Day 1 :
Keynote Forum
Alexander D Verin
Georgia Regents University, USA
Keynote: Extracellular purines in lung endothelial barrier regulation
Time : 09:45-10:20
Biography:
Alexander D Verin has completed his PhD from Moscow State University, Moscow Russia and Postdoctoral studies from University of Indiana, School of Medicine. Currently he is a Professor of Vascular Biology and Medicine at Vascular Biology Center and Pulmonary Division at Georgia Regents University, Augusta, GA. He has published more than 135 papers in reputed journals and serving as an Academic Editor of Cardiology and Angiology and an Editorial Board Member in several other journals in the field of pulmonary and cardiovascular research such as Cardiovascular Pharmacology, Journal of Multidisciplinary Pathology, Journal of Vascular Diagnostics, The Journal of Biopharmaceutics Sciences, Tissue Barriers, World Journal of Respirology. In addition, he served as Editorial Board Member in American Journal of Physiology (Lung) from 2006 to 2011 and was a reviewer for a number of highly regarded journals (ex. Circulation Research, Critical Care Medicine, Physiological Reviews, PNAS).
Abstract:
Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased permeability. The mechanisms that govern the highly clinically relevant process of increased EC permeability are under intense investigation. Little is known about the processes that determine barrier enhancement or preservation. Recently, attention has been given to the therapeutic potential of purinergic agonists in the treatment of cardiovascular and pulmonary diseases. Our data indicate that ATP and its degradation product adenosine are able to protect and restore EC barrier in vitro and in vivo. We and others show that adenosine induces rapid increases in cAMP level and activation of protein kinase A (PKA)/myosin light chain (MLC) phosphatase (MLCP) cascade and this correlates with a significant attenuation of lipopolysaccharide (LPS)-induced EC permeability. In contrast, ATP induced PKA/MLCP activation and EC barrier enhancement without increase in cAMP. We also have shown the involvement of P2Y receptors coupled to Gi2 or Gq (for ATP) and P1 A2A receptors coupled to Gs (for adenosine) in purine-induced EC barrier enhancement. In addition, we have shown that inhibition of MLCP leads to the phosphorylation of several cytoskeletal targets, which correlates with permeability increase suggesting that dephosphorylation of these proteins may be involved in the barrier-enhancing effect. Further, introduction of active MLCP subunits into the lung endothelium reduces LPS-induced lung inflammation strongly supporting the positive role of MLCP activity in EC barrier preservation against ALI in murine model. Collectively, our data strongly suggest that EC barrier preservation induced by extracellular purines is dependent upon activation of specific purinergic receptor/G-protein complexes. Further, purine-induced EC barrier preservation requires the coordinated activation of PKA signaling and MLCP activation leading to EC cytoskeletal changes.
Keynote Forum
Ahmed Al-Jumaily
Auckland University of Technology, New Zealand
Keynote: Airway Passages Narrowness and Pressure Oscillation
Time : 10:20-10:55
Biography:
Ahmed Al-Jumail did PhD and MSc from the Ohio State University and BSc from the University of Baghdad. He is a Fellow member of the ASME, and a member of 11 other international professional societies. He is the Editor of the ASME monograph series-Biomedical and Nanomedical Technologies and the Editor in Chief of the Journal of Biomedical Engineering and Technology, and has been on the editorial and refereeing boards for several international journals. He has published more than 270 papers in international journals and conference proceedings including two ASME books on Vibration and Acoustics in Biomedical Applications and a third one on CPAP devices. He has supervised more than 90 Postgraduate students in biomedical applications, vibrations, biomechanics, and electroactive polymers. During his academic career, he forged strong alliances between academia and industries; in particular in the medical devices area. His current research focuses on biomedical applications with particular interest in the application of vibration and acoustics to airways constriction therapies and artery non-invasive diagnostics.
Abstract:
Obstructive sleep apnea (OSA), asthma and respiratory distress syndrome (RDS) are three lung diseases associated with narrowing of the airway passages which is attributed to either collapse of the upper airways, airway constriction and/or lack of surfactant generation, respectively. These ailments are the major cause of morbidity and mortality worldwide and have serious negative contributions to the quality of life. Each one of these ailments has different mechanisms and are stimulated by various physiological activities, some are biochemical while others are biophysical. Various pharmaceutical treatments are available, but very seldom without side effects. Pressurizing the lung, such as using continuous positive airway pressure (CPAP) method to reduce the airway narrowness has been an effective treatment method for some cases. This presentation elaborates on how this treatment method can be enhanced and improved using pressure oscillation (PO). Some successful cases including clinical trials, tissue testing and an animal model will be discussed to show the successful results of using PO in the treatment of OSA, asthma and RDS. While in vitro as well as in vivo experiments have demonstrated that length oscillations can reduce forces in contracted airway smooth muscles (the main driving mechanism for asthma attack), it has been proven that PO improves lung compliance, inflammatory stresses on patients and preserves surfactant function. This presentation highlights how engineering innovation can convert PO to a lung therapy and how this could be expanded further to the cell level to achieve asthma therapy. Is this an alternative and/or supplement to inhalers? Can oscillation help to reduce the use of current relaxants
Keynote Forum
Janet M Urban
Motivator Tobacco Treatment and Wellness Services, USA
Keynote: Smoking cessation: A review of the literature
Time : 11:20-11:55
Biography:
Janet M Urban is a lifelong resident of Central New York and currently resides in Nedrow. She holds an MS in Special Education and has taught for OCM BOCES for the past fifteen years. She holds certifications as a Tobacco Treatment Specialist from the Mayo Clinic Nicotine Dependence Center, Rochester, MN and as a Facilitator for the “Freedom from Smoking” program through the American Lung Association. She also holds certification as: Personal Trainer through WITS (World Instruction Training Schools), “Practical Yoga for Personal Trainers” and “Holistic Fitness Specialist” through the Academy of Holistic Fitness. She is also certified as a Work-Based Learning Coordinator through SUNY Buffalo. She provides individual consultations, customized treatment plans and group counseling smoking cessation services.
Abstract:
There is much literature on smoking cessation. As a worker in the substance abuse field it is necessary to gain insight into the facts, implications and treatments for smoking cessation. Areas to be briefly discussed in this lecture include the following highlights from my recently published book:There is a long history of tobacco use and findings in regards to tobacco use including the following time periods: “The Emerging Awareness of Tobacco’s Hazardous Effects”, “Taking Action”, and “The New Millennium”. Tobacco Dependence is a chronic Biopsychosocial disease characterized by frequent relapse. It has the same manifestation, maintenance and course that addictions have, and it has the same rationale for treatment as other chemical dependencies. Further, it has been found that there is a high morbidity rate related to tobacco use and dependence in people with co-occurring disorders including alcohol and other drug dependencies along with other serious mental disorders. There are multiple biological reasons that clients use tobacco and one proven solution is Nicotine Replacement Therapy as it is safe and has little potential for abuse. Supportive counseling such as group and individual has been shown to be successful in treatment. Various counseling models include: Psychological, Social, Integrative, The five A’s Intervention Tool, Motivational Interviewing, Stage of Change Model, Cognitive Behavior Therapy, Decisional Balance Model, Relapse Prevention Therapy, Behavior Therapy, and Cognitive Social Learning Therapy among others. Tobacco treatment plans include assessment, Integrated Program Therapy Activities and Relapse Prevention strategies. The tobacco industry targets those with mental health disorders. 44%-80% of this population wants to quit smoking. The system of care for this population should not be limited to a single correct model or approach. Tobacco Treatment Groups include both Tobacco Awareness Groups where it is shown to the client that the relationship with the substance is the problem not the substance itself and Tobacco Recovery Groups where craving management techniques are suggested. In summary, good clinicians assess and evaluate, diagnose substance abuse and dependence, engage patients in treatment, conduct individual and group counseling, and work collaboratively with patients to formulate treatment and treat tobacco dependence.\\\\r\\\\n
- Lung and Metabolism
Lung Infections
Lung Disorders
Session Introduction
Alexander D Verin
Georgia Regents University, USA
Title: Microtubule-mediated signaling in lung endothelial barrier regulation
Time : 12:10-12:40
Biography:
Alexander D Verin has completed his PhD from Moscow State University, Moscow Russia and Postdoctoral studies from University of Indiana, School of Medicine. Currently he is a Professor of Vascular Biology and Medicine at Vascular Biology Center and Pulmonary Division at Georgia Regents University, Augusta, GA. He has published more than 135 papers in reputed journals and serving as an academic editor of Cardiology and Angiology and an Editorial Board Member in several other journals in the field of pulmonary and cardiovascular research such as Cardiovascular Pharmacology, Journal of Multidisciplinary Pathology, Journal of Vascular Diagnostics, The Journal of Biopharmaceutics Sciences, Tissue Barriers, World Journal of Respirology. In addition, he served as Editorial Board Member in American Journal of Physiology (Lung) from 2006 to 2011 and was a reviewer for a number of highly regarded journals (ex. Circulation Research, Critical Care Medicine, Physiological Reviews, PNAS).
Abstract:
The vascular endothelium (EC) acts as a semi-selective barrier between the interior space of blood vessels and underlying tissues. Disruption of the EC barrier is a prominent feature of acute lung injury (ALI). EC permeability is regulated by a balance between contractile and tethering forces and is dependent on the functional coordination of interrelated elements of the cytoskeleton, namely microfilaments (MF) and microtubules (MT). Edemagenic agents such as the serine protease thrombin induce EC barrier dysfunction primarily via MF-driven contraction. In contrast, information about the role of the MT network in EC barrier regulation is limited. Our data indicate that MT remodeling is directly involved in thrombin-induced EC barrier compromise. MT disruption by microtubule inhibitors or thrombin, significantly increases EC permeability. Conversely, stabilization of MTs by taxol attenuates thrombin-induced EC permeability increase indicating the importance of MTs in maintaining the EC barrier. Thrombin-induced EC barrier compromise involves activation of heterotrimeric G-proteins, G12 and G13, followed by activation of Rho and p38 MAPK signaling. Inhibition of this cascade attenuates the effect of thrombin on MT structure suggesting the involvement of these pathways in MT remodeling. Thrombin induces phosphorylation of several MT- and MF-associated regulatory proteins, including caldesmon, HSP-27 and tau, which are potentially responsible for thrombin-induced changes in MF and MF structure. We hypothesize that thrombin-induced activation of G12 and G13 leads to activation of Rho and p38 MAPK signaling, phosphorylation of cytoskeletal regulatory proteins, coordinated MT and MF remodeling and finally to barrier compromise.
Akiko Mammoto
Boston Children’s Hospital, USA
Title: Platelet-rich plasma extract in lung angiogenesis and regeneration
Time : 12:40-13:10
Biography:
Akiko Mammoto received her PhD from Osaka University in Japan and completed her Postdoctoral studies at Boston Children’s Hospital/Harvard Medical School. She is currently an Instructor in Vascular Biology Program at Boston Children’s Hospital. She has published more than 65 papers in high impact journals and serves as an Editorial Board Member of Scientific Reports.
Abstract:
Angiogenesis, the growth of new blood capillaries plays a key role in organ development and regeneration. Recently, we have reported that soluble platelet-rich plasma (PRP) extract which contains abundant angiopoietin-1 and multiple other angiogenic factors stimulates angiogenesis in vitro and in vivo. We have also found that PRP extract maintains endothelial cell (EC) integrity in vitro and prevents endotoxin induced pulmonary edema in a mouse lung injury model. Here we demonstrate that mouse PRP extract also accelerates EC sprouting and lung epithelial cell budding by changing the activity of the Wnt co-receptor low-density lipoprotein receptor-related protein 5 (LRP5) in vitro. PRP extract also enhances compensatory lung growth and recovery of exercise capacity after unilateral pneumonectomy in mice while Lrp5 knockdown attenuates the effects of PRP extract. Since human PRP extract is generated from autologous peripheral blood and can be frozen for long-term storage, these findings may indicate a novel treatment for various angiogenesis-related lung diseases and could potentially advance strategies for lung organ engineering.
Peisong Gao
Johns Hopkins University School of Medicine, USA
Title: Aryl hydrocarbon receptor regulates cockroach allergen induced lung inflammation through controlling the recruitment and function of mesenchymal stem cells
Time : 14:00-14:30
Biography:
Peisong Gao is currently Associate Professor of Medicine at The Johns Hopkins University School of Medicine in Baltimore, Maryland. He received his MD degree and Pulmonary Medicine Training in The Fourth Military Medical University, China. From July 1997 to January 1999, he was a Visiting Research Fellow in Oxford University. He subsequently moved to the University of Wales Swansea pursuing a PhD working in Molecular Genetics of Asthma. In 2002 he became a Postdoctoral Fellow in the Division of Allergy & Clinical Immunology at Johns Hopkins. In 2008 he was promoted to Assistant Professor. His research has been greatly recognized by several awards including the 2004 Research Excellence Award, the 2007 Interest Section Award and Outstanding Pediatric Allergy, Asthma and Immunology Award from AAAAI. His studies mainly focus on gene, environment and development of asthma. He has published more than 60 papers in reputed journals.
Abstract:
Exposure to cockroach allergen can lead to allergic sensitization and an increased risk of developing asthma. Recent studies have suggested that aryl hydrocarbon receptor (AhR) can sense not only environmental pollutants but also microbial insults. To test whether AhR can sense allergens and modulate allergic responses, we examined cockroach allergen induce AhR activation in mesenchymal stem cells (MSCs) and lung inflammation in mouse model of asthma with wild-type (WT) and AhR-deficient (AhR-/-) mice. AhR mediated MSC migration was investigated using Transwell migration assay and GFP+MSCs administration in mouse model. The role of migrated MSCs in suppressing lung inflammation and macrophage polarization was further investigated. Our studies demonstrated that AhR signaling was activated with increased expression of cyp1a1 and cyp1b1, downstream genes of AhR when MSCs were exposed to cockroach allergens. Compared to WT mice, cockroach allergen treated AhR-/- mice showed exacerbation of lung inflammation. AhR mediated allergen-induced inflammation was further validated by using the AhR agonist, 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD). Moreover, TCDD promoted CRE-induced MSCs migration while the AhR antagonist CH122319 suppresses MSCs migration in our Transwell assays. Furthermore, CRE-challenged AhR-/- mice displayed less migrated MSCs to the lungs compared to WT when GFP+MSCs were administrated intravenously. Additionally, the administration of MSCs significantly attenuated allergic inflammation which was in part rescued by TGFβ1 neutralizing antibody. Interestingly, macrophages from MSCs treated mice exhibited M2 phenotypes with increased expression of Agr-1, FIZZ-1 and Ym-1. The macrophage polarization was possibly induced by MSCs and confirmed by co-culturing MSCs with bone marrow-derived macrophages. Our findings provided evidence for a previously unidentified pathophysiological function of the AhR and suggested that AhR may be critical in modulating environmental allergen induced immune inflammation.
Tong-Jun Lin
Dalhousie University, Canada
Title: PTP1B is a negative regulator in the host defense against Pseudomonas aeruginosa infection
Time : 14:30-15:00
Biography:
Professor Lin’s research interests include signaling mechanisms in allergy, host defense mechanisms against bacterial infection, and immune response in cancer development. His work is interdisciplinary, collaborative and geared both to contributing to the academic literature and to developing immunological therapeutic approaches in inflammation
Abstract:
Pseudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals. Toll-like receptors (TLRs) contribute to innate immunity against P. aeruginosa through activation of transcription factors IRF7/IRF3 and NFκB. However, mechanisms involved in the regulation of P. aeruginosa-induced TLR pathway activation remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa infection. PTP1B-deficient mice display greatly enhanced bacterial clearance which is accompanied with increased neutrophil infiltration and cytokine production. Interestingly, PTP1B-deficiency mainly up-regulates the production of IFN-stimulated response elements (ISRE)-regulated cytokines and chemokines including CCL5 (RANTES), CXCL10 (IP-10) and IFN-β production. Further studies reveal that PTP1B-deficiency leads to increased IRF7 activation. Importantly, PTP1B is physically associated with IRF7 in dendritic cells. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-IRF7 interaction. This novel PTP1B-IRF7-ISRE pathway may have broader implications in TLR-mediated innate immunity.
Daqing Ma
Imperial College London,UK
Title: Novel Strategy against Perioperative Remote Lung Injury after Renal Transplantation
Time : 15:00-15:30
Biography:
Dr. Daqing Ma is a Reader and Head of Anaesthesia Research of the Section of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, and Chelsea and Westminster Hospital, London, UK. He has more than 150 publications of original articles being published in the English peer reviewed journals (e.g. PNAS, Annals of Neurology, Annals of Surgery, BMJ, JASN, Kidney International, The FASEB Journal, Critical Care Medicine, Anesthesiology and etc.) covering research fields of Anesthesiology, Pharmacology, Neuroscience, Neurology and Nephrology. He is a Fellow elect of Royal College of Anaesthetists (UK). He is a Board Member of British Journal of Anaesthesia and a council member of Anaesthetic Research Society (UK). He is an Academic Editor of PLoS One and an Associate Editor of Journal Alzheimer Disease and editorial board member of other 5 journals.
Abstract:
Remote lung injury is a common complication which has been reported previously in several pre-clinical settings. However, its clinical significance has been largely ignored. In fact, it may be the major cause of most patients following major surgery who often admit into Intensive Care Unit. Remote lung injury has been suggested to be due to putative mechanisms include the release of pro-inflammatory cytokines such as IL-1β, IL-6 and particularly TNF-α from injury organs or tissue into the systemic and pulmonary circulation and then causing pulmonary tissue injury and inflammation. However, the precise causal relationship between ischemic organ/tissue or surgical trauma and remote lung injury has not been well established and the treatment is even rather limited. Renal transplantation is inevitably associated with ischemic injury due to cold storage in transportation and histocompatibility tests. This injury can be exacerbated upon engraftment, namely ischemia-reperfusion injury, which involves a cascade of events including acute tubular necrosis, inflammation and oxidative damage to renal parenchyma and also remains as one of the most formidable obstacles in the success of renal transplantation although allograft immune-rejection is still a core cause. Recently, accumulating laboratory and clinical evidence have highlighted that acute ischemic renal injury induces remote lung injury; Likewise, early renal graft injury after transplant surgery might be also associated with the rapid development of pulmonary insufficiency. Our novel strategy that was reported recently likely has a hope to tackle this problem. This lecture will cover the mechanism of remote lung injury, its clinical manifestation and novel preventive and treating strategies which has a very high chance to be translated to bedside for the best benefit of transplant patients.
Masanobu Kishikawa
Fukuoka City Hospital, Japan
Title: Re-evaluation of paper bag rebreathing for hyperventilation syndrome
Time : 15:55-16:25
Biography:
Masanobu Kishikaw is a renowned personality in the related field of Hyper Ventilation Syndrome. He is currently working at Fukuoka city Hospital in Japan. He has published several research papers and recently working on paper bag rebreathing for hyperventilation syndrome.
Abstract:
Background: Paper Bag Rebreathing（PBR）as a treatment for Hyper Ventilation Syndrome（HVS）had not recommended since 1990 by the risk of hypoxic exposure. The risk, however, might be preventable by the administration of oxygen in the paper bag. Objectives: To confirm the safety and effectiveness of PBR with administration of oxygen for HVS. Materials & Methods: Four healthy adult volunteers were examined with monitoring end-tidal carbon dioxide (EtCO2) by capnometer accompanied by nasal cannula, and with monitoring SpO2 attached on the finger. The examinees were forced to continuehyper ventilation with respiratory rate of 30/minute, and we started PBR therapy with 2 l/minute of oxygen in the vinyl bag of 3 l attached to the examinees’ mouth and nose when the EtCO2 revealed down to 20 mmHg. The examinees continued hyper ventilation with respiratory rate of 30/minute even after PBR started, and their symptoms such as numbness and lightheadedness were observed every 30 seconds. Result: EtCO2 gradually elevated just after PBR start. Symptoms of numbness and lightheadedness disappeared in 2 minutes after start of PBR when EtCO2 elevated to above 27 mmHg. EtCO2 increased to 40 mmHg within 5 minutes and SpO2 was kept above 99% in all examinees. Conclusion: PBR with administration of oxygen is thought to be safe and effective treatment for HVS.
Marioara Simon
Romanian Pulmonology Society, Romania
Title: Interventional pulmonology in the management of benign tracheal stenosis BTS
Time : 16:25-16:55
Biography:
Marioara Simon has FCCP, MD, PhD degrees in Pulmonology, Bronchologist and Allergologist. She is the Head of Bronchology and Interventional Pulmonology Department, University Hospital Cluj-Napoca, Romania. She is the President of the Romanian Bronchology Section of the Romanian Pulmonology Society and on Board of WABIP as regent, on Board of EABIP as delegate from Romania. She has a strong interest in the diagnosis and endoscopic therapy of lung cancer. She has participated in EABIP, ERS and WABIP Congresses with presentations and posters and has organized and participated in many bronchological workshops. She has published books (Chronic Interstitial Fibrotic Pneumopathies, Bronchoscopist’s Guide) and more than 130 scientific articles and oral presentations, the majority in the diagnostic bronchoscopy and interventional pulmonology field.
Abstract:
Interventional pulmonology (IP) provides comprehensive care to patients with structural airway disorders. Tracheal stenosis is a potentially life-threatening condition. With the development of interventional pulmonology field in the last 20 years, definitive management of tracheal stenosis using minimally invasive endoscopic methods became a possibility. Benign airway stenoses are frequently seen by the interventional pulmonologist. Endoscopic treatment had been shown to be useful, especially in patients who are deemed high risk and too unwell for reconstructive surgery. Many endoscopic therapeutic interventions can be offered: Balloon dilatation, rigid bronchoscopy dilatation, laser or electrosurgery resection and placement of airway stents. We have retrospectively analyzed a series of 21 patients who were referred to our department between 2013-2014 for evaluation and management of symptomatic BTS. The most common condition was post-intubation stenosis that develops after prolonged endotracheal intubation. Symptoms varied according to the severity of the stenosis, being the most frequent different degrees of dyspnea, cough and retained secretions. The endoscopic modalities used were: Balloon and rigid bronchoscopy dilatation and radial incisions with electrosurgery knife. A stent was placed in two patients. Complications were minor and mostly included restenosis. Over a median follow-up of 30 months, the overall success rate was 85.7%, only three patients being referred to surgery. Thus it can be concluded that Tracheobronchial stenoses can be difficult to treat, and patients benefit from a multidisciplinary approach; every case should be discussed within a team of dedicated physicians, including a pulmonary interventionist, an otorhinolaryngologist, and a surgeon, in order to offer the best available solution.
Jane Yu
University of Cincinnati College of Medicine, USA
Title: Dysregulation of prostaglandin metabolism and action in the progression of lymphangioleiomyomatosis
Time : 16:55-17:25
Biography:
Jane Yu has completed her PhD from the Graduate School and University Center of the City University of New York and Postdoctoral training from Fox Chase Cancer Center. She was an Assistant Professor of Medicine at the Brigham and Women’s Hospital-Harvard Medical School. She is an Associate Professor at the Pulmonary Critical Care and Sleep Medicine at University of Cincinnati College of Medicine. Her research focuses are to study mechanisms through tumor suppressor proteins hamartin (TSC1) and tuberin (TSC2) regulate cellular metabolism and cell survival, identify potential biomarkers for tuberous sclerosis complex (TSC) and rare pulmonary disease lymphangioleiomyomatosis (LAM), establish preclinical models for TSC and LAM for translational research, perform bioinformatics and network analyses, conduct high-throughput drug screens, and develop pathway targeted therapies for TSC, LAM and cancers. She has published more than 30 papers in reputed journals.
Abstract:
Lymphangioleiomyomatosis (LAM) is a female predominant and devastating pulmonary disease, characterized by diffusely infiltrated smooth muscle like cells that carry mutations in the tuberous sclerosis complex (TSC) genes. TSC1, TSC2 and TBC1D7 interact and inhibit the mammalian target of rapamycin complex 1 (mTORC1). The reasons that LAM exclusively affects women and how TSC1 or TSC2 deficiency contributes to the pathogenesis of LAM are not yet fully understood. We previously discovered that estrogen promotes the survival and lung metastases of tuberin-deficient. Recently, we reported that estrogen and mTORC2 coordinate to enhance prostaglandin biosynthesis and tumorigenesis in LAM. Prostaglandins are lipid mediators that participate in tumor survival, growth, invasion, and inflammation. Phospholipase A2 (PLA2), Cyclooxygenase-2 (COX-2) and prostacyclin synthase (PTGIS) are critical enzymes responsible for the production of prostaglandins. Prostaglandin receptors (EPs) mediate the biological function of prostaglandins. We performed bioinformatics analysis of public expression arrays and found a rapamycin-insensitive upregulation of prostaglandin biosynthesis genes including PLA2, COX-2, PTGIS, and EP3, in TSC2-deficient LAM patient-derived cells compared to TSC2-addback cells. We validated the enhanced expression of PLA2, COX-2, PTGIS and EP3 in TSC2-deficient cells using real-time RT-PCR, immunoblotting and immunohistochemistry in cell cultures, preclinical models and clinical samples. Interestingly, PGE2 specifically stimulated the growth of TSC2-deficient LAM patient-derived cells compared to TSC2-addback cells. Importantly, treatment of TSC2-deficient LAM patient-derived cells with inhibitors specific to PLA2 COX-2, or EP3 resulted in dose-dependent reduction of cells growth. Our data documents that loss of TSC2 leads to the aberrant expression and accumulation of prostaglandin biosynthesis regulators, thereby enhancing prostaglandin production and promoting TSC2-deficient cell growth and tumor development. Our data supports the potential application of prostaglandin metabolites as biomarkers of disease severity and the development of prostaglandin biosynthesis inhibitors as alternative therapeutic options for LAM patients and in other gender-specific diseases.
- Respiratory Tract Infections
Prevention, Cure and Control Management of Lung Disorders
Session Introduction
Amarjit Mishra
National Institutes of Health, USA
Title: Dendritic cell specific DNA-dependent protein kinase mediates Th2 airway inflammatory responses to house dust mite
Time : 09:30-10:00
Biography:
Amarjit Mishra is a Postdoctoral at Laboratory of Asthma and Lung Inflammation working in National Institutes of Health, USA
Abstract:
The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. DNA-dependent protein kinase (DNA-PK) is a nuclear protein serine/threonine kinase that acts as a molecular sensor in DNA damage and mediates ligation of double stranded DNA break repair, V (D) J recombination and telomere stabilization. Yet, the role of DNA-PK in Th2 immune responses to allergic asthma remains to be completely elucidated. Since DNA-PK can regulate innate immunity and pro-inflammatory signaling pathways, we hypothesized that it might also modulate adaptive Th2-mediated immune responses to house dust mite (HDM) antigen. In the present study, we report that DNA-PK regulates myeloid dendritic cell (DC)-dependent allergic sensitization and Th2 immune responses to HDM. We found that HDM induces DNA-PK phosphorylation in DCs via generation of reactive-oxygen species. Next, the adoptive transfer of HDM-pulsed CD11c+ bone marrow-derived DCs (BMDCs) from Prkdcscid mice or CD11c+ BMDCs from wild-type (WT) mice that had been treated with the pharmacologic DNA-PK inhibitor, NU-7441, or the Akt kinase inhibitor, GDC0068 had an impaired ability to induce HDM-specific airway inflammation in HDM-challenged WT recipient mice. This confirms that Akt is downstream of DNA-PK signaling in DCs. CD11c-specific deletion of DNA-PK in mice (DNA-PKfl/fl; CD11c-Cre) displayed a similar phenotype of reduced allergic sensitization and Th2-mediated airway inflammation as compared to DNA-PKcsfl/fl. In addition, adoptive transfer experiments using CD11b+myeloid DCs isolated from mediastinal lymph nodes of HDM-challenged DNA-PKfl/fl; CD11c-Cre mice to WT mice demonstrated impairment in antigen presentation that limits their ability to induce allergic sensitization and Th2-mediated airway inflammation. Moreover, feeding NU7441-containing chow before and after HDM-challenges to WT mice suppressed mucous cell metaplasia as well as airway inflammation and airway hyper-responsiveness. Our findings highlight a novel function for DNA-PK in myeloid DCs where it mediates antigen presentation and the induction of Th2 immune responses to HDM in the lung. Collectively, these data suggest that DNA-PK contributes to airway inflammation and that targeting DNA-PK kinase activity may be a noveltreatment approach for allergic asthma.
Ahmed Al-Jumaily
Auckland University of Technology, New Zealand
Title: Improvements on CPAP treatment for OSA
Time : 10:00-10:30
Biography:
Ahmed Al-Jumail did PhD and MSc from the Ohio State University and BSc from the University of Baghdad. He is a Fellow member of the ASME, and a member of 11 other international professional societies. He is the Editor of the ASME monograph series-Biomedical and Nanomedical Technologies and the Editor in Chief of the Journal of Biomedical Engineering and Technology, and has been on the editorial and refereeing boards for several international journals. He has published more than 270 papers in international journals and conference proceedings including two ASME books on Vibration and Acoustics in Biomedical Applications and a third one on CPAP devices. He has supervised more than 90 Postgraduate students in biomedical applications, vibrations, biomechanics, and electroactive polymers. During his academic career, he forged strong alliances between academia and industries; in particular in the medical devices area. His current research focuses on biomedical applications with particular interest in the application of vibration and acoustics to airways constriction therapies and artery non-invasive diagnostics.
Abstract:
Over the last three decades the continuous positive airway pressure (CPAP) method has been used as an effective tool for the treatment of obstructive sleep apnea (OSA). It provides air at an elevated pressure, which is normally called the titration pressure, through a nasal or facial mask, creating a pneumatic splint that keeps the pharyngeal upper airway (UA) open during inspiration and expiration. In spite of the CPAP therapy effectiveness, a number of drawbacks and negative impacts have been reported with its use. Over 45% of CPAP patients report negative side effects including discomfort, nasal irritation problems and some possible negative physiological impacts caused by the effect of CPAP on cerebral blood flow. The airway binary fluid layer and the structural characteristics of the UA have significant influence on the activity of the airway muscles by changing airway compliance and collapsibility during OSA. However, modulating the titration pressure has been reported to introduce some improvements to remedy some of these problems. This presentation shows how pressure oscillation can modulate the upper airways and improves airway compliance. Computer simulation and clinical trials have demonstrated that incorporating pressure oscillation helps to improve the UA muscle activities, allowing better air delivery and reducing the requirements for a relatively high titration pressure.
Janet M Urban
Tobacco Treatment and Wellness Services, USA
Title: What are the current facts and evidence-based theories about smoking cessation
Time : 10:55-11:25
Biography:
Janet M Urban is a lifelong resident of Central New York and currently resides in Nedrow. She holds an MS in Special Education and has taught for OCM BOCES for the past fifteen years. She holds certifications as a Tobacco Treatment Specialist from the Mayo Clinic Nicotine Dependence Center, Rochester, MN and as a Facilitator for the “Freedom from Smoking” program through the American Lung Association. She also holds certification as: Personal Trainer through WITS (World Instruction Training Schools), “Practical Yoga for Personal Trainers” and “Holistic Fitness Specialist” through the Academy of Holistic Fitness. She is also certified as a Work-Based Learning Coordinator through SUNY Buffalo. She provides individual consultations, customized treatment plans and group counseling smoking cessation services.
Abstract:
There is much literature on smoking cessation. As a future worker in the substance abuse field, it is necessary to gain insight into the facts, implications and treatments for smoking cessation. The website used for this paper is the most current on the topic as it enables an individual to earn clock hours toward their substance abuse certificate and to become certified in “Smoking Cessation”. Areas to be addressed in this paper include the following: Attitudes, values and beliefs about smoking, history of smoking, rationale for smoking, tobacco dependence and part 856; assessment, diagnosis and the CO monitor, stages of change readiness, and pharmacotherapy basics; motivational interviewing; cognitive behavioral therapy and relapse prevention; facilitating a tobacco awareness group; treatment planning basics; comorbidity and treating the whole patient
Bishoy Y A El-Aarag
Menoufia University, Egypt
Title: Anti-tumor effect of novel thalidomide dithiocarbamate analogs on human lung cancer A549 cells
Time : 11:25-11:55
Biography:
Dr. Bishoy El-Aarag has awarded PhD degree in the field of medical Biochemistry (Cancer Science and Therapy) through a scientific channel between Egypt (Menoufia University) and Japan (Okayama University). He works as a lecturer of Biochemistry at Faculty of Science, Menoufia University, Egypt.
Abstract:
Lung cancer is the leading cause of cancer-related mortality in the word and non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Numerous evidences had shown that thalidomide has potential for the inhibition and therapy of cancer. The present study aimed to investigate the anti-tumor effect of novel two thalidomide dithiocarbamate analogs towards human lung cancer A549 cells. The anti-proliferative, apoptotic and migration effects of lung cancer cells induced by thalidomide analogs were examined. Also, A549 cells were studied in tumor xenograft model. Our results revealed that thalidomide analogs exhibited anti-proliferative and apoptotic effect more than thalidomide itself. Also, analogs 1 and 2 suppressed the expression levels of VEGF165 by 42% and 53.25% and MMP-2 by 45% and 52% respectively. Moreover, thalidomide analogs 1 and 2 showed potent anti-tumor activity in vivo as they reduced the tumor volume by 30.11% and 53.52% respectively while thalidomide recorded 10.3% compared to vehicle control. Taken together, our study improved that thalidomide dithiocarbamate analogs are more potent anti-tumor and anti-angiogenic agents with more pronounced effect than thalidomide itself.
S M Rathnasiri Bandara
Teaching Hospital Gampola, Sri Lanka
Title: Migraine and respiratory disorders, consideration of sinus hypoxic nitric oxide theory: A review article
Time : 11:55-12:25
Biography:
S M Rathnasiri Bandara is pursuing his PhD in 2017 at Faculty of Medicine, University of Peradeniya in Sri Lanka on paranasal nitric oxide and migraine and working as second incharge in youth friendly clinic at Teaching Hospital Kandy, Sri Lanka. He has published 2 papers on hypoxic nitric oxide theory (SHNOT) for migraine and psychiatric disorders in a reputed journal. This was related to a new hypothesis connected to pranasal sinus nitric oxide and neuropsychiatric disorders. He also has served as the President of Human Protection Foundation in Sri Lanka since 2005.
Abstract:
Migraine is an extremely common disorder and has co morbidity with many respiratory illnesses. After reviewing the respiratory physiological, pathology of respiratory illnesses and association of biochemical basis on the research findings of migraine and respiratory disorders, I present to the best of my knowledge the first para-nasal sinus nitric oxide mediated respiratory biophysiological explanation for many respiratory disorders. The etiology of respiratory illnesses is mainly due to infections, immunological disturbances; degenerative changes in acute and chronic inflammation and effects of hypo NO levels and genetic predisposition. According to this para nasal sinus nitric oxide based description, those effects are mainly brought on by the excess sinorhinogenic NO (s NO) distribution of the upper and lower respiratory track except genetic predisposition. Indeed this article explains a new pathophysiological initiation between sinorhinogenic nitric oxide effects and respiratory disorders and provides an etiologically important neuro vascular impulse generating pathway to cause or aggravate migraine as well as respiratory disorders. Therefore the patients who are clinically suspected of having migraine headache and respiratorydisorders or along with susceptible respiratory disorders should receive comprehensive sinorhinological examination and evaluation based on the sinus hypoxic nitric oxide phenomena. A standard surgical and medical management of migraine that links with the sinus hypoxic nitric oxide theory are suggested to be used for even respiratory disorder as a new treatment to prevent or reduce aggravation or cure respiratory disorders locally and to prevent the dysfunction of central specific neural circuitsin migraine centrally. It warrants clinical testing.
Joanna Floros
The Penn State University, USA
Title: Differential regulation and function of SP-A1 and SP-A2: Proteins of lung innate immunity
Time : 12:25-12:55
Biography:
Joanna Floros completed her PhD and working as a Professor in department of Pediatrics and Obstetrics and Gynecology at The Penn State University, College of Medicine, Hershey PA, USA
Abstract:
Surfactant protein A(SP-A) plays an important role in innate immunity and surfactant-related functions. Dysregulation of immunity and/or surfactant function occur in most pulmonary diseases. Because levels and genetic variants of the surfactant protein A have been associated with susceptibility in several pulmonary diseases it is imperative that we understand their regulatory mechanisms with the hope of identifying points of therapeutic intervention. Two functional genes (hSP-A1; hSP-A2) encode SP-A in humans, and several genetic and splice variants have been identified for each gene. Functional and regulatory differences have been observed between hSP-A1 and hSP-A2. Both 5’ and 3’ untranslated regions (UTR) play important roles in the translational regulation and mRNA stability of SP-A1 and SP-A2. The 5’UTRs exhibit alternative splicing of untranslated exons resulting in different splice variants for hSP-A1 and hSP-A2, and the 3’UTRs exhibit sequence variability. The SP-A2 ABD/ABD’ 5’UTR contains exon B (eB) which is absent from the SP-A1 AD 5’UTR. eB is an enhancer of transcription and translation and contains cis regulatory elements. Specific trans-acting factors including several members of the 14-3-3 family of proteins bind eB and inhibition of specific members of the 14-3-3 family results in a decrease of the SP-A2 protein, but not SP-A1, indicating the role and specificity of 14-3-3 in the differential regulation of SP-A1 and SP-A2. Polymorphisms at the 3’UTR are involved in the regulation of SP-A1 and SP-A2 variants as these provide differential binding sites for miRNAs, noncoding RNAs, shown previously to regulate gene expression by affecting mRNA stability and/or translation. The available data indicate that both 5’ and 3’UTR are important regulators of SP-A1 and SP-A2 as these contain cis-elements for trans-acting protein and/or miRNA binding. A better understanding of the SP-A1 and SP-A2 may provide points for therapeutic intervention in disease where there is an SP-A-dependent derangement of innate immunity and/or surfactant. Because SP-A variants differentially affect the function and protein expression profile of the alveolar macrophage, the sentinel cell of lung innate immunity, the knowledge gained may further help to better understand macrophage functions such as phagocytosis and clearance of bacteria and inflammatory processes.
Uzoewulu Ngozi G
University of Benin,Nigeria
Title: Sensitivity of direct smear microscopy for the diagnosis of TB in high HIV prevalent population Nnewi
Biography:
Uzoewulu Ngozi G obtained his PhD in Medical Microbiology and Diploma in Medical Laboratory Science with specialty in Medical Parasitology from University of Benin, Edo state and University of Nigeria Enugu respectively. He is now working in Department of Medical Microbiology and Parasitology Nnamdi Azikiwe University Teaching Hospital Nnewi Anambra state, Nigeria as a Microbiologist.
Abstract:
Background: Diagnosis of tuberculosis (TB) amongst HIV patients is a great challenge due to the low density of Acid Fast bacilli (AFB) in their sputum. Objective: The study was conducted to determine the sensitivity of direct smear microscopy (DSM) for TB diagnosis in HIV endemic setting using culture as a gold standard. Method: Sputum specimen of 550 TB suspects were screened microscopically for AFB using Ziehl-Nielsen method at NAUTH Nnewi and positive samples subjected to culture on Lowenstein-Jensen medium with each patient also screened for HIV status. Result: They comprised of 238 (43%) DSM TB positive cases and 312 (57%) DSM TB negative cases. Out of 238 DSM TB positive cases, 180(33%) were culture positive cases with 12(2.1%) culture negative cases, 13(2.4%) contaminated specimen, 3(0.5%) NTM and 30(5.5%) lost specimen resulting in 58 (10.5%) specimen which were excluded from analysis respectively. Among the 180 culture positive TB cases 34(19%) were HIV-positive patients while 146(81%) were HIV Negative culture positive TB cases, 109(61%) males as compared to 71(39%) females within 21-40 years age group mostly affected. Findings from this study showed that the difference in the detection of PTB between these two methods was statistically significant (p=0.0001), identifying high sensitivity case detection rate of DSM as compared to specificity by culture detection more especially in HIV positive persons. Conclusion: To improve TB case detection for effective treatment, we recommend the use of culture as back up to enhance the specificity and accuracy of DSM especially in HIV positive persons.
- Pulmonary Disease: Tuberculosis
Pulmonary Disease: Pneumonia
Lung Cancer and Treatment Strategies
Session Introduction
Shashank Gupta
Johns Hopkins University, USA
Title: Efflux inhibition during tuberculosis treatment
Time : 11:20-11:50
Biography:
Shashank Gupta completed his graduate studies from ICGEB, New Delhi, India in 2009 and moved to Johns Hopkins University as a Postdoctoral fellow in early 2010. Currently, he is a Research Associate with HHMI and working on tuberculosis field at Johns Hopkins University. His studies with Mycobacterium tuberculosis will help understand the underlying mechanisms of host-pathogen interaction with special focus on mycobacterial pathogenesis and the other pathways involved in tuberculosis. His recent studies with efflux pump inhibitors have shown that verapamil can be used to accelerate both the bactericidal and the sterilizing activity of standard tuberculosis treatment.
Abstract:
Drug resistance during tuberculosis treatment is a major health concern today in the developing countries. One of the mechanisms contributing to the resistance is the efflux of the tuberculosis drugs out of the cell through a variety of pumps. Efflux pump inhibitors such as verapamil may help overcome this tolerance and resistance mechanism and enhance the activity of tuberculosis drugs. Verapamil is an FDA approved drug used to treat heart disease and hypertension. We have recently found that adding verapamil to standard chemotherapy reduced the time required to successful treatment from standard six months to four months, but also significantly decreased the risk of relapse. Another drug that has been recently approved by FDA for tuberculosis treatment is bedaquiline, also known as TMC-207. We found that co-administration of verapamil with sub-inhibitory doses of bedaquiline gave the same bactericidal effect in mice as full bedaquiline dose. In addition to, we also found that adding verapamil to bedaquiline monotherapy protected from development of resistant mutants in vivo. Thus, use of verapamil with bedaquiline may enable use of lower doses of bedaquiline, thereby reducing its dose-related toxicities in tuberculosis patients.
Orna Yariv
University of Tel-Aviv, Israel
Title: EASY AIR - Pulmonary rehabilitation telemedicine
Time : 11:50-12:20
Biography:
Orna Yariv is working as a Physiotherapist in Pulmonary rehabilitation at Laniado Hospital. He served as Medical trainer-A.C.S.M. from 1989- 1998 at Physiotherapy Clinic in Tel Aviv , Israel He also worked as Manager - Telemedicine Pulmonary Rehabilitation in a reputed organization and also serving as Volunteering manager -respiratory Q&A forum since 2012.
Abstract:
Daily treatments and support of patients with lung diseases include drainage, training and education towards physical activity. The overall goal of these treatments is to improve the quality of life of these chronic patients. A primary challenge in the treatment of these patients is the difficulty in achieving an efficient guidance of the patients that will improve the efficacy of their treatment. In the coming lecture I will present my experience in expanding the role of the care-giver using pulmonary rehabilitation telemedicine. I use telemedicine to treat patients in a variety conditions, times and places: at home, while hospitalized, and even while on vacation or at work. Moreover, we use telemedicine specifically for patients leaving in rural areas and for housebound patients. Preliminary communication media are the e-mail and Facebook that are followed by scheduled Skype appointments. Skype-appointments are used (a) to track medical history, (b) to find primary problems that the patient is occupied with, and (c) to understand their level of functionality. This information is used to build a patient-tailored rehabilitation program that is based on traditional Pulmonary Rehabilitation. Following appointments are used to combine education and to demonstrate needed exercises. My patients improve their walking distance and amount of upclimbing stairs. Tele-rehabilitation therapy does not replace traditional pulmonary rehabilitation but rather enhances it by providing an additional way to treat and to ease patients’ life.
Du Toit Loots
North-West University, South Africa
Title: Tuberculosis: Adaptations of man and microbe in order to outcompete and survive
Time : 12:20-12:50
Biography:
Du Toit Loots currently Heads the “Infectious and Acquired Disease Metabolomics” unit at NWU with a focus on new biomarker discovery for better characterizing and diagnosing diseases, TB in particular. He has to date contributed to a total of 68 publications: 60 of which are peer reviewed scientific manuscripts in top international journals, 4 chapters in books and 4 publications in non-peer reviewed popular magazines. He is currently International Editor for Journal of Cell and Tissue Research and has additionally registered 1 full patent with application to TB diagnostics and published a new synthesis method for NaFe (III) EDTA, a highly bio-available form of iron for combating anaemia. In recognition of these efforts, he received a number of awards including the: International Nestle Nutrition Institute for Africa Research Award; Janssen-Cilag Award, International ARP Walker Research Award and International Scripps Centre for Integrative Medicine's Research Award.
Abstract:
Tuberculosis (TB) caused by the organism Mycobacterium tuberculosis is a deadly bacterial disease infecting approximately one-third of the world’s population. The most recent World Health Organization (WHO) report indicates 1.5 million deaths and 9 million newly reported TB cases per annum, 95% of which are in developing countries. Despite the fervent genomic and proteomic based research efforts to date, since its discovery in 1882, TB is still a major global problem and hence new approaches are necessary to better characterize this disease especially the adaptations of the host and microbe/host-microbe interactions as they compete to survive. Using GCxGC-TOFMS metabolomics, we have to date identified 31 new sputum and 12 new urinary metabolite markers never before associated with TB providing new insights into the adaptations of the host and microbe metabolome during active TB. The most significant of these are the TB-induced abnormal metabolites resulting from changes to host fatty acid and amino acid metabolism in particular to that of tryptophan, phenylalanine and tyrosine mediated through INF-γ and possibly also reduced insulin. Additionally, an alternative mechanism by which the host produces hydrogen peroxide via glucose oxidation in order to more efficiently eliminate the bacterial threat is proposed. Through these altered metabolic pathways elevated concentrations of various neurotransmitters and other abnormal toxic metabolites related to some of the symptoms associated with TB were identified, subsequently providing clues to better treatment approaches. Adaptations of the microbe during active TB includes the use of a rather unique citramalic acid cycle in conjunction with an up-regulated glyoxylate cycle accompanied by a greater dependence on fatty acids and glutamate as alternative carbon sources.
Grace Kaguthi
Kenya Medical Research Institute, Kenya
Title: Chest radiographs for pediatric TB diagnosis: Inter-rater agreement and utility
Time : 12:50-13:20
Biography:
Grace Kaguthi is a Medical Doctor and Clinical Trialist with the Centre for Respiratory Diseases Research (KEMRI). She is currently pursuing her PhD in Tuberculosis epidemiology at the University of Amsterdam. She is a lead investigator in phase II and phase III trials of novel tuberculosis vaccines, treatments for sickle cell disease, malaria and tuberculosis treatment trials. She is a Member of the Ethics Review Unit at the Kenya Medical Research Institute which reviews and approves research protocols.
Abstract:
The chest radiograph (CXR) is considered a key diagnostic tool for pediatric tuberculosis (TB) in clinical management and endpoint determination in TB vaccine trials. We set out to compare inter-rater agreement for TB diagnosis in western Kenya. A pediatric pulmonologist and radiologist (experts), a medical officer (M.O), and four clinical officers (C.Os) with basic training in pediatric CXR reading blindly assessed CXRs of infants who were TB suspects in a cohort study. C.Os had access to clinical findings for patient management. Weighted kappa scores summarized inter-rater agreement on lymphadenopathy and abnormalities consistent with TB. Sensitivity and specificity of raters were determined using microbiologically confirmed TB as the gold standard (n=8). A total of 691 radiographs were reviewed. Agreement on abnormalities consistent with TB was poor; k=0.14 (95% CI: 0.10–0.18) and on lymphadenopathy moderate k=0.26 (95% CI: 0.18–0.36). M.O [75% (95% CI: 34.9%–96.8%)] and C.Os [63% (95% CI: 24.5%–91.5%)] had high sensitivity for culture confirmed TB. TB vaccine trials utilizing expert agreement on CXR as a non-microbiologically confirmed endpoint will have reduced specificity and will underestimate vaccine efficacy. C.Os detected many of the bacteriologically confirmed cases; however, this must be interpreted cautiously as they were un-blinded to clinical features.
Abdulhadi Almutairi
King Fahad Specialist Hospital, Saudi Arabia
Title: Extended resections for lung cancer: Can they be justified
Time : 14:10-14:40
Biography:
Abdulhadi Almutairi has graduated from College of Medicine, King Saud University, Saudi Arabia in 2000. He completed his Surgical Residency at King Faisal Specialist Hospital, Saudi Arabia. His passion for thoracic surgery has led him to join a Clinical Thoracic Surgery Fellowship in a world-renowned thoracic surgery program at McMaster University, Hamilton, Ontario. Throughout his career, he has developed a strong interest in thoracic oncology in general and lung cancer specifically. Beside lung cancer surgery, he is also interested in tracheal surgery, mediastinal surgery and chest wall primary tumors. He is an active Member of the Society of Thoracic Surgeons (STS), International Thymic Malignancy Interest group (ITMIG) and Chest Wall International group (CWIG). He has over 20 publications and currently working on Editing a Surgery Textbook. He is a strong Advocate of Quality in Surgical Education and is the Program Director of Surgery Residency training program.
Abstract:
Surgical resection remains a critical component of multidisciplinary therapy for locally advanced lung cancers. However, extended resection for treating locally advanced lung cancer is surrounded by intense debate. The advancements in novel chemotherapy and targeted therapy have influent our decisions on treating these cases by radical surgical intervention that carries a significant morbidity and mortality. Long-term survival is limited to retrospective and anecdotal data. Moreover, in the era of patient-centered care, the patient decision to go for neoadjuvant or definitive systemic therapy remains critical and may alter the landscape of surgical scene. Historically, racialists (thoracic surgeons with enormous surgical experience) have fought locally advanced lung cancer with extended resection that entails lobectomy or pneumonectomy en bloc with adjacent involved structure in order to achieve complete surgical resection and negative margins. This may on itself and by itself improve survival in highly selected patients. The magnitude of this benefit is very difficult to quantify largely because the data is limited to small patient sample and high volume centers. Never the less, this improvement, albeit modest cannot be ignored or rejected. In this talk, we aim to dissect the current literature regarding this important matter and shed some light on the techniques that have been refined over the years in order to serve a well defined subsets of patients with locally advanced lung cancer who may be offered this type of radical surgery knowing the amount of risk taking is massive and the expected results remain a matter of speculation.
Videlis Nduba
Kenya Medical Research Institute, Kenya
Title: Incidence of tuberculosis and cohort retention among adolescents in Western Kenya
Time : 14:40-15:10
Biography:
Videlis Nduba is a Senior Research Officer at the Center for Respiratory Diseases Research, Kenya Medical Research Institute. He is a Medical Officer and Epidemiologist with experience leading several clinical trials. He previously conducted epidemiological trials in infants and adolescents to determine the incidence of tuberculosis in Western Kenya. He is currently involved with TB vaccine and drug trials.
Abstract:
Setting: Karemo division, Siaya County, Western Kenya, with the highest TB notification rates in Kenya (400/100,000). Objective: To determine the incidence of tuberculosis and one year cohort retention in 12–18 year adolescents, in preparation for Phase III TB vaccine trials. Design: Adolescents were enrolled and followed up for 1-2 years to determine TB incidence. Adolescents who had a positive tuberculin skin test, history of cohabitation with a TB case within the previous 2 years, or at least one TB symptom received clinical examination, sputum examination, and a chest X-ray. TB cases were defined as definite if bacteriologically confirmed and clinical if diagnosed by a clinician based on a suggestive chest X-ray scored using Chest Radiograph Review System (CRRS) and having at least one clinical symptom. Risk factors were explored using Poisson regression. Results: Among 4965 adolescents without TB at baseline, 26 TB cases were found during follow up with a corresponding incidence density of 4.4 (95% CI, 3.0-6.4) events per 1000 person years of observation. Tuberculin skin test (TST) conversion (RR=3.5; CI 1.5, 7.7) and history of previous tuberculosis (RR=12.5; CI 1.8, 100) were the strongest predictors of incident TB. Overall (4086/4957) 82.4% of adolescents were retained in the study after 1 year of follow up. Being female, older, out of school and being orphaned were significant risk factors for lower retention rates. Conclusion: Given the high incidence of tuberculosis and good cohort retention, this setting is suitable for TB vaccine trials targeting adolescents.
- Young Researcher Forum
Session Introduction
Nancy Gupta
University of Alberta, Canada
Title: A novel mucosal lipopeptide based vaccine against mycobacteria
Time : 15:45-16:05
Biography:
Nancy Gupta completed her PhD and is working in Laboratory Medicine and Pathology under Dr. Rakesh Kumar, Dr. Dennis Kunimoto University of Alberta Edmonton,Canada.
Abstract:
Tuberculosis (TB) is a major global health threat to humans, with 9.3 million new cases and 2 million deaths annually from Mycobacterium tuberculosis infection. BCG is the only available vaccine which is only 0-80% effective. Development of vaccine against mycobacteria is challenging and several experimental vaccine candidates did not demonstrate sufficient efficacy in clinical trials. Early secreted antigenic target 6-kDa (ESAT-6) has been suggested to be an important antigen for protective immunity and BCG lacks ESAT-6. In this study, we aimed to examine the immune responses generated upon immunization with lipopeptides of ESAT-6 and their protective efficacy in a mouse modal of Mycobacterium tuberculosis infection. Our results demonstrated that intranasal immunization with lipopeptides of ESAT-6 antigen is capable of stimulating potent and multifunctional antigen specific T cell responses in spleen and lead to substantial infiltration of immune cells in the Bronchio Alveolar Lavage (BAL). Subcutaneous immunization also induced immune responses in spleen comparable to that obtained from intranasal route but failed to recruit immune cells in the BAL. Pre-immunization of mice with lipopeptides of ESAT-6intranasallyled to a significant reduction in Mycobacterium tuberculosis (H37Ra) loads in lungs, liver and spleen compared to subcutaneous vaccination. Our study revealed the potential of lipidated peptides of ESAT-6 antigen as a promising mucosal vaccine against tuberculosis.
Saurabh Garg
University of Alberta, Canada
Title: Investigation of novel alkynyl and alkynyloxy pyrimidine nucleoside analogs as antimycobacterial agents
Time : 16:05-16:25
Biography:
Saurabh Garg completed his PhD and is working at Laboratory Medicine and Pathology under Dr. Rakesh Kumar, Dr. Robert Rennie University of Alberta Edmonton,Canada.
Abstract:
A rapid increase of the antibiotic resistance against microbial pathogens over the past several decades has become one of the most serious medical challenges to the world. Tuberculosis (TB) caused by Mycobacterium tuberculosis is the second leading cause of infectious deaths globally. In 2013, an estimated 9 million people developed tuberculosis and 1.4 million died from this disease. The resurgence of TB cases and the emergence of drug-resistant strains of mycobacteria necessitate the search for new antimycobacterial agents that are non toxic and distinct from the current drugs. We have designed, synthesized and evaluated novel pyrimidine nucleosides (1-20) for their antimycobacterial activities in vitro. The 3-N- and or 5-O-propynyl pyrimidine nucleosides (1-14) were synthesized by reacting 5-hydroxy and 5-hydroxymethyl pyrimidine nucleosides with propargyl bromide. 5-Acetylenic nucleosides (15-20) were prepared by coupling 5-iodo pyrimidine nucleosides with trimethylsilyl acetylene followed by de-protection with sodium methoxide. The antimycobacterial activity of compounds 1-20 alone and in combination with first line antituberculosis drug isoniazid was evaluated against Mycobacterium tuberculosis (Mtb), Mycobacterium bovis (M. bovis) and Mycobacterium avium (M. avium) using microplate alamar blue assay. Among alkynyl compounds 5-(2-propynyloxy) uridine (4) and N-3-propynylnucleoside analogs (5 and 12-14) exhibited modest activity against Mtb (H37Ra) and M. bovis with EC50=160-180 μg/mL, however, they demonstrated strong synergistic interactions with isoniazid. C-5 Ethynyl substituted pyrimidine nucleosides analogs (15-20) were found to be inactive as antimycobacterial agents. Compounds 1-20 did not show cytotoxicity up to the highest concentration tested (CC50>200 μg/mL).
Jomo Osborne
The Brooklyn Hospital Center, USA
Title: Catheter-directed thrombolysis in patients with Acute pulmonary thromboembolism - A case series at The Brooklyn Hospital Center
Time : 16:25-16:45
Biography:
Dr. Jomo Osborne earned his medical degree in his native country Guyana and later completed a Masters of Health Science degree in Cuernavaca, Mexico. He has presented at many international conferences and co-authored several peer review articles and conference abstracts. He is currently a surgical resident at The Brooklyn Hospital Centre. His research interest includes sub-massive pulmonary embolism, minimally invasive surgery and surgical quality improvement.
Abstract:
Pharmacomechanical catheter-directed thrombolysis in patients with acute pulmonary thromboembolism (PE) is a proven safe and effective method of preventing complications such as right ventricular collapse, cardiogenic shock and death. Three patients with massive or sub-massive pulmonary embolism presented to the Emergency Department at our institution with shortness of breath and were diagnosed with acute PE using computed tomography pulmonary angiogram (CTA). The patients were: A 57 year-old woman with a history of hypertension and previous thyroid cancer which was treated with thyroidectomy presented with a pulmonary arterial saddle embolus and right cardiac dysfunction; a 55 year-old woman on chemotherapy with a history of deep vein thrombosis (DVT), previous tumor-debulking and extended right hemicolectomy for metastatic leiomyosarcoma presented with a large central pulmonary embolus in the right main pulmonary artery without right ventricular strain; a 54 year-old man with a history of lower extremity DVT with a right main pulmonary artery embolus and right ventricular strain. Based on the clot location in each patient, an EKOS catheter was placed in the main pulmonary artery or its branches and alteplase was infused at a rate of 1mg per hour over 10-24 hours. Simultaneously, the patients were anticoagulated with heparin. The patient’s hemodynamic status, coagulation profile and fibrinogen levels were continuously monitored for clinical improvement. The follow-up CTA showed 75% to 100% clot reduction in each patient. Complications included a right-sided groin hematoma at the catheter-insertion site in one patient which required temporary discontinuation of thrombolytic and anti-coagulation therapy. Our observations of these three patients show that this method of treatment is a safe and effective initial measure to restore pulmonary artery blood flow in patients diagnosed with acute PE. However, it is still associated with the risk of complications.
Suhaj A
Manipal University, India
Title: Impact of patient education on health related quality of life of COPD patients- A randomized controlled study
Time : 16:45-17:05
Biography:
Suhaj A is Assistant Professor-Senior Scale in the Department of Pharmacy Practice at MCOPS. Areas of Interest, Expertise and Research: Pharmaceutical Care, Drug Safety and Pharmacoeconomics, Clinical Pharmacy and Pharmaco therapeutics, Pharmaceutical Care in COPD patients PROFESSIONAL AFFILIATIONS AND CONTRIBUTIONS: He is member of ISPOR.
Abstract:
Background: Chronic Obstructive Pulmonary Disease (COPD) comprises a group of diseases associated with airflow obstruction and breathing-related problems. COPD cannot be cured but adherence to the therapy can improve management of symptoms and delay disease progression. Patients’ knowledge and awareness about the disease are important in improving quality of life. Aim: Our study was aimed to assess the impact of patient education on Health Related Quality of Life (HRQoL) of COPD patients. Method: An open label randomized controlled study was conducted among 206 COPD patients who were admitted in the university hospital after obtaining the ethical clearance. HRQoL of the patients in the control and intervention group at baseline and follow-up visits were measured using St. George Respiratory Questionnaire. Patients were followed up at 6 months during a scheduled visit. Statistical analyses were performed using SPSS® version 20. Result: Mean age of the study population (n=206) was 58.42±9.72. 93.5% were males. There is no significant difference in overall HRQoL between control (45.2%) and intervention group (44.8%) at baseline. After intervention, overall HRQoL was improved in intervention group (P < 0.05) compared to control group (P>0.05) at follow-up. Study population in the intervention group (at follow-up) has reported better HRQoL compared to the intervention group (at baseline), control group (at baseline) and control group (at follow-up). Conclusion: The results of the study suggest that the clinical pharmacist can play a major role in improving patient knowledge and thereby improve medication adherence and health related quality of life.