Life Sciences Commons^™

Self-Complementary Adeno-Associated Virus Vectors Improve Transduction Efficiency Of Corneal Endothelial Cells, Anja K. Gruenert, Marta Czugala, Christian Mueller, Marco Schmeer, Martin Schleef, Friedrich E. Kruse, Thomas A. Fuchsluger

Christian Mueller

Transplantation of a donor cornea to restore vision is the most frequently performed transplantation in the world. Corneal endothelial cells (CEC) are crucial for the outcome of a graft as they maintain corneal transparency and avoid graft failure due to corneal opaqueness. Given the characteristic of being a monolayer and in direct contact with culture medium during cultivation in eye banks, CEC are specifically suitable for gene therapeutic approaches prior to transplantation. Recombinant adeno-associated virus 2 (rAAV2) vectors represent a promising tool for gene therapy of CEC. However, high vector titers are needed to achieve sufficient gene expression. One of …

Targeted Gene Delivery To The Enteric Nervous System Using Aav: A Comparison Across Serotypes And Capsid Mutants, Matthew J. Benskey, Nathan C. Kuhn, James J. Galligan, Joanna Garcia, Shannon E. Boye, William W. Hauswirth, Christian Mueller, Sanford L. Boye, Fredric P. Manfredsson

Christian Mueller

Recombinant adeno-associated virus (AAV) vectors are one of the most widely used gene transfer systems in research and clinical trials. AAV can transduce a wide range of biological tissues, however to date, there has been no investigation on targeted AAV transduction of the enteric nervous system (ENS). Here, we examined the efficiency, tropism, spread, and immunogenicity of AAV transduction in the ENS. Rats received direct injections of various AAV serotypes expressing green fluorescent protein (GFP) into the descending colon. AAV serotypes tested included; AAV 1, 2, 5, 6, 8, or 9 and the AAV2 and AAV8 capsid mutants, AAV2-Y444F, AAV2-tripleY-F, …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Franklin D. Shuler

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K2 (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation of …

The Physiological, Musculoskeletal And Psychological Effects Of Stand Up Paddle Boarding, Ben Schram, Wayne F. Hing, Michael Climstein

Wayne Hing

Background: Stand up paddle boarding (SUP) is a rapidly growing sport and recreational activity where anecdotal evidence exists for its proposed health, fitness and injury rehabilitation benefits. While limited scientific evidence exists to substantiate these claims, previous studies have shown that high levels of fitness, strength and balance exists amongst participants of this sport. The purpose of this study was to conduct a training intervention on a group of previously untrained individuals to ascertain the potential of SUP on various health parameters. Methods: An intervention study was conducted where after being tested initially, subjects were left for 6 weeks to …

The Physiological, Musculoskeletal And Psychological Effects Of Stand Up Paddle Boarding, Ben Schram, Wayne F. Hing, Michael Climstein

Ben Schram

Background: Stand up paddle boarding (SUP) is a rapidly growing sport and recreational activity where anecdotal evidence exists for its proposed health, fitness and injury rehabilitation benefits. While limited scientific evidence exists to substantiate these claims, previous studies have shown that high levels of fitness, strength and balance exists amongst participants of this sport. The purpose of this study was to conduct a training intervention on a group of previously untrained individuals to ascertain the potential of SUP on various health parameters. Methods: An intervention study was conducted where after being tested initially, subjects were left for 6 weeks to …

Strength Training For Plantar Fasciitis And The Intrinsic Foot Musculature: A Systematic Review., Dean Huffer, Wayne Hing, Richard Newton, Mike Clair

Wayne Hing

The aim was to critically evaluate the literature investigating strength training interventions in the treatment of plantar fasciitis and improving intrinsic foot musculature strength. A search of PubMed, CINHAL, Web of Science, SPORTSDiscus, EBSCO Academic Search Complete and PEDRO using the search terms plantar fasciitis, strength, strengthening, resistance training, intrinsic flexor foot, resistance training. Seven articles met the eligibility criteria. Methodological quality was assessed using the modified Downs and Black checklist. All articles showed moderate to high quality, however external validity was low. A comparison of the interventions highlights significant differences in strength training approaches to treating plantar fasciitis and …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jarrod Bailey, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Clinical Methods To Quantify Trunk Mobility In An Elite Male Surfing Population, James Furness, Michael Climstein, Jeremy Sheppard, Allan Abbott, Wayne Hing

James Furness

Background

Thoracic mobility in the sagittal and horizontal planes are key requirements in the sport of surfing; however to date the normal values of these movements have not yet been quantified in a surfing population.

Objectives

To develop a reliable method to quantify thoracic mobility in the sagittal plane; to assess the reliability of an existing thoracic rotation method, and quantify thoracic mobility in an elite male surfing population.

Design

Clinical Measurement, reliability and comparative study.

Methods

A total of 30 subjects were used to determine the reliability component. 15 elite surfers were used as part of a comparative analysis …

Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani

El Nasir Lalani

Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.

Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded …

Alcoholic Hepatitis Accelerates Early Hepatobiliary Cancer By Increasing Stemness And Mir-122-Mediated Hif-1alpha Activation, Aditya Ambade, Abhishek Satishchandran, Gyongyi Szabo

Gyongyi Szabo

Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro-inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in …

Oncology Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer, Mary Insana Fisher

Mary Insana Fisher

Background: The medical treatment of prostate cancer results in multiple impairments in body structure and declines functional abilities, resulting in activity limitations and participation restrictions. Measurement of functional mobility is an essential outcome measure in survivorship care. Purpose: The purpose of this systematic review is to make recommendations of the best measurement tools to assess functional mobility in men treated for prostate cancer based on psychometric properties and clinical utility. Methods: Multiple electronic databases were searched from February to March 2014. Studies of tools used to assess functional mobility were included if they met the following criteria: reported psychometric properties, …

Malnourished Older Adults With Informal Caregivers Admitted To Rural Rehabilitation Units Remain Malnourished During And After Rehabilitation: A Prospective Cohort Study Of Current Practice, Skye Marshall, Adrienne Young, Judith Bauer, Elizabeth Isenring

Skye Marshall

Understanding the nutritional journey older adults make from rehabilitation to home may help to engage and support the patient and their informal caregiver during this process. This study aimed to determine the change in nutritional status, physical function and health-related quality of life (HRQoL) amongst malnourished older adults (≥65years) with informal caregivers admitted to rural rehabilitation and 12 weeks post-discharge to the community.

Malnutrition In Geriatric Rehabilitation: Prevalence, Patient Outcomes And Criterion Validity Of The Scored Patient-Generated Subjective Global Assessment (Pg-Sga) And The Mini Nutritional Assessment (Mna), Skye Marshall, Adrienne Young, Judith Bauer, Elizabeth Isenring

Skye Marshall

No abstract provided.

Malnourished Older Adults Admitted To Rehabilitation In Rural New South Wales Remain Malnourished Throughout Rehabilitation And Once Discharged Back To The Community: A Prospective Cohort Study, Skye Marshall, Adrienne Young, Judith Bauer, Elizabeth Isenring

Skye Marshall

No abstract provided.

Malnutrition In Geriatric Rehabilitation: Prevalence, Patient Outcomes And Criterion Validity Of The Scored Patient-Generated Subjective Global Assessment (Pg-Sga) And The Mini Nutritional Assessment (Mna), Skye Marshall, Adrienne Young, Judith Bauer, Liz Isenring

Skye Marshall

There is strong evidence showing malnutrition is under-recognized and underdiagnosed in the rehabilitation setting. Accurate identification and management of malnutrition is essential so that patient outcomes may be improved and resources used efficaciously.The Scored PG-SGA and MNA require evaluation of their validity in diagnosing malnutrition in rehabilitation. In addition, the prevalence of malnutrition and associated patient outcomes in rural Australian populations has not been reported.

Exosomes Derived From Alcohol-Treated Hepatocytes Horizontally Transfer Liver Specific Mirna-122 And Sensitize Monocytes To Lps, Fatemeh Momen-Heravi, Shashi Bala, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

Hepatocyte damage and inflammation in monocytes/macrophages are central to the pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of these processes. MiRNA-122 is abundantly expressed in hepatocytes while monocytes/macrophages have low levels. The role of exosomes in AH and possible cross talk between hepatocyte-derived exosomes and immune cells is not explored yet. Here, we show that the number of exosomes significantly increases in the sera of healthy individuals after alcohol binge drinking and in mice after binge or chronic alcohol consumption. Exosomes isolated from sera after alcohol consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122. Exosomes derived from …

Blastomyces: Why Be Dimorphic?, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

In introducing the infectious disease focus for this edition of the Journal of Patient-Centered Research and Reviews, the author describes the unsolved mysteries surrounding the dimorphic fungus Blastomyces and the related pathogenesis of pulmonary blastomycosis.

Disease-Causing Fungi In Homes And Yards In The Midwestern United States, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

A number of fungal pathogens that may result in a variety of human diseases are found in residential homes and yards. The growth of these microscopic fungi is often favored by particular characteristics of the dwelling and nearby outdoor environment. Evolved virulence factors or increased ability of specific fungi to grow in diverse, and sometimes harsh, microenvironments presented by the domestic environment may promote growth and pathogenesis. Infection may occur by inhalation or direct inoculation and include endemic fungi in addition to opportunistic or emerging species. Systemic or locally aggressive fungal infections are particularly likely and may be life-threatening in …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Andrew Knight, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Clinical Methods To Quantify Trunk Mobility In An Elite Male Surfing Population, James Furness, Michael Climstein, Jeremy Sheppard, Allan Abbott, Wayne Hing

Allan D. Abbott

Background

Thoracic mobility in the sagittal and horizontal planes are key requirements in the sport of surfing; however to date the normal values of these movements have not yet been quantified in a surfing population.

Objectives

To develop a reliable method to quantify thoracic mobility in the sagittal plane; to assess the reliability of an existing thoracic rotation method, and quantify thoracic mobility in an elite male surfing population.

Design

Clinical Measurement, reliability and comparative study.

Methods

A total of 30 subjects were used to determine the reliability component. 15 elite surfers were used as part of a comparative analysis …

Clinical Methods To Quantify Trunk Mobility In An Elite Male Surfing Population, James Furness, Michael Climstein, Jeremy Sheppard, Allan Abbott, Wayne Hing

Wayne Hing

Background Thoracic mobility in the sagittal and horizontal planes are key requirements in the sport of surfing; however to date the normal values of these movements have not yet been quantified in a surfing population. Objectives To develop a reliable method to quantify thoracic mobility in the sagittal plane; to assess the reliability of an existing thoracic rotation method, and quantify thoracic mobility in an elite male surfing population. Design Clinical Measurement, reliability and comparative study. Methods A total of 30 subjects were used to determine the reliability component. 15 elite surfers were used as part of a comparative analysis …

Β-Thujaplicin: A Soil Antifungal, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Background: β-thujaplicin (β-Th), also known as hinokitiol, naturally occurs in cedar mulch, is found in personal care products and has in vitro antitumor activities. It is antibacterial and antifungal, but has not been tested on soil. Scedosporium apiospermum (Sce) is an emerging “extremophile” fungal pathogen found in built outdoor environments. Purpose: Pilot β-Th as “natural” soil antimicrobial or for isolation of extremophiles, and to explore β-Th resistance as selective advantage to Sce in mulched landscape. Methods: A variety of outdoor and indoor environments were used for 2 sets of 24 paired soil samples. Soil/H20 slurry (0.1 ml) was spread on …

Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. The T4R RHO mutant dog retina shows retinal degeneration with exposures to light comparable to those used in clinical eye examinations of patients. To define the molecular mechanisms of the degeneration, AP-1 DNA-binding activity, composition, posttranslational modification of the protein complex, and modulation of ERK/MAPK signaling pathways were examined in light-exposed mutant retinas. METHODS. Dark-adapted retinas were exposed to short-duration light flashes from a retinal camera used clinically for retinal photography and were collected at different time points after exposure. Electrophoretic mobility shift assay (EMSA), supershift EMSA, Western blot analysis, and immunocytochemistry were used to examine AP-1 signaling. RESULTS. …

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. …

Recombinant Aav-Mediated Best1 Transfer To The Retinal Pigment Epithelium: Analysis Of Serotype-Dependent Retinal Effects, Karina E. Guziewicz, Barbara Zangerl, András M. Komáromy, Simone Iwabe, Vincent A. Chiodo, Sanford L. Boye, William W. Hauswirth, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr), recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In …

Interleukin 10 Restores Gastric Emptying, Electrical Activity, And Interstitial Cells Of Cajal Networks In Diabetic Mice, Anthony J. Bauer

Anthony Bauer