Digital Commons Network^™

Pannexin1 Channels Dominate Atp Release In The Cochlea Ensuring Endocochlear Potential And Auditory Receptor Potential Generation And Hearing, Jin Chen, Yan Zhu, Chun Liang, Jing Chen, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Pannexin1 (Panx1) is a gap junction gene in vertebrates whose proteins mainly function as non-junctional channels on the cell surface. Panx1 channels can release ATP under physiological conditions and play critical roles in many physiological and pathological processes. Here, we report that Panx1 deficiency can reduce ATP release and endocochlear potential (EP) generation in the cochlea inducing hearing loss. Panx1 extensively expresses in the cochlea, including the cochlear lateral wall. We found that deletion of Panx1 in the cochlear lateral wall almost abolished ATP release under physiological conditions. Positive EP is a driving force for current through hair cells to …

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

Combination Of Id2 Knockdown Whole Tumor Cells And Checkpoint Blockade: A Potent Vaccine Strategy In A Mouse Neuroblastoma Model., Lina Chakrabarti, Clifford Morgan, Anthony D. Sandler

Surgery Faculty Publications

Tumor vaccines have held much promise, but to date have demonstrated little clinical success. This lack of success is conceivably due to poor tumor antigen presentation combined with immuno-suppressive mechanisms exploited by the tumor itself. Knock down of Inhibitor of differentiation protein 2 (Id2-kd) in mouse neuroblastoma whole tumor cells rendered these cells immunogenic. Id2-kd neuroblastoma (Neuro2a) cells (Id2-kd N2a) failed to grow in most immune competent mice and these mice subsequently developed immunity against further wild-type Neuro2a tumor cell challenge. Id2-kd N2a cells grew aggressively in immune-compromised hosts, thereby establishing the immunogenicity of these cells. Therapeutic vaccination with Id2-kd …

The Cognition-Enhancing Effects Of Psychostimulants Involve Direct Action In The Prefrontal Cortex, Robert C. Spencer, David M. Devilbiss, Craig Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. …

Alterations In Dna Methylation May Be The Key To Early Detection And Treatment Of Schistosomal Bladder Cancer, Simon L. Conti, Jared Honeycutt, Justin I. Odegaard, Mark L. Gonzalgo, Michael H. Hsieh

Urology Faculty Publications

No abstract provided.

Retinoic Acid And The Development Of The Endoderm, Gregory M. Kelly, Thomas A. Drysdale

Paediatrics Publications

Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of …

Differential Effects Of Cold Atmospheric Plasma In The Treatment Of Malignant Glioma, Alan Siu, Olga Volotskova, Xiaoqian Cheng, Siri S. Khalsa, Ka Bian, Ferid Murad, Michael Keidar, Jonathan H. Sherman

Neurological Surgery Faculty Publications

Objective

Cold atmospheric plasma (CAP) has recently been shown to selectively target cancer cells with minimal effects on normal cells. We systematically assessed the effects of CAP in the treatment of glioblastoma.

Methods

Three glioma cell lines, normal astrocytes, and endothelial cell lines were treated with CAP. The effects of CAP were then characterized for viability, cytotoxicity/apoptosis, and cell cycle effects. Statistical significance was determined with student's t-test.

Results

CAP treatment decreases viability of glioma cells in a dose dependent manner, with the ID50 between 90-120 seconds for all glioma cell lines. Treatment with CAP for more than 120 seconds …

Hyperhomocysteinemia - An Unidentified Risk Factor For Stroke In Our Population, Sabaa Asif, Bashir A Soomro, Kanwal Sartaj, Shafaq Alvi

Pakistan Journal of Neurological Sciences (PJNS)

Introduction:
Various studies show that moderate elevation of plasma homocysteine level has been associated with increased risk for cardiovascular and cerebrovascular disease.

Objective:
To observe the frequency of increased homocysteine level in ischemic stroke patients; and its association with other risk factors.

Methodology:
Observational pilot study was conducted on a sample of 75 ischemic stroke patients, enrolled regardless of their age, gender and comorbidities, at Ziauddin university hospital, Karachi. Fasting serum homocysteine, folate and vitamin B12 levels were measured. Results were interpreted using spss 20.0.

Results and Discussion:
Mean homocysteine level in our population was 19.51 (SD: 11.47)micromol/l. …

Stress Induced Hyperglycemia In Stroke Patients, Aziz U Rehman, Ajeet Kumar, Salma Razzaque, Ashok Kumar, M. Ishaq Ghauri

Pakistan Journal of Neurological Sciences (PJNS)

Background:
Stroke is the third most common cause of death in developed countries and second most common cause of death worldwide. High proportion of patients may develop hyperglycemia after an acute stress such as stroke or myocardial infarction even in the absence of preexisting diagnosis of diabetes mellitus. Prolonged stress hyperglycemia in ischemic stroke increases the risk of in-hospital 28- day mortality, especially in non-diabetic patients.

Aims and objectives:
To determine the frequency of stress-induced hyperglycemia in non-diabetic patients with ischemic or hemorrhagic stroke.

Subjects and methods:
A total of 255 patients admitted with acute stroke, fulfilling the inclusion …

Dicer1 Regulated Let-7 Expression Levels In P53-Induced Cancer Repression Requires Cyclin D1., Xin Sun, Shou-Ching Tang, Chongwen Xu, Chenguang Wang, Sida Qin, Ning Du, Jian Liu, Yiwen Zhang, Xiang Li, Gang Luo, Jie Zhou, Fei Xu, Hong Ren

Department of Cancer Biology Faculty Papers

Let-7 miRNAs act as tumour suppressors by directly binding to the 3'UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback …

Galectin-1: A Biomarker Of Surgical Stress In Murine Model Of Cardiac Surgery, Satwat Hashmi, Suhail Al-Salam

Department of Biological & Biomedical Sciences

Galectin-1 (GAL-1) belongs to the family of β-galactoside-binding lectins. It regulates cell-cell and cell-matrix interactions, the immune response, apoptosis, cell cycle, RNA splicing and neoplastic transformation. We investigate the effect of heart manipulation secondary to cardiac surgery on the level of GAL-1 in murine heart and plasma. Male C57B6/J mice were used for adopted model of cardiac surgery. Heart samples were processed for immunohistochemical and immunofluorescent labeling, Enzyme linked immunosorbent assay and quantitative RT-PCR to identify GAL-1 levels in the heart and plasma during the first 24 hours following cardiac surgery. There is significant increase of GAL-1 in the LV …

Thyroxine Replacement In Patients On Parenteral Nutrition: A Clinical Conundrum, Abdul Rehman, Noor Ul-Ain Baloch, Muhammad Awais

Department of Biological & Biomedical Sciences

No abstract provided.

Quantifying Unnecessary Normal Tissue Complication Risks Due To Suboptimal Planning: A Secondary Study Of Rtog 0126., Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic

Department of Radiation Oncology Faculty Papers

PURPOSE: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.

METHODS AND MATERIALS: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative …

Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the …

Relationship Between Fear, Fall & Balance In Cummunity Dwelling Older Adults, Ayesha Afridi, Sadia Maqbool, Arshad Nawaz Malik

Pakistan Journal of Neurological Sciences (PJNS)

Background:
In older population the risk of fall is always at high risk and there are many contributing factor which increase the prevalence of fall. The impaired balance leads to limited daily activities and confidence level.

Purpose of the study:
The main purpose of this study was to determine the relationship between fall, fear and balance in older population.

Method & methodology:
The descriptive cross sectional study design was used and a sample of 271 older adult were recruited through purpose sampling technique. The detail demographic was noted, history of fall and other related co-morbidities were mention in performa. The …

A Rare Case Of Simple Hereditary Recessive Optic Atrophy, Fazal M. Arain, Prem Chand, Tanveer A. Choudary

Pakistan Journal of Neurological Sciences (PJNS)

Simple Autosomal Recessive Optic Atrophy (AROA) is a rare hereditary disorder that belongs to a group of disorders called Hereditary Optic Atrophy. Patients diagnosed with simple AROA have complete blindness since birth or from first few months of life. This blindness does not improve with age. However, no other organ or system is affected in this disorder. There is no known cause or gene mutation associated with it. Here we report a case of a two year old child diagnosed with simple AROA. Family history of the patient revealed that an older deceased relative also suffered from similar symptoms. Identification …

Salvage Brachytherapy In Combination With Interstitial Hyperthermia For Locally Recurrent Prostate Carcinoma Following External Beam Radiation Therapy: A Prospective Phase Ii Study., Andrzej M Kukiełka, Vratislav Strnad, Paul R. Stauffer, Tomasz Dąbrowski, Marcin Hetnał, Damian Nahajowski, Tomasz Walasek, Piotr Brandys, Robert Matys

Department of Radiation Oncology Faculty Papers

Optimal treatment for patients with only local prostate cancer recurrence after external beam radiation therapy (EBRT) failure remains unclear. Possible curative treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several single institution series proved that high-dose-rate brachytherapy (HDRBT) and pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of patients with acceptable levels of genitourinary and gastrointestinal toxicity. A standard dose prescription and scheme have not been established yet, and the literature presents a wide range of fractionation protocols. Furthermore, hyperthermia has shown the potential to enhance the efficacy of re-irradiation. Consequently, a prospective trial is urgently needed to attain clear …

Postpartum Contraceptive Use And Unmet Need For Family Planning In Five Low-Income Countries., Omrana Pasha, Shivaprasad S. Goudar, Archana Patel, Ana Garces, Fabian Esamai, Elwyn Chomba, Janet L. Moore, Bhalchandra S. Kodkany, Sarah Saleem, Richard J. Derman, Edward A. Liechty, Patricia L. Hibberd, K. Michael Hambidge, Nancy F. Krebs, Waldemar A. Carlo, Elizabeth M. Mcclure, Marion Koso-Thomas, Robert L. Goldenberg

Community Health Sciences

BACKGROUND:

During the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period.

METHODS:

Using the NICHD Global Network for Women's and Children's Health Research's multi-site, prospective, ongoing, active surveillance system to track pregnancies and births …

Volume Iv (2015), Unm Department Of Orthopaedic Surgery

UNM Orthopaedic Research Journal

No abstract provided.

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Wen-Jian Jiang, Yong-Chao Cui, Jin-Hua Li, Xiu-Hui Zhang, Huan-Huan Ding, Yong-Qiang Lai, Hong-Jia Zhang

The Texas Heart Institute Journal

Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium.

We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Arthur W Bracey

The Texas Heart Institute Journal

No abstract provided.

Comparison Of Cardiovascular Risk Profiles Amongst Newly Diagnosed Cancer Patients And Non-Cancer Patients At The Aga Khan University Hospital Nairobi, Majid Lingani-Ncube Sikosana

Master of Medicine in Internal Medicine

Background: Non-Communicable Diseases (NCDs) are fast becoming the leading causes of morbidity and mortality in Low and Middle-income countries (LMIC) with cancers and cardiovascular diseases (CVDs) becoming the most prominent. CVD can be prevented if appropriate measures of screening and treatment of modifiable risk factors are addressed. This may translate to reduced risk of CVDs and some cancers in the long term. Increasing evidence exhibits common risk factors for both CVDs and cancer and that CVDs and their risk factors when present in cancer patients may worsen the overall outcome. Objectives: The primary objective was to determine and compare the …

Intramembranous Bone Healing Process Subsequent To Tooth Extraction In Mice: Micro-Computed Tomography, Histomorphometric And Molecular Characterization, Andreia Espindola Vieira, Carlos Eduardo Repeke, Samuel De Barros Ferreira Junior, Priscila Maria Colavite, Cláudia Cristina Biguetti, Rodrigo Cardoso Oliveira, Gerson Francisco Assis, Rumio Taga, Ana Paula Favaro Trombone, Gustavo P. Garlet

School of Podiatric Medicine Publications

Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray) characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0 h), the development of a provisional immature granulation tissue is evident (7 d), characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors …

Astrocyte Morphology, Heterogeneity, And Density In The Developing African Giant Rat (Cricetomys Gambianus), Matthew A. Olude, Oluwaseun A. Mustapha, Oluwatunde A. Aderounmu, James O. Olopade, Amadi O. Ihunwo

Brain and Mind Institute

Astrocyte morphologies and heterogeneity were described in male African giant rats (AGR; Cricetomys gambianus, Waterhouse) across three age groups (five neonates, five juveniles, and five adults) using Silver impregnation method and immunohistochemistry against glial fibrillary acidic protein. Immunopositive cell signaling, cell size and population were least in neonates, followed by adults and juveniles, respectively. In neonates, astrocyte processes were mostly detected within the glia limitans of the mid and hind brain; their cell bodies measuring 32 ± 4.8 μm in diameter against 91 ± 5.4 μm and 75 ± 1.9 μm in juveniles and adults, respectively. Astrocyte heterogeneity in …

Human Dna Exonuclease Trex1 Is Also An Exoribonuclease That Acts On Single-Stranded Rna, Fenghua Yuan, Tanmay Dutta, Ling Wang, Lei Song, Liya Gu, Liangyue Qian, Anaid Benitez, Shunbin Ning, Arun Malhotra, Murray P. Deutcher, Yanbin Zhang

ETSU Faculty Works

3′ repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune disorders and the antiviral response. In this work, we show that TREX1 is also a RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi-Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1 activity is strongly inhibited by a stretch of pyrimidine residues as is a bacterial homolog, RNase T. Kinetic measurements indicate that the apparent Km of TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in degrading native tRNA …

Genetic Heterogeneity Of Pseudoxanthoma Elasticum: The Chinese Signature Profile Of Abcc6 And Enpp1 Mutations., Liang Jin, Qiujie Jiang, Zhengsheng Wu, Changxia Shao, Yong Zhou, Luting Yang, Jouni Uitto, Gang Wang

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was …

Novel Advances In Alzheimer's Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.¹ Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline …

Aquaporin 1 And 5 Expression Decreases During Human Intervertebral Disc Degeneration: Novel Hif-1-Mediated Regulation Of Aquaporins In Np Cells., Zariel I Johnson, Shilpa S Gogate, Rebecca Day, Abbie Binch, Dessislava Z Markova, Neil Chiverton, Ashley Cole, Matt Conner, Irving Shapiro, Christine L Le Maitre, Makarand V Risbud

Department of Orthopaedic Surgery Faculty Papers

Objectives of this study were to investigate whether AQP1 and AQP5 expression is altered during intervertebral disc degeneration and if hypoxia and HIF-1 regulate their expression in NP cells. AQP expression was measured in human tissues from different degenerative grades; regulation by hypoxia and HIF-1 was studied using promoter analysis and gain- and loss-of-function experiments. We show that both AQPs are expressed in the disc and that mRNA and protein levels decline with human disease severity. Bioinformatic analyses of AQP promoters showed multiple evolutionarily conserved HREs. Surprisingly, hypoxia failed to induce promoter activity or expression of either AQP. While genomic …

Percutaneous Ultrasonic Debridement Of Tendinopathy—A Pilot Achilles Rabbit Model, Srinath Kamineni, Timothy Butterfield, Anthony Sinai

Orthopaedic Surgery and Sports Medicine Faculty Publications

BACKGROUND: Tendinopathy is a common clinical pathology, with mixed treatment results, especially when chronic. In this study, we examine the effects of an ultrasonic debridement modality in a rabbit tendinopathy model. We asked four questions: (1) Was it possible to create and visualize with ultrasound a tendinopathy lesion in a rabbit Achilles tendon? (2) Was it possible to guide a 19-gauge ultrasonic probe into the tendinopathy lesion? (3) Following ultrasonic treatment, was tendinopathy debris histologically present? and (4) Was the collagen profile qualitatively and quantitatively normalized following treatment?

METHODS: Skeletally mature female New Zealand white rabbits (n = 12) …

Prevalence Of Suspicious Ultrasound Findings In Patients With Mammographic Focal Asymmetry At Aga Khan University Hospital, Nairobi, Jacqueline Ndunge Mavuti

Master of Medicine in Imaging and Diagnostic Radiology

Background: Breast cancer has become the leading cancer in women in both economically developed and developing countries, accounting for 25% of all cancers diagnosed worldwide in 2012. The cornerstone of breast cancer control remains early detection in order to improve outcomes and survival. Thus far the only breast cancer screening method that has proved to be effective is mammography. Although mammography is the mainstay of early detection, a fundamental limitation is its low inherent contrast difference between the soft tissue structures in the breast. Mammographic specificity relies on the ability to distinguish benign from malignant breast lesions based on their …