Life Sciences Commons^™

Physical Screening And Testing: From Purpose To Research To Application, Rob Orr

Rob Marc Orr

Session Objectives:

•Discuss the purposes of different physical assessments

•Designing measures useful for assessing tactical personnel

•Applying assessments in the field

Jessicahlawrencemastersportfolio.Pdf, Jessicah Lawrence

Jessicah Lawrence

No abstract provided.

Exploring The Utilisation Of Stand Up Paddle Boarding In Australia, Ben Schram, James Furness

James Furness

Stand Up Paddle Boarding (SUP) has grown exponentially in the last few years with unprecedented participation rates globally. Despite some scientific research on physiological and performance variables, minimal information exists regarding participation and utilisation. The purpose of this study was to discover more about how and where people participate in the relatively new sport of SUP. An open-source online survey application was administered internationally to active SUP participants to capture information relevant to both demographics and participation. Of a total of 240 responses, 154 (64.2%) were Australian. The average SUP rider was 42.9 ± 11.7 years, mass 80.4 ± 18.7 …

Exploring The Utilisation Of Stand Up Paddle Boarding In Australia, Ben Schram, James Furness

Ben Schram

Stand Up Paddle Boarding (SUP) has grown exponentially in the last few years with unprecedented participation rates globally. Despite some scientific research on physiological and performance variables, minimal information exists regarding participation and utilisation. The purpose of this study was to discover more about how and where people participate in the relatively new sport of SUP. An open-source online survey application was administered internationally to active SUP participants to capture information relevant to both demographics and participation. Of a total of 240 responses, 154 (64.2%) were Australian. The average SUP rider was 42.9 ± 11.7 years, mass 80.4 ± 18.7 …

Crystal Structure Of Apobec3a Bound To Single-Stranded Dna Reveals Structural Basis For Cytidine Deamination And Specificity, Takahide Kouno, Tania V. Silvas, Brendan J. Hilbert, Shivender Shandilya, Markus-Frederik Bohn, Brian A. Kelch, William E. Royer, Mohan Somasundaran, Nese Kurt Yilmaz, Hiroshi Matsuo, Celia A. Schiffer

Celia A. Schiffer

Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 A. This structure not only visualizes the active site …

Hepatic Changes Associated With Chronic Alcohol Exposure In An Alpha-1 Antitrypsin Piz Mouse Model, Zhuoyao Lyu, Alisha M. Gruntman, Brian O'Sullivan-Murphy, Christian Mueller, Terence R. Flotte

Christian Mueller

The PiZ mutation in the alpha-1 antitrypsin (AAT) gene causes the PiZ mutant protein to be sequestered in the endoplasmic reticulum of hepatocytes, causing significant liver pathology in ~10% of PiZZ homozygous AAT disease patients. Current transgenic mouse models of the disease include the liver-specific over-expression of mutant PiZ protein. However, these animal models do not efficiently recapitulate the liver damage found in PiZZ homozygous patients. Since only a small percentage of patients develop liver disease and it is not reproducible in animal models of AATD, it suggests that there are other factors that participate in disease pathogenesis. Here, we …

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek

Robert C. Jones, PhD

We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological …

Dengue Virus Ns2b/Ns3 Protease Inhibitors Exploiting The Prime Side, Kuan-Hung Lin, Akbar Ali, Linah Rusere, Djade I. Soumana, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein …

Interdependence Of Inhibitor Recognition In Hiv-1 Protease, Janet L. Paulsen, Florian Leidner, Debra A. Ragland, Nese Kurt Yilmaz, Celia A. Schiffer

Celia A. Schiffer

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. …

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Nader G. Abraham, Joseph I Shapiro

Nader G. Abraham

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

Attenuation Of Na/K-Atpase Mediated Oxidant Amplification With Pnaktide Ameliorates Experimental Uremic Cardiomyopathy, Jiang Liu, Jiang Tian, Muhammad Chaudhry, Nader G. Abraham, Joseph I Shapiro

Jiang Liu

We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic …

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct …

The Glia Response After Peripheral Nerve Injury: A Comparison Between Schwann Cells And Olfactory Ensheathing Cells And Their Uses For Neural Regenerative Therapies, Matthew J Barton, James St John, Alison Wright, Jenny Ekberg

Jenny Ekberg

The peripheral nervous system (PNS) exhibits a much larger capacity for regeneration than the central nervous system (CNS). One reason for this difference is the difference in glial cell types between the two systems. PNS glia respond rapidly to nerve injury by clearing debris from the injury site, supplying essential growth factors and providing structural support; all of which enhances neuronal regeneration. Thus, transplantation of glial cells from the PNS is a very promising therapy for injuries to both the PNS and the CNS. There are two key types of PNS glia: olfactory ensheathing cells (OECs), which populate the olfactory …

Epidemiology Of Injuries In Stand-Up Paddle Boarding, James Furness, Olayinka Olorunnife, Ben Schram, Michael Climstein, Wayne Hing

Ben Schram

Background: Stand-up paddle boarding (SUP) is a recreational activity and sport that has grown exponentially, with participation increasing from 1.1 million in 2010 to 2.8 million in 2014 in the United States alone. Despite this growth in participation, SUP remains underresearched with regard to injury epidemiology. Purpose: To investigate injury epidemiology (severity, location, type, mechanism) in SUP.Study Design:Descriptive epidemiology study. Methods: An open-source online survey was administered to active SUP participants internationally. The survey captured information relevant to demographics, participation, and injury history over the past 12 months. Results: Of 240 participants included in the data analysis, 67.1% were males, …

Changes In Dietary Patterns And Body Composition Within 12 Months Of Liver Transplantation, Mccoy Simone, Katrina Campbell, Annie-Claude Lassemillante, Matthew P. Wallen, Jonathan Fawcett, Maree Jarrett, Graeme A. Macdonald, Ingrid J. Hickman

Katrina Campbell

Background:

Cardiometabolic risk factors are increasing in liver transplant recipients (LTR). Influencing dietary factors have not been assessed. The aim of this observational study was to assess changes in weight, metabolic function, dietary intake and eating behaviours in the first year after orthotopic liver transplantation (OLT).

Methods:

Consecutive recruitment of 17 patients (14 males) awaiting OLT at a single tertiary hospital. Dietary intake, food behaviours and anthropometry were recorded at baseline, and 6 and 12 months post-transplant.

Results:

By 12 months, patients had gained on average 7.3% of body weight. The prevalence of overweight or obesity increased from baseline 53% …

Epidemiology Of Injuries In Stand-Up Paddle Boarding, James Furness, Olayinka Olorunnife, Ben Schram, Michael Climstein, Wayne Hing

Wayne Hing

Background:

Stand-up paddle boarding (SUP) is a recreational activity and sport that has grown exponentially, with participation increasing from 1.1 million in 2010 to 2.8 million in 2014 in the United States alone. Despite this growth in participation, SUP remains underresearched with regard to injury epidemiology.

Purpose:

To investigate injury epidemiology (severity, location, type, mechanism) in SUP.Study Design:Descriptive epidemiology study.

Methods:

An open-source online survey was administered to active SUP participants internationally. The survey captured information relevant to demographics, participation, and injury history over the past 12 months.

Results:

Of 240 participants included in the data analysis, 67.1% were males, …

Prevalence, Predictors And Benefits Of Resistance Training For Improving Gait Speed In Aged Care, Justin Keogh, Timothy Henwood, Hugh Senior, Samantha Fien

Justin Keogh

No abstract provided.

Prevalence, Consequences And Effects Of Exercise On Sarcopenia In Aged Care, Justin Keogh, Timothy Henwood, Hugh Senior, Jennifer Hewitt

Justin Keogh

No abstract provided.

Freshwater Fungal Infections, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Fungal infections as a result of freshwater exposure or trauma are fortunately rare. Etiologic agents are varied, but commonly include filamentous fungi and Candida. This narrative review describes various sources of potential freshwater fungal exposure and the diseases that may result, including fungal keratitis, acute otitis externa and tinea pedis, as well as rare deep soft tissue or bone infections and pulmonary or central nervous system infections following traumatic freshwater exposure during natural disasters or near-drowning episodes. Fungal etiology should be suspected in appropriate scenarios when bacterial cultures or molecular tests are normal or when the infection worsens or fails …

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …

Investigation Of The Impact Of Increased Dietary Insoluble Fiber Through The Feeding Of Distillers Dried Grains With Solubles (Ddgs) On The Incidence And Severity Of Brachyspira-Associated Colitis In Pigs, Bailey Lauren Wilberts, Paulo Elias Arruda, Joann M. Kinyon, Timothy S. Frana, Chong Wang, Drew Robert Magstadt, Darin M. Madson, John F. Patience, Eric Ryan Burrough

Bailey (Wilberts) Arruda

Diet has been implicated as a major factor impacting clinical disease expression of swine dysentery and Brachyspira hyodysenteriae colonization. However, the impact of diet on novel pathogenic strongly beta-hemolytic Brachyspira spp. including “B. hampsonii” has yet to be investigated. In recent years, distillers dried grains with solubles (DDGS), a source of insoluble dietary fiber, has been increasingly included in diets of swine. A randomized complete block experiment was used to examine the effect of increased dietary fiber through the feeding of DDGS on the incidence of Brachyspira-associated colitis in pigs. One hundred 4-week-old pigs were divided …

Symptomatic Surgically Treated Non-Neoplastic Cysts Of The Central Nervous System: A Clinicopathological Study From Pakistan, Nasir Ud Din, Huma Arshad, Zubair Ahmad, Sheema H Hasan, Mohammad Ehsan Bar

Zubair Ahmad

Objective: To report clinicopathologic features of symptomatic surgically removed non-neoplastic cysts of the central nervous system (CNS). Study Design: Case series. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2003 to 2012. Methodology: All non-neoplastic CNS cysts reported during the study period were retrieved and reviewed. Age, gender, location, histologic type and clinical features were noted. Results: A total of 124 cysts were diagnosed in the study period. These included 44 epidermoid cysts (mean age 30.5 ± 13.8 years), 35 colloid cysts (mean age 31 ± 13.2 years), 32 arachnoid cysts (mean age 24.8 ± 20.2 …

In-House Daily Consensus Conference: An Important Quality Control/Quality Assurance Activity--Experience At A Major Referral Center., Amna Khurshid, Zubair Ahmad, Asim Qureshi

Zubair Ahmad

Background:For every practicing histopathologist, improvement of diagnostic accuracy is an important objective. Personal consults are an important component of quality control (QC)/quality assurance (QA) in our Section of Histopathology. In addition, the College of American Pathologists recommends a daily in-house consensus conference, which is a prospective system by which all difficult and problematic cases are reviewed and discussed and signed out by consensus. Design: In-house consensus conference is held daily using a multi-headed microscope. This collegial session is run by the seniormost consultant in the section and is attended by all histopathology consultants and residents. The consultants and residents …

Histological Pattern Of Ovarian Neoplasma., Zubair Ahmad, Naila Kayani, Sheema H. Hasan, Suhail Muzaffar, Muhammad Shafiq Gill

Zubair Ahmad

Abstract Objective: To see the morphological pattern of benign and malignant ovarian neoplasms. Method: Retrospective study of all consecutive cases of ovarian neoplasms diagnosed at Aga Khan University Hospital between 1st January 1993 and 30th September 1998. Setting: The Section of Histopathology, AKUH, Karachi. Observation: Of 855 ovarian tumours 506 (59.18%) were benign and 349(40.81%) malignant. Surface epithelial - stromal tumours comprised 63.50% of all tumours. Benign cystic teratoma was the commonest benign tumour (35.17% of all benign tumours) and serous cystadenocarcinoma was the commonest malignant tumour (33.33% of all malignant tumours). Mucinous cystadenocarcinomas are more common in our population …

Frequency Of Hereditary Thrombophilia: An Akuh Experience., Safoorah Khalid, Raihan Sajid, Salman Adil, Mohammad Khurshid

Salman Naseem Adil

Abstract Objective: To determine the frequency of various causes of hereditary thrombophilia at a referral laboratory and the age and gender distribution. Methods: This is a descriptive study incorporating a retrospective analysis of requests for thrombophilia screening sent to Clinical laboratory, Aga Khan University Hospital from November 1995 to May 2002.Patients were screened for hereditary causes of thrombophilia including Protein C, Protein S, antithrombin III, Factor V Leiden and homocysteine. Frequency of each disorder; and age and sex distribution was determined. Results: All the patients suspected clinically for thrombophilia were screened. Of the 2825 patients, 70 were diagnosed to have …

Emergence Of Carbapenem Resistant Gram Negative And Vancomycin Resistant Gram Positive Organisms In Bacteremic Isolates Of Febrile Neutropenic Patients: A Descriptive Study., Seema Irfan, Faiza Idrees, Vikram Mehraj, Faizah Habib, Salman Adil, Rumina Hasan

Salman Naseem Adil

Background:This study was conducted to evaluate drug resistance amongst bacteremic isolates of febrile neutropenic Patients with particular emphasis on emergence of carbapenem resistant Gram negative bacteria and vancomycin resistant Enterococcus species. Methods: A descriptive study was performed by reviewing the blood culture reports from febrile neutropenic Patients during the two study periods i.e., 1999-00 and 2001-06. Blood cultures were performed using BACTEC 9240 automated system. Isolates were identified and antibiotic sensitivities were done using standard microbiological procedures. Results: Seven twenty six febrile neutropenic Patients were admitted during the study period. A total of 5840 blood cultures were received, off these …

Chromosomal Abnormalities In Primary Myelodysplastic Syndrome, Anila Rashid, Mohammad Khurshid, Usman Shaikh, Salman Adil

Salman Naseem Adil

Objective: To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome (MDS) using conventional karyotyping. Study Design: Case series. Place and Duration of Study: The Clinical Laboratory, The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Methodology: Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature (ISCN, 1995) and described as frequency percentage. Results: …

Central Role Of Il-23 And Il-17 Producing Eosinophils As Immunomodulatory Effector Cells In Acute Pulmonary Aspergillosis And Allergic Asthma, Evelyn V. Santos Guerra, Chrono K. Lee, Charles A. Specht, Bhawna Yadav, Haibin Huang, Ali Akalin, Jun R. Huh, Christian Mueller, Stuart M. Levitz

Christian Mueller

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a >95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with …

Hepatitis C Virus-Induced Monocyte Differentiation Into Polarized M2 Macrophages Promotes Stellate Cell Activation Via Tgf-Beta, Banishree Saha, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND and AIMS: Monocyte and macrophage (MPhi) activation contributes to the pathogenesis of chronic hepatitis C virus (HCV) infection. Disease pathogenesis is regulated by both liver-resident MPhis and monocytes recruited as precursors of MPhis into the damaged liver. Monocytes differentiate into M1 (classic/proinflammatory) or M2 (alternative/anti-inflammatory) polarized MPhis in response to tissue microenvironment. We hypothesized that HCV-infected hepatoma cells (infected with Japanese fulminant hepatitis-1 [Huh7.5/JFH-1]) induce monocyte differentiation into polarized MPhis. METHODS: Healthy human monocytes were co-cultured with Huh7.5/JFH-1 cells or cell-free virus for 7 days and analyzed for MPhi markers and cytokine levels. A similar analysis was performed on …