ALA on insulin‐stimulated glucose uptake is reduced significantly in C2C12 cells transfected with DNAJB3 siRNA.

In summary, our results are supportive of an essential role of DNAJB3 as a molecular target through which ALA alleviates ER stress and improve glucose uptake.

Support or Funding Information

This work was supported by Qatar Biomedical Research Institute, Hamad Bin Khalifa University intramural grant (IGP 2014‐001) to MD
Acute Effect of Coffee on Central Arterial Stiffness and Hemodynamics
Authors: Holmer Brady J. , Lapierre Stephanie , Lim Jisok , Sakarya Yasemin , New William , Eagle Michael , Hwang Chueh-Lung , Schwartz Cody , Bhattal Gurjaspreet , Maharrey Phillip , Handberg Eileen M. , Christou Demetra D. , Alviar Carlos
Published: April 2020

Coffee is widely consumed and several studies have examined the acute effects of coffee consumption on blood pressure. However, little attention has focused on the acute effects of coffee on central arterial stiffness, wave reflection, and aortic blood pressure, independent predictors of cardiovascular disease. The objective of this investigation was to conduct a randomized, placebo‐controlled study of the acute effects of coffee on central arterial stiffness and hemodynamics. Sixteen young males (21±2 yrs; means±SE) who were light caffeine users consumed 16 oz. of cold coffee, containing 160 mg caffeine, or placebo (cold water) on two visits separated by at least a week. Central arterial stiffness (carotid to femoral pulse wave velocity; cfPWV), aortic wave reflection (augmentation index normalized at heart rate 75; AIx75) and aortic blood pressures (systolic, diastolic and mean blood pressure; aoSBP, aoDBP, aoMAP and pulse pressure; aoPP) were assessed using SphygmoCor XCEL (AtCor Medical) before and 1hr and 2hr after beverage consumption. In response to coffee, cfPWV increased at 1hr and remained elevated at 2hr (6.29±0.16 vs. 6.48±0.17 vs. 6.53±0.15 m/sec; P=0.03 for base vs. 1hr and P=0.004 for base vs. 2hr), but did not change in response to placebo (6.48±0.13 vs. 6.41±0.16 vs. 6.37±0.19 m/sec; P>0.5 for base vs. 1hr vs. 2hr and P=0.01 for condition × time). AIx75 decreased at 1hr and remained decreased at 2hr following coffee (5.5±2.9 vs. −2.4±3.1 vs. −1.7±3.3 %; P=0.0002 for base vs. 1hr and P=0.008 for base vs. 2hr) and placebo (3.9±2.8 vs. ‐ 3.7±2.5 vs. −6.7±2.6 %; P<0.0001 for base vs. 1hr and for base vs. 2hr), but to a different degree (P=0.015 for condition × time). AoSBP and aoPP were not affected by coffee or placebo (P>0.05). However, aoDBP and aoMAP increased in response to coffee by 7±2 and 5±1 mmHg, respectively, at 1hr and remained elevated at 2hr (aoDBP: 67±1 vs. 74±1 vs. 72±2 mmHg; P=0.002 for base vs. 1hr and P=0.03 for base vs. 2hr, aoMAP: 80±1 vs. 85±1 vs. 84±2 mmHg; P=0.003 for base vs. 1hr and P=0.04 for base vs. 2hr), but did not change following placebo (P>0.9 and P≥0.001 for condition × time). In conclusion, consumption of coffee containing 160 mg caffeine leads to acute changes in central arterial stiffness and hemodynamics in healthy young men. Future investigations should confirm these findings in women and examine whether responses are exaggerated in individuals who are hypertensive or have other cardiovascular disease risk factors.

Support or Funding Information

This work was supported by the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine.
Angiomatoid Fibrous Histiocytoma With ALK Expression in an Unusual Location and Age Group
Authors: De Noon Solange , Fleming Andrew , Singh Manuraj
Published: April 2020

Angiomatoid fibrous histiocytoma (AFH) is a relatively rare soft tissue tumor of intermediate malignant potential, occurring most commonly in young adults, with a recognized propensity for local recurrence and occasional metastasis. A case of AFH occurring on the finger of a 60-year-old man is described in which the unusual location and age group for this entity raised the original wrong diagnosis of an aneurysmal and cellular fibrous histiocytoma. Further workup demonstrated an EWSR1-CREB1 translocation, confirming the correct diagnosis of AFH. Strong anaplastic lymphoma kinase (ALK) expression using the antibody clone D5F3 was demonstrated in our case on immunohistochemistry, which is in concordance with recent findings of anaplastic lymphoma kinase positivity with this antibody in the majority of AFHs.
Melanoma Ex Blue Nevus With GNA11 Mutation and BAP1 Loss: Case Report and Review of the Literature
Authors: Chang Li-Wei , Kazlouskaya Viktoryia , Kazi Rashek , Davar Diwakar , Ferris Robert L. , Ho Jonhan , Karunamurthy Arivarasan , Jedrych Jaroslaw J. , Bunimovich Yuri L.
Published: April 2020

Cutaneous melanomas may demonstrate a variety of histopathological features and genetic abnormalities. Melanomas that arise in the setting of blue nevi, also known as “malignant blue nevus” or melanoma ex blue nevus (MBN), share a similar histopathological and mutational profile with uveal melanoma. Most uveal melanomas show characteristic GNA11 or GNAQ mutations; additional BAP1 mutation or loss is associated with the highest risk of metastasis and worst prognosis. However, the significance of BAP1 loss in melanomas ex blue nevus remains unclear. We present a case of MBN arising from the scalp of a 21-year-old woman. The diagnosis was established on histopathological findings demonstrating a markedly atypical melanocytic proliferation with increased mitotic activity, necrosis, and a focus of angiolymphatic invasion. Immunohistochemical analysis demonstrated the absence of BAP1 nuclear expression within tumor cells. Next generation sequencing detected GNA11 Q209L mutation and BAP1 loss (chromosome 3p region loss), supporting the diagnosis. We reviewed another 21 MBN cases with reported BAP1 status from the literature. MBN with BAP1 loss presented at a younger average age (41 vs. 61 years), demonstrated larger average lesion thickness (9.0 vs. 7.3 mm), and had a higher rate of metastasis (50% vs. 33%) compared with BAP1-retained MBN. BAP1 expression studies may assist in the diagnosis and management of MBN, but further research is needed.
Characterization of Hearing Loss in Adult Patients With Nondialysis Chronic Kidney Disease
Authors: Lara-Sánchez Hugo , Calvo David Herrero , Sañudo Elisa Gil-Carcedo , Mayo-Iscar Agustín , Cordero Maria Eugenia Plagaro , Monfá-Bosch José M. , Valdezate Luis Ángel Vallejo
Published: April 2020

Objective:

To confirm the association between chronic kidney disease and sensorineural hearing loss in non-dialysis non-diabetic patients and to establish the audiological profile of these patients indicating the possible location of the auditory damage.

Study Design:

Cross-sectional study.

Setting:

Tertiary referral center.

Patients:

Patients between 18 and 60 years old with chronic kidney disease, without diabetes mellitus and without personal history of otology disease, were compared with a healthy control group pared by sex and age to establish differences between their audiological profile.

Interventions:

Pure tone audiometry (PTA), transient evoked otoacoustic emissions (TEOAEs), distortion products otoacoustic emissions (DPOAEs), and auditory brainstem responses (ABR) were performed in both groups.

Main Outcome Measures:

Mean and standard deviation of PTA auditory thresholds, TEOAEs reproducibility, DPOAEs level/noise, and ABR absolute latency and interwave latency were measured, and compared using linear mixed models.

Results:

Fifty one cases were included and compared with 51 healthy volunteers. The audiometric profile found in patients with chronic kidney disease was a sensorineural hearing loss in 4 to 8 kHz frequencies in the PTA, a decrease in the TEOAEs reproducibility and a decrease in the DPOAEs level. An enlargement in the V wave absolute latency and III to V and I to V interwave latency in the ABR were also found but within normal range.

Conclusions:

There is an association between chronic kidney disease in non-dialysis non diabetic adults patients and sensorineural hearing loss, affecting high frequencies and having the cochlea as the main site of auditory damage.
Association between mean platelet volume and major adverse cardiac events in percutaneous coronary interventions: a systematic review and meta-analysis
Authors: Chen Zhongxiu , Li Nan , Wang Jing , Li Chen , He Sen , Zhou Xiaorong , He Yong
Published: April 2020

Platelets with high hemostatic activity play a key role during percutaneous coronary interventions (PCI), and in recent years, mean platelet volume (MPV) has been looked upon as a crucial indicator of platelet reactivity. Thus, MPV may emerge as a potential gauge for the measurement of major adverse cardiac event (MACE) risks in PCI patients. This study aimed to conduct a meta-analysis illustrating the association between MPV and long-term MACE in PCI. The Cochrane Library, Pubmed, EMBASE, Ovid MEDLINE, and BIOSIS databases were used to search for relevant studies from their inception to 30 June 2019. All studies reporting incidences of MACE and MPV in PCI patients were retained. Data extraction was performed by three independent reviewers. A total of 33 studies were included in this meta-analysis. The results indicated that patients with MACE had a significantly larger MPV than those without, with an unstandardized mean difference (USMD) of 0.29 fL (95% CI, 0.04–0.54). The USMD of MPV in deceased patients was 0.39 fL (95% CI, 0.09–0.68). The results also indicated that patients with larger MPV were at greater risks of having MACE and higher incidence of mortality than those with smaller MPV, with a pooled risk ratio of 1.81 (95% CI, 1.29–2.55) and 2.34 (95% CI, 1.52–3.60), respectively. These findings indicate a significant association between larger MPV and MACE in PCI patients. Consequently, MPV, an easily accessible indicator, might be helpful in PCI patients’ risk assessment and stratification.
Fragmented QRS complexes are associated with postoperative atrial fibrillation development after coronary artery bypass grafting surgery
Authors: Keskin Hasan Attila , Kurtul Alparslan
Published: April 2020

Objective

Postoperative atrial fibrillation (PoAF) is one of the most frequent complications and a major risk factor of morbidity and mortality after coronary artery bypass grafting (CABG). Fragmented QRS complex (fQRS) on a 12-lead surface ECG is recently gained increasing attention as a simplified noninvasive ECG marker with diagnostic and prognostic value in various cardiac conditions. The aim of the present study was to evaluate the association between development of PoAF and presence of fQRS on admission ECG in patients undergoing CABG surgery.

Methods

A total of 242 patients who underwent CABG between February 2016 and June 2018 were included in this study. The patients were divided into two groups as developing and nondeveloping PoAF groups in the postoperative period. fQRS was defined as the presence of various RSR′ patterns including an additional R wave, notching of the R or S waves, or the presence of more than one fragmentation in two contiguous leads.

Results

In-hospital mortality was higher in PoAF (+) group compared to PoAF (–) group (20.5 vs. 6.4%, P = 0.004). PoAF rate was higher in fQRS (+) group than fQRS (–) group (25.3 vs. 9.8%, P = 0.001). In multivariate analysis, the presence of fQRS complexes on admission ECG [odds ratio (OR) 2.801, 95% confidence interval (CI) 1.262–6.211, P = 0.011) and hemoglobin (OR 0.794; 95% CI, 0.641–0.985; P = 0.036) were identified as independent predictors of PoAF after CABG surgery.

Conclusion

The presence of fQRS on admission ECG was found to be an independent predictor of PoAF in patients undergoing isolated CABG.
Safety and efficacy study of prourokinase injection during primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction
Authors: Jiang Wenlong , Xiong Xiaoshuan , Du Xiaohui , Ma Hua , Li Wen , Cheng Fangzhou
Published: April 2020

Objectives

To evaluate the efficacy and safety of intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions in patients with acute ST-segment elevation myocardial infarction.

Methods

Acute ST-segment elevation myocardial infarction patients underwent primary percutaneous coronary interventions were randomly divided into two groups: intracoronary prourokinase group (n = 125) and control group (n = 135). During primary percutaneous coronary interventions, prourokinase or saline was injected to the distal end of the culprit lesion via balloon catheter after balloon catheter dilatation. Demographic and clinical characteristics, infarct size, myocardial reperfusion, and cardiac functions were evaluated and compared between two groups. Hemorrhagic complications and major averse cardiovascular events (MACE) occurred in the 6-months follow-up were recorded.

Results

No significant differences were observed between two groups with respect to baseline demographic, clinical, and thrombolysis in myocardial infarction grade (P > 0.05). In the intracoronary prourokinase group, more patients had ST-segment resolution (>50%) compared with control group (P < 0.05). Patients in the intracoronary prourokinase group showed lower levels of serum CK, creatine kinase-MB fraction, and troponin I than those in control group (P < 0.05). No significant differences in bleeding complications were observed between the two groups (P > 0.05). At 6-months follow-up, there was no statistically different of MACE between the two groups (P > 0.05).

Conclusions

Intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions effectively improved myocardial perfusion and no increased bleeding in ST-segment elevation myocardial infarction patients.
The Role of Hippocampal Functional Connectivity on Multisystem Subclinical Abnormalities in Schizophrenia
Authors: Hare Stephanie M. , Chiappelli Joshua , Savransky Anya , Adhikari Bhim M. , Wisner Krista , Kvarta Mark , Goldwaser Eric , Du Xiaoming , Chen Shuo , Rowland Laura M. , Kochunov Peter , Hong L. Elliot
Published: April 2020

Objective

Schizophrenia is associated with excess medical mortality: patients have an average life expectancy one to two decades shorter than the general population. This study investigates the relationship between aberrant hippocampal resting-state functional connectivity in schizophrenia and cumulative subclinical effects of chronic stress on metabolic, cardiovascular, and immune function using the allostatic load index.

Methods

Cumulative stress was estimated using allostatic load total score (range, 0–13) in 46 patients with schizophrenia and 31 controls matched for age and sex (patients: age = 36.1 [13.7] years, sex = 32/14 male/female; controls: age = 35.5 [14.1], sex = 21/10 male/female). Hippocampal functional connectivity was assessed using resting-state functional magnetic resonance imaging; hippocampal structural connectivity was assessed using fornix fractional anisotropy. Linear regression analysis was used a) to test the hypothesis that aberrant hippocampal resting-state functional connectivity in schizophrenia (identified in analysis of schizophrenia − control differences) is associated with elevated allostatic load scores in patients and b) to determine the association between fornix fractional anisotropy with allostatic load.

Results

In patients, higher allostatic load was significantly associated with reduced resting functional connectivity between the left hippocampus and right cingulate cortex and left precentral gyrus, but higher connectivity between the right hippocampus and left cerebellum lobe VI (correctedpvalues <. 05). In controls, reductions in both hippocampal structural connectivity and hippocampal-cingulate functional connectivity were associated with higher allostatic load scores.

Conclusions

These findings support basic neuroscience evidence that cumulative stress and hippocampal function are closely connected and suggest that abnormal hippocampal functional communication in schizophrenia may be related to elevated multisystem subclinical medical issues in patients as indexed by allostatic load.
Arteriovenal Malformation in Parotid Gland
Authors: Yildiz Muhammed Gazi , Paksoy Mustafa , Çakan Doğan
Published: April 2020

Arteriovenous malformation (AVM) is an abnormal vascular formation where the artery and vein are connected directly to each other without capillary connections. Although it is common in the head and neck region, AVMs located in the parotid gland are quite rare. A 12-year-old female patient presented to our clinic with a mass in her left cheek area. As a result of physical examinations and tests, she was diagnosed with an AVM limited to the left parotid gland superficial lobe. Clinical follow-up was performed for AVM which has no sign except for prominence with Valsalva and surface temperature increase. The case was presented with a literature review.
Characteristics of Atypical Orbital Complications of Sinusitis
Authors: Kim Boo-Young , Lee Seoungmin , Jeon Jeongbea , Lim Il Gye , Choi Gyeong Cheol
Published: April 2020

Introduction:

Orbital complications of rhinosinusitis in adults are scarcely discussed in the literature. We defined atypical orbital complications as those without typical orbital invasion and not classified by the Chandler classification. These complications present as visual loss of diplopia without soft tissue swelling, pain, or computed tomography images of an orbital abscess.

Objectives:

The objective of this study was to review our experience with the management of atypical orbital complications of rhinosinusitis and to identify key factors in the characteristics of these patients.

Methods:

A retrospective case series review was conducted from 2015 to 2019 in a tertiary referral center, which included all patients with rhinosinusitis and orbital complications.

Results:

Five patients were identified with atypical complications in the orbital area. Two of the 5 patients exhibited vision loss without any other symptoms. Two patients showed diplopia with or without ptosis. One patient had a headache and ptosis. Complete recovery was noted in 4 of the 5 patients after endoscopic sinus surgery.

Conclusion:

With future studies, new surgical criteria, including retinal destruction, location of the sinusitis, the onset of ophthalmological symptoms, and culture results may be added to the classical surgical criteria to manage orbital complications of paranasal sinus infection cases.