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Sample records for understand pathophysiological mechanisms

  1. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  2. Pathophysiologic mechanisms of biomedical nanomaterials

    International Nuclear Information System (INIS)

    Wang, Liming; Chen, Chunying

    2016-01-01

    Nanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future. - Highlights: • Rapid protein adsorption onto nanomaterials that affects biomedical effects • Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects • Nanomaterials and their interaction with biological barriers • The signaling pathways mediated by nanomaterials and related biomedical effects • Novel techniques for studying translocation and biomedical effects of NMs

  3. Pathophysiological mechanisms ofurbanisation-related ...

    African Journals Online (AJOL)

    Subjects had their blood pressures measured at least three times before the study. Initial blood pressure recordings were generally high compared with those .... Elevated. TXA2/PGI2 appears to be an additional mechanism leading to increased blood pressure in the hypertensives subjected to increased dietary salt intake.

  4. Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

    Directory of Open Access Journals (Sweden)

    D. C. Damasceno

    2014-01-01

    Full Text Available Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

  5. Pathophysiological Mechanisms in Sclerosing Skin Diseases

    Directory of Open Access Journals (Sweden)

    Beate Eckes

    2017-08-01

    Full Text Available Sclerosing skin diseases represent a large number of distinct disease entities, which include systemic sclerosis, localized scleroderma, and scleredema adultorum. These pathologies have a common clinical appearance and share histological features. However, the specific interplay between cytokines and growth factors, which activate different mesenchymal cell populations and production of different extracellular matrix components, determines the biomechanical properties of the skin and the clinical features of each disease. A better understanding of the mechanisms underlying these events is prerequisite for developing novel targeted therapeutic approaches.

  6. Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

    NARCIS (Netherlands)

    Kerckhoffs, A.P.M.

    2009-01-01

    Irritable Bowel Syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with a disordered defecation. No unique pathophysiological mechanism has been identified. It is most likely a multifactorial disease involving alterations in intestinal microbiota

  7. Pathophysiology of gastroesophageal reflux disease: new understanding in a new era.

    Science.gov (United States)

    Herregods, T V K; Bredenoord, A J; Smout, A J P M

    2015-09-01

    The prevalence of gastroesophageal reflux disease (GERD) has increased in the last decades and it is now one of the most common chronic diseases. Throughout time our insight in the pathophysiology of GERD has been characterized by remarkable back and forth swings, often prompted by new investigational techniques. Even today, the pathophysiology of GERD is not fully understood but it is now recognized to be a multifactorial disease. Among the factors that have been shown to be involved in the provocation or increase of reflux, are sliding hiatus hernia, low lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, the acid pocket, obesity, increased distensibility of the esophagogastric junction, prolonged esophageal clearance, and delayed gastric emptying. Moreover, multiple mechanisms influence the perception of GERD symptoms, such as the acidity of the refluxate, its proximal extent, the presence of gas in the refluxate, duodenogastroesophageal reflux, longitudinal muscle contraction, mucosal integrity, and peripheral and central sensitization. Understanding the pathophysiology of GERD is important for future targets for therapy as proton pump inhibitor-refractory GERD symptoms remain a common problem. In this review we provide an overview of the mechanisms leading to reflux and the factors influencing perception, in the light of historical developments. It is clear that further research remains necessary despite the recent advances in the understanding of the pathophysiology of GERD. © 2015 John Wiley & Sons Ltd.

  8. Chikungunya Virus: Pathophysiology, Mechanism, and Modeling

    Science.gov (United States)

    Ganesan, Vaishnavi K.; Reid, St Patrick

    2017-01-01

    Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models. PMID:29194359

  9. Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms

    Directory of Open Access Journals (Sweden)

    Scott E. Friedman

    2012-01-01

    Full Text Available Pulmonary hypertension (PH is a potentially life-threatening condition arising from a wide variety of pathophysiologic mechanisms. Effective treatment requires a systematic diagnostic approach to identify all reversible mechanisms. Many of these mechanisms are relevant to those afflicted with obesity. The unique mechanisms of PH in the obese include obstructive sleep apnea, obesity hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include endothelial dysfunction and hyperuricemia. A wide range of effective therapies exist to mitigate the disability of PH in the obese.

  10. [Hypercapnic respiratory failure. Pathophysiology, indications for mechanical ventilation and management].

    Science.gov (United States)

    Kreppein, U; Litterst, P; Westhoff, M

    2016-04-01

    Acute hypercapnic respiratory failure is mostly seen in patients with chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS). Depending on the underlying cause it may be associated with hypoxemic respiratory failure and places high demands on mechanical ventilation. Presentation of the current knowledge on indications and management of mechanical ventilation in patients with hypercapnic respiratory failure. Review of the literature. Important by the selection of mechanical ventilation procedures is recognition of the predominant pathophysiological component. In hypercapnic respiratory failure with a pH ventilation (NIV) is primarily indicated unless there are contraindications. In patients with severe respiratory acidosis NIV requires a skilled and experienced team and close monitoring in order to perceive a failure of NIV. In acute exacerbation of COPD ventilator settings need a long expiration and short inspiration time to avoid further hyperinflation and an increase in intrinsic positive end-expiratory pressure (PEEP). Ventilation must be adapted to the pathophysiological situation in patients with OHS or overlap syndrome. If severe respiratory acidosis and hypercapnia cannot be managed by mechanical ventilation therapy alone extracorporeal venous CO2 removal may be necessary. Reports on this approach in awake patients are available. The use of NIV is the predominant treatment in patients with hypercapnic respiratory failure but close monitoring is necessary in order not to miss the indications for intubation and invasive ventilation. Methods of extracorporeal CO2 removal especially in awake patients need further evaluation.

  11. Principles of hemodynamic for mechanical circulatory support: patho-physiological key aspects of assisted PCI.

    Science.gov (United States)

    Basile, Eloisa; Russo, Giulio; Leone, Antonio M

    2018-03-15

    It is essential to understand the pathophysiology of cardiogenic shock and the possible deterioration of contractile function during high-risk PCI in order to select those patients who could benefit from mechanical support thus choosing the most suitable device in every situation. Percutaneous Ventricular Assist Devices (pVAD) provide hemodynamic support by improving cardiac output and mean arterial pressure, but their specific features result in different hemodynamic effects and degrees of myocardial ischemic protection and LV unloading. These features, together with ease of use, specific contraindications and individual risk of complications, must be taken into account in the evaluation and selection of the device. Ai of this review is to illustrate the principles of left ventricular mechanic, including the pressure- volume loop analysis, in order to better understand, to quantify the different hemodynamic effects of pVAD supports and to explain the key pathophysiological aspects of assisted PCI.

  12. Understanding Defense Mechanisms.

    Science.gov (United States)

    Cramer, Phebe

    2015-12-01

    Understanding defense mechanisms is an important part of psychotherapy. In this article, we trace the history of the concept of defense, from its origin with Freud to current views. The issue of defense as an unconscious mechanism is examined. The question of whether defenses are pathological, as well as their relation to pathology, is discussed. The effect of psychotherapy on the use of defenses, and their relation to a therapeutic alliance is explored. A series of empirical research studies that demonstrate the functioning of defense mechanisms and that support the theory is presented. Research also shows that as part of normal development, different defenses emerge at different developmental periods, and that gender differences in defense use occur.

  13. POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS OF ULTRAFINE PARTICLE TOXIC EFFECTS IN HUMANS

    Directory of Open Access Journals (Sweden)

    JASMINA JOVIĆ-STOŠIĆ

    2008-03-01

    Full Text Available Epidemiological and clinical studies suggested the association of the particulate matter ambient air pollution and the increased morbidity and mortality, mainly from respiratory and cardiovascular diseases. The size of particles has great influence on their toxicity, because it determines the site in the respiratory tract where they deposit. The most well established theory explaining the mechanisms behind the increased toxicity of ultrafine particles (UFP, < 0.1 µm is that it has to do with the increased surface area and/or the combination with the increased number of particles. Biological effects of UFP are also determined by their shape and chemical composition, so it is not possible to estimate their toxicity in a general way. General hypothesis suggested that exposure to inhaled particles induces pulmonary alveolar inflammation as a basic pathophysiological event, triggering release of various proinflammatory cytokines. Chronic inflammation is a very important underlying mechanism in the genesis of atherosclerosis and cardiovascular diseases. UFP can freely move through the circulation, but their effects on the secondary organs are not known yet, so more studies on recognizing toxicological endpoints of UFP are needed. Determination of UFP toxicity and the estimation of their internal and biologically active dose are necessary for the evidence based conclusions connecting air pollution by UFP and human diseases.

  14. [Understanding the pathophysiology of malnutrition for better treatment].

    Science.gov (United States)

    De Bandt, J-P

    2015-09-01

    Malnutrition results from an imbalance between intake and protein-energy requirements resulting in tissue losses with adverse functional consequences. However, it would be better to speak of "states of malnutrition" rather than "malnutrition". Indeed, the mechanisms involved associate, with varying degrees, intake deficiency and increased needs with different clinical consequences. Adaptation to nutrient deficiency aims at establishing lasting saving conditions by promoting optimization of energy reserve utilization while preserving protein pool. This is achieved by reducing basal metabolism (low T3), by decreasing the secretion of anabolic factors and moderately increasing catabolic hormones. Unlike the previous process, the metabolic response to injury or stress, which will sometime induce major increase in requirements, will have as immediate purpose the defense of the organism. The body will draw sometime substantially in its protein pool to produce the glucose required for example by the immune cells. Stress response stems from both an endocrine response, and an immuno-inflammatory one with the important role of pro-inflammatory cytokines released in response to pathogens and more recently alarmins in response to endogenous stress in the inflammatory phenomena of the stress response and in the resulting malnutrition state. Treatment of these malnutrition conditions will thus differ: promoting anabolism in one case and fighting resistance to anabolism and hypercatabolism in the other. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. Myocardial Bridging: Contemporary Understanding of Pathophysiology with Implications for Diagnostic and Therapeutic Strategies

    Science.gov (United States)

    Eshtehardi, Parham; Rasoul-Arzrumly, Emad; McDaniel, Michael; Mekonnen, Girum; Timmins, Lucas H.; Lutz, Jerre; Guyton, Robert A; Samady, Habib

    2014-01-01

    Patients with myocardial bridges are often asymptomatic but this anomaly may be associated with exertional angina, acute coronary syndromes, cardiac arrhythmias, syncope or even sudden cardiac death. This review presents our understanding of the pathophysiology of myocardial bridging and describes prevailing diagnostic modalities and therapeutic options for this challenging clinical entity. PMID:24583304

  16. Metabolomics Insights Into Pathophysiological Mechanisms of Interstitial Cystitis

    Science.gov (United States)

    Fiehn, Oliver

    2014-01-01

    Interstitial cystitis (IC), also known as painful bladder syndrome or bladder pain syndrome, is a chronic lower urinary tract syndrome characterized by pelvic pain, urinary urgency, and increased urinary frequency in the absence of bacterial infection or identifiable clinicopathology. IC can lead to long-term adverse effects on the patient's quality of life. Therefore, early diagnosis and better understanding of the mechanisms underlying IC are needed. Metabolomic studies of biofluids have become a powerful method for assessing disease mechanisms and biomarker discovery, which potentially address these important clinical needs. However, limited intensive metabolic profiles have been elucidated in IC. The article is a short review on metabolomic analyses that provide a unique fingerprint of IC with a focus on its use in determining a potential diagnostic biomarker associated with symptoms, a response predictor of therapy, and a prognostic marker. PMID:25279237

  17. Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression

    OpenAIRE

    Verduijn, J; Milaneschi, Y; Schoevers, R A; van Hemert, A M; Beekman, A T F; Penninx, B W J H

    2015-01-01

    Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical ...

  18. Meconium aspiration syndrome: possible pathophysiological mechanisms and future potential therapies.

    Science.gov (United States)

    Lindenskov, Paal Helge Haakonsen; Castellheim, Albert; Saugstad, Ola Didrik; Mollnes, Tom Eirik

    2015-01-01

    Does meconium cause meconium aspiration syndrome (MAS) or is meconium discharge only a marker of fetal hypoxia? This dispute has lasted for centuries, but since the 1960s, detrimental effects of meconium itself on the lungs have been demonstrated in animal experiments. In clinical MAS, persistent pulmonary hypertension of the newborn is the leading cause of death in MAS. Regarding the complex chemical composition of meconium, it is difficult to identify a single agent responsible for the pathophysiology. However, considering that meconium is stored in the intestines, partly unexposed to the immune system, aspirated meconium could be recognized as ‘danger', representing damaged self. The common denominator in the pathophysiology could therefore be activation of innate immunity. Thus, a bulk of evidence implies that meconium is a potent activator of inflammatory mediators, including cytokines, complement, prostaglandins and reactive oxygen species. We hypothesize that the two main recognition systems of innate immunity, the Toll-like receptors and the complement system, recognize meconium as ‘danger', which leads not only to lung dysfunction but also to a systemic inflammatory response. This might have therapeutic implications in the future.

  19. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

    Science.gov (United States)

    Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

    2017-05-10

    Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

  20. EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

    Science.gov (United States)

    Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

    2017-01-01

    Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

  1. Understanding mechanical ventilators.

    Science.gov (United States)

    Chatburn, Robert L

    2010-12-01

    The respiratory care academic community has not yet adopted a standardized system for classifying and describing modes of ventilation. As a result, there is enough confusion that patient care, clinician education and even ventilator sales are all put at risk. This article summarizes a ventilator mode taxonomy that has been extensively published over the last 15 years. Specifically, the classification system has three components: a description of the control variables within breath; a description of the sequence of mandatory and spontaneous breaths; and a specification for the targeting scheme. This three-level specification provides scalability of detail to make the mode description appropriate for the particular need. At the bedside, we need only refer to a mode briefly using the first or perhaps first and second components. To distinguish between similar modes and brand names, we would need to include all components. This taxonomy uses the equation of motion for the respiratory system as the underlying theoretical framework. All terms relevant to describing modes of mechanical ventilation are defined in an extensive appendix.

  2. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

    Science.gov (United States)

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  3. Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

    Directory of Open Access Journals (Sweden)

    Shaobin Yu

    2015-01-01

    Full Text Available Methamphetamine (METH is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

  4. Regulation of Nox enzymes expression in vascular pathophysiology: Focusing on transcription factors and epigenetic mechanisms.

    Science.gov (United States)

    Manea, Simona-Adriana; Constantin, Alina; Manda, Gina; Sasson, Shlomo; Manea, Adrian

    2015-08-01

    NADPH oxidases (Nox) represent a family of hetero-oligomeric enzymes whose exclusive biological function is the generation of reactive oxygen species (ROS). Nox-derived ROS are essential modulators of signal transduction pathways that control key physiological activities such as cell growth, proliferation, migration, differentiation, and apoptosis, immune responses, and biochemical pathways. Enhanced formation of Nox-derived ROS, which is generally associated with the up-regulation of different Nox subtypes, has been established in various pathologies, namely cardiovascular diseases, diabetes, obesity, cancer, and neurodegeneration. The detrimental effects of Nox-derived ROS are related to alterations in cell signalling and/or direct irreversible oxidative damage of nucleic acids, proteins, carbohydrates, and lipids. Thus, understanding of transcriptional regulation mechanisms of Nox enzymes have been extensively investigated in an attempt to find ways to counteract the excessive formation of Nox-derived ROS in various pathological states. Despite the numerous existing data, the molecular pathways responsible for Nox up-regulation are not completely understood. This review article summarizes some of the recent advances and concepts related to the regulation of Nox expression in the vascular pathophysiology. It highlights the role of transcription factors and epigenetic mechanisms in this process. Identification of the signalling molecules involved in Nox up-regulation, which is associated with the onset and development of cardiovascular dysfunction may contribute to the development of novel strategies for the treatment of cardiovascular diseases. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment

    Science.gov (United States)

    ROBINSON, ANDREW P.; HARP, CHRISTOPHER T.; NORONHA, AVERTANO; MILLER, STEPHEN D.

    2014-01-01

    While no single model can exactly recapitulate all aspects of multiple sclerosis (MS), animal models are essential in understanding the induction and pathogenesis of the disease and to develop therapeutic strategies that limit disease progression and eventually lead to effective treatments for the human disease. Several different models of MS exist, but by far the best understood and most commonly used is the rodent model of experimental autoimmune encephalomyelitis (EAE). This model is typically induced by either active immunization with myelin-derived proteins or peptides in adjuvant or by passive transfer of activated myelin-specific CD4+ T lymphocytes. Mouse models are most frequently used because of the inbred genotype of laboratory mice, their rapid breeding capacity, the ease of genetic manipulation, and availability of transgenic and knockout mice to facilitate mechanistic studies. Although not all therapeutic strategies for MS have been developed in EAE, all of the current US Food and Drug Administration (FDA)-approved immunomodulatory drugs are effective to some degree in treating EAE, a strong indicator that EAE is an extremely useful model to study potential treatments for MS. Several therapies, such as glatiramer acetate (GA: Copaxone), and natalizumab (Tysabri), were tested first in the mouse model of EAE and then went on to clinical trials. Here we discuss the usefulness of the EAE model in understanding basic disease pathophysiology and developing treatments for MS as well as the potential drawbacks of this model. PMID:24507518

  6. An update on pathophysiological mechanisms related to idiopathic oro-facial pain conditions with implications for management.

    Science.gov (United States)

    Forssell, H; Jääskeläinen, S; List, T; Svensson, P; Baad-Hansen, L

    2015-04-01

    Chronic oro-facial pain conditions such as persistent idiopathic facial pain (PIFP), atypical odontalgia (AO) and burning mouth syndrome (BMS), usually grouped together under the concept of idiopathic oro-facial pain, remain a diagnostic and therapeutic challenge. Lack of understanding of the underlying pathophysiological mechanisms of these pain conditions is one of the important reasons behind the problems in diagnostic and management. During the last two decades, neurophysiological, psychophysical, brain imaging and neuropathological methods have been systematically applied to study the trigeminal system in idiopathic oro-facial pain. The findings in these studies have provided evidence for neuropathic involvement in the pathophysiology of PIFP, AO and BMS. The present qualitative review is a joint effort of a group of oro-facial pain specialists and researchers to appraise the literature on idiopathic oro-facial pain with special focus on the currently available studies on their pathophysiological mechanisms. The implications of the findings of these studies for the clinical diagnosis and treatment of idiopathic oro-facial pain conditions are discussed. © 2014 John Wiley & Sons Ltd.

  7. A better understanding of urogenital tuberculosis pathophysiology based on radiological findings

    International Nuclear Information System (INIS)

    Figueiredo, Andre A.; Lucon, Antonio M.; Arvellos, Andre N.; Ramos, Claudio O.P.; Toledo, Antonio C.T.; Falci, Renato; Gomes, Cristiano M.; Recaverren, Fernando E.Q.; Netto, Jose Murillo B.; Srougi, Miguel

    2010-01-01

    Purpose: To assess the radiological findings of urogenital tuberculosis (UGT) in patients at different disease stages, for a better understanding of its pathophysiology. Patients and methods: We retrospectively reviewed the radiological exams of 20 men (median age 41 years; range: 28-65) with urogenital tuberculosis diagnosis. The patients were classified in the following groups: (1) bilateral renal tuberculosis with predominantly parenchymatous involvement; (2) unilateral renal tuberculosis; (3) unilateral renal tuberculosis with bladder tuberculosis and (4) bilateral renal tuberculosis with bladder tuberculosis. Results: One AIDS patient had multiple bilateral renal tuberculosis abscesses (group 1). Six patients had unilateral renal tuberculosis with hydronephrosis due to stenosis and thickening of the collecting system, without involvement of the bladder or contralateral kidney (group 2). Six patients had bladder tuberculosis with diffuse thickening of the bladder wall, with one very low or no function kidney while the other kidney was normal (group 3). Seven patients had bladder tuberculosis associated to a very low or no function kidney with the other kidney with high-grade vesicoureteral reflux-associated ureterohydronephrosis (group 4). In two patients, sequential exams showed evolution of tuberculosis from a unilateral renal and ureteral lesion to contracted bladder and dilatation of the contralateral kidney secondary to high-grade reflux. Conclusions: UGT may have variable radiological presentations. However, in two of our cases we have seen that tuberculosis involvement of the urinary tract may be sequential. Further evidences are necessary to confirm this hypothesis.

  8. Understanding the mechanisms of lung mechanical stress

    Directory of Open Access Journals (Sweden)

    C.S.N.B. Garcia

    2006-06-01

    Full Text Available Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area or strain (any forced change in length in relation to the initial length and shear stress (the stress component parallel to a given surface. The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

  9. The contribution of inspiratory muscles function to exercise limitation in heart failure: pathophysiological mechanisms

    OpenAIRE

    Ribeiro,Jorge P.; Chiappa,Gaspar R.; Callegaro,Carine C.

    2012-01-01

    BACKGROUND: Heart failure induces histological, metabolic and functional adaptations in the inspiratory muscles. This inspiratory muscle weakness, which occurs in 30% to 50% of the heart failure patients, is associated with reduction in the functional capacity, reduction in the quality of life and with a poor prognosis in these individuals. OBJECTIVES: The objective of this review was to discuss the pathophysiological mechanisms that may explain the role of the inspiratory muscles in the exer...

  10. The Pathophysiology of Insomnia

    Science.gov (United States)

    Levenson, Jessica C.; Kay, Daniel B.

    2015-01-01

    Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented. PMID:25846534

  11. Understanding the Pathophysiology of Spinocerebellar Ataxias through genetics, neurophysiology, structural and functional neuroimaging

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Pal

    2015-12-01

    largely absent with additional activity in contralateral cortices and in thalami in patients with SCA1; increased thalamic function could be one of the causes for disinhibition of the motor cortex contributing to uncoordinated movements.Studies on larger cohort of each subtype of SCAs to validate the above findings, follow-up studies to determine the rate and nature of progression of neurodegeneration and evaluation of pre-symptomatic genetically confirmed SCAs will help understand the pathophysiology of the SCAs.

  12. Management of Psychosis in Parkinson’s Disease: Emphasizing Clinical Subtypes and Pathophysiological Mechanisms of the Condition

    Directory of Open Access Journals (Sweden)

    Raquel N. Taddei

    2017-01-01

    Full Text Available Investigation into neuropsychiatric symptoms in Parkinson’s disease (PD is sparse and current drug development is mainly focused on the motor aspect of PD. The tight association of psychosis with an impaired quality of life in PD, together with an important underreporting of this comorbid condition, contributes to its actual insufficient assessment and management. Furthermore, the withdrawal from access to readily available treatment interventions is unacceptable and has an impact on PD prognosis. Despite its impact, to date no standardized guidelines to the adequate management of PD psychosis are available and they are therefore highly needed. Readily available knowledge on distinct clinical features as well as early biomarkers of psychosis in PD justifies the potential for its timely diagnosis and for early intervention strategies. Also, its specific characterisation opens up the possibility of further understanding the underlying pathophysiological mechanisms giving rise to more targeted therapeutic developments in the nearer future. A literature review on the most recent knowledge with special focus on specific clinical subtypes and pathophysiological mechanisms will not only contribute to an up to date practical approach of this condition for the health care providers, but furthermore open up new ideas for research in the near future.

  13. Understanding Bohmian mechanics: A dialogue

    OpenAIRE

    Tumulka, Roderich

    2004-01-01

    This paper is an introduction to the ideas of Bohmian mechanics, an interpretation of quantum mechanics in which the observer plays no fundamental role. Bohmian mechanics describes, instead of probabilities of measurement results, objective microscopic events. In recent years, Bohmian mechanics has attracted increasing attention by researchers. The form of a dialogue allows me to address questions about the Bohmian view that often arise.

  14. Current Understanding of the Pathophysiology of Myocardial Fibrosis and Its Quantitative Assessment in Heart Failure

    Directory of Open Access Journals (Sweden)

    Tong Liu

    2017-04-01

    Full Text Available Myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. Myocardial fibrosis results from increased myofibroblast activity and excessive extracellular matrix deposition. Various cells and molecules are involved in this process, providing targets for potential drug therapies. Currently, the main detection methods of myocardial fibrosis rely on serum markers, cardiac magnetic resonance imaging, and endomyocardial biopsy. This review summarizes our current knowledge regarding the pathophysiology, quantitative assessment, and novel therapeutic strategies of myocardial fibrosis.

  15. Splanchnic vein thrombosis in myeloproliferative neoplasms: pathophysiology and molecular mechanisms of disease

    Science.gov (United States)

    How, Joan; Zhou, Amy; Oh, Stephen T.

    2016-01-01

    Myeloproliferative neoplasms (MPNs) are the most common underlying prothrombotic disorder found in patients with splanchnic vein thrombosis (SVT). Clinical risk factors for MPN-associated SVTs include younger age, female sex, concomitant hypercoagulable disorders, and the JAK2 V617F mutation. These risk factors are distinct from those associated with arterial or deep venous thrombosis (DVT) in MPN patients, suggesting disparate disease mechanisms. The pathophysiology of SVT is thought to derive from local interactions between activated blood cells and the unique splanchnic endothelial environment. Other mutations commonly found in MPNs, including CALR and MPL, are rare in MPN-associated SVT. The purpose of this article is to review the clinical and molecular risk factors for MPN-associated SVT, with particular focus on the possible mechanisms of SVT formation in MPN patients. PMID:28246554

  16. A translational neuroscience approach to understanding the development of social anxiety disorder and its pathophysiology.

    Science.gov (United States)

    Fox, Andrew S; Kalin, Ned H

    2014-11-01

    This review brings together recent research from molecular, neural circuit, animal model, and human studies to help understand the neurodevelopmental mechanisms underlying social anxiety disorder. Social anxiety disorder is common and debilitating, and it often leads to further psychopathology. Numerous studies have demonstrated that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk of developing social anxiety disorder. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including the central nucleus of the amygdala, the anterior hippocampus, and the orbitofrontal cortex. Studies in nonhuman primates have demonstrated that alterations in this circuit are trait-like in that they are stable over time and across contexts. Notably, the components of this circuit are differentially influenced by heritable and environmental factors, and specific lesion studies have demonstrated a causal role for multiple components of the circuit. Molecular studies in rodents and primates point to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology.

  17. Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

    Directory of Open Access Journals (Sweden)

    Abu Shmais Ghada A

    2012-02-01

    Full Text Available Abstract Background There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism. Methods The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA, glutamate:glutamine (Glu:Gln ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA were determined in plasma samples from both groups. Results We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio. Conclusion A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.

  18. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

    Science.gov (United States)

    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Complicated Pericarditis: Understanding Risk Factors and Pathophysiology to Inform Imaging and Treatment.

    Science.gov (United States)

    Cremer, Paul C; Kumar, Arnav; Kontzias, Apostolos; Tan, Carmela D; Rodriguez, E Rene; Imazio, Massimo; Klein, Allan L

    2016-11-29

    Most patients with acute pericarditis have a benign course and a good prognosis. However, a minority of patients develop complicated pericarditis, and the care of these patients is the focus of this review. Specifically, we address risk factors, multimodality imaging, pathophysiology, and novel treatments. The authors conclude that: 1) early high-dose corticosteroids, a lack of colchicine, and an elevated high-sensitivity C-reactive protein are associated with the development of complicated pericarditis; 2) in select cases, cardiovascular magnetic resonance imaging may aid in the assessment of pericardial inflammation and constriction; 3) given phenotypic similarities between recurrent idiopathic pericarditis and periodic fever syndromes, disorders of the inflammasome may contribute to relapsing attacks; and 4) therapies that target the inflammasome may lead to more durable remission and resolution. Finally, regarding future investigations, the authors discuss the potential of cardiovascular magnetic resonance to inform treatment duration and the need to compare steroid-sparing treatments to pericardiectomy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. The controversial relationship between exercise and atrial fibrillation: clinical studies and pathophysiological mechanisms.

    Science.gov (United States)

    D'Ascenzi, Flavio; Cameli, Matteo; Ciccone, Marco M; Maiello, Maria; Modesti, Pietro A; Mondillo, Sergio; Muiesan, Maria L; Scicchitano, Pietro; Novo, Salvatore; Palmiero, Pasquale; Saba, Pier S; Pedrinelli, Roberto

    2015-12-01

    Atrial fibrillation is the most common clinically significant arrhythmia observed both in the general population and in competitive athletes. The most important risk factors are all preventable by regular physical activity. However, although the benefits of moderate physical activity in controlling cardiovascular risk factors and decreasing the risk of atrial fibrillation have been extensively proved, concerns have arisen about the potential negative effects of vigorous exercise, particularly in endurance athletes. Furthermore, in a subset of patients with atrial fibrillation younger than 60 years, routine evaluation does not reveal any cardiovascular disease or any other known causal factor. This condition is called 'lone atrial fibrillation', and the potential mechanisms underlying this condition are speculative and remain to be clarified. Atrial ectopy, increased vagal tone, changes in electrolytes, left atrial dilatation, and fibrosis have been proposed among others as potential mechanisms. However, no convincing data still exist. Particularly, the increase in left atrial size represents in athletes a physiological adaptation to exercise conditioning and the presence of biatrial fibrosis has not been demonstrated in humans. Thus, contrary to patients with cardiovascular disorders, the atrial substrate seems to play a secondary role in healthy athletes. This review article analyzes the controversial relationship between atrial fibrillation and physical activity, with a particular attention on the pathophysiological mechanisms that could be responsible for atrial fibrillation in the athletic population.

  1. Understanding Mechanical Design with Respect to Manufacturability

    Science.gov (United States)

    Mondell, Skyler

    2010-01-01

    At the NASA Prototype Development Laboratory in Kennedy Space Center, Fl, several projects concerning different areas of mechanical design were undertaken in order to better understand the relationship between mechanical design and manufacturabiIity. The assigned projects pertained specifically to the NASA Space Shuttle, Constellation, and Expendable Launch Vehicle programs. During the work term, mechanical design practices relating to manufacturing processes were learned and utilized in order to obtain an understanding of mechanical design with respect to manufacturability.

  2. The Interface of Mechanics and Nociception in Joint Pathophysiology: Insights From the Facet and Temporomandibular Joints

    Science.gov (United States)

    Sperry, Megan M.; Ita, Meagan E.; Kartha, Sonia; Zhang, Sijia; Yu, Ya-Hsin; Winkelstein, Beth

    2017-01-01

    Chronic joint pain is a widespread problem that frequently occurs with aging and trauma. Pain occurs most often in synovial joints, the body's load bearing joints. The mechanical and molecular mechanisms contributing to synovial joint pain are reviewed using two examples, the cervical spinal facet joints and the temporomandibular joint (TMJ). Although much work has focused on the macroscale mechanics of joints in health and disease, the combined influence of tissue mechanics, molecular processes, and nociception in joint pain has only recently become a focus. Trauma and repeated loading can induce structural and biochemical changes in joints, altering their microenvironment and modifying the biomechanics of their constitutive tissues, which themselves are innervated. Peripheral pain sensors can become activated in response to changes in the joint microenvironment and relay pain signals to the spinal cord and brain where pain is processed and perceived. In some cases, pain circuitry is permanently changed, which may be a potential mechanism for sustained joint pain. However, it is most likely that alterations in both the joint microenvironment and the central nervous system (CNS) contribute to chronic pain. As such, the challenge of treating joint pain and degeneration is temporally and spatially complicated. This review summarizes anatomy, physiology, and pathophysiology of these joints and the sensory pain relays. Pain pathways are postulated to be sensitized by many factors, including degeneration and biochemical priming, with effects on thresholds for mechanical injury and/or dysfunction. Initiators of joint pain are discussed in the context of clinical challenges including the diagnosis and treatment of pain. PMID:28056123

  3. Understanding Mechanisms of Radiological Contamination

    Energy Technology Data Exchange (ETDEWEB)

    Rick Demmer; John Drake; Ryan James, PhD

    2014-03-01

    Over the last 50 years, the study of radiological contamination and decontamination has expanded significantly. This paper addresses the mechanisms of radiological contamination that have been reported and then discusses which methods have recently been used during performance testing of several different decontamination technologies. About twenty years ago the Idaho Nuclear Technology Engineering Center (INTEC) at the INL began a search for decontamination processes which could minimize secondary waste. In order to test the effectiveness of these decontamination technologies, a new simulated contamination, termed SIMCON, was developed. SIMCON was designed to replicate the types of contamination found on stainless steel, spent fuel processing equipment. Ten years later, the INL began research into methods for simulating urban contamination resulting from a radiological dispersal device (RDD). This work was sponsored by the Defense Advanced Research Projects Agency (DARPA) and included the initial development an aqueous application of contaminant to substrate. Since 2007, research sponsored by the US Environmental Protection Agency (EPA) has advanced that effort and led to the development of a contamination method that simulates particulate fallout from an Improvised Nuclear Device (IND). The IND method diverges from previous efforts to create tenacious contamination by simulating a reproducible “loose” contamination. Examining these different types of contamination (and subsequent decontamination processes), which have included several different radionuclides and substrates, sheds light on contamination processes that occur throughout the nuclear industry and in the urban environment.

  4. Study protocol subacromial impingement syndrome: the identification of pathophysiologic mechanisms (SISTIM

    Directory of Open Access Journals (Sweden)

    de Witte Pieter

    2011-12-01

    muscle activation controlled acromiohumeral translation assessments; Clinical phenotyping (Constant Score, DASH, WORC, and SF-36 scores. Discussion By relating anatomic properties, kinematics and muscle dynamics to subacromial volume, we expect to identify one or more predominant pathophysiological mechanisms in every SIS patient. These differences in underlying mechanisms are a reflection of the variations in symptoms, clinical scores and outcomes reported in literature. More insight in these mechanisms is necessary in order to optimize future diagnostic and treatment strategies for patients with SIS symptoms. Trial registration Dutch Trial Registry (Nederlands Trial Register NTR2283.

  5. Venous System in Acute Brain Injury: Mechanisms of Pathophysiological Change and Function

    Science.gov (United States)

    Xu, Liang; Matei, Nathanael; Tang, Jiping; Feng, Hua; Zhang, JohnH

    2015-01-01

    Cerebral vascular injury is a major component of acute brain injury. Currently, neuroprotective strategies primarily focus on the recanalization of cerebral arteries and capillaries, and the protection of insulted neurons. Hitherto, the role of vein drainage in the pathophysiology of acute brain injury has been overlooked, due to an under appreciation of the magnitude of the impact of veins in circulation. In this review, we summarize the changes in the vein morphology and functions that are known, or likely to occur related to acute brain injury, and aim to advance the therapeutic management of acute brain injury by shifting the focus from reperfusion to another term: recirculation. Recent progress in the neurobiological understanding of the vascular neural network has demonstrated that cerebral venous systems are able to respond to acute brain injury by regulating the blood flow disharmony following brain edema, blood brain barrier disruption, ischemia, and hemorrhage. With the evidence presented in this review, future clinical management of acutely brain injured patients will expand to include the recirculation concept, establishing a harmony between arterial and venous systems, in addition to the established recanalization and reperfusion strategies. PMID:25783658

  6. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options.

    Science.gov (United States)

    Tanbo, Tom; Fedorcsak, Peter

    2017-06-01

    Endometriosis is a common condition in women of reproductive age. In addition to pain, endometriosis may also reduce fertility. The causes of infertility in women with endometriosis may range from anatomical distortions due to adhesions and fibrosis to endocrine abnormalities and immunological disturbances. In some cases, the various pathophysiological disturbances seem to interact through mechanisms so far not fully understood. Whether surgery should be offered as a treatment option in endometriosis-associated infertility has become controversial, partly due to its modest or undocumented effect. Medical or hormonal treatment alone has little or no effect and should only be used in conjunction with assisted reproductive technology (ART). Of the various methods of ART, intrauterine insemination, due to its simplicity, can be recommended in women with minimal or mild peritoneal endometriosis, even though insemination may yield a lower success rate than in women without endometriosis. In vitro fertilization (IVF) is an effective treatment option in less-advanced disease stages, and the success rates are similar to the results in other causes of infertility. However, women with more advanced stages of endometriosis have lower success rates with IVF. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  7. Understanding the Pathophysiology of Portosystemic Shunt by Simulation Using an Electric Circuit.

    Science.gov (United States)

    Kim, Moonhwan; Lee, Keon-Young

    2016-01-01

    Portosystemic shunt (PSS) without a definable cause is a rare condition, and most of the studies on this topic are small series or based on case reports. Moreover, no firm agreement has been reached on the definition and classification of various forms of PSS, which makes it difficult to compare and analyze the management. The blood flow can be seen very similar to an electric current, governed by Ohm's law. The simulation of PSS using an electric circuit, combined with the interpretation of reported management results, can provide intuitive insights into the underlying mechanism of PSS development. In this article, we have built a model of PSS using electric circuit symbols and explained clinical manifestations as well as the possible mechanisms underlying a PSS formation.

  8. Contribution of TMS and rTMS in the understanding of the pathophysiology and in the treatment of dystonia.

    Directory of Open Access Journals (Sweden)

    Pierre Lozeron

    2016-11-01

    valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

  9. Understanding biochar mechanisms for practical implementation

    Energy Technology Data Exchange (ETDEWEB)

    Glaser, Bruno [Halle-Wittenberg Univ. (Germany). Inst. fuer Agrar- und Ernaehrungeswissenschaften Bodenbiogeochemie; Kammann, Claudia [Arbeitskreis zur Nutzung von Sekundaerrohstoffen und fuer Klimaschutz (ANS) e.V., Braunschweig (Germany). Fachausschuss Biokohle; Hochschule Geisenheim Univ. (Germany). Klimafolgenforschung-Klimawandel in Spezialkulturen; Loewen, Achim (ed.) [Arbeitskreis zur Nutzung von Sekundaerrohstoffen und fuer Klimaschutz (ANS) e.V., Braunschweig (Germany); HAWK Hochschule fuer Angewandte Wissenschaft und Kunst Hildesheim, Holzminden, Goettingen (Germany). Fachgebiet Nachhaltige Energie- und Umwelttechnik NEUtec

    2015-07-01

    The conference on ''understanding biochar mechanisms for practical implementation'' 2015 at the Geisenheim University aims at understanding biochar mechanism, that are crucial for beneficial and safety biochar technology implementation. Further issues are ecotoxicology, biochar in agriculture, horticulture, and animal husbandry. Practical issues concern analysis and characterization of technological processes, sustainable uses and certification, regulation and marketing aspects. The Conference is structured in 10 sessions.

  10. High fructose diet-induced metabolic syndrome: Pathophysiological mechanism and treatment by traditional Chinese medicine.

    Science.gov (United States)

    Pan, Ying; Kong, Ling-Dong

    2018-02-19

    Fructose is a natural monosaccharide broadly used in modern society. Over the past few decades, epidemiological studies have demonstrated that high fructose intake is an etiological factor of metabolic syndrome (MetS). This review highlights research advances on fructose-induced MetS, especially the underlying pathophysiological mechanism as well as pharmacotherapy by traditional Chinese medicine (TCM), using the PubMed, Web of science, China National Knowledge Infrastructure, China Science and Technology Journal and Wanfang Data. This review focuses on de novo lipogenesis (DNL) and uric acid (UA) production, two unique features of fructolysis different from glucose glycolysis. High level of DNL and UA production can result in insulin resistance, the key pathological event in developing MetS, mostly through oxidative stress and inflammation. Some other pathologies like the disturbance in brain and gut microbiota in the development of fructose-induced MetS in the past years, are also discussed. In management of MetS, TCM is an excellent representative in alternative and complementary medicine with a complete theory system and substantial herbal remedies. TCMs against MetS or MetS components, including Chinese patent medicines, TCM compound formulas, single TCM herbs and active compounds of TCM herbs, are reviewed on their effects and molecular mechanisms. TCMs with hypouricemic activity, which specially target fructose-induced MetS, are highlighted. And new technologies and strategies (such as high-throughput assay and systems biology) in this field are further discussed. In summary, fructose-induced MetS is a multifactorial disorder with the underlying complex mechanisms. Current clinical and pre-clinical evidence supports the potential of TCMs in management of MetS. Additionally, TCMs may show some advantages against complex MetS as their holistic feature through multiple target actions. However, further work is needed to confirm the effectivity and safety of TCMs

  11. Association of Ozone Exposure With Cardiorespiratory Pathophysiologic Mechanisms in Healthy Adults.

    Science.gov (United States)

    Day, Drew B; Xiang, Jianbang; Mo, Jinhan; Li, Feng; Chung, Mingkei; Gong, Jicheng; Weschler, Charles J; Ohman-Strickland, Pamela A; Sundell, Jan; Weng, Wenguo; Zhang, Yinping; Zhang, Junfeng Jim

    2017-09-01

    Exposure to ozone has been associated with cardiovascular mortality, but the underlying biological mechanisms are not yet understood. To examine the association between ozone exposure and cardiopulmonary pathophysiologic mechanisms. A longitudinal study involving 89 healthy adult participants living on a work campus in Changsha City, China, was conducted from December 1, 2014, to January 31, 2015. This unique quasiexperimental setting allowed for better characterization of air pollutant exposure effects because the participants spent most of their time in controlled indoor environments. Concentrations of indoor and outdoor ozone, along with the copollutants particulate matter, nitrogen dioxide, and sulfur dioxide, were monitored throughout the study period and then combined with time-activity information and filtration conditions of each residence and office to estimate 24-hour and 2-week combined indoor and outdoor mean exposure concentrations. Associations between each exposure measure and outcome measure were analyzed using single-pollutant and 2-pollutant linear mixed models controlling for ambient temperature, secondhand smoke exposure, and personal-level time-varying covariates. Biomarkers indicative of inflammation and oxidative stress, arterial stiffness, blood pressure, thrombotic factors, and spirometry were measured at 4 sessions. Of the 89 participants, 25 (28%) were women and the mean (SD) age was 31.5 (7.6) years. The 24-hour ozone exposure concentrations ranged from 1.4 to 19.4 parts per billion (ppb), corresponding to outdoor concentrations ranging from 4.3 to 47.9 ppb. Within this range, in models controlling for a second copollutant and other potential confounders, a 10-ppb increase in 24-hour ozone was associated with mean increases of 36.3% (95% CI, 29.9%-43.0%) in the level of platelet activation marker soluble P-selectin, 2.8% (95% CI, 0.6%-5.1%) in diastolic blood pressure, 18.1% (95% CI, 4.5%-33.5%) in pulmonary inflammation markers

  12. MECHANISMS IN ENDOCRINOLOGY: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review.

    Science.gov (United States)

    Levelt, Eylem; Gulsin, Gaurav; Neubauer, Stefan; McCann, Gerry P

    2018-04-01

    Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies. © 2018 The authors.

  13. Understanding Neurological Disease Mechanisms in the Era of Epigenetics

    Science.gov (United States)

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

    The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

  14. Improving students' understanding of quantum mechanics

    Science.gov (United States)

    Singh, Chandralekha

    2011-03-01

    Learning quantum mechanics is especially challenging, in part due to the abstract nature of the subject. We have been conducting investigations of the difficulties that students have in learning quantum mechanics. To help improve student understanding of quantum concepts, we are developing quantum interactive learning tutorials (QuILTs) as well as tools for peer-instruction. The goal of QuILTs and peer-instruction tools is to actively engage students in the learning process and to help them build links between the formalism and the conceptual aspects of quantum physics without compromising the technical content. They focus on helping students integrate qualitative and quantitative understanding, confront and resolve their misconceptions and difficulties, and discriminate between concepts that are often confused. In this talk, I will give examples from my research in physics education of how students' prior knowledge relevant for quantum mechanics can be assessed, and how learning tools can be designed to help students develop a robust knowledge structure and critical thinking skills. Supported by the National Science Foundation.

  15. [General concept and pathophysiological mechanisms of progression of macrovascular complications in diabetes].

    Science.gov (United States)

    Kashiwagi, Atsunori

    2010-05-01

    Macrovascular complications in diabetes consist of 2 basic pathophysiological characteristics such as obstructive atherosclerotic lesions and non-obstructive sclerotic arterial lesions. The patients with former lesions are frequently complicated with postprandial hyperglycemia, insulin resistance, hyperinsulinemia, metabolic syndrome, smoking or high LDL-C concentrations. The latter lesions are usually characterized by diffuse, multi-vessel diseases and typically found in patients with long duration of diabetes and advanced diabetic retinopathy as well as nephropathy. Cardiovascular events or death in diabetes are as equally high as non-diabetic patients with a previous history of ischemic coronary artery diseases in not only Finish study but also Japanese J-ACCES study. It is now very clear that the progression of macrovascular complications in diabetes can be efficiently prevented by a strict multifactorial control of all coronary risk factors including hyperglycemia.

  16. Does Parkinson's disease and type-2 diabetes mellitus present common pathophysiological mechanisms and treatments?

    Science.gov (United States)

    Lima, Marcelo M S; Targa, Adriano D S; Noseda, Ana C D; Rodrigues, Lais S; Delattre, Ana Marcia; dos Santos, Fabiola V; Fortes, Mariana H; Maturana, Maira J; Ferraz, Anete C

    2014-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease afflicting about 1% of people over 65 years old and 4-5% of people over 85 years. It is proposed that a cascade of deleterious factors is set in motion within that neuron made not of one, but rather of multiple factors such as free radicals, excitotoxicity, neuroinflammation, and apoptosis to cite only some of the most salient. In this scenario, chronic systemic inflammation, as well as impaired mitochondrial metabolism, have also been suspected of playing a role in the development of type-2 diabetes, and the possibility of a shared pathophysiology of PD and type-2 diabetes has been proposed. The discussion about the interactions between PD and type-2 diabetes mellitus began in the 1960's and there is still controversy. Insulin and dopamine may exert reciprocal regulation hence; hypoinsulinemia induced by streptozotocin decreased the amounts of dopamine transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta. Accordingly, dopamine depletion in the striatum is able to decreases insulin signaling in basal ganglia, indicating that, perhaps, PD may be considered as a risk factor for the development of type-2 diabetes mellitus. In this sense, it is described that peroxisome proliferator-activated receptor-γ, ATP-sensitive K(+) channels, AMP-activated protein kinase, glucagon-like peptide-1 and dipeptidyl peptidase-4 are important therapeutic targets for PD and reinforces the association with diabetes. Therefore, the objective of the present review is to contextualize the mutual pathophysiological interactions between PD and type-2 diabetes mellitus, as well as the potential common treatments.

  17. Systemic cobalt toxicity from total hip arthroplasties: review of a rare condition Part 1 - history, mechanism, measurements, and pathophysiology.

    Science.gov (United States)

    Cheung, A C; Banerjee, S; Cherian, J J; Wong, F; Butany, J; Gilbert, C; Overgaard, C; Syed, K; Zywiel, M G; Jacobs, J J; Mont, M A

    2016-01-01

    Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties. Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications. ©2016 The British Editorial Society of Bone & Joint Surgery.

  18. Hypothermia – mechanism of action and pathophysiological changes in the human body

    Directory of Open Access Journals (Sweden)

    Przemysław Sosnowski

    2015-01-01

    Full Text Available This review focuses on the physiological responses and pathophysiological changes induced by hypothermia. Normal body function depends on its ability to maintain thermal homeostasis. The human body can be divided arbitrarily into two thermal compartments: a core compartment (trunk and head, with precisely regulated temperature around 37°C, and a peripheral compartment (skin and extremities with less strictly controlled temperature, and lower than the core temperature. Thermoregulatory processes occur in three phases: afferent thermal sensing, central regulation, mainly by the preoptic area of the anterior hypothalamus, and efferent response. Exposure to cold induces thermoregulatory responses including cutaneous vasoconstriction, shivering and non-shivering thermogenesis, and behavioral changes. Alterations of body temperature associated with impaired thermoregulation, decreased heat production or increased heat loss can lead to hypothermia. Hypothermia is defined as a core body temperature below 35ºC, and may be classified according to the origin as accidental (e.g. caused by exposure to a cold environment, drugs, or illness or intentional (i.e. therapeutic, or by the degree of hypothermia as mild, moderate or severe. Classification by temperature is not universal. Lowering of body temperature disrupts the physiological processes at the molecular, cellular and system level, but hypothermia induced prior to cardiosurgical or neurosurgical procedures, by the decrease in tissue oxygen demand, can reduce the risk of cerebral or cardiac ischemic damage. Therapeutic hypothermia has been recommended as a clinical procedure in situations characterized by ischemia, such as cardiac arrest, stroke and brain injuries.

  19. Understanding the molecular mechanisms of reprogramming

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Marie N. [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); University Hospital of Würzburg, Department of Pediatrics, 2 Josef-Schneiderstrasse, 97080 Würzburg (Germany); Sancho-Martinez, Ignacio [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States); Centre for Stem Cells and Regenerative Medicine, King' s College London, 28th Floor, Tower Wing, Guy' s Hospital, Great Maze Pond, London (United Kingdom); Izpisua Belmonte, Juan Carlos, E-mail: belmonte@salk.edu [Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla 92037, CA (United States)

    2016-05-06

    Despite the profound and rapid advancements in reprogramming technologies since the generation of the first induced pluripotent stem cells (iPSCs) in 2006[1], the molecular basics of the process and its implications are still not fully understood. Recent work has suggested that a subset of TFs, so called “Pioneer TFs”, play an important role during the stochastic phase of iPSC reprogramming [2–6]. Pioneer TFs activities differ from conventional transcription factors in their mechanism of action. They bind directly to condensed chromatin and elicit a series of chromatin remodeling events that lead to opening of the chromatin. Chromatin decondensation by pioneer factors progressively occurs during cell division and in turn exposes specific gene promoters in the DNA to which TFs can now directly bind to promoters that are readily accessible[2, 6]. Here, we will summarize recent advancements on our understanding of the molecular mechanisms underlying reprogramming to iPSC as well as the implications that pioneer Transcription Factor activities might play during different lineage conversion processes. - Highlights: • Pioneer transcription factor activity underlies the initial steps of iPSC generation. • Reprogramming can occur by cis- and/or trans- reprogramming events. • Cis-reprogramming implies remodeling of the chromatin for enabling TF accessibility. • Trans-reprogramming encompasses direct binding of Tfs to their target gene promoters.

  20. Pathophysiological mechanisms of Staphylococcus non-aureus bone and joint infection: interspecies homogeneity and specific behaviour of S. pseudintermedius

    Directory of Open Access Journals (Sweden)

    Yousef Maali

    2016-07-01

    Full Text Available Implicated in more than 60% of bone and joint infections (BJIs, Staphylococci have a particular tropism for osteoarticular tissue and lead to difficult-to-treat clinical infections. To date, Staphylococcus aureus internalization in non-professional phagocytic cells (NPPCs is a well-explored virulence mechanism involved in BJI chronicity. Conversely, the pathophysiological pathways associated with Staphylococcus non-aureus (SNA BJIs have scarcely been studied despite their high prevalence. In this study, fifteen reference strains from 15 different SNA species were compared in terms of (i adhesion to human fibronectin based on adhesion microplate assays and (ii internalization ability, intracellular persistence and cytotoxicity based on an in vitro infection model using human osteoblasts. Compared to S. aureus, Staphylococcus pseudintermedius was the only species that significantly adhered to human fibronectin. This species was also associated with high (even superior to S. aureus internalization ability, intracellular persistence and cytotoxicity. These findings were confirmed using a panel of 17 different S. pseudintermedius isolates. Additionally, S. pseudintermedius internalization by osteoblasts was completely abolished in β1 integrin-deficient murine osteoblasts. These results suggest the involvement of β1 integrin in the invasion process, although this mechanism was previously restricted to S. aureus. In summary, our results suggest that internalization into NPPCs is not a classical pathophysiologic mechanism of SNA BJIs. S. pseudintermedius appears to be an exception, and its ability to invade and subsequently induce cytotoxicity in NPPCs could explain its severe and necrotic forms of infection, notably in dogs, which exhibit a high prevalence of S. pseudintermedius infection.

  1. [Pathophysiology of neuropathic pain: molecular mechanisms underlying central sensitization in the dorsal horn in neuropathic pain].

    Science.gov (United States)

    Yamanaka, Hiroki; Noguchi, Koichi

    2012-11-01

    Neuropathic pain syndromes are clinically characterized by spontaneous pain and evoked pain (hyperalgesia and allodynia). The optimal treatment approach for neuropathic pain is still under development because of the complex pathological mechanisms underlying this type of pain. The spinal cord is an important gateway thorough which peripheral pain signals are transmitted to the brain, and sensitization of the spinal neurons is one of the important mechanisms underlying neuropathic pain. Central sensitization represents enhancement of the function of neuronal circuits in nociceptive pathways and is a manifestation of the remarkable plasticity of the somatosensory nervous system after nerve injury. This review highlights the pathological features of central sensitization, which develops because of (1) injury-induced abnormal inputs from primary afferents, (2) increase in the excitability of dorsal horn neurons, and (3) activated glial cell-derived signals.

  2. Oscillation mechanics of the respiratory system in never-smoking patients with silicosis: pathophysiological study and evaluation of diagnostic accuracy.

    Science.gov (United States)

    Sá, Paula Morisco de; Lopes, Agnaldo José; Jansen, José Manoel; Melo, Pedro Lopes de

    2013-05-01

    Silicosis is a chronic and incurable occupational disease that can progress even after the cessation of exposure. Recent studies suggest that the forced oscillation technique may help to clarify the changes in lung mechanics resulting from silicosis as well as the detection of these changes. We investigated the effects of airway obstruction in silicosis on respiratory impedance and evaluated the diagnostic efficacy of the forced oscillation technique in these patients. Spirometry was used to classify the airway obstruction, which resulted in four subject categories: controls (n=21), patients with a normal exam (n=12), patients with mild obstruction (n=22), and patients with moderate-to-severe obstruction (n=12). Resistive data were interpreted using the zero-intercept resistance (R0), the resistance at 4 Hz (Rrs4), and the mean resistance. We also analyzed the mean reactance (Xm) and the dynamic compliance. The total mechanical load was evaluated using the absolute value of the respiratory impedance (Z4Hz). The diagnostic potential was evaluated by investigating the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01725971. We observed significant (p0.80) and highly accurately in the detection of moderate-to-severe obstruction (area under the curve>0.90). The forced oscillation technique may contribute to the study of the pathophysiology of silicosis and may improve the treatment offered to these patients, thus representing an alternative and/or complementary tool for evaluating respiratory mechanics.

  3. Emerging understanding of the mechanism of action of Bronchial Thermoplasty in asthma.

    Science.gov (United States)

    d'Hooghe, J N S; Ten Hacken, N H T; Weersink, E J M; Sterk, P J; Annema, J T; Bonta, P I

    2018-01-01

    Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate-to-severe asthma patients who are uncontrolled despite optimal medical therapy. Effectiveness of BT has been demonstrated in several randomized clinical trials. However, the asthma phenotype that benefits most of this treatment is unclear, partly because the mechanism of action is incompletely understood. BT was designed to reduce the amount of airway smooth muscle (ASM), but additional direct and indirect effects on airway pathophysiology are expected. This review will provide an overview of the different components of airway pathophysiology including remodeling, with the ASM as the key player. Current concepts in the understanding of BT clinical effectiveness with a focus on its impact on airway remodeling will be reviewed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. StartReact effects support different pathophysiological mechanisms underlying freezing of gait and postural instability in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Jorik Nonnekes

    Full Text Available The pathophysiology underlying postural instability in Parkinson's disease is poorly understood. The frequent co-existence with freezing of gait raises the possibility of shared pathophysiology. There is evidence that dysfunction of brainstem structures contribute to freezing of gait. Here, we evaluated whether dysfunction of these structures contributes to postural instability as well. Brainstem function was assessed by studying the StartReact effect (acceleration of latencies by a startling acoustic stimulus (SAS.We included 25 patients, divided in two different ways: 1 those with postural instability (HY = 3, n = 11 versus those without (HY<3, n = 14; and 2 those with freezing (n = 11 versus those without freezing (n = 14. We also tested 15 matched healthy controls. We tested postural responses by translating a balance platform in the forward direction, resulting in backward balance perturbations. In 25% of trials, the start of the balance perturbation was accompanied by a SAS.The amplitude of automatic postural responses and length of the first balance correcting step were smaller in patients with postural instability compared to patients without postural instability, but did not differ between freezers and non-freezers. In contrast, the StartReact effect was intact in patients with postural instability but was attenuated in freezers.We suggest that the mechanisms underlying freezing of gait and postural instability in Parkinson's disease are at least partly different. Underscaling of automatic postural responses and balance-correcting steps both contribute to postural instability. The attenuated StartReact effect was seen only in freezers and likely reflects inadequate representation of motor programs at upper brainstem level.

  5. First report of the characterization of the pathophysiological mechanisms caused by the freshwater catfish Pimelodus maculatus (order: Siluriformes).

    Science.gov (United States)

    Sarmiento, Beatriz Elena; Rangel, Marisa; Gonçalves, Jacqueline Coimbra; Pereira, Lilibete; Rego, Solange; Campos, Leandro Ambrósio; Haddad, Vidal; Mortari, Márcia Renata; Schwartz, Elisabeth F

    2015-07-01

    Injuries caused by aquatic animals in Brazil in most cases are provoked by marine and freshwater catfish. Pimelodus maculatus is a freshwater catfish very common in Brazilian basins that causes frequent accidents mainly amongst fishermen, and whose venom characteristics and pathological mechanisms of the venom are poorly known. In the present study for the first time, we have characterized the main pathophysiological mechanisms associated with the clinical manifestation (pain, local inflammation and edema) of the envenomations caused by P. maculatus crude venom. It was estimated that the crude venom of one P. maculatus stinger contains approximately 100 μg of protein, likely the quantity involved in the envenomation. P. maculatus crude venom induced marked nociceptive and edematogenic effects and caused vascular permeability alterations at doses from 30 to 100 μg/animal. Additionally, P. maculatus crude venom caused a decrease in the contraction force in in situ frog heart, did not cause hemorrhage or alterations in clotting times (prothrombin time and activated partial thromboplastin time), but induced significant changes in the levels of CK and its isoenzyme CK-MB in mice. In the present work, we present a correlation between the effects obtained experimentally and the main symptoms observed in the human accidents provoked by P. maculatus. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms.

    Science.gov (United States)

    Deiteren, A; de Wit, A; van der Linden, L; De Man, J G; Pelckmans, P A; De Winter, B Y

    2016-03-01

    Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways. © Acta Gastro-Enterologica Belgica.

  7. Botulinum Toxin A and Lower Urinary Tract Dysfunction: Pathophysiology and Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Jia-Fong Jhang

    2016-04-01

    Full Text Available The use of onabotulinumtoxinA (BoNT-A for the treatment of lower urinary tract diseases (LUTD has increased markedly in recent years. The indications for BoNT-A treatment of LUTD now include neurogenic or idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome and voiding dysfunction. The mechanisms of BoNT-A action on LUTDs affect many different aspects. Traditionally, the effects of BoNT-A were believed to be attributable to inhibition of acetylcholine release from the presynaptic efferent nerves at the neuromuscular junctions in the detrusor or urethral sphincter. BoNT-A injection in the bladder also regulated sensory nerve function by blocking neurotransmitter release and reducing receptor expression in the urothelium. In addition, recent studies revealed an anti-inflammatory effect for BoNT-A. Substance P and nerve growth factor in the urine and bladder tissue decreased after BoNT-A injection. Mast cell activation in the bladder also decreased. BoNT-A-induced improvement of urothelium function plays an important mitigating role in bladder dysfunction. Vascular endothelial growth factor expression in urothelium decreased after BoNT-A injection, as did apoptosis. Studies also revealed increased apoptosis in the prostate after BoNT-A injection. Although BoNT-A injection has been widely used to treat different LUTDs refractory to conventional treatment, currently, onabotulinumtoxinA has been proven effective only on urinary incontinence due to IDO and NDO in several large-scale clinical trials. The effects of onabotulinumtoxinA on other LUTDs such as interstitial cystitis, benign prostatic hyperplasia, dysfunctional voiding or detrusor sphincter dyssynergia have not been well demonstrated.

  8. Pathophysiology of acute small bowel disease with CT correlation

    Energy Technology Data Exchange (ETDEWEB)

    Sarwani, N., E-mail: nsarwani@hmc.psu.ed [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States); Tappouni, R.; Tice, J. [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States)

    2011-01-15

    The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

  9. Understanding molecular structure from molecular mechanics.

    Science.gov (United States)

    Allinger, Norman L

    2011-04-01

    Molecular mechanics gives us a well known model of molecular structure. It is less widely recognized that valence bond theory gives us structures which offer a direct interpretation of molecular mechanics formulations and parameters. The electronic effects well-known in physical organic chemistry can be directly interpreted in terms of valence bond structures, and hence quantitatively calculated and understood. The basic theory is outlined in this paper, and examples of the effects, and their interpretation in illustrative examples is presented.

  10. Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications

    Directory of Open Access Journals (Sweden)

    Hyunjoo Park

    2013-03-01

    Full Text Available A cellular-level study of the pathophysiology is crucial for understanding the mechanisms behind human diseases. Recent advances in quantitative phase imaging (QPI techniques show promises for the cellular-level understanding of the pathophysiology of diseases. To provide important insight on how the QPI techniques potentially improve the study of cell pathophysiology, here we present the principles of QPI and highlight some of the recent applications of QPI ranging from cell homeostasis to infectious diseases and cancer.

  11. Understanding Kinetic Energy paradox in Quantum Mechanics

    OpenAIRE

    Kornyushin, Yuri

    2008-01-01

    A concept of Kinetic Energy in Quantum Mechanics is analyzed. Kinetic Energy is not zero in many cases where there are no motion and flux. This paradox can be understood, using expansion of the wave function in Fourier integral, that is on the basis of virtual plane waves.

  12. Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging

    Science.gov (United States)

    Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter

    2017-06-01

    Abdominal aortic aneurysms (AAA) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term AAA rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of AAA development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without AAA, and AAA patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the AAA group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and AAA patients is a promising step towards a new method for in vivo assessment of AAA wall strength or stratification of AAA rupture risk as basis for improved clinical decision making on surgical or endovascular

  13. Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Svenningsen, Katrine; Knudsen, Lina Almind

    2015-01-01

    transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1...... with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies....... pathogen-free Abcb1 KO mice. The Abcb1 KO mice might thus serve as a model in which diet/environmental factors and microbes may be controlled and investigated in relation to intestinal inflammation. Potential molecular mechanisms include defective transport of inflammatory mediators and/or phospholipid...

  14. Current concepts in the pathophysiology of glaucoma

    Directory of Open Access Journals (Sweden)

    Agarwal Renu

    2009-01-01

    Full Text Available Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.

  15. Toward a new understanding of attention-deficit hyperactivity disorder pathophysiology: an important role for prefrontal cortex dysfunction.

    Science.gov (United States)

    Arnsten, Amy F T

    2009-01-01

    Recent advances in neurobiology have aided our understanding of attention-deficit hyperactivity disorder (ADHD). The higher-order association cortices in the temporal and parietal lobes and prefrontal cortex (PFC) interconnect to mediate aspects of attention. The parietal association cortices are important for orienting attentional resources in time/space, while the temporal association cortices analyse visual features critical for identifying objects/places. These posterior cortices are engaged by the salience of a stimulus (its physical characteristics such as movement and colour). Conversely, the PFC is critical for regulating attention based on relevance (i.e. its meaning). The PFC is important for screening distractions, sustaining attention and shifting/dividing attention in a task-appropriate manner. The PFC is critical for regulating behaviour/emotion, especially for inhibiting inappropriate emotions, impulses and habits. The PFC is needed for allocating/planning to achieve goals and organizing behaviour/thought. These regulatory abilities are often referred to as executive functions. In humans, the right hemisphere of the PFC is important for regulating distractions, inappropriate behaviour and emotional responses. Imaging studies of patients with ADHD indicate that these regions are underactive with weakened connections to other parts of the brain. The PFC regulates attention and behaviour through networks of interconnected pyramidal cells. These networks excite each other to store goals/rules to guide actions and are highly dependent on their neurochemical environment, as small changes in the catecholamines noradrenaline (NA) or dopamine (DA) can have marked effects on PFC function. NA and DA are released in the PFC according to our arousal state; too little (during fatigue or boredom) or too much (during stress) impairs PFC function. Optimal amounts are released when we are alert/interested. The beneficial effects of NA occur at postsynaptic alpha(2A

  16. Preeclampsia: from Pathophysiology to Treatment

    Directory of Open Access Journals (Sweden)

    Kaculini Enton

    2016-12-01

    Full Text Available Preeclampsia is a multisystem disorder unique to human pregnancy and is its most common glomerular complication. It occurs in 2% to 8% of pregnancies and is a major contributor to maternal mortality worldwide. Although the pathophysiology of this syndrome is not fully understood, many pathogenetic mechanisms are involved in this disorder. The role of the placenta is crucial in the development of this disorder. Some pathogenetic mechanisms involved in this disease comprise defective deep placentation, autoantibodies to type-1 angiotensin II receptor, endothelial dysfunction, oxidative stress, platelet and thrombin activation, intravascular inflammation, and the imbalance between angiogenic and antiangiogenic factors which is thought to be one of the most crucial mechanisms. Further understanding of the full picture could enhance our current knowledge of the pathogenesis of preeclampsia and improve its treatment. Thus, based on specific biomarkers the diagnosis and subclassification of preeclampsia might be more accurate in identifying patients at risk, monitoring disease progression and providing effective interventions

  17. Obesity: Pathophysiology and Intervention

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2014-11-01

    Full Text Available Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

  18. Understanding Mechanism of Photocatalytic Microbial Decontamination of Environmental Wastewater

    Directory of Open Access Journals (Sweden)

    Chhabilal Regmi

    2018-02-01

    Full Text Available Several photocatalytic nanoparticles are synthesized and studied for potential application for the degradation of organic and biological wastes. Although these materials degrade organic compounds by advance oxidation process, the exact mechanisms of microbial decontamination remains partially known. Understanding the real mechanisms of these materials for microbial cell death and growth inhibition helps to fabricate more efficient semiconductor photocatalyst for large-scale decontamination of environmental wastewater or industries and hospitals/biomedical labs generating highly pathogenic bacteria and toxic molecules containing liquid waste by designing a reactor. Recent studies on microbial decontamination by photocatalytic nanoparticles and their possible mechanisms of action is highlighted with examples in this mini review.

  19. Pathophysiology of osteoporosis: new mechanistic insights.

    Science.gov (United States)

    Armas, Laura A G; Recker, Robert R

    2012-09-01

    Understanding of the pathophysiology of osteoporosis has evolved to include compromised bone strength and skeletal fragility caused by several factors: (1) defects in microarchitecture of trabeculae, (2) defective intrinsic material properties of bone tissue, (3) defective repair of microdamage from normal daily activities, and (4) excessive bone remodeling rates. These factors occur in the context of age-related bone loss. Clinical studies of estrogen deprivation, antiresorptives, mechanical loading, and disuse have helped further knowledge of the factors affecting bone quality and the mechanisms that underlie them. This progress has led to several new drug targets in the treatment of osteoporosis. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. AUTOMOTIVE DIESEL MAINTENANCE 2. UNIT I, UNDERSTANDING MECHANICAL CLUTCHES.

    Science.gov (United States)

    Minnesota State Dept. of Education, St. Paul. Div. of Vocational and Technical Education.

    ONE OF A 25-MODULE COURSE DESIGNED TO UPGRADE THE JOB SKILLS AND TECHNICAL KNOWLEDGE OF DIESEL MAINENANCE MECHANICS THIS MATERIAL WAS DEVELOPED BY INDUSTRIAL TRAINING AND SUBJECT-MATTER SPECIALISTS AND TESTED IN INDUSTRIAL TRAINING SITUATIONS. THE PURPOSE OF THIS FIRST UNIT IS TO DEVELOP AN UNDERSTANDING OF COMPONENTS, OPERATION, AND ADJUSTMENTS…

  1. Student Understanding of Time Dependence in Quantum Mechanics

    Science.gov (United States)

    Emigh, Paul J.; Passante, Gina; Shaffer, Peter S.

    2015-01-01

    The time evolution of quantum states is arguably one of the more difficult ideas in quantum mechanics. In this article, we report on results from an investigation of student understanding of this topic after lecture instruction. We demonstrate specific problems that students have in applying time dependence to quantum systems and in recognizing…

  2. Advanced waterflooding in chalk reservoirs: Understanding of underlying mechanisms

    DEFF Research Database (Denmark)

    Zahid, Adeel; Sandersen, Sara Bülow; Stenby, Erling Halfdan

    2011-01-01

    Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recove...... of a microemulsion phase could be the possible reasons for the observed increase in oil recovery with sulfate ions at high temperature in chalk reservoirs besides the mechanism of the rock wettability alteration, which has been reported in most previous studies.......Over the last decade, a number of studies have shown SO42−, Ca2+ and Mg2+ to be potential determining ions, which may be added to the injected brine for improving oil recovery during waterflooding in chalk reservoirs. However the understanding of the mechanism leading to an increase in oil recovery...

  3. Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked?

    Science.gov (United States)

    Rehman, Kanwal; Akash, Muhammad Sajid Hamid

    2017-11-01

    Oxidative stress has been considered as a major hallmark for the pathogenesis and development of type 2 diabetes mellitus (T2DM), but still it is debatable whether it is a mere aggregation of inflammatory-induced responses or clinical entity that underlies with various pathophysiological factors. In this regard, the latest studies have shown the increasing trends for the involvement of reactive oxygen species (ROS) and oxidative stress in the pathogenesis and development of T2DM. ROS are highly reactive species and almost all cellular components are chemically changed due to the influence of ROS that ultimately results in the production of lipid peroxidation. Lipid peroxidation is a major causative factor for the development of oxidative stress that leads to overt T2DM and its associated micro- and macro-vascular complications. In this article, we have briefly described the role of various causative factors, transcriptional and metabolic pathways which are responsible to increase the production of oxidative stress, a most pivotal factor for the pathogenesis and development of T2DM. Therefore, we conclude that measurement of oxidative stress biomarkers may be one of the optional tool for the diagnosis and prediction of T2DM. Moreover, the key findings described in this article also provides a new conceptual framework for forthcoming investigations on the role of oxidative stress in pathogenesis of T2DM and drug discovery. J. Cell. Biochem. 118: 3577-3585, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Pathophysiological mechanisms of sino-atrial dysfunction and ventricular conduction disease associated with SCN5A deficiency: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Christopher L-H Huang

    2012-07-01

    Full Text Available Genetically modified mice provide a number of models for studying cardiac channelopathies related to cardiac Na+ channel (SCN5A abnormalities. We review key pathophysiological features in these murine models that may underlie clinical features observed in sinus node dysfunction and progressive cardiac conduction disease, thereby providing insights into their pathophysiological mechanisms. We describe loss of Na+ channel function and fibrotic changes associated with both loss and gain-of-function Na+ channel mutations. Recent reports further relate the progressive fibrotic changes to upregulation of TGF-β1 production and the transcription factors, Atf3, a stress-inducible gene, and Egr1, to the presence of heterozygous Scn5a inactivation. Both changes are thus directly implicated in the clinically observed disruptions in sino-atrial node pacemaker function, and sino-atrial and ventricular conduction, and their progression with age. Murine systems with genetic modifications in Scn5a thus prove a useful tool to address questions concerning roles of genetic and environmental modifiers on human SCN5A disease phenotypes.

  5. Advances in the understanding of crystal growth mechanisms

    CERN Document Server

    Nishinaga, T; Harada, J; Sasaki, A; Takei, H

    1997-01-01

    This book contains the results of a research project entitled Crystal Growth Mechanisms on an Atomic Scale, which was carried out for 3 years by some 72 reseachers. Until recently in Japan, only the technological aspects of crystal growth have been emphasized and attention was paid only to its importance in industry. However the scientific aspects also need to be considered so that the technology of crystal growth can be developed even further. This project therefore aimed at understanding crystal growth and the emphasis was on finding growth mechanisms on an atomic scale.

  6. Changes in blood monocyte Toll-like receptor and serum surfactant protein A reveal a pathophysiological mechanism for community-acquired pneumonia in patients with type 2 diabetes.

    Science.gov (United States)

    Que, Y; Shen, X

    2016-02-01

    The lung is one of the target organs of microangiopathy in diabetes mellitus (DM); patients with type 2 diabetes mellitus (T2DM) are vulnerable to pneumonia, and a variety of pathophysiological mechanisms has been described. This study aimed to determine the pathophysiological mechanism of community-acquired pneumonia (CAP) in T2DM patients. A total of 90 individuals was included in this study comprised of three groups (n = 30): healthy control, T2DM and T2DM+ CAP groups. Toll-like receptor (TLR)2 and 4 protein and messenger RNA expression in peripheral blood monocytes(PBMC) was assessed by western blot and reverse transcription-polymerase chain reaction, respectively, and surfactant protein A (SP-A) levels were examined in serum samples by enzyme-linked immunosorbent assay. In T2DM and T2DM+CAP groups, levels of both TLR2/4 protein and mRNA in PBMC were decreased compared with controls (P <0.05), with lower levels observed in the T2DM+CAP group in comparison with T2DM patients (P <0.05). The serum SP-A levels in T2DM+CAP individuals were significantly higher than the values obtained for T2DM patients (P <0.05). It also showed apparent increases when compared with that in controls although no statistical significance was detected. In T2DM patients with pneumonia, TLR2/4 levels in PBMC and serum SP-A were altered, maybe playing an important role in the susceptibility to pneumonia in T2DM patients. © 2016 Royal Australasian College of Physicians.

  7. Understanding and imitating unfamiliar actions: distinct underlying mechanisms.

    Directory of Open Access Journals (Sweden)

    Joana C Carmo

    Full Text Available The human "mirror neuron system" has been proposed to be the neural substrate that underlies understanding and, possibly, imitating actions. However, since the brain activity with mirror properties seems insufficient to provide a good description for imitation of actions outside one's own repertoire, the existence of supplementary processes has been proposed. Moreover, it is unclear whether action observation requires the same neural mechanisms as the explicit access to their meaning. The aim of this study was two-fold as we investigated whether action observation requires different processes depending on 1 whether the ultimate goal is to imitate or understand the presented actions and 2 whether the to-be-imitated actions are familiar or unfamiliar to the subject. Participants were presented with both meaningful familiar actions and meaningless unfamiliar actions that they had to either imitate or discriminate later. Event-related Potentials were used as differences in brain activity could have been masked by the use of other techniques with lower temporal resolution. In the imitation task, a sustained left frontal negativity was more pronounced for meaningless actions than for meaningful ones, starting from an early time-window. Conversely, observing unfamiliar versus familiar actions with the intention of discriminating them led to marked differences over right centro-posterior scalp regions, in both middle and latest time-windows. These findings suggest that action imitation and action understanding may be sustained by dissociable mechanisms: while imitation of unfamiliar actions activates left frontal processes, that are likely to be related to learning mechanisms, action understanding involves dedicated operations which probably require right posterior regions, consistent with their involvement in social interactions.

  8. Pathophysiology of acute heart failure: a world to know.

    Science.gov (United States)

    Sánchez-Marteles, M; Rubio Gracia, J; Giménez López, I

    2016-01-01

    Our understanding of the pathophysiological mechanisms of heart failure (HF) has changed considerably in recent years, progressing from a merely haemodynamic viewpoint to a concept of systemic and multifactorial involvement in which numerous mechanisms interact and concatenate. The effects of these mechanisms go beyond the heart itself, to other organs of vital importance such as the kidneys, liver and lungs. Despite this, the pathophysiology of acute HF still has aspects that elude our deeper understanding. Haemodynamic overload, venous congestion, neurohormonal systems, natriuretic peptides, inflammation, oxidative stress and its repercussion on cardiac and vascular remodelling are currently considered the main players in acute HF. Starting with the concept of acute HF, this review provides updates on the various mechanisms involved in this disease. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  9. Understanding mechanisms of toxicity: Insights from drug discovery research

    International Nuclear Information System (INIS)

    Houck, Keith A.; Kavlock, Robert J.

    2008-01-01

    Toxicology continues to rely heavily on use of animal testing for prediction of potential for toxicity in humans. Where mechanisms of toxicity have been elucidated, for example endocrine disruption by xenoestrogens binding to the estrogen receptor, in vitro assays have been developed as surrogate assays for toxicity prediction. This mechanistic information can be combined with other data such as exposure levels to inform a risk assessment for the chemical. However, there remains a paucity of such mechanistic assays due at least in part to lack of methods to determine specific mechanisms of toxicity for many toxicants. A means to address this deficiency lies in utilization of a vast repertoire of tools developed by the drug discovery industry for interrogating the bioactivity of chemicals. This review describes the application of high-throughput screening assays as experimental tools for profiling chemicals for potential for toxicity and understanding underlying mechanisms. The accessibility of broad panels of assays covering an array of protein families permits evaluation of chemicals for their ability to directly modulate many potential targets of toxicity. In addition, advances in cell-based screening have yielded tools capable of reporting the effects of chemicals on numerous critical cell signaling pathways and cell health parameters. Novel, more complex cellular systems are being used to model mammalian tissues and the consequences of compound treatment. Finally, high-throughput technology is being applied to model organism screens to understand mechanisms of toxicity. However, a number of formidable challenges to these methods remain to be overcome before they are widely applicable. Integration of successful approaches will contribute towards building a systems approach to toxicology that will provide mechanistic understanding of the effects of chemicals on biological systems and aid in rationale risk assessments

  10. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    Science.gov (United States)

    Pingel, Jessica; Suhr, Frank

    2017-08-01

    Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle-related extracellular matrix (ECM), specifically collagens, plays a role in CP-related contractures. Herein, we focus on mechanically sensitive complexes, known as costameres (Cstms), and discuss their potential role in CP-related contractures. We extend our discussion to the ECM due to the limited knowledge of its role in CP-related contractures. The aims of this review are (1) to summarize CP-related contracture mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a focus on Cstms, and (3) to stimulate novel approaches to study CP-related contractures.

  11. Understanding the mechanisms of glutamine action in critically ill patients

    Directory of Open Access Journals (Sweden)

    Gisele P. Oliveira

    2010-06-01

    Full Text Available Glutamine (Gln is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.A glutamina (Gln é uma importante fonte de energia e tem sido usada como substrato energético suplementar. Além disso, a Gln é um componente essencial para numerosas funções metabólicas tais como: homeostase ácido-base, gliconeogênese, transporte de nitrogênio e síntese de proteínas e ácidos nucléicos. Portanto, a glutamina desempenha um papel importante na homeostase celular e no metabolismo dos órgãos. Esse artigo objetiva rever os mecanismos de ação da glutamina na doen

  12. Tako-tsubo cardiomyopathy: how to understand possible pathophysiological mechanism and the role of (123)I-MIBG imaging

    NARCIS (Netherlands)

    Verschure, Derk O.; Somsen, G. Aernout; van Eck-Smit, Berthe L. F.; Knol, Remco J. J.; Booij, Jan; Verberne, Hein J.

    2014-01-01

    Tako-tsubo cardiomyopathy (TCM) is an increasingly recognized clinical syndrome characterized by acute reversible apical ventricular dysfunction, commonly preceded by exposure to severe physical or emotional stress. In this review, we give a short overview on clinical presentation and treatment of

  13. Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

    DEFF Research Database (Denmark)

    Pingel, Jessica; Suhr, Frank

    2017-01-01

    mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young...... and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle......Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle...

  14. Understanding the mechanism of nanoparticle formation in wire explosion process

    International Nuclear Information System (INIS)

    Bora, B.; Wong, C.S.; Bhuyan, H.; Lee, Y.S.; Yap, S.L.; Favre, M.

    2013-01-01

    The mechanism of nanoparticle formation by wire explosion process has been investigated by optical emission spectroscopy in Antony et al. 2010 [2] [J Quant Spectrosc Radiat Transfer 2010; 111:2509]. It was reported that the size of the nanoparticles formed in Ar ambience increases with increasing pressure, while an opposite trend was observed for the nanoparticles produced in N 2 and He ambiences. However, the physics behind this opposite trend seems unclear. In this work, we have investigated the probable mechanism behind the opposite trend in particle size with pressure of different gases and understand the mechanism of nanoparticle formation in wire explosion process. The experiment was carried out to investigate the effect of ambient gas species (Ar and N 2 ) and pressure on arc plasma formation and its corresponding effects on the characteristics of the produced nanoparticles in wire explosion process. Our results show that the arc plasma formation is probably the mechanism that may account for the opposite trend of particle size with pressure of different gases. -- Highlights: ► Cu nanoparticles have been synthesized by wire explosion technique. ► Investigate the effect of the ambient gas species and pressure. ► Arc plasma formation in wire explosion process is investigated. ► Arc plasma formation plays a crucial role in characteristic of the nanoparticles

  15. The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.

    Science.gov (United States)

    Köhler, Cristiano A; Maes, Michael; Slyepchenko, Anastasiya; Berk, Michael; Solmi, Marco; Lanctôt, Krista L; Carvalho, André F

    2016-01-01

    Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

  16. Understanding the thermal, mechanical and electrical properties of epoxy nanocomposites

    International Nuclear Information System (INIS)

    Sarathi, R.; Sahu, R.K.; Rajeshkumar, P.

    2007-01-01

    In the present work, the electrical, mechanical and thermal properties of epoxy nanocomposite materials were studied. The electrical insulation characteristics were analyzed through short time breakdown voltage test, accelerated electrical ageing test, and by tracking test. The breakdown voltage increases with increase in nano-clay content up to 5 wt%, under AC and DC voltages. The volume resistivity, permittivity and tan(δ) of the epoxy nanocomposites were measured. The Weibull studies indicate that addition of nanoclay upto 5 wt% enhances the characteristic life of epoxy nanocomposite insulation material. The tracking test results indicate that the tracking time is high with epoxy nanocomposites as compared to pure epoxy. Ageing studies were carried out to understand the surface characteristic variation through contact angle measurement. The hydrophobicity of the insulating material was analysed through contact angle measurement. The diffusion coefficients of the material with different percentage of clay in epoxy nanocomposites were calculated. The exfoliation characteristics in epoxy nanocomposites were analyzed through wide angle X-ray diffraction (WAXD) studies. The thermal behaviour of the epoxy nanocomposites was analyzed by carrying out thermo gravimetric-differential thermal analysis (TG-DTA) studies. Heat deflection temperature of the material was measured to understand the stability of the material for intermittent temperature variation. The dynamic mechanical analysis (DMA) results indicated that storage modulus of the material increases with small amount of clay in epoxy resin. The activation energy of the material was calculated from the DMA results

  17. Unravelling Endogenous MicroRNA System Dysfunction as a New Pathophysiological Mechanism in Machado-Joseph Disease.

    Science.gov (United States)

    Carmona, Vitor; Cunha-Santos, Janete; Onofre, Isabel; Simões, Ana Teresa; Vijayakumar, Udaya; Davidson, Beverly L; Pereira de Almeida, Luís

    2017-04-05

    Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3' UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3' UTR and whether they can alleviate MJD neuropathology in vivo. Our results demonstrate that endogenous miRNAs, by targeting sequences in the 3' UTR, robustly reduce ATXN3 expression and aggregation in vitro and neurodegeneration and neuroinflammation in vivo. Importantly, we found an abnormal MJD-associated downregulation of genes involved in miRNA biogenesis and silencing activity. Finally, we identified three miRNAs-mir-9, mir-181a, and mir-494-that interact with the ATXN3-3' UTR and whose expression is dysregulated in human MJD neurons and in other MJD cell and animal models. Furthermore, overexpression of these miRNAs in mice resulted in reduction of mutATXN3 levels, aggregate counts, and neuronal dysfunction. Altogether, these findings indicate that endogenous miRNAs and the 3' UTR of ATXN3 play a crucial role in MJD pathogenesis and provide a promising opportunity for MJD treatment. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  18. Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Svenningsen, Katrine; Almind Knudsen, Lina

    2015-01-01

    AIM: To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS: Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette....../Mdr1a, abcc2/Mrp2, abcg2/Bcrp, knock-out mice, tight junction, membrane lipid function. RESULTS: Recently, human studies reported that changes in the levels of ABC transporters were early events in the adenoma-carcinoma sequence leading to CRC. A link between ABCB1, high fat diet and gut microbes...... translocation from one side to the other of the cell membrane lipid bilayer by ABC transporters affecting inflammatory response and/or function of tight junctions, phagocytosis and vesicle trafficking. Also, diet and microbes give rise to molecules which are potential substrates for the ABC transporters...

  19. [A history and review of cholesterol ester transfer protein inhibitors and their contribution to the understanding of the physiology and pathophysiology of high density lipoprotein].

    Science.gov (United States)

    Corral, Pablo; Schreier, Laura

    2014-01-01

    There is irrefutable evidence that statins reduce the risk of cardiovascular events in a magnitude proportional to the intensity of the decrease in cholesterol transport by the low density lipoproteins. Despite this great advance there is still a residual risk of cardiovascular events. For this reason, an increase in the levels of high density lipoprotein is considered in order to boost the main action of this lipoprotein, which is reverse cholesterol transport. Distinct classes of evidence (epidemiological, genetic, and pathophysiological) show that the inhibition and/or modulation of cholesterol ester transfer protein increases plasma high density lipoprotein-cholesterol levels. The main reason for presenting this review is to look at the physiology of cholesterol ester transfer protein, its interrelationship with high density lipoproteins, and to give an update on the development of different cholesterol ester transfer protein inhibitor/modulator molecules. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  20. An update on oxidative stress-mediated organ pathophysiology.

    Science.gov (United States)

    Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

    2013-12-01

    Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Understanding Liver Regeneration: From Mechanisms to Regenerative Medicine.

    Science.gov (United States)

    Gilgenkrantz, Hélène; Collin de l'Hortet, Alexandra

    2018-04-16

    Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Activation and Inhibition of Sodium-Hydrogen Exchanger Is a Mechanism That Links the Pathophysiology and Treatment of Diabetes Mellitus With That of Heart Failure.

    Science.gov (United States)

    Packer, Milton

    2017-10-17

    The mechanisms underlying the progression of diabetes mellitus and heart failure are closely intertwined, such that worsening of one condition is frequently accompanied by worsening of the other; the degree of clinical acceleration is marked when the 2 coexist. Activation of the sodium-hydrogen exchanger in the heart and vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as a common mechanism that links both disorders and may underlie their interplay. Insulin insensitivity and adipokine abnormalities (the hallmarks of type 2 diabetes mellitus) are characteristic features of heart failure; conversely, neurohormonal systems activated in heart failure (norepinephrine, angiotensin II, aldosterone, and neprilysin) impair insulin sensitivity and contribute to microvascular disease in diabetes mellitus. Each of these neurohormonal derangements may act through increased activity of both NHE1 and NHE3. Drugs used to treat diabetes mellitus may favorably affect the pathophysiological mechanisms of heart failure by inhibiting either or both NHE isoforms, and drugs used to treat heart failure may have beneficial effects on glucose tolerance and the complications of diabetes mellitus by interfering with the actions of NHE1 and NHE3. The efficacy of NHE inhibitors on the risk of cardiovascular events may be enhanced when heart failure and glucose intolerance coexist and may be attenuated when drugs with NHE inhibitory actions are given concomitantly. Therefore, the sodium-hydrogen exchanger may play a central role in the interplay of diabetes mellitus and heart failure, contribute to the physiological and clinical progression of both diseases, and explain certain drug-drug and drug-disease interactions that have been reported in large-scale randomized clinical trials. © 2017 American Heart Association, Inc.

  3. The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

    Science.gov (United States)

    Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

    2015-01-01

    The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Pathophysiological mechanisms in antiphospholipid syndrome

    Science.gov (United States)

    Harper, Brock E; Wills, Rohan; Pierangeli, Silvia S

    2013-01-01

    Antiphospholipid syndrome is a systemic autoimmune disease associated with thrombosis and recurrent fetal loss in the setting of detectable antiphospholipid (aPL) antibodies. The major antigenic target has been identifed as β2-glycoprotein I (β2GPI), which mediates binding of aPL antibodies to target cells including endothelial cells, monocytes, platelets and trophoblasts, leading to prothrombotic and proinfammatory changes that ultimately result in thrombosis and fetal loss. This article summarizes recent insights into the role of β2GPI in normal hemostasis, interactions between aPL antibodies, β2GPI and cell-surface molecules, molecular prothrombotic and proinfammatory changes induced by aPL antibodies and pathogenic changes leading to fetal loss in antiphospholipid syndrome. New directions in therapy using these insights are examined. PMID:23487578

  5. [Pathophysiology and genetics of obesity].

    Science.gov (United States)

    Oberkofler, Hannes; Krempler, Franz; Patsch, Wolfgang

    2002-01-01

    Obesity has become the most prevalent nutritional disorder in post-industrialised societies and it is associated with the development of severe and costly complications such as type 2 diabetes mellitus and coronary heart disease or cancer. A large proportion of the risk of obesity is determined by the genetic susceptibility of an individual, but environmental factors conducive for the disorder play an important role in its phenotypic expression. Several candidate genes emerged from studies in animal models of obesity, but human pathophysiology is likely to be more complex. Thus, most cases of human obesity probably result from subtle interactions of susceptibility genes with environmental factors favouring deposition of excess calories as fat. The recent surge of obesity may relate to past evolutionary pressure which favoured selection of mechanisms defending body-weight against caloric restriction rather than against caloric excess. Rapidly developing new techniques in quantitative genetics and growing information from functional genomics will help to understand the interaction of environmental factors with signalling networks that regulate energy metabolism. The role of previously unknown pathways in the aetiology of obesity will be uncovered. The typing of numerous genetic variants will become possible and allow individual risk assessment for obesity and/or its associated disorders. Thus, rational and individually tailored therapies may be developed to combat obesity and its associated disorders.

  6. Bronchopulmonary dysplasia: understanding of the underlying pathological mechanisms

    Directory of Open Access Journals (Sweden)

    Daniela Fanni

    2014-06-01

    Full Text Available Bronchopulmonary dysplasia (BPD is a chronic lung disease occurring in preterm infants, typically before 28 weeks of gestational age, characterized by a prolonged need for supplemental oxygen or positive pressure ventilation. The normal stages of lung development and their relation to the timing of preterm birth is strategic in order to understand the pathogenesis of BPD. In embryonic and pseudoglandular stages the lungs arise from the anterior foregut as a bud where the branching morphogenesis generate a tree-like network of airways. The canalicular stage is characterized by increasing proliferation of distal lung epithelial cells and rapid expansion of the intra-acinar capillaries. The complexity of the airways increases, secondary crests begin to form and full maturation of the alveolus occurs during the saccular and the alveolar stages. Mesechyme components, expecially elastin and myofibroblast, display a major role in normal lung development. BPD is thought to result after an acute insult to the neonatal lung following therapy with oxygen supplementation and mechanical ventilation. Chorioamnionitis, infections and genetic susceptibly are hypothesized to contribute to the injury that affect the normal human lung development. Abnormalities in the mesenchyme were consistently seen in association with inhibition of alveolarization. The pathological features that characterize BPD are complex and differ according with the disease progression. Alveolar simplification, interstitial fibrosis, septal thickness, large airways, smooth muscle hypertrophy, fetal artery persistance and decrease in the arterial number can be histologically observed. In conclusion, in order to reach a complete clinical-pathological diagnosis, the correlation of the pathological features with the fundamental steps of lung morphogenesis and a strict dialogue between the neonatologist and the perinatal pathologist are required. Given these conditions, in our experience, a

  7. Understanding the mechanisms behind coking pressure: Relationship to pore structure

    Energy Technology Data Exchange (ETDEWEB)

    John J. Duffy; M. Castro Diaz; Colin E. Snape; Karen M. Steel; Merrick R. Mahoney [University of Nottingham, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

    2007-09-15

    Three low volatile coals A, B and C with oven wall pressures of 100 kPa, 60 kPa and 20 kPa respectively were investigated using high-temperature rheometry, {sup 1}H NMR, thermogravimetric analysis and SEM, with the primary aim to better understand the mechanisms behind the coking pressure phenomenon. Rheometer plate displacement measurements ({Delta}L) have shown differences in the expansion and contraction behaviour of the three coals, which seem to correlate with changes in rheological properties; while SEM images have shown that the expansion process coincides with development of pore structure. It is considered that the point of maximum plate height ({Delta}L{sub max}) prior to contraction may be indicative of a cell opening or pore network forming process, based on analogies with other foam systems. Such a process may be considered important for coking pressure since it provides a potential mechanism for volatile escape, relieving internal gas pressure and inducing charge contraction. For coal C, which has the highest fluidity {delta}L{sub max} occurs quite early in the softening process and consequently a large degree of contraction is observed; while for the lower fluidity coal B, the process is delayed since pore development and consequently wall thinning progress at a slower rate. When {Delta}L{sub max} is attained, a lower degree of contraction is observed because the event occurs closer to resolidification where the increasing viscosity/elasticity can stabilise the expanded pore structure. For coal A which is relatively high fluidity, but also high coking pressure, a greater degree of swelling is observed prior to cell rupture, which may be due to greater fluid elasticity during the expansion process. This excessive expansion is considered to be a potential reason for its high coking pressure. 58 refs., 15 figs., 1 tab.

  8. Understanding sleep-wake mechanisms and drug discovery.

    Science.gov (United States)

    Equihua-Benítez, Ana Clementina; Guzmán-Vásquez, Khalil; Drucker-Colín, René

    2017-07-01

    Although not discernible at first glance, sleep is a highly active and regulated brain state. Although we spend practically one third of our lifetimes in this stage, its importance is often taken for granted. Sleep loss can lead to disease, error and economic loss. Our understanding of how sleep is achieved has greatly advanced in recent years, and with that, the management of sleep disorders has improved. There is still room for improvement and recently many new compounds have reached clinical trials with a few being approved for commercial use. Areas covered: In this review, the authors make the case of sleep disorders as a matter of public health. The mechanisms of sleep transition are discussed emphasizing the wake and sleep promoting interaction of different brain regions. Finally, advances in pharmacotherapy are examined in the context of chronic insomnia and narcolepsy. Expert opinion: The orexinergic system is an example of a breakthrough in sleep medicine that has catalyzed drug development. Nevertheless, sleep is a topic still with many unanswered questions. That being said, the melanin-concentrating hormone system is becoming increasingly relevant and we speculate it will be the next target of sleep medication.

  9. Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement

    DEFF Research Database (Denmark)

    Gallo, Jiri; Vaculova, Jana; Goodman, Stuart B

    2014-01-01

    Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening...... of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies....... molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution...

  10. Maternal syphilis: pathophysiology and treatment.

    OpenAIRE

    Berman, Stuart M.

    2004-01-01

    Despite the long history of medical interest in syphilis and its effects on pregnancy outcome, many fundamental questions about the pathophysiology and treatment of syphilis during pregnancy remain unanswered. However, understanding has been advanced by recent scientific reports such as those which delineate the complete sequence of the genome of the syphilis spirochaete, provide a more precise description of fetal and neonate infection by use of rabbit infectivity tests and describe the gest...

  11. Understanding the mechanism of base development of hydrogen silsesquioxane

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Chao, Weilun; Liang, Xiaogan; Griedel, Brian D.; Olynick, Deirdre L

    2009-01-09

    There have been numerous studies of electron beam exposed hydrogen silsesquioxane (HSQ) development conditions in order to improve the developer contrast. For TMAH based development, improvements were made by going to higher TMAH normalities and heating the developer. Yang and Berggren showed development of electron beam exposed (HSQ) by NaOH with added Na salts (various anions) significantly improves the contrast. Here, we study the contrast and etching rates of 100 keV exposed HSQ in NaOH in the presence of LiCl, NaCl, and KCl salts and use this as a segway to understand the mechanisms governing contrast during development HSQ development. The basic mechanism of development of HSQ can be understood by comparing to etching of quartz in basic solutions. Hydroxide ions act as nucleophiles which attack silicon. When a silicon-oxygen bond of the Si-O-Si matrix is broken, Si-O{sup -} and Si-OH are formed which can reversibly react to form the original structure. When a Si-H bond is broken via reaction with hydroxide, Si-O{sup -} and H{sub 2} gas are formed. Salts can change the etching rates as a function of dose in a non-linear fashion to increase etch contrast. Figs. 1, 2, and 3 show contrast curves for HSQ developed in 0.25 N sodium hydroxide and with the addition of NaCl, LiCl and KCl salts at several concentrations. NaCl addition resulted in the highest contrast. Contrast improves with additional salt concentration while sensitivity decreases. Interestingly enough, addition of salt decreases the removal of material of NaOH alone at higher doses while increasing the rate at lower concentrations. Addition of LiCl salts improves contrast over NaOH alone. Furthermore, the sensitivity at all doses increases as the LiCl concentration increases, a salting out effect. Similar to NaCl salt behavior, the addition of KCl salts, improves contrast at the expense of sensitivity. However, unlike NaCl, even at very high doses, KCl addition increases removal rate of HSQ. We

  12. Focal venous hypertension as a pathophysiologic mechanism for tissue hypertrophy, port-wine stains, the Sturge-Weber syndrome, and related disorders: proof of concept with novel hypothesis for underlying etiological cause (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Parsa, Cameron F

    2013-09-01

    To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence. Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications. Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion. Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology-prenatal venous thrombo-occlusion-is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic tissue hypertrophy in these syndromes clarifies

  13. Focal Venous Hypertension as a Pathophysiologic Mechanism for Tissue Hypertrophy, Port-Wine Stains, the Sturge-Weber Syndrome, and Related Disorders: Proof of Concept with Novel Hypothesis for Underlying Etiological Cause (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Parsa, Cameron F.

    2013-01-01

    Purpose: To provide an in-depth re-examination of assumed causes of tissue hypertrophy, port-wine stains, and the Sturge-Weber, Cobb, Klippel-Trénaunay, and related syndromes to support an alternative unifying pathophysiologic mechanism of venous dysplasia producing focal venous hypertension with attendant tissue responses; to provide proof of concept with new patient data; to propose a novel etiological hypothesis for the venous dysplasia in these syndromes and find supportive evidence. Methods: Data from 20 patients with port-wine stains and corneal pachymetry readings was collected prospectively by the author in an institutional referral-based practice. The literature was searched using MEDLINE, and articles and textbooks were obtained from the bibliographies of these publications. Results: Newly obtained dermatologic, corneal pachymetry, fundus ophthalmoscopic, ocular and orbital venous Doppler ultrasonography, and magnetic resonance imaging findings in patients with the Sturge-Weber syndrome or isolated port-wine stains, along with published data, reveal diffusely thickened tissues and neural atrophy in all areas associated with venous congestion. Conclusions: Contrary to traditional understanding, signs and symptoms in the Sturge-Weber and related syndromes, including both congenital and acquired port-wine stains, are shown to arise from effects of localized primary venous dysplasia or acquired venous obstruction rather than neural dysfunction, differentiating these syndromes from actual phacomatoses. Effects of focal venous hypertension are transmitted to nearby areas via compensatory collateral venous channels in the above conditions, as in the Parkes Weber syndrome. A novel underlying etiology—prenatal venous thrombo-occlusion—is proposed to be responsible for the absence of veins with persistence and enlargement of collateral circulatory pathways with data in the literature backing this offshoot hypothesis. The mechanism for isolated pathologic

  14. Understanding human action: integrating meanings, mechanisms, causes, and contexts

    NARCIS (Netherlands)

    Keestra, M.; Repko, A.F.; Newell, W.H.; Szostak, R.

    2012-01-01

    Humans are capable of understanding an incredible variety of actions performed by other humans. Even though these range from primary biological actions like eating and fleeing, to acts in parliament or in poetry, humans generally can make sense of each other’s actions. Understanding other people’s

  15. [Immune pathophysiology of refractory anemias].

    Science.gov (United States)

    Nakao, Shinji

    2008-03-01

    Among different immune pathophysiologies of anemia, those of bone marrow failure syndromes such as aplastic anemia and myelodysplastic syndrome are most difficult to understand. An increase in the proportion of glycosylphosphatidyl-inositol anchored protein-deficient cells has been identified as the best marker for the presence of immune pathophysiology in this elusive syndrome. The significance of detecting small populations of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells was substantiated by a recent observation that PNH-type cells arose from a donor-derived hematopoietic stem cell with a PIG-A mutation in an aplastic anemia patient with late graft failure which responded well to immunosuppressive therapy. Identification of auto-antigens capable of inducing cytotoxic T cells against hematopoietic stem cells is necessary to prove the escape of PIG-A mutant clone from the immune system attack using animal models.

  16. Constipation: Pathophysiology and Current Therapeutic Approaches.

    Science.gov (United States)

    Sharma, Amol; Rao, Satish

    2017-01-01

    addition of sensory retraining. Our understanding of the pathophysiology of STC is evolving. The advent of high-resolution colonic manometry allows for the improved identification of colonic motor patterns and may provide further insight into pathophysiological mechanisms. In a minority of cases of STC, identification of colonic neuropathy suggests a medically refractory condition, warranting consideration of colectomy. The pathophysiology of IBS-C is poorly understood with multiple etiological factors implicated. Pharmacological advances in the treatment of primary constipation have added therapeutic options to the armamentarium of this disorder. Drug development in the secretagogue, serotonergic prokinetic, and ileal bile acid transporter inhibition pathways has yielded current and future medical treatment options for primary chronic constipation.

  17. Understanding the mechanism of base development of HSQ

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jihoon; Chao, Weilun; Griedel, Brian; Liang, Xiaogan; Lewis, Mark; Hilken, Dawn; Olynick, Deirdre

    2009-06-16

    We study the dissolution mechanism of HSQ (hydrogen silsesquioxane) in base solutions with the addition of chloride salts to elucidate the development mechanism. Reaction mechanisms are proposed based on the dissolution mechanism of quartz. Development kinetics points to two dose-dependent development mechanisms. Considering ion sizes, both hydrated and non-hydrated, and ion exchange, we propose that a combination of a surface dominated reaction at higher doses and a matrix dominated reaction at lower doses accounts for the high development contrast with a NaOH base/NaCl salt mixture. The interplay between the hydrated and non-hydrated ion size leads to higher contrast developers, such as tetramethyl ammonium hydroxide (TMAH) with NaCl.

  18. Pathophysiology of overactive bladder.

    Science.gov (United States)

    Banakhar, Mai A; Al-Shaiji, Tariq F; Hassouna, Magdy M

    2012-08-01

    Overactive bladder (OAB) is a common disorder that negatively affects the quality of life of our patients and carries a large socioeconomic burden. According to the International Continence Society, it is characterized as urinary urgency, with or without urge incontinence, usually, with frequency and nocturia in the absence of causative infection. The pathophysiology of this disease entity varies between neurogenic, myogenic, or idiopathic factors. This paper provides a review of the contemporary theories behind the pathophysiology of OAB.

  19. [Pathophysiology of urticaria].

    Science.gov (United States)

    Nosbaum, A; Augey, F; Nicolas, J-F; Bérard, F

    2014-11-01

    Urticaria is a dermal edema resulting from vascular dilatation and leakage of fluid into the skin in response to molecules released from mast cells. The major mediator responsible for urticaria is histamine. However, the clinical spectrum and pattern of lesions indicate that other molecules, including prostaglandins, leukotrienes, cytokines, and chemokines, produced at different times after mast cell activation contribute to the polymorphism of this symptom and the variable evolution of this disease. It is a common practice to distinguish immunological and nonimmunological urticaria. Immunological urticaria is a hypersensitivity reaction mediated by antibodies and/or T-cells that results in mast cell activation. Although immunoglobulin (Ig) E-mediated type I hypersensitivity (HS) was long postulated to be the major immunological pathway associated with mast cell activation, interaction between IgEbound mast cells and allergens is unlikely to be the mechanism by which urticaria develops in most patients. It is now well established that urticaria may result from the binding of IgG auto-antibodies to IgE and/or to the receptor for IgE molecules on mast cells, thus corresponding to a type II HS reaction. These auto-immune urticarias represent up to 50 % of patients with chronic urticaria. Mast cell activation can also result from type III HS through the binding of circulating immune complexes to mast cell-expressing Fc receptors for IgG and IgM. Finally, under certain circumstances, T-cells can induce activation of mast cells, as well as histamine release (type IV HS). Nonimmunological urticarias result from mast cell activation through membrane receptors involved in innate immunity (e.g., complement, Toll-like, cytokine/chemokine, opioid) or by direct toxicity of xenobiotics (haptens, drugs). In conclusion, urticaria may result from different pathophysiological mechanisms that explain the great heterogeneity of clinical symptoms and the variable responses to treatment

  20. [Pathophysiology of overuse tendon injury].

    Science.gov (United States)

    Kannus, P; Paavola, M; Paakkala, T; Parkkari, J; Järvinen, T; Järvinen, M

    2002-10-01

    Overuse tendon injury is one of the most common injuries in sports. The etiology as well as the pathophysiological mechanisms leading to tendinopathy are of crucial medical importance. At the moment intrinsic and extrinsic factors are assumed as mechanisms of overuse tendon injury. Except for the acute, extrinsic trauma, the chronic overuse tendon injury is a multifactorial process. There are many other factors, such as local hypoxia, less of nutrition, impaired metabolism and local inflammatory that may also contribute to the development of tissue damage. The exact interaction of these factors cannot be explained entirely at the moment. Further studies will be necessary in order to get more information.

  1. Understanding the pathophysiology of intra-uterine growth retardation: the role of the 'lower limb reflex' in redistribution of blood flow.

    Science.gov (United States)

    Akalin-Sel, T; Campbell, S

    1992-09-23

    Doppler ultrasound was used to investigate the circulatory redistribution and underlying reflex responses of fetal cardiovascular compensation in 30 small-for-gestational age (SGA) fetuses. The utero-placental bed, umbilical artery and vein, thoracic and abdominal aorta, internal and external cerebral arteries were evaluated. The values were compared to reference ranges constructed from 135 normal pregnancies, correlated to fetal blood gases obtained by cordocentesis and compared to the outcomes. In Group I (mortality and morbidity), all fetuses had loss of end-diastolic frequencies (L-EDF) in the abdominal aorta (100%), but only 20 (87%) and 13 (56%) had L-EDF in the thoracic aorta and umbilical artery respectively. High vascular resistance in the placental bed and low impedance in the middle cerebral and common carotid arteries was found in 14 (61%), 12 (52%) and 20 (87%) fetuses, respectively. In Group II (Healthy infants) two fetuses had high utero-placental vascular resistance and one had brain-sparing. Doppler indices did not always reflect fetal hypoxaemia demonstrating that redistribution in SGA fetuses may not be triggered by a fall in pO2, and that hypoxaemia is an associated pathology but may not be the underlying cause. It is postulated that redistribution in SGA fetuses is regulated by reflex mechanisms (the 'lower limb reflex') which result in severe vasoconstriction in the abdominal aorta, mesentery and carcass, favouring the brain and cardiac muscles. This mechanism explains the good predictive value of L-EDF in the abdominal aorta for poor neonatal outcome (sensitivity, specificity and positive predictive value, all 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

  2. The role of autoantibodies in the pathophysiology of rheumatoid arthritis.

    Science.gov (United States)

    Derksen, V F A M; Huizinga, T W J; van der Woude, D

    2017-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

  3. The Nobel Prize for understanding autophagy, a cellular mechanism ...

    Indian Academy of Sciences (India)

    The Nobel Prize in Physiology or Medicine, 2016, was awarded to Prof Yoshinori Ohsumi from TokyoInstitute of Technology, Yokohoma, Japan, for his work that helped in understanding the molecularmechanisms of autophagy, a process used by most eukaryotic cells to degrade a portion of cytoplasmincluding damaged ...

  4. New insights into pathophysiology of vestibular migraine

    Directory of Open Access Journals (Sweden)

    Juan Manuel Espinosa-Sanchez

    2015-02-01

    Full Text Available Vestibular migraine (VM is a common disorder in which genetic, epigenetic and environmental factors probably contribute to its development. The pathophysiology of VM is unknown; nevertheless in the last few years, several studies are contributing to understand the neurophysiological pathways involved in VM. The current hypotheses are mostly based on the knowledge of migraine itself. The evidence of trigeminal innervation of the labyrinth vessels and the localization of vasoactive neuropeptides in the perivascular afferent terminals of these trigeminal fibers support the involvement of the trigemino-vascular system. The neurogenic inflammation triggered by activation of the trigeminal-vestibulocochlear reflex, with the subsequent inner ear plasma protein extravasation and the release of inflammatory mediators, can contribute to a sustained activation and sensitization of the trigeminal primary afferent neurons explaining VM symptoms. The reciprocal connections between brainstem vestibular nuclei and the structures that modulate trigeminal nociceptive inputs (rostral ventromedial medulla, ventrolateral periaqueductal grey, locus coeruleus and nucleus raphe magnus are critical to understand the pathophysiology of VM. Although cortical spreading depression can affect cortical areas involved in processing vestibular information, functional neuroimaging techniques suggest a dysmodulation in the multimodal sensory integration and processing of vestibular and nociceptive information, resulting from a vestibulo-thalamo-cortical dysfunction, as the pathogenic mechanism underlying VM. The elevated prevalence of VM suggests that multiple functional variants may confer a genetic susceptibility leading to a dysregulation of excitatory-inhibitory balance in brain structures involved in the processing of sensory information, vestibular inputs and pain. The interactions among several functional and structural neural networks could explain the pathogenic

  5. Understanding "Understanding" Flow for Network-Centric Warfare: Military Knowledge-Flow Mechanics

    National Research Council Canada - National Science Library

    Nissen, Mark

    2002-01-01

    Network-centric warfare (NCW) emphasizes information superiority for battlespace efficacy, but it is clear that the mechanics of how knowledge flows are just as important as those pertaining to the networks and communication...

  6. Understanding the Role and Mechanism of Metformin in Obesity ...

    African Journals Online (AJOL)

    Metformin, a biguanide, is a widely used drug for the treatment of type 2 diabetes mellitus. The drug also found to be beneficial in other class of diseases like obesity but its role and mechanism of action in obesity is still not well established. A literature survey was done in order to evaluate the evidence supporting metformin ...

  7. Understanding the Mechanism behind Maternal Imprisonment and Adolescent School Dropout

    Science.gov (United States)

    Cho, Rosa M.

    2011-01-01

    This study empirically tested 3 mechanisms commonly suggested to disadvantage youths whose mothers are incarcerated in prison. An event history analysis of school dropout was conducted on a sample of 6,008 adolescents in a large city created by merging several Illinois state administrative data. Findings revealed that adolescents are indeed at…

  8. Understanding the biological mechanisms of Zika virus disease ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This project will use advanced biomolecular, genomics and proteomics techniques to explain the molecular mechanisms by which the Zika virus infects and persists in the human body, how it affects the human reproductive and central nervous system, and how the risk of fetal abnormalities can be better predicted in infected ...

  9. How Electroconvulsive Therapy Works?: Understanding the Neurobiological Mechanisms

    Science.gov (United States)

    Singh, Amit; Kar, Sujita Kumar

    2017-01-01

    Electroconvulsive therapy (ECT) is a time tested treatment modality for the management of various psychiatric disorders. There have been a lot of modifications in the techniques of delivering ECT over decades. Despite lots of criticisms encountered, ECT has still been used commonly in clinical practice due to its safety and efficacy. Research evidences found multiple neuro-biological mechanisms for the therapeutic effect of ECT. ECT brings about various neuro-physiological as well as neuro-chemical changes in the macro- and micro-environment of the brain. Diverse changes involving expression of genes, functional connectivity, neurochemicals, permeability of blood-brain-barrier, alteration in immune system has been suggested to be responsible for the therapeutic effects of ECT. This article reviews different neurobiological mechanisms responsible for the therapeutic efficacy of ECT. PMID:28783929

  10. Molecular pathophysiology of cerebral edema.

    Science.gov (United States)

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. © The Author(s) 2015.

  11. Narcolepsy: Pathophysiology and Neuropsychological Changes

    Directory of Open Access Journals (Sweden)

    Angela Naumann

    2003-01-01

    Full Text Available Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.

  12. Advances in understanding Giardia: determinants and mechanisms of chronic sequelae

    Science.gov (United States)

    Sartor, R. Balfour

    2015-01-01

    Giardia lamblia is a flagellated protozoan that is the most common cause of intestinal parasitic infection in children living in resource-limited settings. The pathogenicity of Giardia has been debated since the parasite was first identified, and clinical outcomes vary across studies. Among recent perplexing findings are diametrically opposed associations between Giardia and acute versus persistent diarrhea and a poorly understood potential for long-term sequelae, including impaired child growth and cognitive development. The mechanisms driving these protean clinical outcomes remain elusive, but recent advances suggest that variability in Giardia strains, host nutritional status, the composition of microbiota, co-infecting enteropathogens, host genetically determined mucosal immune responses, and immune modulation by Giardia are all relevant factors influencing disease manifestations after Giardia infection. PMID:26097735

  13. Pathophysiology of migraine

    Directory of Open Access Journals (Sweden)

    Peter J Goadsby

    2012-01-01

    Full Text Available Migraine is a common disabling brain disorder whose pathophysiology is now being better understood. The study of anatomy and physiology of pain producing structures in the cranium and the central nervous system modulation of the input have led to the conclusion that migraine involves alterations in the sub-cortical aminergic sensory modulatory systems that influence the brain widely.

  14. Pathophysiology of Equine Neonatal Septicemia

    Directory of Open Access Journals (Sweden)

    Juan Carlos Ospina Chirivi

    2014-07-01

    Full Text Available Neonatal septicemia is a major cause of mortality and morbidity in horses in their first seven days of life and within their pathophysiology. It is important to consider the extrinsic and intrinsic predisposing factors which make foals susceptible to agents of primarily bacterial etiology. However, other types of infectious etiology (viruses and fungi should be considered too, as well as noninfectious etiologies. The paper mentions a wide variety of mechanisms that produce different injuries that must be addressed with measures of critical neonatal care, so it is imperative for the veterinarian to know the pathogenic mechanisms of the disease, its clinical presentation and anatomo-pathological lesions. Thus, systemic inflammatory response syndrome (SIRS, multiple organ dysfunction syndrome (MODS, and peripheral circulatory collapse or shock are some of the elements defined as the pillars of the pathophysiology of neonatal septicemia, extensively studied in equine medicine. This paper presents a short review of the triggering mechanisms of neonatal septicemia highlighting the importance of epidemiological investigations in Colombia. It shows the need for retrospective and prospective studies and for divulgation of some of the preventive measures of the disease in horses.

  15. Understanding mechanisms of autoimmunity through translational research in vitiligo

    Science.gov (United States)

    Strassner, James P; Harris, John E

    2016-01-01

    Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible. PMID:27764715

  16. Understanding the kinetic mechanism of RNA single base pair formation.

    Science.gov (United States)

    Xu, Xiaojun; Yu, Tao; Chen, Shi-Jie

    2016-01-05

    RNA functions are intrinsically tied to folding kinetics. The most elementary step in RNA folding is the closing and opening of a base pair. Understanding this elementary rate process is the basis for RNA folding kinetics studies. Previous studies mostly focused on the unfolding of base pairs. Here, based on a hybrid approach, we investigate the folding process at level of single base pairing/stacking. The study, which integrates molecular dynamics simulation, kinetic Monte Carlo simulation, and master equation methods, uncovers two alternative dominant pathways: Starting from the unfolded state, the nucleotide backbone first folds to the native conformation, followed by subsequent adjustment of the base conformation. During the base conformational rearrangement, the backbone either retains the native conformation or switches to nonnative conformations in order to lower the kinetic barrier for base rearrangement. The method enables quantification of kinetic partitioning among the different pathways. Moreover, the simulation reveals several intriguing ion binding/dissociation signatures for the conformational changes. Our approach may be useful for developing a base pair opening/closing rate model.

  17. Understanding cracking failures of coatings: A fracture mechanics approach

    Science.gov (United States)

    Kim, Sung-Ryong

    A fracture mechanics analysis of coating (paint) cracking was developed. A strain energy release rate (G(sub c)) expression due to the formation of a new crack in a coating was derived for bending and tension loadings in terms of the moduli, thicknesses, Poisson's ratios, load, residual strain, etc. Four-point bending and instrumented impact tests were used to determine the in-situ fracture toughness of coatings as functions of increasing baking (drying) time. The system used was a thin coating layer on a thick substrate layer. The substrates included steel, aluminum, polycarbonate, acrylonitrile-butadiene-styrene (ABS), and Noryl. The coatings included newly developed automotive paints. The four-point bending configuration promoted nice transversed multiple coating cracks on both steel and polymeric substrates. The crosslinked type automotive coatings on steel substrates showed big cracks without microcracks. When theoretical predictions for energy release rate were compared to experimental data for coating/steel substrate samples with multiple cracking, the agreement was good. Crosslinked type coatings on polymeric substrates showed more cracks than theory predicted and the G(sub c)'s were high. Solvent evaporation type coatings on polymeric substrates showed clean multiple cracking and the G(sub c)'s were higher than those obtained by tension analysis of tension experiments with the same substrates. All the polymeric samples showed surface embrittlement after long baking times using four-point bending tests. The most apparent surface embrittlement was observed in the acrylonitrile-butadiene-styrene (ABS) substrate system. The impact properties of coatings as a function of baking time were also investigated. These experiments were performed using an instrumented impact tester. There was a rapid decrease in G(sub c) at short baking times and convergence to a constant value at long baking times. The surface embrittlement conditions and an embrittlement toughness

  18. Understanding ozone mechanisms to alleviate ceramic membrane fouling

    Science.gov (United States)

    Chu, Irma Giovanna Llamosas

    Ceramic membranes are a strong prospect as an advanced treatment in the drinking water domain. But their high capital cost and the lack of specific research on their performance still discourage their application in this field. Thus, knowing that fouling is the main drawback experienced in filtration processes, this bench-scale study was aimed to assess the impact of an ozonation pre-treatment on the alleviation of the fouling of UF ceramic membranes. Preozonation and filtration steps were performed under two different pH and ozone doses. Chosen pH values were at the limits of natural surface waters range (6.5 and 8.5) to keep practicability. Raw water from the Thousand Isle's river at Quebec-Canada was used for the tests. The filtration setup involved an unstirred dead-end filtration cell operated at constant flux. Results showed that pre-oxidation by ozone indeed reduced the fouling degree of the membranes according to the dose applied (up to 60 and 85% for membranes 8 and 50 kDa, respectively). Direct NOM oxidation was found responsible for this effect as the presence of molecular ozone was not essential to achieve these results. In the context of this experiment, however, pH showed to be more effective than the ozonation pre-treatment to keep fouling at low levels: 70% lower at pH 6.5 than at pH 8.5 for un-ozonated waters, which was contrary to most of the literature found on the topic (Changwon, 2013; De Angelis & Fidalgo, 2013; Karnik et al., 2005; S. Lee & Kim, 2014). This behaviour results mainly from the operation mode used in the experiment, the electrical repulsions between MON molecules at basic pH that led to the accumulation of material on the feed side of the membranes (concentration polarisation) and ulterior cake formation. In addition, solution pH showed an influence in the definition of fouling mechanisms. At solution pH 6.5, which was precisely the isoelectric point of the membranes (+/-6.5), the blocking fouling mode was frequently detected

  19. Pathophysiology of the Belgrade Rat

    Directory of Open Access Journals (Sweden)

    Tania eVeuthey

    2014-04-01

    Full Text Available The Belgrade rat is an animal model of Divalent Metal Transporter-1 (DMT1 deficiency. This strain originates from an X-irradiation experiment first reported in 1966. Since then, the Belgrade rat’s pathophysiology has helped to reveal the importance of iron balance and the role of DMT1. This review discusses our current understanding of iron transport homeostasis and summarizes molecular details of DMT1 function. We describe how studies of the Belgrade rat have revealed key roles for DMT1 in iron distribution to red blood cells as well as duodenal iron absorption. The Belgrade rat’s pathology has extended our knowledge of hepatic iron handling, pulmonary and olfactory iron transport as well as brain iron uptake and renal iron handling. For example, relationships between iron and manganese metabolism have been discerned since both are essential metals transported by DMT1. Pathophysiologic features of the Belgrade rat provide us with a unique and interesting animal model to understand iron homeostasis.

  20. Sixth-Grade Students' Progress in Understanding the Mechanisms of Global Climate Change

    Science.gov (United States)

    Visintainer, Tammie; Linn, Marcia

    2015-01-01

    Developing solutions for complex issues such as global climate change requires an understanding of the mechanisms involved. This study reports on the impact of a technology-enhanced unit designed to improve understanding of global climate change, its mechanisms, and their relationship to everyday energy use. Global Climate Change, implemented in…

  1. Risks of flexible ureterorenoscopy: pathophysiology and prevention.

    Science.gov (United States)

    Osther, Palle J S

    2018-02-01

    Currently, indications for flexible ureterorenoscopy (fURS) are expanding, mainly due to technological advancements. Although data from clinical series definitely presents fURS as a safe procedure, serious complications including sepsis and ureteral lesions do occur. These complications seem to be a result of the unique elements of fURS, ureteral access and irrigation, pushing normal upper urinary tract physiology into pathophysiological processes, including intrarenal/pyelo-veneous backflow and ureteral contractions, potentially resulting in septic, haemorrhagic and ureteral lesional complications. Knowledge on normal upper urinary tract physiology are crucial for understanding how these harmful effects of fURS may be avoided or minimized. The pathophysiology of intrarenal pressure increases and ureteral access will be discussed as a basis for understanding preventive measures. Role of antibiotics, ureteral access sheaths, safty guidewires, pain medication, prestenting and pharmacologic modulation of pyeloureteral dynamics are reviewed from a pathophysiological perspective.

  2. The Pathophysiology of Autism

    OpenAIRE

    Compart, Pamela J.

    2013-01-01

    Autism has been classically defined by its behavioral symptoms. Traditional medical research has focused on genetic or intrinsic brain-based causes of autism. While both of these are important, additional research has focused on the underlying disordered biochemistry seen in many individuals with autism. Many of these biomedical factors are amenable to treatment. This article will review the main pathophysiologic factors seen in individuals with autism spectrum disorders.

  3. The fibromyalgia syndrome: musculoskeletal pathophysiology.

    Science.gov (United States)

    Geel, S E

    1994-04-01

    Fibromyalgia (FM) is a chronic pain disorder that afflicts predominantly middle-aged women with cardinal symptoms of diffuse musculoskeletal pain, defined tender points, deprived sleep, and fatigue. The etiology and pathological mechanisms are poorly understood, and treatment approaches are largely ineffective. The clinical features of the syndrome are presented, and the relevance of muscle dysfunction in the etiopathogenesis of the disorder is explored. The evidence for involvement of muscle pathophysiology as a primary mechanism mediating the onset of symptoms is not compelling. Musculoskeletal dysfunction can be considered secondary to central abnormalities of pain modulation and altered sleep physiology precipitated by emotional stress in genetically predisposed individuals. Contemporary evidence favors treatment strategies that emphasize pain control, sleep enhancement, and a program of conditioning.

  4. Pathophysiology, Functional Implications and Management of ...

    African Journals Online (AJOL)

    The management of spasticity in stroke requires a multidisciplinary approach but more importantly, an understanding of the pathophysiology of its consequences. This paper reviews different definitions from neurophysiology and medical literature which try to place spasticity in stroke in its proper context and describes the ...

  5. Pathophysiology of Retinopathy of Prematurity

    Directory of Open Access Journals (Sweden)

    İmren Akkoyun

    2012-12-01

    Full Text Available Retinopathy of prematurity (ROP, an ocular disease characterized by onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex multifactorial disease that occurs with microvascular degeneration followed by neovascularization which passing through different stages can progress to retinal detachment. Currently used ablative therapies like cryocoagulation and laser photocoagulation for proliferative ROP have limitations, and patients can still have long-term complications despite a successful treatment. Based on the knowledge regarding ROP pathophysiology, new treatment modalities are being developed. First results of intravitreal anti-VEGF therapy using bevacizumab are promising. Furthermore, besides intravitreal anti-VEGF therapy, systemic therapy with mediators like insulin-like growth factor (IGF-1 and/or ω3-fatty acids outlines the pharmacological approach to treatment of ROP. One of the most destructive manifestations of ROP is preretinal neovascularization. As we continue to decipher the underlying pathophysiological cellular mechanisms governing proliferative retinopathy, fostering normal retinal revascularization will open new therapeutic possibilities. All efforts should be focused on developing preventive strategies for ROP in order to avoid the need for nondestructive therapy modalities. (Turk J Ophthalmol 2012; 42: Supplement 63-7

  6. [PATHOPHYSIOLOGY OF THE CARDIORENAL SYNDROME].

    Science.gov (United States)

    Balint, I; Vučak, J; Bašić-Marković, N; Klarić, D; Šakić, V Amerl

    2016-12-01

    Cardiorenal syndrome, a complex pathophysiological disorder of both the heart and kidneys, is a condition in which acute or chronic damage to one organ can lead to acute or chronic dysfunction of the other organ. Depending on primary organ dysfunction and disease duration, there are five different types of cardiorenal syndrome. Type 1 cardiorenal syndrome (acute cardiorenal syndrome) is defined as acute kidney injury caused by sudden decrease in heart function. Type 2 cardiorenal syndrome (chronic cardiorenal syndrome) refers to chronic kidney disease linked to chronic heart failure. Type 3 cardiorenal syndrome (acute renocardial syndrome) is caused by acute kidney injury that leads to heart failure. Type 4 cardiorenal syndrome (chronic renocardial syndrome) includes chronic heart failure due to chronic kidney disease. Type 5 cardiorenal syndrome (secondary cardiorenal syndrome) is reversible or irreversible condition marked by simultaneous heart and kidney insufficiency, as a result of multiorgan disease such as sepsis, diabetes mellitus, sarcoidosis, amyloidosis, etc. The pathophysiological patterns of cardiorenal syndrome are extremely complicated. Despite numerous publications, perplexed physiological, biochemical and hormonal disturbances as parts of the main pathogenic mechanisms of cardiorenal syndrome remain obscure. Even though there are guidelines for the treatment of patients with heart failure and chronic kidney disease, similar guidelines for the treatment of cardiorenal syndrome are lacking. In everyday practice, it is crucial to diagnose cardiorenal syndrome and use all diagnostic and therapeutic procedures available to prevent or alleviate kidney and heart failure.

  7. A mathematical model towards understanding the mechanism of neuronal regulation of wake-NREMS-REMS states.

    Directory of Open Access Journals (Sweden)

    Rupesh Kumar

    Full Text Available In this study we have constructed a mathematical model of a recently proposed functional model known to be responsible for inducing waking, NREMS and REMS. Simulation studies using this model reproduced sleep-wake patterns as reported in normal animals. The model helps to explain neural mechanism(s that underlie the transitions between wake, NREMS and REMS as well as how both the homeostatic sleep-drive and the circadian rhythm shape the duration of each of these episodes. In particular, this mathematical model demonstrates and confirms that an underlying mechanism for REMS generation is pre-synaptic inhibition from substantia nigra onto the REM-off terminals that project on REM-on neurons, as has been recently proposed. The importance of orexinergic neurons in stabilizing the wake-sleep cycle is demonstrated by showing how even small changes in inputs to or from those neurons can have a large impact on the ensuing dynamics. The results from this model allow us to make predictions of the neural mechanisms of regulation and patho-physiology of REMS.

  8. Central voice production and pathophysiology of spasmodic dysphonia.

    Science.gov (United States)

    Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

    2018-01-01

    Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Pathophysiology of enteric infections with Giardia duodenalis

    Directory of Open Access Journals (Sweden)

    Buret A.G.

    2008-09-01

    Full Text Available Giardia is the most prevalent human intestinal parasitic protist in the world, and one of the most common parasite of companion animals and young livestock. Giardia is a major cause of diarrhea in children and in travelers. The host-microbial interactions that govern the outcome of infection remain incompletely understood. Findings available to date indicate that the infection causes diarrhea via a combination of intestinal malabsorption and hypersecretion. Malabsorption and maldigestion mainly result from a diffuse shortening of epithelial microvilli. This enterocytic injury is mediated by activated host T lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia-induced disruption of epithelial tight junctions, which in turn increases intestinal permeability. Loss of epithelial barrier function is a result of Giardia-induced enterocyte apoptosis. Recent findings suggest that these effects may facilitate the development of chronic enteric disorders, including inflammatory bowel disease, irritable bowel syndrome, and allergies, via mechanisms that remain poorly understood. A newly discovered SGLT-1 glucose uptake-mediated host cytoprotective mechanism may represent an effective modulator of the epithelial apoptosis induced by this parasite, and, possibly, by other enteropathogens. A better understanding of the pathogenesis of giardiasis will shed light on new potential therapeutic targets.

  10. Maternal syphilis: pathophysiology and treatment.

    Science.gov (United States)

    Berman, Stuart M

    2004-06-01

    Despite the long history of medical interest in syphilis and its effects on pregnancy outcome, many fundamental questions about the pathophysiology and treatment of syphilis during pregnancy remain unanswered. However, understanding has been advanced by recent scientific reports such as those which delineate the complete sequence of the genome of the syphilis spirochaete, provide a more precise description of fetal and neonate infection by use of rabbit infectivity tests and describe the gestational age distribution of fetal death secondary to syphilis. It appears that fetal syphilitic involvement progresses in a rather predictable fashion, and although there is disagreement about the optimal prenatal treatment regimen, programmatic efforts to prevent fetal death must provide seropositive pregnant women with a recommended treatment early in pregnancy, and certainly before the third trimester.

  11. Understanding mechanisms of raveling to extend open graded friction course (OGFC) service life.

    Science.gov (United States)

    2016-03-01

    To understand the mechanisms of raveling in open graded friction course (OGFC) mixtures, this project was divided into experimental measurements and finite element (FE) modeling. For the experimental part, mixtures with good and poor field performanc...

  12. The pathophysiology of bronchiectasis

    Directory of Open Access Journals (Sweden)

    Paul T King

    2009-10-01

    Full Text Available Paul T KingDepartment of Medicine, Department of Respiratory and Sleep Medicine, Monash University, Monash Medical Centre, Melbourne, Victoria, AustraliaAbstract: Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. It is usually diagnosed using computed tomography scanning to visualize the larger bronchi. Bronchiectasis is also characterized by mild to moderate airflow obstruction. This review will describe the pathophysiology of noncystic fibrosis bronchiectasis. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As most of the bronchial tree is composed of small airways, the net effect is obstruction. The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It has recently been demonstrated that patients with bronchiectasis have a progressive decline in lung function. There are a large number of etiologic risk factors associated with bronchiectasis. As there is generally a long-term retrospective history, it may be difficult to determine the exact role of such factors in the pathogenesis. Extremes of age and smoking/chronic obstructive pulmonary disease may be important considerations. There are a variety of different pathogens involved in bronchiectasis, but a common finding despite the presence of purulent sputum is failure to identify any pathogenic microorganisms. The bacterial flora appears to change with progression of disease. Keywords: bronchiectasis, inflammation, obstructive lung disease, pathophysiology, pathology

  13. Understanding the mechanism(s) of mosaic trisomy 21 by using DNA polymorphism analysis

    Energy Technology Data Exchange (ETDEWEB)

    Pangalos, C.; Abazis, D.; Avramopoulos, D.; Blouin, J.L.; Antonaraksi, S.E. (Univ. of Patras Medical School (Greece)); Raoul, O.; deBlois, M.C.; Prieur, M. (Cytogenetics Laboratory, Paris (France)); Schinzel, A.A.

    1994-03-01

    In order to investigate the mechanism(s) underlying mosaicism for trisomy 21, the authors genotyped 17 families with mosaic trisomy 21 probands, using 28 PCR-detectable DNA polymorphic markers that map in the pericentromeric region and long arm of chromosome 21. The percentage of cells with trisomy 21 in the probands' blood lymphocytes was 6%-94%. There were two classes of autoradiographic results: In class I, a third allele' of lower intensity was detected in the proband's DNA for at least two chromosome 21 markers. The interpretation of this result was that the proband had inherited three chromosomes 21 after meiotic nondisjunction (NDJ) (trisomy 21 zygote) and subsequently lost one because of mitotic (somatic) error, the lost chromosome 21 being that with the lowest-intensity polymorphic allele. The parental origin and the meiotic stage of NDJ could also be determined. In class II, a third allele' was never detected. In these cases, the mosaicism probably occurred either by a postzygotic, mitotic error in anormal zygote that followed a normal meiosis (class IIA mechanism); by premeiotic, mitotic NDJ yielding an aneusomic zygote after meiosis, and subsequent mitotic loss (class IIB mechanism); or by a meiosis II error with lack of crossover in the preceding meiosis I, followed by mitotic loss after fertilization (class IIC mechanism). Among class II mechanisms, the most likely is mechanism IIA, while IIC is the least likely. There were 10 cases of class I and 7 cases of class II results. Within class I, there were nine cases with maternal meitoic errors (six meiosis I and three meiosis II errors, on the basis of pericentromeric markers) and one with paternal meiosis I error. The postzygotic loss of chromosome 21 was determined in eight maternal class I cases, and it was maternally derived in five cases and paternally derived in three; this suggests that the postzygotic loss of chromosome 21 is probably random. 28 refs., 1 fig., 2 tabs.

  14. Transcranial magnetic stimulation and sleep disorders: pathophysiologic insights.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Brigo, Francesco; Tezzon, Frediano; Golaszewski, Stefan; Trinka, Eugen

    2013-11-01

    The neural mechanisms underlying the development of the most common intrinsic sleep disorders are not completely known. Therefore, there is a great need for noninvasive tools which can be used to better understand the pathophysiology of these diseases. Transcranial magnetic stimulation (TMS) offers a method to noninvasively investigate the functional integrity of the motor cortex and its corticospinal projections in neurologic and psychiatric diseases. To date, TMS studies have revealed cortical and corticospinal dysfunction in several sleep disorders, with cortical hyperexcitability being a characteristic feature in some disorders (i.e., the restless legs syndrome) and cortical hypoexcitability being a well-established finding in others (i.e., obstructive sleep apnea syndrome narcolepsy). Several research groups also have applied TMS to evaluate the effects of pharmacologic agents, such as dopaminergic agent or wake-promoting substances. Our review will focus on the mechanisms underlying the generation of abnormal TMS measures in the different types of sleep disorders, the contribution of TMS in enhancing the understanding of their pathophysiology, and the potential diagnostic utility of TMS techniques. We also briefly discussed the possible future implications for improving therapeutic approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Framework for Understanding the Patterns of Student Difficulties in Quantum Mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2015-01-01

    Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. Here, we describe a framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that…

  16. Pathophysiology of nocturnal enuresis

    DEFF Research Database (Denmark)

    Rittig, Søren; Kamperis, Konstantinos

    2015-01-01

    overactivity, or a defect intrinsic circadian control of bladder function. The role of sleep is currently under scrutiny as recent evidence point towards poor sleep with increased sleep fragmentation, arousal index, and periodic limb movements as important factors. One unifying pathophysiologic theory suggests...... vasopressin levels and renal factors such as increased GFR and solute excretion (e.g. sodium) as well as increased prostaglandin PGE2 excretion. Furthermore, nocturnal polyuria has been associated with poor sleep (e.g. sleep fragmentation) and increased nocturnal arterial blood pressure levels. Another...... important part of enuresis pathogenesis is reduced bladder capacity, either during night-time only or present during daytime also (i.e. reduced MVV on a FV chart). The background behind the reduced nocturnal reservoir function is not fully clarified but may involve CNS regulatory centers, detrusor...

  17. Pathophysiology of glucagon secretion

    International Nuclear Information System (INIS)

    Boettger, J.; Pabst, H.W.

    1980-01-01

    Pathophysiology of glucagon secretion is reviewed in brief separating hyperglucagonemic from hypoclucagonemic states. Many questions concerning the role of glucagon in diabetes mellitus and in other diseases are still unresolved. The clucagon RIA is of clinical significance in a few diseases like glucagonoma, which may present without symptoms of the 'glucagonoma syndrome', the probably very rare hyperglucagonemia and some of the spontaneous hypoglycemias. Glucagon secretion may be evaluated by the determination of fasting immunoreactive glucagon (IRG) and by appropriate function tests as stimulation with i.v. arginine and suppression with oral glucose. However, the glucagon RIA at present is not a routine method, although commercial kits are available. Many pitfalls of radioimmunological glucagon determination still exist. (orig.) [de

  18. Acute colonic diverticulitis: modern understanding of pathomechanisms, risk factors, disease burden and severity

    NARCIS (Netherlands)

    Søreide, Kjetil; Boermeester, Marja A.; Humes, David J.; Velmahos, George C.

    2016-01-01

    Conservative, non-antibiotic and non-surgical management of acute diverticulitis is currently being investigated. To better inform clinical decisions, better understanding of disease mechanisms, disease burden and severity is needed. Literature search of risk factors, pathophysiology, epidemiology

  19. Pathophysiology and Immune Dysfunction in Endometriosis

    Directory of Open Access Journals (Sweden)

    Soo Hyun Ahn

    2015-01-01

    Full Text Available Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis.

  20. Pathophysiology and Immune Dysfunction in Endometriosis

    Science.gov (United States)

    Ahn, Soo Hyun; Monsanto, Stephany P.; Miller, Caragh; Singh, Sukhbir S.; Thomas, Richard; Tayade, Chandrakant

    2015-01-01

    Endometriosis is an estrogen-dependent, chronic, proinflammatory disease prevalent in 10% of women of reproductive age worldwide. Characterized by the growth of endometrium-like tissue in aberrant locations outside of the uterus, it is responsible for symptoms including chronic pelvic pain, dysmenorrhea, and subfertility that degrade quality of life of women significantly. In Canada, direct and indirect economic cost of endometriosis amounts to 1.8 billion dollars, and this is elevated to 20 billion dollars in the United States. Despite decades of research, the etiology and pathophysiology of endometriosis still remain to be elucidated. This review aims to bring together the current understanding regarding the pathogenesis of endometriosis with specific focus on mechanisms behind vascularization of the lesions and the contribution of immune factors in facilitating lesion establishment and development. The role of hormones, immune cells, and cytokine signaling is highlighted, in addition to discussing the current pharmaceutical options available for management of pain symptoms in women with endometriosis. PMID:26247027

  1. A model-based approach to investigating the pathophysiological mechanisms of hypertension and response to antihypertensive therapies: extending the Guyton model.

    Science.gov (United States)

    Hallow, K Melissa; Lo, Arthur; Beh, Jeni; Rodrigo, Manoj; Ermakov, Sergey; Friedman, Stuart; de Leon, Hector; Sarkar, Anamika; Xiong, Yuan; Sarangapani, Ramesh; Schmidt, Henning; Webb, Randy; Kondic, Anna Georgieva

    2014-05-01

    Reproducibly differential responses to different classes of antihypertensive agents are observed among hypertensive patients and may be due to interindividual differences in hypertension pathology. Computational models provide a tool for investigating the impact of underlying disease mechanisms on the response to antihypertensive therapies with different mechanisms of action. We present the development, calibration, validation, and application of an extension of the Guyton/Karaaslan model of blood pressure regulation. The model incorporates a detailed submodel of the renin-angiotensin-aldosterone system (RAAS), allowing therapies that target different parts of this pathway to be distinguished. Literature data on RAAS biomarker and blood pressure responses to different classes of therapies were used to refine the physiological actions of ANG II and aldosterone on renin secretion, renal vascular resistance, and sodium reabsorption. The calibrated model was able to accurately reproduce the RAAS biomarker and blood pressure responses to combinations of dual-RAAS agents, as well as RAAS therapies in combination with diuretics or calcium channel blockers. The final model was used to explore the impact of underlying mechanisms of hypertension on the blood pressure response to different classes of antihypertensive agents. Simulations indicate that the underlying etiology of hypertension can impact the magnitude of response to a given class of therapy, making a patient more sensitive to one class and less sensitive others. Given that hypertension is usually the result of multiple mechanisms, rather than a single factor, these findings yield insight into why combination therapy is often required to adequately control blood pressure.

  2. Teaching pathophysiology: strategies to enliven the traditional lecture.

    Science.gov (United States)

    Van Horn, Elizabeth R; Hyde, Yolanda M; Tesh, Anita S; Kautz, Donald D

    2014-01-01

    The depth and breadth of pathophysiology content, foundational for nursing practice, is well suited for traditional lecture delivery. Use of creative strategies can deepen students' understanding while respecting students' diverse talents and ways of learning. The authors discuss strategies they used, including case studies, questions asked during lecture using immediate feedback technology, creative visual demonstrations, group pathophysiologic theory projects, short videos, and games, to enhance students' understanding and retention of content.

  3. New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis

    Science.gov (United States)

    2015-11-01

    Award Number: W81XWH-12-1-0449 TITLE: New Drugs for Anemia Treatment Based on a New Understanding of the Mechanisms of Stress Erythropoiesis...COVERED 1Sep2012 - 31Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER New Drugs for Anemia Treatment Based on a New Understanding of the...cell formation in "Nan" (neonatal anemia ) mice, raising the level of red cells to almost normal. It also causes an increase in the numbers of splenic

  4. Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

    DEFF Research Database (Denmark)

    Blegvad, C.; Skjolding, A D; Broholm, H

    2013-01-01

    We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms....

  5. Air leak after lung resection: pathophysiology and patients’ implications

    Science.gov (United States)

    Miserocchi, Giuseppe

    2016-01-01

    Protocols for the management of air leaks are critical aspects in the postoperative course of patients following lung resections. Many investigations in the last decade are focusing on the chest tube modalities or preventative measures, however, little is known about the pathophysiology of air leak and the patient perception of this common complication. This review concentrates on understanding the reasons why a pulmonary parenchyma may start to leak or an air leak may be longer than others. Experimental works support the notion that lung overdistension may favor air leak. These studies may represent the basis of future investigations. Furthermore, the standardization of nomenclature in the field of pleural space management and the creation of novel air leak scoring systems have contributed to improve the knowledge among thoracic surgeons and facilitate the organization of trials on this matter. We tried to summarize available evidences about the patient perception of a prolonged air leak and about what would be useful for them in order to prevent worsening of their quality of life. Future investigations are warranted to better understand the pathophysiologic mechanisms responsible of prolonged air leak in order to define tailored treatments and protocols. Improving the care at home with web-based telemonitoring or real time connected chest drainage may in a future improve the quality of life of the patients experience this complication and also enhance hospital finances. PMID:26941970

  6. Understanding Creep Mechanisms in Graphite with Experiments, Multiscale Simulations, and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Eapen, Jacob [North Carolina State Univ., Raleigh, NC (United States); Murty, Korukonda [North Carolina State Univ., Raleigh, NC (United States); Burchell, Timothy [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-06-02

    Disordering mechanisms in graphite have a long history with conflicting viewpoints. Using Raman and x-ray photon spectroscopy, electron microscopy, x-ray diffraction experiments and atomistic modeling and simulations, the current project has developed a fundamental understanding of early-to-late state radiation damage mechanisms in nuclear reactor grade graphite (NBG-18 and PCEA). We show that the topological defects in graphite play an important role under neutron and ion irradiation.

  7. Studies on the Pathophysiology and Genetic Basis of Migraine

    Science.gov (United States)

    Gasparini, Claudia F; Sutherland, Heidi G.; Griffiths, Lyn R

    2013-01-01

    Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies. PMID:24403849

  8. Sixth-Grade Students' Progress in Understanding the Mechanisms of Global Climate Change

    Science.gov (United States)

    Visintainer, Tammie; Linn, Marcia

    2015-04-01

    Developing solutions for complex issues such as global climate change requires an understanding of the mechanisms involved. This study reports on the impact of a technology-enhanced unit designed to improve understanding of global climate change, its mechanisms, and their relationship to everyday energy use. Global Climate Change, implemented in the Web-based Inquiry Science Environment (WISE), engages sixth-grade students in conducting virtual investigations using NetLogo models to foster an understanding of core mechanisms including the greenhouse effect. Students then test how the greenhouse effect is enhanced by everyday energy use. This study draws on three data sources: (1) pre- and post-unit interviews, (2) analysis of embedded assessments following virtual investigations, and (3) contrasting cases of two students (normative vs. non-normative understanding of the greenhouse effect). Results show the value of using virtual investigations for teaching the mechanisms associated with global climate change. Interviews document that students hold a wide range of ideas about the mechanisms driving global climate change. Investigations with models help students use evidence-based reasoning to distinguish their ideas. Results show that understanding the greenhouse effect offers a foundation for building connections between everyday energy use and increases in global temperature. An impediment to establishing coherent understanding was the persistence of an alternative conception about ozone as an explanation for climate change. These findings illustrate the need for regular revision of curriculum based on classroom trials. We discuss key design features of models and instructional revisions that can transform the teaching and learning of global climate change.

  9. Pathophysiology of constipation in the older adult

    OpenAIRE

    McCrea, G Lindsay; Miaskowski, Christine; Stotts, Nancy A; Macera, Liz; Varma, Madhulika G

    2008-01-01

    This review provides information on the definition of constipation, normal continence and defecation and a description of the pathophysiologic mechanisms of constipation. In addition, changes in the anatomy and physiology of the lower gastrointestinal tract associated with aging that may contribute to constipation are described. MEDLINE (1966-2007) and CINAHL (1980-2007) were searched. The following MeSH terms were used: constipation/etiology OR constipation/physiology OR constipation/physiop...

  10. Effects of Representation Sequences and Spatial Ability on Students' Scientific Understandings about the Mechanism of Breathing

    Science.gov (United States)

    Wu, Hsin-Kai; Lin, Yu-Fen; Hsu, Ying-Shao

    2013-01-01

    The purpose of this study was to investigate the effects of representation sequences and spatial ability on students' scientific understandings about the mechanism of breathing in human beings. 130 seventh graders were assigned to two groups with different sequential combinations of static and dynamic representations: SD group (i.e., viewing…

  11. Enhanced understanding of the relationship between chemical modification and mechanical properties of wood

    Science.gov (United States)

    Charles R. Frihart; Daniel J. Yelle; John Ralph; Robert J. Moon; Donald S. Stone; Joseph E. Jakes

    2008-01-01

    Chemical additions to wood often change its bulk properties, which can be determined using conventional macroscopic mechanical tests. However, the controlling interactions between chemicals and wood take place at and below the scale of individual cells and cell walls. To better understand the effects of chemical additions to wood, we have adapted and extended two...

  12. TFOS DEWS II pathophysiology report.

    Science.gov (United States)

    Bron, Anthony J; de Paiva, Cintia S; Chauhan, Sunil K; Bonini, Stefano; Gabison, Eric E; Jain, Sandeep; Knop, Erich; Markoulli, Maria; Ogawa, Yoko; Perez, Victor; Uchino, Yuichi; Yokoi, Norihiko; Zoukhri, Driss; Sullivan, David A

    2017-07-01

    The TFOS DEWS II Pathophysiology Subcommittee reviewed the mechanisms involved in the initiation and perpetuation of dry eye disease. Its central mechanism is evaporative water loss leading to hyperosmolar tissue damage. Research in human disease and in animal models has shown that this, either directly or by inducing inflammation, causes a loss of both epithelial and goblet cells. The consequent decrease in surface wettability leads to early tear film breakup and amplifies hyperosmolarity via a Vicious Circle. Pain in dry eye is caused by tear hyperosmolarity, loss of lubrication, inflammatory mediators and neurosensory factors, while visual symptoms arise from tear and ocular surface irregularity. Increased friction targets damage to the lids and ocular surface, resulting in characteristic punctate epithelial keratitis, superior limbic keratoconjunctivitis, filamentary keratitis, lid parallel conjunctival folds, and lid wiper epitheliopathy. Hybrid dry eye disease, with features of both aqueous deficiency and increased evaporation, is common and efforts should be made to determine the relative contribution of each form to the total picture. To this end, practical methods are needed to measure tear evaporation in the clinic, and similarly, methods are needed to measure osmolarity at the tissue level across the ocular surface, to better determine the severity of dry eye. Areas for future research include the role of genetic mechanisms in non-Sjögren syndrome dry eye, the targeting of the terminal duct in meibomian gland disease and the influence of gaze dynamics and the closed eye state on tear stability and ocular surface inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery: epigenetic regulation of the hypoxic response via hypoxia-inducible factor and histone modifying enzymes.

    Science.gov (United States)

    Mimura, Imari; Tanaka, Tetsuhiro; Wada, Youichiro; Kodama, Tatsuhiko; Nangaku, Masaomi

    2011-01-01

    The hypoxia response regulated primarily by hypoxia-inducible factor (HIF) influences metabolism, cell survival, and angiogenesis to maintain biological homeostasis. In addition to the traditional transcriptional regulation by HIF, recent studies have shown that epigenetic modulation such as histone methylation, acetylation, and DNA methylation could change the regulation of the response to hypoxia. Eukaryotic chromatin is known to be modified by multiple post-translational histone methylation and demethylation, which result in the chromatin conformation change to adapt to hypoxic stimuli. Interestingly, some of the histone demethylase enzymes, which have the Jumonji domain-containing family, require oxygen to function and are induced by hypoxia in an HIF-1-dependent manner. Recent studies have demonstrated that histone modifiers play important roles in the hypoxic environment such as that in cancer cells and that they may become new therapeutic targets for cancer patients. It may lead to finding a new therapy for cancer to clarify a new epigenetic mechanism by HIF and histone demethylase such as JMJD1A (KDM3A) under hypoxia.

  14. Role of Adenosine A2A Receptors in Modulating Synaptic Functions and Brain Levels of BDNF: a Possible Key Mechanism in the Pathophysiology of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Maria Teresa Tebano

    2010-01-01

    Full Text Available In the last few years, accumulating evidence has shown the existence of an important cross-talk between adenosine A2A receptors (A2ARs and brain-derived neurotrophic factor (BDNF. Not only are A2ARs involved in the mechanism of transactivation of BDNF receptor TrkB, they also modulate the effect of BDNF on synaptic transmission, playing a facilitatory and permissive role. The cAMP-PKA pathway, the main transduction system operated by A2ARs, is involved in such effects. Furthermore, a basal tonus of A2ARs is required to allow the regulation of BDNF physiological levels in the brain, as demonstrated by the reduced protein levels measured in A2ARs KO mice. The crucial role of adenosine A2ARs in the maintenance of synaptic functions and BDNF levels will be reviewed here and discussed in the light of possible implications for Huntington's disease therapy, in which a joint impairment of BDNF and A2ARs seems to play a pathogenetic role.

  15. Extracellular Vesicles in Renal Pathophysiology.

    Science.gov (United States)

    Pomatto, Margherita A C; Gai, Chiara; Bussolati, Benedetta; Camussi, Giovanni

    2017-01-01

    Extracellular vesicles are a heterogeneous population of microparticles released by virtually all living cells which have been recently widely investigated in different biological fields. They are typically composed of two primary types (exosomes and microvesicles) and are recently commanding increasing attention as mediators of cellular signaling. Indeed, these vesicles can affect recipient cells by carrying and delivering complex cargos of biomolecules (including proteins, lipids and nucleic acids), protected from enzymatic degradation in the environment. Their importance has been demonstrated in the pathophysiology of several organs, in particular in kidney, where different cell types secrete extracellular vesicles that mediate their communication with downstream urinary tract cells. Over the past few years, evidence has been shown that vesicles participate in kidney development and normal physiology. Moreover, EVs are widely demonstrated to be implicated in cellular signaling during renal regenerative and pathological processes. Although many EV mechanisms are still poorly understood, in particular in kidney, the discovery of their role could help to shed light on renal biological processes which are so far elusive. Lastly, extracellular vesicles secreted by renal cells gather in urine, thus becoming a great resource for disease or recovery markers and a promising non-invasive diagnostic instrument for renal disease. In the present review, we discuss the most recent findings on the role of extracellular vesicles in renal physiopathology and their potential implication in diagnosis and therapy.

  16. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    Science.gov (United States)

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The pathophysiology of diarrhea.

    Science.gov (United States)

    Sellin, J H

    2001-01-01

    Diarrhea is a very common event after transplantation, but its cause may be difficult to identify. The first step in determining the cause in any particular case is an understanding of the etiology of diarrhea in general. Although diarrhea often is categorized into such types as secretory versus osmotic, or electrolyte transport-related versus motility-related, a thorough understanding of the problem requires knowledge of how the paracrine, immune, nervous and endocrine systems react to each other as well as to infection, drugs or other stimuli.

  18. Unit Mechanisms of Fission Gas Release: Current Understanding and Future Needs

    Energy Technology Data Exchange (ETDEWEB)

    Tonks, Michael; Andersson , David; Devanathan, Ram; Dubourg, Roland; El-Azab, Anter A.; Freyss, Michel; Iglesias, Fernando; Kulacsy, Katalin; Pastore, Giovanni; Phillpot, Simon R.; Welland, Michael

    2018-03-16

    Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel properties and, once the gas is released into the gap between the fuel and cladding, lowering gap thermal conductivity and increasing gap pressure. While gaseous fission product behavior has been investigated with bulk reactor experiments and simplified analytical models, recent improvements in experimental and modeling approaches at the atomistic and mesoscales are being applied to provide unprecedented understanding of the unit mechanisms that define the fission product behavior. In this article, existing research on the basic mechanisms behind the various stages of fission gas release during normal reactor operation are summarized and critical areas where experimental and simulation work is needed are identified. This basic understanding of the fission gas behavior mechanisms has the potential to revolutionize our ability to predict fission product behavior during reactor operation and to design fuels that have improved fission product retention. In addition, this work can serve as a model on how a coupled experimental and modeling approach can be applied to understand the unit mechanisms behind other critical behaviors in reactor materials.

  19. How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.

    Science.gov (United States)

    Penmatsa, Aravind; Gouaux, Eric

    2014-03-01

    Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.

  20. Understanding the growth mechanism of carbon nanotubes via the ``cluster volume to surface area" model

    Science.gov (United States)

    Mandati, Sreekanth; Kunstmann, Jens; Boerrnert, Felix; Schoenfelder, Ronny; Ruemmeli, Mark; Kar, Kamal K.; Cuniberti, Gianaurelio

    2010-03-01

    The influence of mixed catalysts for the high yield production of carbon nanotubes (CNTs) has been studied systematically. Based on extensive experimental data a ``Catalyst Volume to Surface Area'' (CVSA) model was developed to understand the influence of the process parameters on the yield and CNT diameter distribution [1]. In our study, we present a refined version of the CVSA model developed by combining experiments and simulations. We discuss our current understanding of the growth mechanism and how the model might be used to increase CNT yields by using mixed catalysts.[4pt] [1] S. Tetali et al., ACS Nano (2009), DOI: 10.1021/nn9012548.

  1. Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

    Science.gov (United States)

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

    The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

  2. Pathophysiology of Hyperhidrosis.

    Science.gov (United States)

    Schick, Christoph H

    2016-11-01

    Studies and case reports on excessive sweating frequently state that hyperhidrosis is a disease whose origin and mechanism are unknown. However, the term excessive is rarely based on systematic diagnostic measurements, instead being a description of the symptoms from patient histories, which suggests that hyperhidrosis is purely a problem involving the quantity of sweat, whereas it is a change in the control mechanism of sweating in which the need for and production of sweat are strongly disproportionate. This lack of proportion is perceived by those affected to be a limitation of activities of daily living and is thus pathologic. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Understanding the Mechanisms of Radiation Belt Dropouts Observed by Van Allen Probes

    Science.gov (United States)

    Xiang, Zheng; Tu, Weichao; Li, Xinlin; Ni, Binbin; Morley, S. K.; Baker, D. N.

    2017-10-01

    To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and the μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. The evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.

  4. Concussion: the history of clinical and pathophysiological concepts and misconceptions.

    Science.gov (United States)

    McCrory, P R; Berkovic, S F

    2001-12-26

    Concussion is a well-recognized clinical entity; however, its pathophysiologic basis remains a mystery. One unresolved issue is whether concussion is associated with lesser degrees of diffuse structural change seen in severe traumatic brain injury, or is the mechanism entirely caused by reversible functional changes. This issue is clouded not only by the lack of critical data, but also by confusion in terminology, even in contemporary literature. This confusion began in ancient times when no distinction was made between the transient effects of concussion and severe traumatic brain injury. The first clear separate recognition of concussion was made by the Persian physician, Rhazes, in the 10th century. Lanfrancus subsequently expanded this concept as brain "commotion" in the 13th century, although other Renaissance physicians continued to obscure this concept. By the 18th century, a variety of hypotheses for concussion had emerged. The 19th century discovery of petechial hemorrhagic lesions in severe traumatic brain injury led to these being posited as the basis of concussion, and a similar logic was used later to suggest diffuse axonal injury was responsible. The neuropathology and pathophysiology of concussion has important implications in neurology, sports medicine, medicolegal medicine, and in the understanding of consciousness. Fresh approaches to these questions are needed and modern research tools, including functional imaging and experimental studies of ion-channel function, could help elucidate this puzzle that has evolved over the past 3,000 years.

  5. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

    Science.gov (United States)

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F.; Ebihara, Hideki; Scott, Dana P.; Hjelle, Brian; Feldmann, Heinz

    2014-01-01

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  6. Unified understanding of folding and binding mechanisms of globular and intrinsically disordered proteins.

    Science.gov (United States)

    Arai, Munehito

    2018-01-06

    Extensive experimental and theoretical studies have advanced our understanding of the mechanisms of folding and binding of globular proteins, and coupled folding and binding of intrinsically disordered proteins (IDPs). The forces responsible for conformational changes and binding are common in both proteins; however, these mechanisms have been separately discussed. Here, we attempt to integrate the mechanisms of coupled folding and binding of IDPs, folding of small and multi-subdomain proteins, folding of multimeric proteins, and ligand binding of globular proteins in terms of conformational selection and induced-fit mechanisms as well as the nucleation-condensation mechanism that is intermediate between them. Accumulating evidence has shown that both the rate of conformational change and apparent rate of binding between interacting elements can determine reaction mechanisms. Coupled folding and binding of IDPs occurs mainly by induced-fit because of the slow folding in the free form, while ligand binding of globular proteins occurs mainly by conformational selection because of rapid conformational change. Protein folding can be regarded as the binding of intramolecular segments accompanied by secondary structure formation. Multi-subdomain proteins fold mainly by the induced-fit (hydrophobic collapse) mechanism, as the connection of interacting segments enhances the binding (compaction) rate. Fewer hydrophobic residues in small proteins reduce the intramolecular binding rate, resulting in the nucleation-condensation mechanism. Thus, the folding and binding of globular proteins and IDPs obey the same general principle, suggesting that the coarse-grained, statistical mechanical model of protein folding is promising for a unified theoretical description of all mechanisms.

  7. Material properties of biofilms – key methods for understanding permeability and mechanics

    Science.gov (United States)

    Billings, Nicole; Birjiniuk, Alona; Samad, Tahoura S.; Doyle, Patrick S.; Ribbeck, Katharina

    2015-01-01

    Microorganisms can form biofilms, which are multicellular communities surrounded by a hydrated extracellular matrix of polymers. Central properties of the biofilm are governed by this extracellular matrix, which provides mechanical stability to the three-dimensional biofilm structure, regulates the ability of the biofilm to adhere to surfaces, and determines the ability of the biofilm to adsorb gasses, solutes, and foreign cells. Despite their critical relevance for understanding and eliminating of biofilms, the materials properties of the extracellular matrix are understudied. Here, we offer the reader a guide to current technologies that can be utilized to specifically assess the permeability and mechanical properties of the biofilm matrix and its interacting components. In particular, we highlight technological advances in instrumentation and interactions between multiple disciplines that have broadened the spectrum of methods available to conduct these studies. We review pioneering work that furthers our understanding of the material properties of biofilms. PMID:25719969

  8. Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

    Science.gov (United States)

    Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

    2017-06-01

    Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes.

  9. Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

    Science.gov (United States)

    Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

    2017-01-01

    Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes. PMID:28660882

  10. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  11. Improving student understanding of addition of angular momentum in quantum mechanics

    Directory of Open Access Journals (Sweden)

    Guangtian Zhu

    2013-01-01

    Full Text Available We describe the difficulties advanced undergraduate and graduate students have with concepts related to addition of angular momentum in quantum mechanics. We also describe the development and implementation of a research-based learning tool, Quantum Interactive Learning Tutorial (QuILT, to reduce these difficulties. The preliminary evaluation shows that the QuILT related to the basics of the addition of angular momentum is helpful in improving students’ understanding of these concepts.

  12. Understanding treatment effect mechanisms of the CAMBRA randomized trial in reducing caries increment

    OpenAIRE

    Cheng, J; Chaffee, BW; Cheng, NF; Gansky, SA; Featherstone, JDB

    2015-01-01

    © International & American Associations for Dental Research 2014. The Caries Management By Risk Assessment (CAMBRA) randomized controlled trial showed that an intervention featuring combined antibacterial and fluoride therapy significantly reduced bacterial load and suggested reduced caries increment in adults with 1 to 7 baseline cavitated teeth. While trial results speak to the overall effectiveness of an intervention, insight can be gained from understanding the mechanism by which an int...

  13. Pathophysiological mechanisms of urbanisation-related ...

    African Journals Online (AJOL)

    Twenty-seven urban hypertensive patients and the same number of normotensive controls were studied on baseline diet, after 5 days of sodium restriction and after 5 days of sodium loading. Mean arterial blood pressure, plasma and ET values, PRA, TXA2/PGI2 and ALDO were assessed on each diet. The results showed ...

  14. Obesity-related hypertension: possible pathophysiological mechanisms

    Czech Academy of Sciences Publication Activity Database

    Vaněčková, Ivana; Maletínská, Lenka; Behuliak, Michal; Nagelová, Veronika; Zicha, Josef; Kuneš, Jaroslav

    2014-01-01

    Roč. 223, č. 3 (2014), R63-R78 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 ; RVO:61388963 Keywords : obesity * hypertension * sympathetic nervous system * renin-angiotensin system * critical developmental periods * epigenetics * rat Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.718, year: 2014

  15. Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents

    Directory of Open Access Journals (Sweden)

    Ja Hye Kim

    2013-12-01

    Full Text Available The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11β-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding, effective treatment for hypothalamic obesity has not yet been developed. Therefore, understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology, endocrine characteristics, and treatment strategies of hypothalamic obesity.

  16. Saturation diving; physiology and pathophysiology.

    Science.gov (United States)

    Brubakk, Alf O; Ross, John A S; Thom, Stephen R

    2014-07-01

    . Furthermore, divers who are required to return to the surface quickly are under higher risk of serious injury as no adequate decompression procedures for such situations are available. Decompression also leads to the production of endothelial microparticles that may reduce endothelial function. As good endothelial function is a documented indicator of health that can be influenced by regular exercise, regular physical exercise is recommended for saturation divers. Nowadays, saturation diving is a reasonably safe and well controlled method for working under water. Until now, no long-term impact on health due to diving has been documented. However, we still have limited knowledge about the pathophysiologic mechanisms involved. In particular we know little about the effect of long exposure to hyperoxia and microparticles on the endothelium. © 2014 American Physiological Society.

  17. Integrating Classical with Emerging Concepts for Better Understanding of Salinity Stress Tolerance Mechanisms in Rice

    Directory of Open Access Journals (Sweden)

    Navdeep Kaur

    2017-07-01

    Full Text Available Rice is an important cereal crop responsible for world's food security. The sensitivity of rice plants toward a range of abiotic stresses is a prime challenge for its overall growth and productivity. Among these, salinity is a major stress which results in a significant loss of global rice yield annually. For finding straightforward and strict future solutions in order to assure the food security to growing world population, understanding of the various mechanisms responsible for salt stress tolerance in rice is of paramount importance. In classical studies, identification of salt tolerant cultivars and the genetic markers linked to salt tolerance and breeding approaches have been given emphasis. It further affirmed on the identification of various pathways regulating the complex process of salt stress adaptation. However, only limited success has been achieved in these approaches as salt tolerance is a complex process and is governed by multiple factors. Hence, for better understanding of salt tolerance mechanisms, a comprehensive approach involving physiological, biochemical and molecular studies is much warranted. Modern experimental and genetic resources have provided a momentum in this direction and have provided molecular insights into different salt stress responsive pathways at the signaling and regulatory level. The integrative knowledge of classical and modern research of the understanding of salt stress adaptive pathways can help the researchers for designing effective strategies to fight against salt stress. Hence, the present review is focused on the understanding of the salt stress tolerance mechanisms in rice through the consolidative knowledge of classical and modern concepts. It further highlights the emerging new trends of salt stress adaptive pathways in rice.

  18. Pathophysiology of epileptic encephalopathies.

    Science.gov (United States)

    Lado, Fred A; Rubboli, Guido; Capovilla, Giuseppe; Capovilla, Pippo; Avanzini, Giuliano; Moshé, Solomon L

    2013-11-01

    The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

  19. Pathophysiology diabetic foot ulcer

    Science.gov (United States)

    Syafril, S.

    2018-03-01

    Diabetes Mellitus (DM) is known to have many complications. Diabetes and its complications are rapidly becoming the world’s most significant cause of morbidity and mortality, and one of the most distressing is Diabetic Foot Ulcer (DFU). Chronic wound complications are a growing concern worldwide, and the effect is a warning to public health and the economy. The etiology of a DFU is multifaceted, and several components cause added together create a sufficient impact on ulceration: neuropathy, vasculopathy, immunopathy, mechanical stress, and neuroarthropathy. There are many classifications of the diabetic foot. About 50% of patients with foot ulcers due to DM present clinical signs of infection. It is essential to manage multifactorial etiology of DFU to get a good outcome.

  20. OCT monitoring of pathophysiological processes

    Science.gov (United States)

    Gladkova, Natalia D.; Shakhova, Natalia M.; Shakhov, Andrei; Petrova, Galina P.; Zagainova, Elena; Snopova, Ludmila; Kuznetzova, Irina N.; Chumakov, Yuri; Feldchtein, Felix I.; Gelikonov, Valentin M.; Gelikonov, Grigory V.; Kamensky, Vladislav A.; Kuranov, Roman V.; Sergeev, Alexander M.

    1999-04-01

    Based on results of clinical examination of about 200 patients we discuss capabilities of the optical coherence tomography (OCT) in monitoring and diagnosing of various pathophysiological processes. Performed in several clinical areas including dermatology, urology, laryngology, gynecology, and dentistry, our study shows the existence of common optical features in manifestation of a pathophysiological process in different organs. In this paper we focus at such universal tomographic optical signs for processes of inflammation, necrosis and tumor growth. We also present data on dynamical OCT monitoring of evolution of pathophysiological processes, both at the stage of disease development and following-up results of different treatments such as drug application, radiation therapy, cryodestruction, and laser vaporization. The discovered peculiarities of OCT images for structural and functional imaging of biological tissues can be put as a basis for application of this method for diagnosing of pathology, guidance of treatment, estimation of its adequacy and assessing of the healing process.

  1. Pathophysiology of the underactive bladder

    Directory of Open Access Journals (Sweden)

    Naoki Aizawa

    2017-12-01

    Full Text Available Underactive bladder (UAB, which has been described as a symptom complex suggestive of detrusor underactivity, is usually characterized by prolonged urination time with or without a sensation of incomplete bladder emptying, usually with hesitancy, reduced sensation on filling, and slow stream often with storage symptoms. Several causes such as aging, bladder outlet obstruction, diabetes mellitus, neurologic disorders, and nervous injury to the spinal cord, cauda equine, and peripheral pelvic nerve have been assumed to be responsible for the development of UAB. Several contributing factors have been suggested in the pathophysiology of UAB, including myogenic failure, efferent and/or afferent dysfunctions, and central nervous system dysfunction. In this review article, we have described relationships between individual contributing factors and the pathophysiology of UAB based on previous reports. However, many pathophysiological uncertainties still remain, which require more investigations using appropriate animal models.

  2. Understanding cellular responses to toxic agents: a model for mechanism-choice in bacterial metal resistance.

    Science.gov (United States)

    Rouch, D A; Lee, B T; Morby, A P

    1995-02-01

    Bacterial resistances to metals are heterogeneous in both their genetic and biochemical bases. Metal resistance may be chromosomally-, plasmid- or transposon-encoded, and one or more genes may be involved: at the biochemical level at least six different mechanisms are responsible for resistance. Various types of resistance mechanisms can occur singly or in combination and for a particular metal different mechanisms of resistance can occur in the same species. To understand better the diverse responses of bacteria to metal ion challenge we have constructed a qualitative model for the selection of metal resistance in bacteria. How a bacterium becomes resistant to a particular metal depends on the number and location of cellular components sensitive to the specific metal ion. Other important selective factors include the nature of the uptake systems for the metal, the role and interactions of the metal in the normal metabolism of the cell and the availability of plasmid (or transposon) encoded resistance mechanisms. The selection model presented is based on the interaction of these factors and allows predictions to be made about the evolution of metal resistance in bacterial populations. It also allows prediction of the genetic basis and of mechanisms of resistance which are in substantial agreement with those in well-documented populations. The interaction of, and selection for resistance to, toxic substances in addition to metals, such as antibiotics and toxic analogues, involve similar principles to those concerning metals. Potentially, models for selection of resistance to any substance can be derived using this approach.

  3. Lafora disease: epidemiology, pathophysiology and management.

    LENUS (Irish Health Repository)

    Monaghan, Thomas S

    2010-07-01

    Lafora disease is a rare, fatal, autosomal recessive, progressive myoclonic epilepsy. It may also be considered as a disorder of carbohydrate metabolism because of the formation of polyglucosan inclusion bodies in neural and other tissues due to abnormalities of the proteins laforin or malin. The condition is characterized by epilepsy, myoclonus and dementia. Diagnostic findings on MRI and neurophysiological testing are not definitive and biopsy or genetic studies may be required. Therapy in Lafora disease is currently limited to symptomatic management of the epilepsy, myoclonus and intercurrent complications. With a greater understanding of the pathophysiological processes involved, there is justified hope for future therapies.

  4. Pathophysiology of muscle contractures in cerebral palsy.

    Science.gov (United States)

    Mathewson, Margie A; Lieber, Richard L

    2015-02-01

    Patients with cerebral palsy present with a variety of adaptations to muscle structure and function. These pathophysiologic symptoms include functional deficits such as decreased force production and range of motion, in addition to changes in muscle structure such as decreased muscle belly size, increased sarcomere length, and altered extracellular matrix structure and composition. On a cellular level, patients with cerebral palsy have fewer muscle stem cells, termed satellite cells, and altered gene expression. Understanding the nature of these changes may present opportunities for the development of new muscle treatment therapies. Published by Elsevier Inc.

  5. Preeclampsia: pathophysiology and implications for care.

    Science.gov (United States)

    Townsend, Nancy S; Drummond, Susan B

    2011-01-01

    Nurses are increasingly encountering pregnant/postpartum women with hypertensive disorders of pregnancy, of which preeclampsia is one of the most common. The Joint Commission published a Sentinel Event Alert in 2010 on prevention of maternal death. This report notes that one of the 5 leading causes of pregnancy-related mortality between 1991 and 1997 was "hypertensive disorder." Preeclampsia presents significant risk to the health of the mother and the fetus. Clearly, nurses must understand the pathophysiology, assessment, management, recurrence risk, and long-term implications of preeclampsia to participate fully in a management plan that promotes safe patient care.

  6. Pathophysiological dilemmas of lipedema.

    Science.gov (United States)

    Szél, E; Kemény, L; Groma, G; Szolnoky, G

    2014-11-01

    Lipedema is a common, but often underdiagnosed masquerading disease of obesity, which almost exclusively affects females. There are many debates regarding the diagnosis as well as the treatment strategies of the disease. The clinical diagnosis is relatively simple, however, knowledge regarding the pathomechanism is less than limited and curative therapy does not exist at all demanding an urgent need for extensive research. According to our hypothesis, lipedema is an estrogen-regulated polygenetic disease, which manifests in parallel with feminine hormonal changes and leads to vasculo- and lymphangiopathy. Inflammation of the peripheral nerves and sympathetic innervation abnormalities of the subcutaneous adipose tissue also involving estrogen may be responsible for neuropathy. Adipocyte hyperproliferation is likely to be a secondary phenomenon maintaining a vicious cycle. Herein, the relevant articles are reviewed from 1913 until now and discussed in context of the most likely mechanisms leading to the disease, which could serve as a starting point for further research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Pathophysiology of Hemophilic Arthropathy.

    Science.gov (United States)

    Melchiorre, Daniela; Manetti, Mirko; Matucci-Cerinic, Marco

    2017-06-25

    Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy-a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin-OPG; receptor activator of nuclear factor κB-RANK; RANK ligand-RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy.

  8. Chemical sensitivity: pathophysiology or pathopsychology?

    Science.gov (United States)

    Genuis, Stephen J

    2013-05-01

    symptoms in some cases. Sustained resolution of the CS state occurs after successful elimination of the accrued body burden of toxicants through natural mechanisms of toxicant bioelimination and/or interventions of clinical detoxification. Despite extensive clinical evidence to support the veracity of this clinical state, many members of the medical community are reluctant to accept this condition as a pathophysiologic disorder. The emerging problem of ubiquitous adverse toxicant exposures in modern society has resulted in escalating numbers of individuals developing a CS disorder. As usual in medical history, iconoclastic ideas and emerging evidence regarding novel disease mechanisms, such as the pathogenesis of CS, have been met with controversy, resistance, and sluggish knowledge translation. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  9. MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation.

    Science.gov (United States)

    Lee, Juneyoung; Park, Eun Jeong; Kiyono, Hiroshi

    2016-05-01

    The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation. [BMB Reports 2016; 49(5): 263-269].

  10. Hypertension and obesity after pediatric kidney transplantation: management based on pathophysiology: A mini review

    Directory of Open Access Journals (Sweden)

    Eunice G John

    2014-01-01

    Full Text Available Hypertension after pediatric renal transplant is a common and important risk factor for graft loss and patient survival. The mechanism of post kidney transplant hypertension is complex and multifactorial. Control of blood pressure in renal transplant patients is important but often times blood pressures remain uncontrolled. The management of hypertension and obesity in pediatric kidney transplant patients is based on the pathophysiology. Compared to the general pediatric hypertensive population, special attention needs to be focused on the additional impact of immunosuppressive medications side effects and interactions, recurrent disease, and donor and recipient comorbidities such as obesity on blood pressure control with thoughtful consideration of the risk of graft failure. In general, there is a need for prospective studies in pediatric kidney transplant patients to understand the pathophysiology of hypertension and obesity and the appropriate approach to achieve a balance between the primary need to avoid rejection and the need to lower blood pressure and prevent obesity.

  11. It's Rather like Learning a Language: Development of talk and conceptual understanding in mechanics lessons

    Science.gov (United States)

    Rincke, Karsten

    2011-01-01

    Although a broad literature exists concerning the development of conceptual understanding of force and other topics within mechanics, little is known about the role and development of students' talk about the subject. The paper presents an in-depth investigation of students' talk whilst being introduced to the concept of force. The main research goal was to investigate and understand how students develop an understanding of the concept of force and how they use and understand the term 'force'. Therefore, we make relation to the research field of students' preconceptions and the field of second language learning. Two classes of students (N = 47) were videotaped during a time period of nine lessons, each transcribed and analysed using a category system. Additional data were obtained via written tasks, logs kept by the students, and tests. The detailed analysis of the talk and the results of the tests indicate that students face difficulties in using the term 'force' scientifically similar to those in a foreign language instruction. Vygotsky already recognised a relationship between learning in science and learning a language. In this paper, important aspects of this relationship are discussed based upon empirical data. We conclude that in some respects it might be useful to make reference to the research related to language learning when thinking about improving science education. In particular, according to Selinker's concept of interlanguage describing language-learning processes within language instruction, the language used by the students during physics lessons can be viewed as a 'scientific interlanguage'.

  12. Understanding dental CAD/CAM for restorations--the digital workflow from a mechanical engineering viewpoint.

    Science.gov (United States)

    Tapie, L; Lebon, N; Mawussi, B; Fron Chabouis, H; Duret, F; Attal, J-P

    2015-01-01

    As digital technology infiltrates every area of daily life, including the field of medicine, so it is increasingly being introduced into dental practice. Apart from chairside practice, computer-aided design/computer-aided manufacturing (CAD/CAM) solutions are available for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental solutions can be considered a chain of digital devices and software for the almost automatic design and creation of dental restorations. However, dentists who want to use the technology often do not have the time or knowledge to understand it. A basic knowledge of the CAD/CAM digital workflow for dental restorations can help dentists to grasp the technology and purchase a CAM/CAM system that meets the needs of their office. This article provides a computer-science and mechanical-engineering approach to the CAD/CAM digital workflow to help dentists understand the technology.

  13. Cognitive neuroepigenetics: the next evolution in our understanding of the molecular mechanisms underlying learning and memory?

    Science.gov (United States)

    Marshall, Paul; Bredy, Timothy W.

    2016-07-01

    A complete understanding of the fundamental mechanisms of learning and memory continues to elude neuroscientists. Although many important discoveries have been made, the question of how memories are encoded and maintained at the molecular level remains. So far, this issue has been framed within the context of one of the most dominant concepts in molecular biology, the central dogma, and the result has been a protein-centric view of memory. Here, we discuss the evidence supporting a role for neuroepigenetic mechanisms, which constitute dynamic and reversible, state-dependent modifications at all levels of control over cellular function, and their role in learning and memory. This neuroepigenetic view suggests that DNA, RNA and protein each influence one another to produce a holistic cellular state that contributes to the formation and maintenance of memory, and predicts a parallel and distributed system for the consolidation, storage and retrieval of the engram.

  14. Contrast medium-induced nephropathy: the pathophysiology

    DEFF Research Database (Denmark)

    Persson, P B; Tepel, Martin

    2006-01-01

    A widespread, rather general, definition of contrast-induced nephropathy (CIN) is an impairment in renal function occurring within 3 days following the intravascular administration of contrast media (CM) and the absence of an alternative aetiology. In spite of the vast clinical importance of CIN...... the current knowledge of the mechanisms causing CIN, it is not possible to recommend a certain class of contrast media, except to avoid large doses of CM of the first generation. From a pathophysiological perspective, volume expansion is effective in avoiding CIN, since water permeability of the collecting...

  15. Pathophysiology of the anorexia of aging.

    Science.gov (United States)

    Morley, John E

    2013-01-01

    Anorexia represents a major problem for older persons leading to weight loss, sarcopenia, functional decline, and mortality. There is increasing information on the pathophysiological mechanisms that lead to anorexia. Increasing evidence has shown the importance of gastrointestinal hormones (ghrelin, cholecystokinin, and glucagon-like peptide) and adipokines in producing the anorexia of aging. Numerous neurotransmitters have been shown to be involved in this aging anorexia, but evidence in humans is lacking. The early recognition of anorexia of aging is important to allow intervention and prevent functional deterioration in older persons. Screening tests for anorexia have been developed. New approaches to managing anorexia are being tested.

  16. Evidence from pharmacology and pathophysiology suggests that chemicals with dissimilar mechanisms of action could be of bigger concern in the toxicological risk assessment of chemical mixtures than chemicals with a similar mechanism of action

    DEFF Research Database (Denmark)

    Hadrup, Niels

    2014-01-01

    such as cancer or HIV, it is generally recognised that pharmacological combination therapy targeting different mechanisms of action is more effective than a strategy where only one mechanism is targeted. Moreover, in diseases such as acute myocardial infarction and congestive heart failure, several organ systems...

  17. Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

    International Nuclear Information System (INIS)

    Wilson, Vickie S.; Keshava, Nagalakshmi; Hester, Susan; Segal, Deborah; Chiu, Weihsueh; Thompson, Chad M.; Euling, Susan Y.

    2013-01-01

    The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanism or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment

  18. Twenty-five years of progress in understanding pollination mechanisms in palms (Arecaceae)

    Science.gov (United States)

    Barfod, Anders S.; Hagen, Melanie; Borchsenius, Finn

    2011-01-01

    Background With more than 90 published studies of pollination mechanisms, the palm family is one of the better studied tropical families of angiosperms. Understanding palm–pollinator interactions has implications for tropical silviculture, agroforestry and horticulture, as well as for our understanding of palm evolution and diversification. We review the rich literature on pollination mechanisms in palms that has appeared since the last review of palm pollination studies was published 25 years ago. Scope and Conclusions Visitors to palm inflorescences are attracted by rewards such as food, shelter and oviposition sites. The interaction between the palm and its visiting fauna represents a trade-off between the services provided by the potential pollinators and the antagonistic activities of other insect visitors. Evidence suggests that beetles constitute the most important group of pollinators in palms, followed by bees and flies. Occasional pollinators include mammals (e.g. bats and marsupials) and even crabs. Comparative studies of palm–pollinator interactions in closely related palm species document transitions in floral morphology, phenology and anatomy correlated with shifts in pollination vectors. Synecological studies show that asynchronous flowering and partitioning of pollinator guilds may be important regulators of gene flow between closely related sympatric taxa and potential drivers of speciation processes. Studies of larger plant–pollinator networks point out the importance of competition for pollinators between palms and other flowering plants and document how the insect communities in tropical forest canopies probably influence the reproductive success of palms. However, published studies have a strong geographical bias towards the South American region and a taxonomic bias towards the tribe Cocoseae. Future studies should try to correct this imbalance to provide a more representative picture of pollination mechanisms and their evolutionary

  19. A review on Alzheimer's disease pathophysiology and its management: an update.

    Science.gov (United States)

    Kumar, Anil; Singh, Arti; Ekavali

    2015-04-01

    Alzheimer's disease acknowledged as progressive multifarious neurodegenerative disorder, is the leading cause of dementia in late adult life. Pathologically it is characterized by intracellular neurofibrillary tangles and extracellular amyloidal protein deposits contributing to senile plaques. Over the last two decades, advances in the field of pathogenesis have inspired the researchers for the investigation of novel pharmacological therapeutics centered more towards the pathophysiological events of the disease. Currently available treatments i.e. acetylcholinesterase inhibitors (rivastigmine, galantamine, donepezil) and N-methyl d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. While the neuropathological features of Alzheimer's disease are recognized but the intricacies of the mechanism have not been clearly defined. This lack of understanding regarding the pathogenic process may be the likely reason for the non-availability of effective treatment which can prevent onset and progression of the disease. Owing to the important progress in the field of pathophysiology in the last couple of years, new therapeutic targets are available that should render the underlying disease process to be tackled directly. In this review, authors will discusses the different aspects of pathophysiological mechanisms behind Alzheimer's disease and its management through conventional drug therapy, including modern investigational therapeutic strategies, recently completed and ongoing. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics

    KAUST Repository

    Mateker, William R.

    2016-12-23

    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect.

  1. Progress in Understanding Degradation Mechanisms and Improving Stability in Organic Photovoltaics.

    Science.gov (United States)

    Mateker, William R; McGehee, Michael D

    2017-03-01

    Understanding the degradation mechanisms of organic photovoltaics is particularly important, as they tend to degrade faster than their inorganic counterparts, such as silicon and cadmium telluride. An overview is provided here of the main degradation mechanisms that researchers have identified so far that cause extrinsic degradation from oxygen and water, intrinsic degradation in the dark, and photo-induced burn-in. In addition, it provides methods for researchers to identify these mechanisms in new materials and device structures to screen them more quickly for promising long-term performance. These general strategies will likely be helpful in other photovoltaic technologies that suffer from insufficient stability, such as perovskite solar cells. Finally, the most promising lifetime results are highlighted and recommendations to improve long-term performance are made. To prevent degradation from oxygen and water for sufficiently long time periods, OPVs will likely need to be encapsulated by barrier materials with lower permeation rates of oxygen and water than typical flexible substrate materials. To improve stability at operating temperatures, materials will likely require glass transition temperatures above 100 °C. Methods to prevent photo-induced burn-in are least understood, but recent research indicates that using pure materials with dense and ordered film morphologies can reduce the burn-in effect. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Understanding comorbidity among internalizing problems: Integrating latent structural models of psychopathology and risk mechanisms

    Science.gov (United States)

    Hankin, Benjamin L.; Snyder, Hannah R.; Gulley, Lauren D.; Schweizer, Tina H.; Bijttebier, Patricia; Nelis, Sabine; Toh, Gim; Vasey, Michael W.

    2016-01-01

    It is well known that comorbidity is the rule, not the exception, for categorically defined psychiatric disorders, and this is also the case for internalizing disorders of depression and anxiety. This theoretical review paper addresses the ubiquity of comorbidity among internalizing disorders. Our central thesis is that progress in understanding this co-occurrence can be made by employing latent dimensional structural models that organize both psychopathology as well as vulnerabilities and risk mechanisms and by connecting the multiple levels of risk and psychopathology outcomes together. Different vulnerabilities and risk mechanisms are hypothesized to predict different levels of the structural model of psychopathology. We review the present state of knowledge based on concurrent and developmental sequential comorbidity patterns among common discrete psychiatric disorders in youth, and then we advocate for the use of more recent bifactor dimensional models of psychopathology (e.g., p factor, Caspi et al., 2014) that can help to explain the co-occurrence among internalizing symptoms. In support of this relatively novel conceptual perspective, we review six exemplar vulnerabilities and risk mechanisms, including executive function, information processing biases, cognitive vulnerabilities, positive and negative affectivity aspects of temperament, and autonomic dysregulation, along with the developmental occurrence of stressors in different domains, to show how these vulnerabilities can predict the general latent psychopathology factor, a unique latent internalizing dimension, as well as specific symptom syndrome manifestations. PMID:27739389

  3. Features of Knowledge Building in Biology: Understanding Undergraduate Students’ Ideas about Molecular Mechanisms

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. PMID:26931398

  4. Understanding the Impact of Root Morphology on Overturning Mechanisms: A Modelling Approach

    Science.gov (United States)

    Fourcaud, Thierry; Ji, Jin-Nan; Zhang, Zhi-Qiang; Stokes, Alexia

    2008-01-01

    Background and Aims The Finite Element Method (FEM) has been used in recent years to simulate overturning processes in trees. This study aimed at using FEM to determine the role of individual roots in tree anchorage with regard to different rooting patterns, and to estimate stress distribution in the soil and roots during overturning. Methods The FEM was used to carry out 2-D simulations of tree uprooting in saturated soft clay and loamy sand-like soil. The anchorage model consisted of a root system embedded in a soil block. Two root patterns were used and individual roots removed to determine their contribution to anchorage. Key Results In clay-like soil the size of the root–soil plate formed during overturning was defined by the longest roots. Consequently, all other roots localized within this plate had no influence on anchorage strength. In sand-like soil, removing individual root elements altered anchorage resistance. This result was due to a modification of the shape and size of the root–soil plate, as well as the location of the rotation axis. The tap root and deeper roots had more influence on overturning resistance in sand-like soil compared with clay-like soil. Mechanical stresses were higher in the most superficial roots and also in leeward roots in sand-like soil. The relative difference in stresses between the upper and lower sides of lateral roots was sensitive to root insertion angle. Assuming that root eccentricity is a response to mechanical stresses, these results explain why eccentricity differs depending on root architecture. Conclusions A simple 2-D Finite Element model was developed to better understand the mechanisms involved during tree overturning. It has been shown how root system morphology and soil mechanical properties can modify the shape of the root plate slip surface as well as the position of the rotation axis, which are major components of tree anchorage. PMID:17942593

  5. Using the glacial geomorphology of palaeo-ice streams to understand mechanisms of ice sheet collapse

    Science.gov (United States)

    Stokes, Chris R.; Margold, Martin; Clark, Chris; Tarasov, Lev

    2017-04-01

    Processes which bring about ice sheet deglaciation are critical to our understanding of glacial-interglacial cycles and ice sheet sensitivity to climate change. The precise mechanisms of deglaciation are also relevant to our understanding of modern-day ice sheet stability and concerns over global sea level rise. Mass loss from ice sheets can be broadly partitioned between melting and a 'dynamic' component whereby rapidly-flowing ice streams/outlet glaciers transfer ice from the interior to the oceans. Surface and basal melting (e.g. of ice shelves) are closely linked to atmospheric and oceanic conditions, but the mechanisms that drive dynamic changes in ice stream discharge are more complex, which generates much larger uncertainties about their future contribution to ice sheet mass loss and sea level rise. A major problem is that observations of modern-day ice streams typically span just a few decades and, at the ice-sheet scale, it is unclear how the entire drainage network of ice streams evolves during deglaciation. A key question is whether ice streams might increase and sustain rates of mass loss over centuries or millennia, beyond those expected for a given ocean-climate forcing. To address this issue, numerous workers have sought to understand ice stream dynamics over longer time-scales using their glacial geomorphology in the palaeo-record. Indeed, our understanding of their geomorphology has grown rapidly in the last three decades, from almost complete ignorance to a detailed knowledge of their geomorphological products. Building on this body of work, this paper uses the glacial geomorphology of 117 ice streams in the North American Laurentide Ice Sheet to reconstruct their activity during its deglaciation ( 22,000 to 7,000 years ago). Ice stream activity was characterised by high variability in both time and space, with ice streams switching on and off in different locations. During deglaciation, we find that their overall number decreased, they occupied a

  6. Treatment of cellulite: Part I. Pathophysiology.

    Science.gov (United States)

    Khan, Misbah H; Victor, Frank; Rao, Babar; Sadick, Neil S

    2010-03-01

    Cellulite is a topographic skin change that is nearly ubiquitous in postpubertal women. Treatment remains elusive. The various treatments currently available are only partially or temporarily effective. Newer therapeutic modalities continue to evolve without much understanding of the complex nature of cellulite. The successful treatment of cellulite will ultimately depend upon our understanding of the pathophysiology of cellulite adipose tissue. Part I of this two-part series on cellulite reviews how the concept and perception of cellulite has evolved over time and its proposed etiologies. The article also focuses on the physiology of human adipose tissue, particularly regarding cellulite. Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  7. Estrogens and Androgens in Skeletal Physiology and Pathophysiology

    Science.gov (United States)

    Almeida, Maria; Laurent, Michaël R.; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A.; Bouillon, Roger; Vanderschueren, Dirk

    2016-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. PMID:27807202

  8. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome.

    Science.gov (United States)

    Ellis, Demetrius

    2015-01-01

    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na(+)) and water retention; this is known as the "underfill hypothesis." Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is "primary" or "pathophysiological," Na(+) and water retention; this is known as the "overfill hypothesis." A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema.

  9. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome

    Science.gov (United States)

    Ellis, Demetrius

    2016-01-01

    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na+) and water retention; this is known as the “underfill hypothesis.” Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is “primary” or “pathophysiological,” Na+ and water retention; this is known as the “overfill hypothesis.” A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema. PMID:26793696

  10. Pathophysiology, Evaluation and Management of Edema in Childhood Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Demetrius eEllis

    2016-01-01

    Full Text Available Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS exemplified by such primary conditions as minimal change disease (MCD. In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiologic mechanisms which enhance renal sodium (Na+ and water retention; this is known as the underfill hypothesis. Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions the predominant mechanism of edema formation is primary or pathophysiologic, Na+ and water retention; this is known as the overfill hypothesis. A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill. This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation and management of such edema

  11. [Pathophysiology and treatment of ARMD].

    Science.gov (United States)

    Musat, O; Ochinciuc, Uliana; Gutu, Tatiana; Cristescu, T R; Coman, Corina

    2012-01-01

    A review regarding the pathophysiology of AMD as shown in the literature Targets in AMD treatment include: 1. Protection against oxidative stress; 2. Prevention of the accumulation of lipofuscin; 3. Reduction or elimination of chronic inflammation; 4. Changes involving the participation of complement inflammatory phenomena; 5. Changes in the phenomena of chronic inflammation which do not involve the participation of complement (eg. Mitochondria and extracellular matrix). The Neovascularization process includes: 1. Production of angiogenic factor; 2. Release of angiogenic factor; 3. The binding of factors to extracellular receptors and activation of intracellular signaling; 4. Activation of endothelial cells with basement membrane degradation; 5. Endothelial cell proliferation; 6. Endothelial cell migration; 7. Remodeling of extracellular matrix; 8. Tube formation; 9. Vascular stabilization. Therapy inAMD, based on physiological characteristics of early and late stages, is possible nowadays. It is possible to apply a specific treatment for each stage of AMD, but effective treatment requires combinations of specific therapeutic remedies involving different pathophysiological pathways.

  12. Delayed Ejaculation: Pathophysiology, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Ibrahim A. Abdel-Hamid

    2018-01-01

    Full Text Available Delayed ejaculation (DE is a poorly defined and uncommon form of male sexual dysfunction, characterized by a marked delay in ejaculation or an inability to achieve ejaculation. It is often quite concerning to patients and their partners, and sometimes frustrates couples’ attempts to conceive. This article aims to review the pathophysiology of DE and anejaculation (AE, to explore our current understanding of the diagnosis, and to present the treatment options for this condition. Electronic databases were searched from 1966 to October 2017, including PubMed (MEDLINE and Embase. We combined “delayed ejaculation,” “retarded ejaculation,” “inhibited ejaculation,” or “anejaculation” as Medical Subject Headings (MeSH terms or keywords with “epidemiology,” “etiology,” “pathophysiology,” “clinical assessment,” “diagnosis,” or “treatment.” Relevant sexual medicine textbooks were searched as well. The literature suggests that the pathophysiology of DE/AE is multifactorial, including both organic and psychosocial factors. Despite the many publications on this condition, the exact pathogenesis is not yet known. There is currently no single gold standard for diagnosing DE/AE, as operationalized criteria do not exist. The history is the key to the diagnosis. Treatment should be cause-specific. There are many approaches to treatment planning, including various psychological interventions, pharmacotherapy, and specific treatments for infertile men. An approved form of drug therapy does not exist. A number of approaches can be employed for infertile men, including the collection of nocturnal emissions, prostatic massage, prostatic urethra catheterization, penile vibratory stimulation, probe electroejaculation, sperm retrieval by aspiration from either the vas deferens or the epididymis, and testicular sperm extraction.

  13. The Pathophysiology and Treatment of Glaucoma

    Science.gov (United States)

    Weinreb, Robert N.; Aung, Tin; Medeiros, Felipe A.

    2015-01-01

    IMPORTANCE Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. OBJECTIVE To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. EVIDENCE REVIEW A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. FINDINGS The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. CONCLUSIONS AND RELEVANCE Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries. PMID:24825645

  14. Pathophysiological approach to chronic diarrhoea.

    Science.gov (United States)

    Corazziari, Enrico Stefano

    2012-10-01

    Chronic diarrhoea disrupts everyday life because of urgency, incontinence and frequent bowel movements. Non-inflammatory diarrhoea may be secondary to altered process of absorption, secretion or digestion. The most prevalent functional diarrhoea is due to altered gut-brain interaction and often after an acute gastroenteritis. Microscopic colitis, rare cases of eosinophilic colitis, congenital diarrhoeal disorders and bile acid malabsorption have been more frequently reported and their pathophysiology elucidated.

  15. Gender differences in conceptual understanding of Newtonian mechanics: a UK cross-institution comparison

    International Nuclear Information System (INIS)

    Bates, Simon; Donnelly, Robyn; MacPhee, Cait; Sands, David; Birch, Marion; Walet, Niels R

    2013-01-01

    We present the results of a combined study from three UK universities where we investigate the existence and persistence of a performance gender gap in conceptual understanding of Newtonian mechanics. Using the Force Concept Inventory, we find that students at all three universities exhibit a statistically significant gender gap, with males outperforming females. This gap is narrowed but not eliminated after instruction, using a variety of instructional approaches. Furthermore, we find that before instruction the quartile with the lowest performance on the diagnostic instrument comprises a disproportionately high fraction (∼50%) of the total female cohort. The majority of these students remain in the lowest-performing quartile post-instruction. Analysis of responses to individual items shows that male students outperform female students on practically all items on the instrument. Comparing the performance of the same group of students on end-of-course examinations, we find no statistically significant gender gaps. (paper)

  16. The contributions of cognitive neuroscience and neuroimaging to understanding mechanisms of behavior change in addiction.

    Science.gov (United States)

    Morgenstern, Jon; Naqvi, Nasir H; Debellis, Robert; Breiter, Hans C

    2013-06-01

    In the last decade, there has been an upsurge of interest in understanding the mechanisms of behavior change (MOBC) and effective behavioral interventions as a strategy to improve addiction-treatment efficacy. However, there remains considerable uncertainty about how treatment research should proceed to address the MOBC issue. In this article, we argue that limitations in the underlying models of addiction that inform behavioral treatment pose an obstacle to elucidating MOBC. We consider how advances in the cognitive neuroscience of addiction offer an alternative conceptual and methodological approach to studying the psychological processes that characterize addiction, and how such advances could inform treatment process research. In addition, we review neuroimaging studies that have tested aspects of neurocognitive theories as a strategy to inform addiction therapies and discuss future directions for transdisciplinary collaborations across cognitive neuroscience and MOBC research. 2013 APA, all rights reserved

  17. Deaths during apprehensions of agitated persons. A review of proposed pathophysiological theories

    Directory of Open Access Journals (Sweden)

    Tamsen Fredrik

    2014-06-01

    Full Text Available The pathophysiology of sudden death during apprehension remains largely unclear. The most frequently discussed mechanisms are excited delirium, positional asphyxia, metabolic acidosis, acute and chronic drug abuse, and autonomic instability. As in most areas of forensic medicine, much of the knowledge comes from case reports, which are of little use in understanding causality. Experimental studies of some aspects have been performed, and they show somewhat divergent results and interpretations. The aim of this review is to summarize the different proposed theories, and to point out important issues for further research.

  18. Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.

    Science.gov (United States)

    King, Suzanne N; Dunlap, Neal E; Tennant, Paul A; Pitts, Teresa

    2016-06-01

    Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

  19. Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity

    Science.gov (United States)

    2014-01-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress (“hormetic stress”). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses (“toxic stress”) and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. PMID:24833580

  20. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

    Science.gov (United States)

    Epel, Elissa S; Lithgow, Gordon J

    2014-06-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods

    Science.gov (United States)

    Alsaleh, Mansour; Alomar, Noura; Alarifi, Abdulrahman

    2017-01-01

    Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users’ security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users’ behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals’ awareness of the consequences of security threats. By comparing participants’ behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users’ security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones. PMID:28297719

  2. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods.

    Science.gov (United States)

    Alsaleh, Mansour; Alomar, Noura; Alarifi, Abdulrahman

    2017-01-01

    Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users' security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users' behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals' awareness of the consequences of security threats. By comparing participants' behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users' security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones.

  3. Understanding dental CAD/CAM for restorations--accuracy from a mechanical engineering viewpoint.

    Science.gov (United States)

    Tapie, Laurent; Lebon, Nicolas; Mawussi, Bernardin; Fron-Chabouis, Hélène; Duret, Francois; Attal, Jean-Pierre

    2015-01-01

    As is the case in the field of medicine, as well as in most areas of daily life, digital technology is increasingly being introduced into dental practice. Computer-aided design/ computer-aided manufacturing (CAD/CAM) solutions are available not only for chairside practice but also for creating inlays, crowns, fixed partial dentures (FPDs), implant abutments, and other dental prostheses. CAD/CAM dental practice can be considered as the handling of devices and software processing for the almost automatic design and creation of dental restorations. However, dentists who want to use dental CAD/CAM systems often do not have enough information to understand the variations offered by such technology practice. Knowledge of the random and systematic errors in accuracy with CAD/CAM systems can help to achieve successful restorations with this technology, and help with the purchasing of a CAD/CAM system that meets the clinical needs of restoration. This article provides a mechanical engineering viewpoint of the accuracy of CAD/ CAM systems, to help dentists understand the impact of this technology on restoration accuracy.

  4. Investigating and improving student understanding of the expectation values of observables in quantum mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2017-07-01

    The expectation value of an observable is an important concept in quantum mechanics since measurement outcomes are, in general, probabilistic and we only have information about the probability distribution of measurement outcomes in a given quantum state of a system. However, we find that upper-level undergraduate and PhD students in physics have both conceptual and procedural difficulties when determining the expectation value of a physical observable in a given quantum state in terms of the eigenstates and eigenvalues of the corresponding operator, especially when using Dirac notation. Here we first describe the difficulties that these students have with determining the expectation value of an observable in Dirac notation. We then discuss how the difficulties found via student responses to written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of the expectation value. The QuILT strives to help students integrate conceptual understanding and procedural skills to develop a coherent understanding of the expectation value. We discuss the effectiveness of the QuILT in helping students learn this concept from in-class evaluations.

  5. Smartphone users: Understanding how security mechanisms are perceived and new persuasive methods.

    Directory of Open Access Journals (Sweden)

    Mansour Alsaleh

    Full Text Available Protecting smartphones against security threats is a multidimensional problem involving human and technological factors. This study investigates how smartphone users' security- and privacy-related decisions are influenced by their attitudes, perceptions, and understanding of various security threats. In this work, we seek to provide quantified insights into smartphone users' behavior toward multiple key security features including locking mechanisms, application repositories, mobile instant messaging, and smartphone location services. To the best of our knowledge, this is the first study that reveals often unforeseen correlations and dependencies between various privacy- and security-related behaviors. Our work also provides evidence that making correct security decisions might not necessarily correlate with individuals' awareness of the consequences of security threats. By comparing participants' behavior and their motives for adopting or ignoring certain security practices, we suggest implementing additional persuasive approaches that focus on addressing social and technological aspects of the problem. On the basis of our findings and the results presented in the literature, we identify the factors that might influence smartphone users' security behaviors. We then use our understanding of what might drive and influence significant behavioral changes to propose several platform design modifications that we believe could improve the security levels of smartphones.

  6. Towards understanding the mechanisms and the kinetics of nanoparticle penetration through protective gloves

    International Nuclear Information System (INIS)

    Vinches, L; Boutrigue, N; Zemzem, M; Hallé, S; Peyrot, C; Lemarchand, L; Wilkinson, K J; Tufenkji, N

    2015-01-01

    Parallel to the increased use of engineered nanoparticles (ENP) in the formulation of commercial products or in medicine, numerous health and safety agencies have recommended the application of the precautionary principle to handle ENP; namely, the recommendation to use protective gloves against chemicals. However, recent studies reveal the penetration of titanium dioxide nanoparticles through nitrile rubber protective gloves in conditions simulating occupational use. This project is designed to understand the links between the penetration of gold nanoparticles (nAu) through nitrile rubber protective gloves and the mechanical and physical behaviour of the elastomer material subjected to conditions simulating occupational use (i.e., mechanical deformations (MD) and sweat). Preliminary analyses show that nAu suspensions penetrate selected glove materials after exposure to prolonged (3 hours) dynamic deformations. Significant morphological changes are observed on the outer surface of the glove sample; namely, the number and the surface of the micropores on the surface increase. Moreover, nitrile rubber protective gloves are also shown to be sensitive to the action of nAu suspension and to the action of the saline solution used to simulate sweat (swelling). (paper)

  7. Understanding the mechanisms of familiar voice-identity recognition in the human brain.

    Science.gov (United States)

    Maguinness, Corrina; Roswandowitz, Claudia; Von Kriegstein, Katharina

    2018-03-31

    Humans have a remarkable skill for voice-identity recognition: most of us can remember many voices that surround us as 'unique'. In this review, we explore the computational and neural mechanisms which may support our ability to represent and recognise a unique voice-identity. We examine the functional architecture of voice-sensitive regions in the superior temporal gyrus/sulcus, and bring together findings on how these regions may interact with each other, and additional face-sensitive regions, to support voice-identity processing. We also contrast findings from studies on neurotypicals and clinical populations which have examined the processing of familiar and unfamiliar voices. Taken together, the findings suggest that representations of familiar and unfamiliar voices might dissociate in the human brain. Such an observation does not fit well with current models for voice-identity processing, which by-and-large assume a common sequential analysis of the incoming voice signal, regardless of voice familiarity. We provide a revised audio-visual integrative model of voice-identity processing which brings together traditional and prototype models of identity processing. This revised model includes a mechanism of how voice-identity representations are established and provides a novel framework for understanding and examining the potential differences in familiar and unfamiliar voice processing in the human brain. Copyright © 2018. Published by Elsevier Ltd.

  8. The use of micro-/milli-fluidics to better understand the mechanisms behind deep venous thrombosis

    Science.gov (United States)

    Schofield, Zoe; Alexiadis, Alessio; Brill, Alexander; Nash, Gerard; Vigolo, Daniele

    2016-11-01

    Deep venous thrombosis (DVT) is a dangerous and painful condition in which blood clots form in deep veins (e.g., femoral vein). If these clots become unstable and detach from the thrombus they can be delivered to the lungs resulting in a life threatening complication called pulmonary embolism (PE). Mechanisms of clot development in veins remain unclear but researchers suspect that the specific flow patterns in veins, especially around the valve flaps, play a fundamental role. Here we show how it is now possible to mimic the current murine model by developing micro-/milli-fluidic experiments. We exploited a novel detection technique, ghost particle velocimetry (GPV), to analyse the velocity profiles for various geometries. These vary from regular microfluidics with a rectangular cross section with a range of geometries (mimicking the presence of side and back branches in veins, closed side branch and flexible valves) to a more accurate venous representation with a 3D cylindrical geometry obtained by 3D printing. In addition to the GPV experiments, we analysed the flow field developing in these geometries by using computational fluid dynamic simulations to develop a better understanding of the mechanisms behind DVT. ZS gratefully acknowledges financial support from the EPSRC through a studentship from the Sci-Phy-4-Health Centre for Doctoral Training (EP/L016346/1).

  9. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  10. Effects of ADMA upon gene expression: an insight into the pathophysiological significance of raised plasma ADMA.

    Directory of Open Access Journals (Sweden)

    Caroline L Smith

    2005-10-01

    Full Text Available Asymmetric dimethylarginine (ADMA is a naturally occurring inhibitor of nitric oxide synthesis that accumulates in a wide range of diseases associated with endothelial dysfunction and enhanced atherosclerosis. Clinical studies implicate plasma ADMA as a major novel cardiovascular risk factor, but the mechanisms by which low concentrations of ADMA produce adverse effects on the cardiovascular system are unclear.We treated human coronary artery endothelial cells with pathophysiological concentrations of ADMA and assessed the effects on gene expression using U133A GeneChips (Affymetrix. Changes in several genes, including bone morphogenetic protein 2 inducible kinase (BMP2K, SMA-related protein 5 (Smad5, bone morphogenetic protein receptor 1A, and protein arginine methyltransferase 3 (PRMT3; also known as HRMT1L3, were confirmed by Northern blotting, quantitative PCR, and in some instances Western blotting analysis to detect changes in protein expression. To determine whether these changes also occurred in vivo, tissue from gene deletion mice with raised ADMA levels was examined. More than 50 genes were significantly altered in endothelial cells after treatment with pathophysiological concentrations of ADMA (2 microM. We detected specific patterns of changes that identify pathways involved in processes relevant to cardiovascular risk and pulmonary hypertension. Changes in BMP2K and PRMT3 were confirmed at mRNA and protein levels, in vitro and in vivo.Pathophysiological concentrations of ADMA are sufficient to elicit significant changes in coronary artery endothelial cell gene expression. Changes in bone morphogenetic protein signalling, and in enzymes involved in arginine methylation, may be particularly relevant to understanding the pathophysiological significance of raised ADMA levels. This study identifies the mechanisms by which increased ADMA may contribute to common cardiovascular diseases and thereby indicates possible targets for therapies.

  11. Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

    Science.gov (United States)

    Globus, Ruth

    2016-01-01

    factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

  12. Raman analysis of DLC coated engine components with complex shape: Understanding wear mechanisms

    International Nuclear Information System (INIS)

    Jaoul, C.; Jarry, O.; Tristant, P.; Merle-Mejean, T.; Colas, M.; Dublanche-Tixier, C.; Jacquet, J.-M.

    2009-01-01

    Hydrogenated amorphous carbon (a-C:H) films were deposited on flat samples and engine components using an industrial scale reactor. Characterization of the coating allowed validating its application on engine parts due to high hardness (32 GPa) and high level of adhesion achieved using sublayers. The original approach of this work concerned the use of Raman analysis not only on flat samples after tribometer tests but also directly on coated engine parts with complex shape (like cam/follower system), in order to understand wear mechanisms occurring in motorsport engines. As wear could lead to a coating thickness decrease, a particular attention was paid on the Raman signal of the sublayers. Among the different values extracted from Raman spectrum to characterize structural organization, the value of G peak intensity appeared as a criterion of validity of analyses because it is directly linked to the remaining thickness of the a-C:H layer. For flat samples tested on ball-on-disc tribometer, structure of a-C:H film observed by Raman spectroscopy in the wear track remained stable in depth. Then, a-C:H coated engine components were studied before and after working in real conditions. Two different wear mechanisms were identified. The first one did not show any structural modification of the bulk a-C:H layer. In the second one, the high initial roughness of samples (R t = 1.15 μm) lead to coating delaminations after sliding. Massive graphitization which decreases drastically mechanical properties of the coatings was observed by Raman analyses on the contact area. The increase of the temperature on rough edges of the scratches could explain this graphitization.

  13. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms.

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections between ideas, and reorganize and restructure prior knowledge. Semistructured, clinical think-aloud interviews were conducted with introductory and upper-division MCB students. Interviews included a written conceptual assessment, a concept-mapping activity, and an opportunity to explain the biomechanisms of DNA replication, transcription, and translation. Student reasoning patterns were explored through mixed-method analyses. Results suggested that students must sort mechanistic entities into appropriate mental categories that reflect the nature of MCB mechanisms and that conflation between these categories is common. We also showed how connections between molecular mechanisms and their biological roles are part of building an integrated knowledge network as students develop expertise. We observed differences in the nature of connections between ideas related to different forms of reasoning. Finally, we provide a tentative model for MCB knowledge integration and suggest its implications for undergraduate learning. © 2016 K. Southard et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. Perinatal asphyxia pathophysiology in pig and human: a review.

    Science.gov (United States)

    Alonso-Spilsbury, María; Mota-Rojas, Daniel; Villanueva-García, Dina; Martínez-Burnes, Julio; Orozco, Héctor; Ramírez-Necoechea, Ramiro; Mayagoitia, Alfonso López; Trujillo, María Elena

    2005-11-01

    In utero fetuses are evidently exposed to several factors that cause an interruption of the oxygen flow through the umbilical cord causing asphyxia leading to hypoxia and metabolic acidosis. These conditions are important causes of intra-partum and neonatal mortality. The main objective of this review is to provide current information regarding the pathophysiology of asphyxia in piglets around parturition; the physiological mechanisms invoked by affected piglets to compensate perinatal hypoxemia are discussed. This review also addresses some similarities and differences of asphyxia between piglets and other mammals, including human neonates. Metabolic acidosis and hypoxia are sequela to asphyxia and can cause profound health effects in postnatal performance because of an abnormal suckling, a reduced absorption of colostrum and inadequate passive transfer of neonatal immunity. Acidosis also cause hypothermia, increased mortality and reduced survival in neonates. One of the first deleterious effects of intrauterine hypoxia is the expulsion of meconium into the amniotic sac leading to meconium staining of the skin, and in severe cases, meconium aspiration into the lungs. Even though there have been technological changes and improvements in husbandry, piglet mortality due to asphyxia remains a major problem. One potential alternative to reduce neonatal mortality in pigs is the monitoring of fetal stress during birth and the implemention of strategies such as the Apgar score, that is often used in human pediatrics. It is also important to consider the physiological, behavioral and biochemical changes that take place during parturition which subsequently impact the vitality, maturity and development of neonatal pigs. Understanding the pathophysiology of fetal hypoxia should help practitioners and farmers implement more effective delivery techniques aimed at reducing neonatal mortality and improving postnatal performance.

  15. Pathogenesis and Pathophysiology of Pneumococcal Meningitis

    Science.gov (United States)

    Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

    2011-01-01

    Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

  16. Retinovascular physiology and pathophysiology: new experimental approach/new insights

    Science.gov (United States)

    Puro, Donald G.

    2012-01-01

    An important challenge in visual neuroscience is understand the physiology and pathophysiology of the intra-retinal vasculature, whose function is required for ophthalmoception by humans and most other mammals. In the quest to learn more about this highly specialized portion of the circulatory system, a newly developed method for isolating vast microvascular complexes from the rodent retina has opened the way for using techniques such as patch-clamping, fluorescence imaging and time-lapse photography to elucidate the functional organization of a capillary network and its pre-capillary arteriole. For example, the ability to obtain dual perforated-patch recordings from well-defined sites within an isolated microvascular complex permitted the first characterization of the electrotonic architecture of a capillary/arteriole unit. This analysis revealed that this operational unit is not simply a homogenous synctium, but has a complex functional organization that is dynamically modulated by extracellular signals such as angiotensin II. Another recent discovery is that a capillary and its pre-capillary arteriole have distinct physiological differences; capillaries have an abundance of ATP-sensitive potassium (KATP) channels and a dearth of voltage-dependent calcium channels (VDCCs) while the converse is true for arterioles. In addition, voltage transmission between abluminal cells and the endothelium is more efficient in the capillaries. Thus, the capillary network is well-equipped to generate and transmit voltages, and the pre-capillary arteriole is well-adapted to transduce a capillary-generated voltage into a change in abluminal cell calcium and thereby, a vasomotor response. Use of microvessels isolated from the diabetic retina has led to new insights concerning retinal vascular pathophysiology. For example, soon after the onset of diabetes, the efficacy of voltage transmission through the endothelium is diminished; arteriolar VDCCs is inhibited, and there is increased

  17. [Etiology and pathophysiology of fibromyalgia syndrome].

    Science.gov (United States)

    Sommer, C; Häuser, W; Burgmer, M; Engelhardt, R; Gerhold, K; Petzke, F; Schmidt-Wilcke, T; Späth, M; Tölle, T; Uçeyler, N; Wang, H; Winkelmann, A; Thieme, K

    2012-06-01

    The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. Current data do not identify distinct etiologic or pathophysiological factors mediating development of FMS. The development of FMS is associated with inflammatory rheumatic diseases (EL2b), with gene polymorphisms of the 5-hydroxytryptamine (HT)(2) receptor (EL3a), lifestyle factors (smoking, obesity, lack of physical activity; EL2b), physical and sexual abuse in childhood and adulthood (EL3a). FMS is most likely the result of various pathogenetic factors and pathophysiological mechanisms. The English full-text version of this article is available at SpringerLink (under "Supplemental").

  18. Adropin – physiological and pathophysiological role

    Directory of Open Access Journals (Sweden)

    Natalia Marczuk

    2016-09-01

    Full Text Available Adropin is a peptide hormone that was discovered in 2008 by Kumar et al. This protein consists of 76 amino acids, and it was originally described as a secreted peptide, with residues 1-33 encoding a secretory signal peptide sequence. The amino acid sequence of this protein in humans, mice and rats is identical. While our knowledge of the exact physiological roles of this poorly understood peptide continues to evolve, recent data suggest a role in energy homeostasis and the control of glucose and fatty acid metabolism. This protein is encoded by the Enho gene, which is expressed primarily in the liver and the central nervous system. The regulation of adropin secretion is controversial. Adropin immunoreactivity has been reported by several laboratories in the circulation of humans, non-human primates and rodents. However, more recently it has been suggested that adropin is a membrane-bound protein that modulates cell-cell communication. Moreover, adropin has been detected in various tissues and body fluids, such as brain, cerebellum, liver, kidney, heart, pancreas, small intestine, endothelial cells, colostrum, cheese whey and milk. The protein level, as shown by previous research, changes in various physiological and pathophysiological conditions. Adropin is involved in carbohydrate-lipid metabolism, metabolic diseases, central nervous system function, endothelial function and cardiovascular disease. The knowledge of this interesting protein, its exact role and mechanism of action is insufficient. This article provides an overview of the existing literature about the role of adropin, both in physiological and pathophysiological conditions.

  19. Understanding the hydrolysis mechanism of ethyl acetate catalyzed by an aqueous molybdocene: a computational chemistry investigation.

    Science.gov (United States)

    Tílvez, Elkin; Cárdenas-Jirón, Gloria I; Menéndez, María I; López, Ramón

    2015-02-16

    , in general, the information reported here could be of interest in designing new catalysts and understanding the reaction mechanism of these and other metal-catalyzed hydrolysis reactions.

  20. Understanding the molecular mechanism of pulse current charging for stable lithium-metal batteries.

    Science.gov (United States)

    Li, Qi; Tan, Shen; Li, Linlin; Lu, Yingying; He, Yi

    2017-07-01

    High energy and safe electrochemical storage are critical components in multiple emerging fields of technologies. Rechargeable lithium-metal batteries are considered to be promising alternatives for current lithium-ion batteries, leading to as much as a 10-fold improvement in anode storage capacity (from 372 to 3860 mAh g -1 ). One of the major challenges for commercializing lithium-metal batteries is the reliability and safety issue, which is often associated with uneven lithium electrodeposition (lithium dendrites) during the charging stage of the battery cycling process. We report that stable lithium-metal batteries can be achieved by simply charging cells with square-wave pulse current. We investigated the effects of charging period and frequency as well as the mechanisms that govern this process at the molecular level. Molecular simulations were performed to study the diffusion and the solvation structure of lithium cations (Li + ) in bulk electrolyte. The model predicts that loose association between cations and anions can enhance the transport of Li + and eventually stabilize the lithium electrodeposition. We also performed galvanostatic measurements to evaluate the cycling behavior and cell lifetime under pulsed electric field and found that the cell lifetime can be more than doubled using certain pulse current waveforms. Both experimental and simulation results demonstrate that the effectiveness of pulse current charging on dendrite suppression can be optimized by choosing proper time- and frequency-dependent pulses. This work provides a molecular basis for understanding the mechanisms of pulse current charging to mitigating lithium dendrites and designing pulse current waveforms for stable lithium-metal batteries.

  1. Epigenetic regulation in the pathophysiology of Alzheimer's disease

    NARCIS (Netherlands)

    Chouliaras, L.; Rutten, B.P.F.; Kenis, G.; Peerbooms, O.; Visser, P.J.; Verhey, F.; van Os, J; Steinbusch, H.W.M.; van der Hove, D.L.A.

    2010-01-01

    With the aging of the population, the growing incidence and prevalence of Alzheimer's disease (AD) increases the burden on individuals and society as a whole. To date, the pathophysiology of AD is not yet fully understood. Recent studies have suggested that epigenetic mechanisms may play a pivotal

  2. Pathophysiology and Treatment of Hyperhidrosis.

    Science.gov (United States)

    Fujimoto, Tomoko

    2016-01-01

    Primary focal hyperhidrosis is a disease of unknown cause with profuse perspiration of local sites (head, face, palms, soles of feet, and axillae) that adversely affects daily life. Guidelines have been proposed in the USA [1], Canada [2], and Japan [3]. The symptoms impair quality of life, with significant negative effects on daily existence and personal relationships. The current goal in medical practice for patients with hyperhidrosis is to provide guidance and encourage coping skills for a normal daily life, as well as give appropriate advice regarding treatment options. On occasion, in order to improve quality of life, it is necessary to recommend surgical therapy when conservative treatment fails; this requires an understanding of the mechanisms of available treatments and their effects. This paper reviews theories of primary focal hyperhidrosis with regard to pathology, epidemiology, and treatment. © 2016 S. Karger AG, Basel.

  3. Velopharyngeal sphincter pathophysiologic aspects in the in cleft palat

    Directory of Open Access Journals (Sweden)

    Collares, Marcus Vinicius Martins

    2008-09-01

    Full Text Available Introduction: Cleft lip and palate are common congenital abnormalities with typical functional disorders on speech, deglutition and middle ear function. Objective: This article reviews functional labiopalatine disorders through a pathophysiological view. Method: We performed a literature search on line, as well as books and periodicals related to velopharyngeal sphincter. Our sources were LILACS, MEDLINE and SciELO databases, and we applied to the research Keywords of interest on the velopharyngeal pathophysiology, for articles published between 1965 and 2007. Conclusion: Velopharyngeal sphincter plays a central role in speech, swallowing and middle ear physiology in patients with labiopalatine cleft. At the end of our bibliographic review, pursuant to the velopharyngeal physiology in individuals with this disorder in the functional speech, deglutition and otologic function, we observed that although there is a great number of published data discussing this issue, further studies are necessary to completely understand the pathophysiology, due to the fact they have been exploited superficially.

  4. Understanding creep in sandstone reservoirs - theoretical deformation mechanism maps for pressure solution in granular materials

    Science.gov (United States)

    Hangx, Suzanne; Spiers, Christopher

    2014-05-01

    Subsurface exploitation of the Earth's natural resources removes the natural system from its chemical and physical equilibrium. As such, groundwater extraction and hydrocarbon production from subsurface reservoirs frequently causes surface subsidence and induces (micro)seismicity. These effects are not only a problem in onshore (e.g. Groningen, the Netherlands) and offshore hydrocarbon fields (e.g. Ekofisk, Norway), but also in urban areas with extensive groundwater pumping (e.g. Venice, Italy). It is known that fluid extraction inevitably leads to (poro)elastic compaction of reservoirs, hence subsidence and occasional fault reactivation, and causes significant technical, economic and ecological impact. However, such effects often exceed what is expected from purely elastic reservoir behaviour and may continue long after exploitation has ceased. This is most likely due to time-dependent compaction, or 'creep deformation', of such reservoirs, driven by the reduction in pore fluid pressure compared with the rock overburden. Given the societal and ecological impact of surface subsidence, as well as the current interest in developing geothermal energy and unconventional gas resources in densely populated areas, there is much need for obtaining better quantitative understanding of creep in sediments to improve the predictability of the impact of geo-energy and groundwater production. The key problem in developing a reliable, quantitative description of the creep behaviour of sediments, such as sands and sandstones, is that the operative deformation mechanisms are poorly known and poorly quantified. While grain-scale brittle fracturing plus intergranular sliding play an important role in the early stages of compaction, these time-independent, brittle-frictional processes give way to compaction creep on longer time-scales. Thermally-activated mass transfer processes, like pressure solution, can cause creep via dissolution of material at stressed grain contacts, grain

  5. Sepsis in Obstetrics: Pathophysiology and Diagnostic Definitions.

    Science.gov (United States)

    Parfitt, Sheryl E; Bogat, Mary L; Hering, Sandra L; Roth, Cheryl

    In spite of many medical breakthroughs, sepsis continues to be challenging to identify, treat, and successfully resolve, including among the obstetric population. Sepsis is the result of an overactive, complex inflammatory response that is not completely understood. Currently there are no nationally agreed-upon criteria for systemic inflammatory response syndrome or sepsis in pregnant or peripartum women, as the physiologic changes of pregnancy have not been taken into consideration.This article is the first in a series of three that discuss the importance of sepsis and septic shock in pregnancy. The focus of this article is to understand the proposed pathophysiology of sepsis and new definitions associated with sepsis and septic shock. Knowledge of these conditions can assist in better identification of sepsis in the obstetric population.

  6. Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

    Directory of Open Access Journals (Sweden)

    Pinar Guzel Ozdemir

    2014-09-01

    Full Text Available Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 271-283

  7. Towards Understanding the Catalytic Mechanism of Human Paraoxonase 1: Experimental and In Silico Mutagenesis Studies.

    Science.gov (United States)

    Tripathy, Rajan K; Aggarwal, Geetika; Bajaj, Priyanka; Kathuria, Deepika; Bharatam, Prasad V; Pande, Abhay H

    2017-08-01

    Human paraoxonase 1 (h-PON1) is a ~45-kDa serum enzyme that can hydrolyze a variety of substrates, including organophosphate (OP) compounds. It is a potential candidate for the development of antidote against OP poisoning in humans. However, insufficient OP-hydrolyzing activity of native enzyme affirms the urgent need to develop improved variant(s) having enhanced OP-hydrolyzing activity. The crystal structure of h-PON1 remains unsolved, and the molecular details of how the enzyme catalyses hydrolysis of different types of substrates are also not clear. Understanding the molecular details of the catalytic mechanism of h-PON1 is essential to engineer better variant(s) of enzyme. In this study, we have used a random mutagenesis approach to increase the OP-hydrolyzing activity of recombinant h-PON1. The mutants not only showed a 10-340-fold increased OP-hydrolyzing activity against different OP substrates but also exhibited differential lactonase and arylesterase activities. In order to investigate the mechanistic details of the effect of observed mutations on the hydrolytic activities of enzyme, molecular docking studies were performed with selected mutants. The results suggested that the observed mutations permit differential binding of substrate/inhibitor into the enzyme's active site. This may explain differential hydrolytic activities of the enzyme towards different substrates.

  8. Understanding the mechanisms of secondary nucleation for protein aggregation: an analytical approach

    Science.gov (United States)

    Michaels, Thomas; Knowles, Tuomas P. J.

    2013-03-01

    Filamentous protein self-assembly is a general type of behaviour accessible to a wide range of different polypeptide sequences. This phenomenon underlies key molecular events both in normal and aberrant biology, but a general theory of the crucial nucleation steps that govern this process has remained elusive. In this talk we discuss our attempts to provide a general description of secondary nucleation in filamentous protein assembly based on the Becker-Döring kinetic scheme to describe cluster-catalytic effects. This systematic procedure allows extracting low-dimensional systems of equations out of the full kinetic model, in a master equation formalism typically consisting of infinitely many coupled non-linear equations. Using this procedure, we propose and discuss various mechanisms that can underlie the secondary nucleation process. Using data curve-fitting and analysis we show that the addition of a monomer to heterogeneous nuclei is effectively irreversible and discuss the implications of our framework for the more general understanding of the physics of multi-step nucleation phenomena in nature.

  9. Understanding the mechanisms of sickle cell disease by simulations with a discrete particle model

    Science.gov (United States)

    Hui, Katrina; Lin, Guang; Pan, Wenxiao

    2013-01-01

    Sickle cell disease (SCD) is an inherited blood disorder characterized by rigid, sickle-shaped red blood cells (RBCs). Because of their rigidity and shape, sickle cells can get stuck in smaller blood vessels, causing blockages and depriving oxygen to tissues. This study develops and applies mathematical models to better understand the mechanism of SCD. Two-dimensional models of RBCs and blood vessels have been constructed by representing them as discrete particles interacting with different forces. The nonlinear, elastic property of healthy RBCs could be adequately reproduced using a cosine angle bending force and a worm-like chain spring force. With the ability to deform, RBCs can squeeze through narrow blood vessels. In modeling sickle cells as rigid bodies and applying repelling and friction forces from the blood vessel, this study shows that geometrical factors (dimensions of the sickle cell and blood vessels) as well as rigidity and adhesiveness of the sickle cell all play an important role in determining how, and if, sickle cells become trapped within narrow blood capillaries. With lack of data to validate the model, this study primarily provides a sensitivity analysis of factors influencing sickle cell occlusion and identified critical data to support future modeling.

  10. The Pathophysiology of Eosinophilic Esophagitis

    Directory of Open Access Journals (Sweden)

    Daniel Avi Lemberg

    2014-05-01

    Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

  11. Cell volume regulation: physiology and pathophysiology

    DEFF Research Database (Denmark)

    Lambert, I H; Hoffmann, E K; Pedersen, Stine Helene Falsig

    2008-01-01

    not only under physiological conditions, e.g. following accumulation of nutrients, during epithelial absorption/secretion processes, following hormonal/autocrine stimulation, and during induction of apoptosis, but also under pathophysiological conditions, e.g. hypoxia, ischaemia and hyponatremia....../hypernatremia. On the other hand, it has recently become clear that an increase or reduction in cell volume can also serve as a specific signal in the regulation of physiological processes such as transepithelial transport, cell migration, proliferation and death. Although the mechanisms by which cell volume perturbations...... are sensed are still far from clear, significant progress has been made with respect to the nature of the sensors, transducers and effectors that convert a change in cell volume into a physiological response. In the present review, we summarize recent major developments in the field, and emphasize...

  12. Current understanding of the driving mechanisms for spatiotemporal variations of atmospheric speciated mercury: a review

    Directory of Open Access Journals (Sweden)

    H. Mao

    2016-10-01

    Full Text Available Atmospheric mercury (Hg is a global pollutant and thought to be the main source of mercury in oceanic and remote terrestrial systems, where it becomes methylated and bioavailable; hence, atmospheric mercury pollution has global consequences for both human and ecosystem health. Understanding of spatial and temporal variations of atmospheric speciated mercury can advance our knowledge of mercury cycling in various environments. This review summarized spatiotemporal variations of total gaseous mercury or gaseous elemental mercury (TGM/GEM, gaseous oxidized mercury (GOM, and particulate-bound mercury (PBM in various environments including oceans, continents, high elevation, the free troposphere, and low to high latitudes. In the marine boundary layer (MBL, the oxidation of GEM was generally thought to drive the diurnal and seasonal variations of TGM/GEM and GOM in most oceanic regions, leading to lower GEM and higher GOM from noon to afternoon and higher GEM during winter and higher GOM during spring–summer. At continental sites, the driving mechanisms of TGM/GEM diurnal patterns included surface and local emissions, boundary layer dynamics, GEM oxidation, and for high-elevation sites mountain–valley winds, while oxidation of GEM and entrainment of free tropospheric air appeared to control the diurnal patterns of GOM. No pronounced diurnal variation was found for Tekran measured PBM at MBL and continental sites. Seasonal variations in TGM/GEM at continental sites were attributed to increased winter combustion and summertime surface emissions, and monsoons in Asia, while those in GOM were controlled by GEM oxidation, free tropospheric transport, anthropogenic emissions, and wet deposition. Increased PBM at continental sites during winter was primarily due to local/regional coal and wood combustion emissions. Long-term TGM measurements from the MBL and continental sites indicated an overall declining trend. Limited measurements suggested TGM

  13. Understanding treatment effect mechanisms of the CAMBRA randomized trial in reducing caries increment.

    Science.gov (United States)

    Cheng, J; Chaffee, B W; Cheng, N F; Gansky, S A; Featherstone, J D B

    2015-01-01

    The Caries Management By Risk Assessment (CAMBRA) randomized controlled trial showed that an intervention featuring combined antibacterial and fluoride therapy significantly reduced bacterial load and suggested reduced caries increment in adults with 1 to 7 baseline cavitated teeth. While trial results speak to the overall effectiveness of an intervention, insight can be gained from understanding the mechanism by which an intervention acts on putative intermediate variables (mediators) to affect outcomes. This study conducted mediation analyses on 109 participants who completed the trial to understand whether the intervention reduced caries increment through its action on potential mediators (oral bacterial load, fluoride levels, and overall caries risk based on the composite of bacterial challenge and salivary fluoride) between the intervention and dental outcomes. The primary outcome was the increment from baseline in decayed, missing, and filled permanent surfaces (ΔDMFS) 24 mo after completing restorations for baseline cavitated lesions. Analyses adjusted for baseline overall risk, bacterial challenge, and fluoride values under a potential outcome framework using generalized linear models. Overall, the CAMBRA intervention was suggestive in reducing the 24-mo DMFS increment (reduction in ΔDMFS: -0.96; 95% confidence interval [CI]: -2.01 to 0.08; P = 0.07); the intervention significantly reduced the 12-mo overall risk (reduction in overall risk: -19%; 95% CI, -7 to -41%;], P = 0.005). Individual mediators, salivary log10 mutans streptococci, log10 lactobacilli, and fluoride level, did not represent statistically significant pathways alone through which the intervention effect was transmitted. However, 36% of the intervention effect on 24-mo DMFS increment was through a mediation effect on 12-mo overall risk (P = 0.03). These findings suggest a greater intervention effect carried through the combined action on multiple aspects of the caries process rather than

  14. Thermometers: Understand the Options

    Science.gov (United States)

    ... the options Thermometers come in a variety of styles. Understand the different types of thermometers and how ... MA. Fever in infants and children: Pathophysiology and management. http://www.uptodate.com/home. Accessed July 23, ...

  15. Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium: Shared Pathophysiologic Traits Identify Novel Treatment Strategies?

    Directory of Open Access Journals (Sweden)

    Brian R. Weil

    2015-01-01

    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and is associated with a high risk of morbidity and mortality. However, there are limited treatment strategies for prevention of disease onset and progression. Development of novel therapies for primary and secondary prevention of AF is critical and requires improved understanding of the cellular and molecular mechanisms underlying the AF disease process. Translational and clinical studies conducted over the past twenty years have revealed that atrial remodeling in AF shares several important pathophysiologic traits with the remodeling processes exhibited by hibernating myocardium that develop in response to chronic ischemia. These shared features, which include an array of structural, metabolic, and electrophysiologic changes, appear to represent a conserved adaptive myocyte response to chronic stress that involves dedifferentiation towards a fetal phenotype to promote survival. In this review, we discuss the pathophysiology of AF, summarize studies supporting a common remodeling program in AF and hibernating myocardium, and propose future therapeutic implications of this emerging paradigm. Ultimately, better understanding of the molecular mechanisms of atrial myocyte remodeling during the onset of AF and the transition from paroxysmal to persistent stages of the disease may facilitate discovery of new therapeutic targets.

  16. Understanding and Exploration of the Biomineralization Mechanisms for the Controllable Synthesis of Nanomaterials

    Science.gov (United States)

    Xiao, Junwu

    This thesis is mainly concerned with understanding the biomineralization mechanisms, and further extrapolating them for the controllable synthesis of transition metal compound nanomaterials on graphene sheets for energy storage applications in electrochemical capacitors and lithium ion batteries (LIB). Firstly, we have studied the mimetic biomineralization process of CaCO 3 on a stearic acid or 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) Langmuir monolayer at the air-water interface by in-situ Brewster angle microscopy (BAM) and ex-situ electron microscopy. Amorphous calcium carbonate (ACC) precursors are directly nucleated from solvated ions prior to the crystal nuclei on a Langmuir monolayer. On a DPPC monolayer, numerous fresh ACC nanoparticles heterogeneously and continuously nucleated at the air-water interface are transformed into the metastable vaterite nanocrystals. Driven by the trend to decrease surface energy, the vaterite nanocrystals self-aggregate and grow into the loose-packed hollow ellipsoidal vaterite polycrystals. These nanocrystals in vaterite polycrystals are then gradually orientated in the same direction to evolve into tight-packed ellipsoidal mesocrystals. As the crystallization time is further increased, the metastable vaterite mesocrystals are eventually transformed into the most thermodynamically stable calcite crystals. Secondly, organic and inorganic additives control over the shapes, sizes and phases of inorganic nanocrystals and arrange them into ordered structures from amorphous precursors in the organisms. This interesting phenomenon has galvanized many attempts to mimic the biomineralization process for synthesizing novel materials. We have studied the crystallization processes from small citrate molecules stabilized ACC precursors under cetyltrimethyl ammonium bromide (CTAB) micellar structures. Amorphous precursors, with a hydrated and disordered structure, are easily transformed and molded into CaCO 3 crystals with

  17. The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

    Science.gov (United States)

    Staudacher, Heidi M; Whelan, Kevin

    2017-08-01

    There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Pathophysiology of Headaches with a Prominent Vascular Component

    Directory of Open Access Journals (Sweden)

    Juan A Pareja

    1996-01-01

    Full Text Available Vascular changes, whether preliminary or secondary, seem to accompany most headaches. The literature concerning pathophysiological mechanisms in headaches where vascular phenomena are a major, integral part, ie, migraine and cluster headache syndrome, is reviewed and the most common forms of headache associated with cerebrovascular disease are discussed. Emphasis is placed on the vascular phenomena and on the abundant hypotheses and theories regarding headache mechanisms. This review also presents alternative explanatory models, and compares the available anatomical, physiological and biochemical results.

  19. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  20. Understanding the mechanisms that change the conductivity of damaged ITO-coated polymeric films: A micro-mechanical investigation

    KAUST Repository

    Nasr Saleh, Mohamed

    2014-11-01

    Degradation from mechanical loading of transparent electrodes made of indium tin oxide (ITO) endangers the integrity of any material based on these electrodes, including flexible organic solar cells. However, how different schemes of degradation change the conductivity of ITO devices remains unclear. We propose a systematic micro-mechanics-based approach to clarify the relationship between degradation and changes in electrical resistance. By comparing experimentally measured channel crack densities to changes in electrical resistance returned by the different micro-mechanical schemes, we highlight the key role played by the residual conductivity in the interface between the ITO electrode and its substrate after delamination. We demonstrate that channel cracking alone does not explain the experimental observations. Our results indicate that delamination has to take place between the ITO electrode and the substrate layers and that the residual conductivity of this delaminated interface plays a major role in changes in electrical resistance of the degraded device. © 2014 Elsevier B.V.

  1. The role of reactive oxygen species in the pathophysiology of cardiovascular diseases and the clinical significance of myocardial redox.

    Science.gov (United States)

    Moris, Demetrios; Spartalis, Michael; Spartalis, Eleftherios; Karachaliou, Georgia-Sofia; Karaolanis, Georgios I; Tsourouflis, Gerasimos; Tsilimigras, Diamantis I; Tzatzaki, Eleni; Theocharis, Stamatios

    2017-08-01

    Acute and chronic excessive intracellular increase of reactive oxygen species (ROS) is involved in the development and progression of cardiovascular diseases. ROS are by-products of various oxidative physiological and biochemical processes. Sources of ROS are mitochondrial respiration, NADH/NADPH oxidase, xanthine oxidoreductase or the uncoupling of nitric oxide synthase (NOS) in vascular cells. ROS mediate various signaling pathways that underlie cardiovascular pathophysiology. The delicate equilibrium between free-radical generation and antioxidant defense is altered in favor of the former, thus leading to redox imbalance, oxidative stress, and increased cellular injury. An understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of cardiovascular diseases.

  2. Pathophysiology of Migraine: A Disorder of Sensory Processing.

    Science.gov (United States)

    Goadsby, Peter J; Holland, Philip R; Martins-Oliveira, Margarida; Hoffmann, Jan; Schankin, Christoph; Akerman, Simon

    2017-04-01

    Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the "humors" through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT 1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT 1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu 5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology. Copyright © 2017 the American Physiological Society.

  3. Host parasite interactions and pathophysiology in Giardia infections.

    Science.gov (United States)

    Cotton, James A; Beatty, Jennifer K; Buret, Andre G

    2011-08-01

    Giardia is a protozoan parasite of the small intestine, and a leading cause of diarrhoeal disease worldwide in a variety of animals, including humans. The host-parasite interaction and pathophysiological processes of giardiasis remain incompletely understood. Current research suggests that Giardia-induced diarrhoeal disease is mediated by small intestinal malabsorption and maldigestion, chloride hypersecretion and increased rates of small intestinal transit. Small intestinal malabsorption and maldigestion results from the CD8+ lymphocyte-induced diffuse shortening of brush border microvilli. Activation of CD8+ lymphocytes occurs secondary to small intestinal barrier dysfunction, which results from heightened rates of enterocyte apoptosis and disruption of epithelial tight junctions. Both host and parasite factors contribute to the pathogenesis of giardiasis and ongoing research in this field may elucidate genotype/assemblage-specific pathogenic mechanisms. Giardia infections can result in chronic gastrointestinal disorders such as post-infectious Irritable Bowel Syndrome and symptoms may manifest at extra-intestinal sites, even though the parasite does not disseminate beyond the gastrointestinal tract. The infection can cause failure to thrive in children. Furthermore, there is now evidence suggesting that Giardia symptoms may vary between industrialised and developing areas of the world, for reasons that remain obscure. More research is needed to improve our understanding of this parasitic infection which was recently included in the World Health Organisation "Neglected Disease Initiative". Copyright © 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  4. Targeting autophagy in obesity: from pathophysiology to management.

    Science.gov (United States)

    Zhang, Yingmei; Sowers, James R; Ren, Jun

    2018-04-23

    Obesity poses a severe threat to human health, including the increased prevalence of hypertension, insulin resistance, diabetes mellitus, cancer, inflammation, sleep apnoea and other chronic diseases. Current therapies focus mainly on suppressing caloric intake, but the efficacy of this approach remains poor. A better understanding of the pathophysiology of obesity will be essential for the management of obesity and its complications. Knowledge gained over the past three decades regarding the aetiological mechanisms underpinning obesity has provided a framework that emphasizes energy imbalance and neurohormonal dysregulation, which are tightly regulated by autophagy. Accordingly, there is an emerging interest in the role of autophagy, a conserved homeostatic process for cellular quality control through the disposal and recycling of cellular components, in the maintenance of cellular homeostasis and organ function by selectively ridding cells of potentially toxic proteins, lipids and organelles. Indeed, defects in autophagy homeostasis are implicated in metabolic disorders, including obesity, insulin resistance, diabetes mellitus and atherosclerosis. In this Review, the alterations in autophagy that occur in response to nutrient stress, and how these changes alter the course of obesogenesis and obesity-related complications, are discussed. The potential of pharmacological modulation of autophagy for the management of obesity is also addressed.

  5. Laboratory experiments for understanding mechanical properties of fractured granite under supercritical conditions

    Science.gov (United States)

    Kitamura, M.; Takahashi, M.; Takagi, K.; Hirano, N.; Tsuchiya, N.

    2017-12-01

    To extract geothermal energy effectively and safely from magma and/or adjacent hot rock, we need to tackle many issues which require new technology development, such as a technique to control a risk from induced-earthquakes. On a development of induced-earthquake mitigation technology, it is required to understand roles of factors on occurrences of the induced-earthquake (e.g., strength, crack density, and fluid-rock reaction) and their intercorrelations (e.g., Asanuma et al., 2012). Our purpose of this series of experiments is to clarify a relationship between the rock strength and the crack density under supercritical conditions. We conducted triaxial deformation test on intact granite rock strength under high-temperature (250 - 750°C), high-pressure (104 MPa) condition at a constant load velocity (0.1 μm/sec) using a gas-rig at AIST. We used Oshima granite, which has initially stress drop became smaller at higher temperature. Young's modulus increased with decreasing the temperature from 32.3 GPa at 750°C to 57.4 GPa at 250°C. At 400 °C, the stress drop accelerated the deformation with 98 times faster velocity than that at load-point. In contrast, at 650°C and 750°C, the velocity during stress drop kept the same order of the load-point velocity. Therefore, the deformation mechanism may start to be changed from brittle to ductile when the temperature exceeds 650°C. Highly dense cracked granite specimens were formed by a rapid decompression test (RDT) using an autoclave settled at Tohoku University (Hirano et al., 2016JpGU), caused by a reduction of fluid pressure within 1-2 sec from vapor/supercritical state (10 - 48 MPa, 550 °C) to ambient pressure. The specimens after RDT show numerous microcracks on X-ray CT images. The RDT imposed the porosity increasing towards 3.75 % and Vp and Vs decreasing towards 1.37±0.52 km/s and 0.97±0.25 km/s. The Poisson's ratio shows the negative values in dry and 0.5 in wet. In the meeting, we will present results of

  6. Toward Understanding Mechanisms Controlling Urea Delivery in a Coastal Plain Watershed

    Science.gov (United States)

    Tzilkowski, S. S.; Buda, A. R.; Boyer, E. W.; Bryant, R. B.; May, E. B.

    2012-12-01

    Improved understanding of nutrient mobilization and delivery to surface waters is critical to protecting water quality in agricultural watersheds. Urea, a form of organic nitrogen, is a common nutrient found in fertilizers, manures, and human waste, and is gaining recognition as an important driver of coastal eutrophication, particularly through the development of harmful algal blooms. While several studies have documented elevated urea concentrations in tributaries draining to the Chesapeake Bay, little is known about the potential sources and flow pathways responsible for urea delivery from the landscape to surface waters, as well as how these sources and pathways might vary with changing seasons, antecedent conditions, and storm types. In this study, we investigated hydrologic controls on urea delivery in the Manokin River watershed through the analysis of urea concentration dynamics and hysteresis patterns during seven storm events that occurred in 2010 and 2011. The Manokin River is a Coastal Plain watershed (11.1 km2) on the Delmarva Peninsula that drains directly to the Chesapeake Bay and is characterized by extensive rural development coupled with intensive agriculture, particularly poultry production. Sampling was conducted through monthly grab sampling at baseflow conditions and by time-weighted, automated (Sigma) samplers during stormflow events. Monitored storms were chosen to represent a spectrum of antecedent conditions based on precipitation and groundwater levels in the area. Flushing from the landscape during events was found to be the predominant urea delivery mechanism, as urea concentrations increased 3-9 times above baseflow concentrations during storms. The timing and number of flushes, as well as the degree of increased concentrations were dependent on antecedent conditions and the characteristics of the storm event. For instance, during an intense (13.7 mm hr-1), short-duration (4 hrs) storm in August of 2010 when antecedent conditions were

  7. Pathophysiological consequences of hemolysis. Role of cell-free hemoglobin

    Directory of Open Access Journals (Sweden)

    Tomasz Misztal

    2011-09-01

    Full Text Available Abundant hemolysis is associated with a number of inherent and acquired diseases including sickle-cell disease (SCD, polycythemia, paroxysmal nocturnal hemoglobinuria (PNH and drug-induced hemolytic anemia. Despite different etiopathology of hemolytic diseases, many concomitant symptoms are comparable and include e.g. hypertension, hemoglobinuria and hypercoagulation state. Studies in the last years have shown a growing list of mechanisms lying at the basis of those symptoms, in particular irreversible reaction between cell-free hemoglobin (Hb and nitric oxide (NO – endogenous vasorelaxant and anti-thrombotic agent. Saturation of protective physiological cell-free Hb-scavenging mechanisms results in accumulation of Hb in plasma and hemoglobinemia. Extensive hemoglobinemia subsequently leads to hemoglobinuria, which may cause kidney damage and development of Fanconi syndrome. A severe problem in patients with SCD and PNH is pulmonary and systemic hypertension. It may lead to circulation failure, including stroke, and it is related to abolition of NO bioavailability for vascular smooth muscle cells. Thrombotic events are the major cause of death in SCD and PNH. It ensues from lack of platelet inhibition evoked by Hb-mediated NO scavenging. A serious complication that affects patients with excessive hemolysis is erectile dysfunction. Also direct cytotoxic, prooxidant and proinflammatory effects of cell-free hemoglobin and heme compose the clinical picture of hemolytic diseases. The pathophysiological role of plasma Hb, mechanisms of its elimination, and direct and indirect (via NO scavenging deleterious effects of cell-free Hb are presented in detail in this review. Understanding the critical role of hemolysis and cell-free Hb is important in the perspective of treating patients with hemolytic diseases and to design new effective therapies in future.

  8. The pathophysiology of amenorrhea in the adolescent.

    Science.gov (United States)

    Golden, Neville H; Carlson, Jennifer L

    2008-01-01

    Menstrual irregularity is a common occurrence during adolescence, especially within the first 2-3 years after menarche. Prolonged amenorrhea, however, is not normal and can be associated with significant medical morbidity, which differs depending on whether the adolescent is estrogen-deficient or estrogen-replete. Estrogen-deficient amenorrhea is associated with reduced bone mineral density and increased fracture risk, while estrogen-replete amenorrhea can lead to dysfunctional uterine bleeding in the short term and predispose to endometrial carcinoma in the long term. In both situations, appropriate intervention can reduce morbidity. Old paradigms of whom to evaluate for amenorrhea have been challenged by recent research that provides a better understanding of the normal menstrual cycle and its variability. Hypothalamic amenorrhea is the most prevalent cause of amenorrhea in the adolescent age group, followed by polycystic ovary syndrome. In anorexia nervosa, exercise-induced amenorrhea, and amenorrhea associated with chronic illness, an energy deficit results in suppression of hypothalamic secretion of GnRH, mediated in part by leptin. Administration of recombinant leptin to women with hypothalamic amenorrhea has been shown to restore LH pulsatility and ovulatory menstrual cycles. The use of recombinant leptin may improve our understanding of the pathophysiology of hypothalamic amenorrhea in adolescents and may also have therapeutic possibilities.

  9. Understanding Exercise-Associated Hyponatraemia: From Pathophysiology to Treatment

    Directory of Open Access Journals (Sweden)

    Sidonie Hubert

    2014-12-01

    Full Text Available The practice of extreme sports is becoming more and more common. Despite physiological adaptation, people who intensively exercise are exposed to exercise-associated complications, including hyponatraemia. Exercise-associated hyponatraemia seems to be a consequence of alteration of water regulation, particularly by excessive expression of vasopressin, sodium mobilisation, and interleukin-6 production by muscular cells. Preventing overhydration, both before and during effort, and prohibiting hypotonic solutes during treatment are the leading interventions to correct hyponatraemia.

  10. Towards a neurobiological understanding of pain in chronic pancreatitis: mechanisms and implications for treatment

    Directory of Open Access Journals (Sweden)

    Søren S. Olesen

    2017-12-01

    Conclusion:. Chronic pancreatitis is associated with abnormal processing of pain at the peripheral and central level of the pain system. This neurobiological understanding of pain has important clinical implications for treatment and prevention of pain chronification.

  11. Tuberculosis 2: Pathophysiology and microbiology of pulmonary ...

    African Journals Online (AJOL)

    2005-08-01

    Aug 1, 2005 ... February 2013 Downloaded from www.southsudanmedicaljournal.com. MaIN arTIClES. 10. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. Robert L. Serafino Wania MBBS, MrCP, MSc (Trop Med). Pathophysiology. Inhalation of Mycobacterium tuberculosis leads to one of.

  12. Advances in understanding of soil biogeochemical cycles: the mechanism of HS entry into the root interior

    Science.gov (United States)

    Aleksandrova, Olga

    2017-04-01

    Humic substances represent the major reservoir of carbon (C) in ecosystems, and their turnover is crucial for understanding the global C cycle. As shown by some investigators [1-2], the phenomenon of the uptake of the whole humic particles by plant roots is a significant step of biogeochemical cycle of carbon in soils. The mechanism of HS entry the root interior remained unknown for a long time. However recently, the last one was discovered [3]. An advanced model [3] includes two hypotheses. These hypotheses are as follows: (1) each nano-size particle possesses a quantum image that can be revealed as a packet of electromagnetic waves; (2) the interaction of nano-size particle with the membrane (plasma membrane) of living cells, on which it is adsorbed, occurs via the development of the Rayleigh-Taylor (RT) instability on the membrane surface. An advanced model allows us to look insight some into some phenomena that were observed by experiments but remained not understood [2]. The authors [2] applied tritium autoradiography to wheat seedlings cultivated with tritium-labeled HS to consider the uptake of humic particles by plant roots. They found a significant increase in the content of some polar (monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG) and phosphatidylcholine (PC)) and neutral (free fatty acids, FFA) lipids which were detected in the wheat seedlings treated with humic particles. Authors [2] pointed that lipids MGDG, DGDG, SQDG are crucial for functional and structural integrity of the photosystem complex. Therefore, a stimulating action of adsorbed humic particles evoked phenomena like photosynthesis in root cells that can be interpreted using an advanced model: humic particles being nano-size particles become adsorbed on the plant roots in soils, and influence their micro environment, where they are located, with the specific electromagnetic exposure. Another finding of authors consisted in the

  13. Oxide nanoparticle EUV resists: toward understanding the mechanism of positive and negative tone patterning

    KAUST Repository

    Chakrabarty, Souvik

    2013-04-01

    DUV, EUV and e-beam patterning of hybrid nanoparticle photoresists have been reported previously by Ober and coworkers. The present work explores the underlying mechanism that is responsible for the dual tone patterning capability of these photoresist materials. Spectroscopic results correlated with mass loss and dissolution studies suggest a ligand exchange mechanism responsible for altering the solubility between the exposed and unexposed regions. © 2013 SPIE.

  14. Using realist synthesis to understand the mechanisms of interprofessional teamwork in health and social care.

    Science.gov (United States)

    Hewitt, Gillian; Sims, Sarah; Harris, Ruth

    2014-11-01

    Realist synthesis offers a novel and innovative way to interrogate the large literature on interprofessional teamwork in health and social care teams. This article introduces realist synthesis and its approach to identifying and testing the underpinning processes (or "mechanisms") that make an intervention work, the contexts that trigger those mechanisms and their subsequent outcomes. A realist synthesis of the evidence on interprofessional teamwork is described. Thirteen mechanisms were identified in the synthesis and findings for one mechanism, called "Support and value" are presented in this paper. The evidence for the other twelve mechanisms ("collaboration and coordination", "pooling of resources", "individual learning", "role blurring", "efficient, open and equitable communication", "tactical communication", "shared responsibility and influence", "team behavioural norms", "shared responsibility and influence", "critically reviewing performance and decisions", "generating and implementing new ideas" and "leadership") are reported in a further three papers in this series. The "support and value" mechanism referred to the ways in which team members supported one another, respected other's skills and abilities and valued each other's contributions. "Support and value" was present in some, but far from all, teams and a number of contexts that explained this variation were identified. The article concludes with a discussion of the challenges and benefits of undertaking this realist synthesis.

  15. Platelet pathophysiology, pharmacology, and function in coronary artery disease.

    Science.gov (United States)

    Ibrahim, Homam; Kleiman, Neal S

    2017-11-01

    Platelets play a key role in the pathophysiology of coronary artery disease and acute coronary syndromes. Our understanding of platelet function in thrombus formation has increased considerably, resulting in the development of clinically effective treatment strategies and identification of new targets. An underappreciated platelet function is their contribution toward acute and chronic inflammatory processes including atherogenesis. In this review, we discuss the role of platelets in atherosclerosis and thrombosis, platelet function testing, and the pharmacology of currently available antiplatelet drugs.

  16. [Mirror neurons: from anatomy to pathophysiological and therapeutic implications].

    Science.gov (United States)

    Mathon, B

    2013-04-01

    Mirror neurons are a special class of neurons discovered in the 1990s. They respond when we perform an action and also when we see someone else perform that action. They play a role in the pathophysiology of some neuropsychiatric diseases. Mirror neurons have been identified in humans: in Broca's area and the inferior parietal cortex. Their responses are qualitative and selective depending on the observed action. Emotions (including disgust) and empathy seem to operate according to a mirror mechanism. Indeed, the mirror system allows us to encode the sensory experience and to simulate the emotional state of others. This results in our improved identification of the emotions in others. Additionally, mirror neurons can encode an observed action in motor stimuli and allow its reproduction; thus, they are involved in imitation and learning. Current studies are assessing the role of mirror neurons in the pathopysiology of social-behavior disorders, including autism and schizophrenia. Understanding this mirror system will allow us to develop psychotherapy practices based on empathic resonance between the patient and the therapist. Also, some authors report that a passive rehabilitation technique, based on stimulation of the mirror-neuron system, has a beneficial effect in the treatment of patients with post-stroke motor deficits. Mirror neurons are an anatomical entity that enables improved understanding of behavior and emotions, and serves as a base for developing new cognitive therapies. Additional studies are needed to clarify the exact role of this neuronal system in social cognition and its role in the development of some neuropsychiatric diseases. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Understanding User Preferences and Awareness: Privacy Mechanisms in Location-Based Services

    Science.gov (United States)

    Burghardt, Thorben; Buchmann, Erik; Müller, Jens; Böhm, Klemens

    Location based services (LBS) let people retrieve and share information related to their current position. Examples are Google Latitude or Panoramio. Since LBS share user-related content, location information etc., they put user privacy at risk. Literature has proposed various privacy mechanisms for LBS. However, it is unclear which mechanisms humans really find useful, and how they make use of them. We present a user study that addresses these issues. To obtain realistic results, we have implemented a geotagging application on the web and on GPS cellphones, and our study participants use this application in their daily lives. We test five privacy mechanisms that differ in the awareness, mental effort and degree of informedness required from the users. Among other findings, we have observed that in situations where a single simple mechanism does not meet all privacy needs, people want to use simple and sophisticated mechanisms in combination. Further, individuals are concerned about the privacy of others, even when they do not value privacy for themselves.

  18. Pathophysiology in mountain yellow-legged frogs (Rana muscosa during a chytridiomycosis outbreak.

    Directory of Open Access Journals (Sweden)

    Jamie Voyles

    Full Text Available The disease chytridiomycosis is responsible for declines and extirpations of amphibians worldwide. Chytridiomycosis is caused by a fungal pathogen (Batrachochytrium dendrobatidis that infects amphibian skin. Although we have a basic understanding of the pathophysiology from laboratory experiments, many mechanistic details remain unresolved and it is unknown if disease development is similar in wild amphibian populations. To gain a better understanding of chytridiomycosis pathophysiology in wild amphibian populations, we collected blood biochemistry measurements during an outbreak in mountain yellow-legged frogs (Rana muscosa in the Sierra Nevada Mountains of California. We found that pathogen load is associated with disruptions in fluid and electrolyte balance, yet is not associated with fluctuations acid-base balance. These findings enhance our knowledge of the pathophysiology of this disease and indicate that disease development is consistent across multiple species and in both laboratory and natural conditions. We recommend integrating an understanding of chytridiomycosis pathophysiology with mitigation practices to improve amphibian conservation.

  19. Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design.

    Science.gov (United States)

    Albanaz, Amanda T S; Rodrigues, Carlos H M; Pires, Douglas E V; Ascher, David B

    2017-06-01

    Mutations introduce diversity into genomes, leading to selective changes and driving evolution. These changes have contributed to the emergence of many of the current major health concerns of the 21st century, from the development of genetic diseases and cancers to the rise and spread of drug resistance. The experimental systematic testing of all mutations in a system of interest is impractical and not cost-effective, which has created interest in the development of computational tools to understand the molecular consequences of mutations to aid and guide rational experimentation. Areas covered: Here, the authors discuss the recent development of computational methods to understand the effects of coding mutations to protein function and interactions, particularly in the context of the 3D structure of the protein. Expert opinion: While significant progress has been made in terms of innovative tools to understand and quantify the different range of effects in which a mutation or a set of mutations can give rise to a phenotype, a great gap still exists when integrating these predictions and drawing causality conclusions linking variants. This often requires a detailed understanding of the system being perturbed. However, as part of the drug development process it can be used preemptively in a similar fashion to pharmacokinetics predictions, to guide development of therapeutics to help guide the design and analysis of clinical trials, patient treatment and public health policy strategies.

  20. Laboratory Activities to Support Student Understanding of the Molecular Mechanisms of Mutation & Natural Selection

    Science.gov (United States)

    Hubler, Tina; Adams, Patti; Scammell, Jonathan

    2015-01-01

    The molecular basis of evolution is an important and challenging concept for students to understand. In a previous article, we provided some of the scientific background necessary to teach this topic. This article features a series of laboratory activities demonstrating that molecular events can alter the genomes of organisms. These activities are…

  1. Towards an understanding of hot carrier cooling mechanisms in multiple quantum wells

    Science.gov (United States)

    Conibeer, Gavin; Zhang, Yi; Bremner, Stephen P.; Shrestha, Santosh

    2017-09-01

    Multiple quantum wells have been shown significantly reduced hot carrier cooling rates compared to bulk material and are thus a promising candidate for hot carrier solar cell absorbers. However, the mechanism(s) by which hot carrier cooling is restricted is not clear. A systematic study of carrier cooling rates in GaAs/AlAs multiple quantum wells (MQWs) with either varying barrier thickness or varying well thickness is presented in this paper. These allow an investigation as to whether the mechanisms of either a modification in hot carrier diffusion or a localisation of phonons emitted by hot carriers are primarily responsible for reduced carrier cooling rates. With the conclusion that for the structures investigated the situation is rather more complex with both carrier mobility to modify hot carrier diffusion, different diffusion rates for electrons and holes and reflection and localisation of phonons to enhance phonon bottleneck all playing their parts in modulating phonon reabsorption and hot carrier behaviour.

  2. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  3. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

    Science.gov (United States)

    Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them

  4. Understanding the mechanism of nanotube synthesis for controlled production of specific (n,m) structures

    Energy Technology Data Exchange (ETDEWEB)

    Resasco, Daniel E.

    2010-02-11

    This report shows the extensive research on the mechanism responsible for the formation of single walled carbon nanotubes in order to get control over their structural parameters (diameter and chirality). Catalyst formulations, pre-treatment conditions, and reaction conditions are described in detail as well as mechanisms to produce nanotubes structures of specific arrays (vertical forest, nanotube pillars). Applications of SWNT in different fields are also described in this report. In relation to this project five students have graduated (3 PhD and 2 MS) and 35 papers have been published.

  5. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management

    OpenAIRE

    Mollan, Susan P; Ali, Fizzah; Hassan-Smith, Ghaniah; Botfield, Hannah; Friedman, Deborah I; Sinclair, Alexandra J

    2016-01-01

    Idiopathic intracranial hypertension (IIH) is a rare but important disease associated with significant morbidity. There is an expected rise in prevalence in line with the escalating global burden of obesity. Modern revisions in the terminology and diagnostic criteria for IIH help guide clinicians in investigations and researchers in standardising recruitment criteria for clinical trials. The pathophysiology of IIH is incompletely characterised; suggested underpinning mechanisms include the ro...

  6. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  7. Understanding the antimicrobial mechanism of TiO2-based nanocomposite films in a pathogenic bacterium

    NARCIS (Netherlands)

    Kubacka, A.; Suarez Diez, M.; Rojo, D.; Bargiela, R.; Ciordia, S.; Zapico, I.; Albar, J.P.; Barbas, C.; Martins Dos Santos, V.A.P.; Fernández-García, M.; Ferrer, M.

    2014-01-01

    Titania (TiO2)-based nanocomposites subjected to light excitation are remarkably effective in eliciting microbial death. However, the mechanism by which these materials induce microbial death and the effects that they have on microbes are poorly understood. Here, we assess the low dose

  8. Understanding the mechanism of action of triazine-phosphonate derivatives as flame retardants for cotton fabrics

    Science.gov (United States)

    Countless hours of research and studies on triazine, phosphonate and their combination have provided insightful information into their flame retardant properties on polymeric systems. However, only limited number of studies shed light on the mechanism of flame retardant cotton fabrics. The purpose...

  9. Investigating and improving student understanding of quantum mechanics in the context of single photon interference

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2017-06-01

    Single photon experiments involving a Mach-Zehnder interferometer can illustrate the fundamental principles of quantum mechanics, e.g., the wave-particle duality of a single photon, single photon interference, and the probabilistic nature of quantum measurement involving single photons. These experiments explicitly make the connection between the abstract quantum theory and concrete laboratory settings and have the potential to help students develop a solid grasp of the foundational issues in quantum mechanics. Here we describe students' conceptual difficulties with these topics in the context of Mach-Zehnder interferometer experiments with single photons and how the difficulties found in written surveys and individual interviews were used as a guide in the development of a Quantum Interactive Learning Tutorial (QuILT). The QuILT uses an inquiry-based approach to learning and takes into account the conceptual difficulties found via research to help upper-level undergraduate and graduate students learn about foundational quantum mechanics concepts using the concrete quantum optics context. It strives to help students learn the basics of quantum mechanics in the context of single photon experiment, develop the ability to apply fundamental quantum principles to experimental situations in quantum optics, and explore the differences between classical and quantum ideas in a concrete context. We discuss the findings from in-class evaluations suggesting that the QuILT was effective in helping students learn these abstract concepts.

  10. Improving Student Understanding of Addition of Angular Momentum in Quantum Mechanics

    Science.gov (United States)

    Zhu, Guangtian; Singh, Chandralekha

    2013-01-01

    We describe the difficulties advanced undergraduate and graduate students have with concepts related to addition of angular momentum in quantum mechanics. We also describe the development and implementation of a research-based learning tool, Quantum Interactive Learning Tutorial (QuILT), to reduce these difficulties. The preliminary evaluation…

  11. A Changing Landscape of Advanced Prostate Cancer: Understanding Mechanisms of Resistance to Potent Hormonal Therapies

    Science.gov (United States)

    2016-10-01

    mechanisms of NEPC progression using deep sequencing techniques of metastatic tumor biopsies and non-invasively using liquid biopsies including...from each site. (b) AR signaling (right) based on abundance of mRNA transcripts included in the AR signaling signature described in ref 19. Violin

  12. Recent advances in understanding the reinforcing ability and mechanism of carbon nanotubes in ceramic matrix composites

    International Nuclear Information System (INIS)

    Estili, Mehdi; Sakka, Yoshio

    2014-01-01

    Since the discovery of carbon nanotubes (CNTs), commonly referred to as ultimate reinforcement, the main purpose for fabricating CNT–ceramic matrix composites has been mainly to improve the fracture toughness and strength of the ceramic matrix materials. However, there have been many studies reporting marginal improvements or even the degradation of mechanical properties. On the other hand, those studies claiming noticeable toughening measured using indentation, which is an indirect/unreliable characterization method, have not demonstrated the responsible mechanisms applicable to the nanoscale, flexible CNTs; instead, those studies proposed those classical methods applicable to microscale fiber/whisker reinforced ceramics without showing any convincing evidence of load transfer to the CNTs. Therefore, the ability of CNTs to directly improve the macroscopic mechanical properties of structural ceramics has been strongly questioned and debated in the last ten years. In order to properly discuss the reinforcing ability (and possible mechanisms) of CNTs in a ceramic host material, there are three fundamental questions to our knowledge at both the nanoscale and macroscale levels that need to be addressed: (1) does the intrinsic load-bearing ability of CNTs change when embedded in a ceramic host matrix?; (2) when there is an intimate atomic-level interface without any chemical reaction with the matrix, could one expect any load transfer to the CNTs along with effective load bearing by them during crack propagation?; and (3) considering their nanometer-scale dimensions, flexibility and radial softness, are the CNTs able to improve the mechanical properties of the host ceramic matrix at the macroscale when individually, intimately and uniformly dispersed? If so, how? Also, what is the effect of CNT concentration in such a defect-free composite system? Here, we briefly review the recent studies addressing the above fundamental questions. In particular, we discuss the new

  13. Obesity: Pathophysiology and Management.

    Science.gov (United States)

    Gadde, Kishore M; Martin, Corby K; Berthoud, Hans-Rudolf; Heymsfield, Steven B

    2018-01-02

    Obesity continues to be among the top health concerns across the globe. Despite our failure to contain the high prevalence of obesity, we now have a better understanding of its pathophysiology, and how excess adiposity leads to type 2 diabetes, hypertension, and cardiovascular disease. Lifestyle modification is recommended as the cornerstone of obesity management, but many patients do not achieve long-lasting benefits due to difficulty with adherence as well as physiological and neurohormonal adaptation of the body in response to weight loss. Fortunately, 5 drug therapies-orlistat, lorcaserin, liraglutide, phentermine/topiramate, and naltrexone/bupropion-are available for long-term weight management. Additionally, several medical devices are available for short-term and long-term use. Bariatric surgery yields substantial and sustained weight loss with resolution of type 2 diabetes, although due to the high cost and a small risk of serious complications, it is generally recommended for patients with severe obesity. Benefit-to-risk balance should guide treatment decisions. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Understanding NOx SCR Mechanism and Activity on Cu/Chabazite Structures throughout the Catalyst Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Fabio; Delgass, Nick; Gounder, Rajmani; Schneider, William F.; Miller, Jeff; Yezerets, Aleksey; McEwen, Jean-Sabin; Peden, Charles HF; Howden, Ken

    2014-12-09

    Oxides of nitrogen (NOx) compounds contribute to acid rain and photochemical smog and have been linked to respiratory ailments. NOx emissions regulations continue to tighten, driving the need for high performance, robust control strategies. The goal of this project is to develop a deep, molecular level understanding of the function of Cu-SSZ-13 and Cu-SAPO-34 materials that catalyze the SCR of NOx with NH3.

  15. Progress in understanding the mechanical behavior of pressure-vessel materials at elevated temperatures

    International Nuclear Information System (INIS)

    Swindeman, R.W.; Brinkman, C.R.

    1981-01-01

    Progress during the 1970's on the production of high-temperature mechanical properties data for pressure vessel materials was reviewed. The direction of the research was toward satisfying new data requirements to implement advances in high-temperature inelastic design methods. To meet these needs, servo-controlled testing machines and high-resolution extensometry were developed to gain more information on the essential behavioral features of high-temperature alloys. The similarities and differences in the mechanical response of various pressure vessel materials were identified. High-temperature pressure vessel materials that have received the most attention included Type 304 stainless steel, Type 316 stainless steel, 2 1/4 Cr-1 Mo steel, alloy 800H, and Hastelloy X

  16. Understanding reaction mechanisms in organic chemistry from catastrophe theory applied to the electron localization function topology.

    Science.gov (United States)

    Polo, Victor; Andres, Juan; Berski, Slawomir; Domingo, Luis R; Silvi, Bernard

    2008-08-07

    Thom's catastrophe theory applied to the evolution of the topology of the electron localization function (ELF) gradient field constitutes a way to rationalize the reorganization of electron pairing and a powerful tool for the unambiguous determination of the molecular mechanisms of a given chemical reaction. The identification of the turning points connecting the ELF structural stability domains along the reaction pathway allows a rigorous characterization of the sequence of electron pair rearrangements taking place during a chemical transformation, such as multiple bond forming/breaking processes, ring closure processes, creation/annihilation of lone pairs, transformations of C-C multiple bonds into single ones. The reaction mechanism of some relevant organic reactions: Diels-Alder, 1,3-dipolar cycloaddition and Cope rearrangement are reviewed to illustrate the potential of the present approach.

  17. Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer

    Science.gov (United States)

    van den Eijnde, Wilbert A.J.; Peppelman, Malou; Lamers, Edwin A.D.; van de Kerkhof, Peter C.M.; van Erp, Piet E.J.

    2014-01-01

    Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin. PMID:26535330

  18. Understanding the Personality and Behavioral Mechanisms Defining Hypersexuality in Men Who Have Sex With Men.

    Science.gov (United States)

    Miner, Michael H; Romine, Rebecca Swinburne; Raymond, Nancy; Janssen, Erick; MacDonald, Angus; Coleman, Eli

    2016-09-01

    Hypersexuality has been conceptualized as sexual addiction, compulsivity, and impulsivity, among others, in the absence of strong empirical data in support of any specific conceptualization. To investigate personality factors and behavioral mechanisms that are relevant to hypersexuality in men who have sex with men. A sample of 242 men who have sex with men was recruited from various sites in a moderate-size mid-western city. Participants were assigned to a hypersexuality group or a control group using an interview similar to the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. Self-report inventories were administered that measured the broad personality constructs of positive emotionality, negative emotionality, and constraint and more narrow constructs related to sexual behavioral control, behavioral activation, behavioral inhibition, sexual excitation, sexual inhibition, impulsivity, attention-deficit/hyperactivity disorder, and sexual behavior. Hierarchical logistic regression was used to determine the relation between these personality and behavioral variables and group membership. A hierarchical logistic regression controlling for age showed a significant positive relation between hypersexuality and negative emotionality and a negative relation with constraint. None of the behavioral mechanism variables entered this equation. However, a hierarchical multiple regression analysis predicting sexual behavioral control indicated that lack of such control was positively related to sexual excitation and sexual inhibition owing to the threat of performance failure and negatively related to sexual inhibition owing to the threat of performance consequences and general behavioral inhibition Hypersexuality was found to be related to two broad personality factors that are characterized by emotional reactivity, risk taking, and impulsivity. The associated lack of sexual behavior control is influenced by sexual

  19. The effects of bariatric surgery – will understanding its mechanism render the knife unnecessary?

    OpenAIRE

    Browning, Kirsteen N; Hajnal, Andras

    2013-01-01

    The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for severe obesity with, until recently, Roux-en-Y gastric bypass (RYGB) being the most commonly performed procedures, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From both basic science as well as clinical standpoints, there are several areas of current int...

  20. Understanding Freshness Perception from the Cognitive Mechanisms of Flavor: The Case of Beverages

    Science.gov (United States)

    Roque, Jérémy; Auvray, Malika; Lafraire, Jérémie

    2018-01-01

    Freshness perception has received recent consideration in the field of consumer science mainly because of its hedonic dimension, which is assumed to influence consumers’ preference and behavior. However, most studies have considered freshness as a multisensory attribute of food and beverage products without investigating the cognitive mechanisms at hand. In the present review, we endorse a slightly different perspective on freshness. We focus on (i) the multisensory integration processes that underpin freshness perception, and (ii) the top–down factors that influence the explicit attribution of freshness to a product by consumers. To do so, we exploit the recent literature on the cognitive underpinnings of flavor perception as a heuristic to better characterize the mechanisms of freshness perception in the particular case of beverages. We argue that the lack of consideration of particular instances of flavor, such as freshness, has resulted in a lack of consensus about the content and structure of different types of flavor representations. We then enrich these theoretical analyses, with a review of the cognitive mechanisms of flavor perception: from multisensory integration processes to the influence of top–down factors (e.g., attentional and semantic). We conclude that similarly to flavor, freshness perception is characterized by hybrid content, both perceptual and semantic, but that freshness has a higher-degree of specificity than flavor. In particular, contrary to flavor, freshness is characterized by specific functions (e.g., alleviation of oropharyngeal symptoms) and likely differs from flavor with respect to the weighting of each sensory contributor, as well as to its subjective location. Finally, we provide a comprehensive model of the cognitive mechanisms that underlie freshness perception. This model paves the way for further empirical research on particular instances of flavor, and will enable advances in the field of food and beverage cognition

  1. Angioedema: etiology, pathophysiology, current and emerging therapies.

    Science.gov (United States)

    Lewis, Lawrence M

    2013-11-01

    Angioedema (AE) is characterized by nonpitting edema of the dermis and subcutaneous layers. The most common sites of involvement are the tongue, lips, face, and throat; however, swelling can also occur in the extremities, genitalia, and viscera. Life-threatening airway swelling can also occur. AE may be allergic or nonallergic. The overall lifetime incidence of AE is reported to be as high as 15%. This article summarizes the etiology, pathophysiology, and current treatment of several forms of nonallergic AE (including hereditary, acquired, and idiopathic AE) and focuses on angiotensin-converting enzyme inhibitor-induced angioedema (ACEi-AE), which is responsible for 30%-40% of all AE seen in United States emergency departments. Although the triggers, which are primary biologic mechanisms, and treatments for ACEi-AE may differ from those of the hereditary and acquired forms of AE, the clinical effects of ACEi-AE are mediated through a shared pathway, the kallikrein-kinin system. Thus, although current therapeutic options for ACEi-AE are limited, recent advances in the treatment of hereditary AE (HAE) appear promising for improving the outcomes of patients with ACEi-AE. New HAE medications that correct imbalances in the kallikrein-kinin system may prove safe and efficacious in the treatment of ACEi-AE. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Investigating and improving student understanding of quantum mechanical observables and their corresponding operators in Dirac notation

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2018-01-01

    In quantum mechanics, for every physical observable, there is a corresponding Hermitian operator. According to the most common interpretation of quantum mechanics, measurement of an observable collapses the quantum state into one of the possible eigenstates of the operator and the corresponding eigenvalue is measured. Since Dirac notation is an elegant notation that is commonly used in upper-level quantum mechanics, it is important that students learn to express quantum operators corresponding to observables in Dirac notation in order to apply the quantum formalism effectively in diverse situations. Here we focus on an investigation that suggests that, even though Dirac notation is used extensively, many advanced undergraduate and PhD students in physics have difficulty expressing the identity operator and other Hermitian operators corresponding to physical observables in Dirac notation. We first describe the difficulties students have with expressing the identity operator and a generic Hermitian operator corresponding to an observable in Dirac notation. We then discuss how the difficulties found via written surveys and individual interviews were used as a guide in the development of a quantum interactive learning tutorial (QuILT) to help students develop a good grasp of these concepts. The QuILT strives to help students become proficient in expressing the identity operator and a generic Hermitian operator corresponding to an observable in Dirac notation. We also discuss the effectiveness of the QuILT based on in-class evaluations.

  3. Marine phospholipids: The current understanding of their oxidation mechanisms and potential uses for food fortification

    DEFF Research Database (Denmark)

    Lu, Henna Fung Sieng; Nielsen, Nina Skall; Baron, Caroline P.

    2017-01-01

    and storage of marine PL. For example, nonenzymatic browning reactions may occur between lipid oxidation products and primary amine group from phosphatidylethanolamine or amino acid residues that are present inmarine PL. Therefore, marine PL contain products from nonenzymatic browning and lipid oxidation...... reactions, namely, Strecker aldehydes, pyrroles, oxypolymers, and other impurities that may positively or negatively affect the oxidative stability and quality of marine PL. This review was undertaken to provide the industry and academia with an overview of the current understanding of the quality changes...... taking place in PL during their production and their storage as well as with regards to their utilization for food fortification....

  4. Understanding the Atomic Scale Mechanisms that Control the Attainment of Ultralow Friction and Wear in Carbon-Based Materials

    Science.gov (United States)

    2016-01-16

    2015. 15. Invited. New Insights into Friction and Wear through In-Situ Nanotribology. Joint Symposium of the Surface Science Society of Japan and...and Carpick, R.W. Influence of Surface Passivation on the Friction and Wear Behavior of Ultrananocrystalline Diamond and Tetrahedral Amorphous Carbon...AFRL-AFOSR-JP-TR-2016-0053 Understanding the Atomic Scale Mechanism that controls the attainment of ultralow friction and wear in carbon based

  5. The effects of students' reasoning abilities on conceptual understandings and problem-solving skills in introductory mechanics

    International Nuclear Information System (INIS)

    Ates, S; Cataloglu, E

    2007-01-01

    The purpose of this study was to determine if there are relationships among freshmen/first year students' reasoning abilities, conceptual understandings and problem-solving skills in introductory mechanics. The sample consisted of 165 freshmen science education prospective teachers (female = 86, male = 79; age range 17-21) who were enrolled in an introductory physics course. Data collection was done during the fall semesters in two successive years. At the beginning of each semester, the force concept inventory (FCI) and the classroom test of scientific reasoning (CTSR) were administered to assess students' initial understanding of basic concepts in mechanics and reasoning levels. After completing the course, the FCI and the mechanics baseline test (MBT) were administered. The results indicated that there was a significant difference in problem-solving skill test mean scores, as measured by the MBT, among concrete, formal and postformal reasoners. There were no significant differences in conceptual understanding levels of pre- and post-test mean scores, as measured by FCI, among the groups. The Benferroni post hoc comparison test revealed which set of reasoning levels showed significant difference for the MBT scores. No statistical difference between formal and postformal reasoners' mean scores was observed, while the mean scores between concrete and formal reasoners and concrete and postformal reasoners were statistically significantly different

  6. Understanding of bonding and mechanical characteristics of cementitious mineral tobermorite from first principles.

    Science.gov (United States)

    Tunega, Daniel; Zaoui, Ali

    2011-01-30

    This paper reports density functional theory study of the structural and mechanical properties of tobermorite mineral (9 Å phase) as one of the main component of cementitious materials in a concrete chemistry. Calculated bulk modulus and elastic constants reflect a relatively high resistance of the tobermorite structure with respect to external isostatic compression. Moreover, the elastic constants proved the anisotropic character of the tobermorite structure. The directions parallel to the axb plane are more resistant to the compression than the perpendicular direction. The largest contribution to this resistance comes from the "dreierketten" silicate chains. The bonding analysis linked macroscopic mechanical properties and the atomic structure of the tobermorite. It was found that polar covalent Si-O bonds are stiffer than iono-covalent Ca-O bonds. The SiO(4) tetrahedra are resistant with respect to the compression and the effect of external pressure is reflected by the large mutual tilting of these tetrahedra as it is shown by changes of the Si-O-Si bridging angles. Polyhedra with the seven-fold coordinated Ca(2+) cations undergo large structural changes. Especially, axial Ca-O bonds perpendicular to the axb plane are significantly shortened. Besides, it was shown that structural parameters, more or less in parallel orientation to the axb plane, are mainly responsible for the high resistance of the tobermorite structure to external pressure. The main mechanism of a dissipation of energy entered to the structure through the compression is proceeded by the tilting of the tetrahedra of the silicate chains and by large shortening of the axial Ca-O distances. Copyright © 2010 Wiley Periodicals, Inc.

  7. Understanding flocculation mechanism of graphene oxide for organic dyes from water: Experimental and molecular dynamics simulation

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2015-11-01

    Full Text Available Flocculation treatment processes play an important role in water and wastewater pretreatment. Here we investigate experimentally and theoretically the possibility of using graphene oxide (GO as a flocculant to remove methylene blue (MB from water. Experimental results show that GO can remove almost all MB from aqueous solutions at its optimal dosages and molecular dynamics simulations indicate that MB cations quickly congregate around GO in water. Furthermore, PIXEL energy contribution analysis reveals that most of the strong interactions between GO and MB are of a van der Waals (London dispersion character. These results offer new insights for shedding light on the molecular mechanism of interaction between GO and organic pollutants.

  8. Understanding organometallic reaction mechanisms and catalysis experimental and computational tools computational and experimental tools

    CERN Document Server

    Ananikov, Valentin P

    2014-01-01

    Exploring and highlighting the new horizons in the studies of reaction mechanisms that open joint application of experimental studies and theoretical calculations is the goal of this book. The latest insights and developments in the mechanistic studies of organometallic reactions and catalytic processes are presented and reviewed. The book adopts a unique approach, exemplifying how to use experiments, spectroscopy measurements, and computational methods to reveal reaction pathways and molecular structures of catalysts, rather than concentrating solely on one discipline. The result is a deeper

  9. Thalassemia: Pathophysiology and management. Part A

    International Nuclear Information System (INIS)

    Fucharoen, S.; Rowley, P.T.; Paul, N.W.

    1988-01-01

    This book contains papers divided among the following sections: molecular biology and pathogenesis; pathophysiology - molecular and cellular; clinical manifestations and hematologic changes; cardiopulmonary defects and platelet function; hormones and minerals; and infection and immunology

  10. A Multiscale Understanding of the Thermodynamic and Kinetic Mechanisms of Laser Additive Manufacturing

    Directory of Open Access Journals (Sweden)

    Dongdong Gu

    2017-10-01

    Full Text Available Selective laser melting (SLM additive manufacturing (AM technology has become an important option for the precise manufacturing of complex-shaped metallic parts with high performance. The SLM AM process involves complicated physicochemical phenomena, thermodynamic behavior, and phase transformation as a high-energy laser beam melts loose powder particles. This paper provides multiscale modeling and coordinated control for the SLM of metallic materials including an aluminum (Al-based alloy (AlSi10Mg, a nickel (Ni-based super-alloy (Inconel 718, and ceramic particle-reinforced Al-based and Ni-based composites. The migration and distribution mechanisms of aluminium nitride (AlN particles in SLM-processed Al-based nanocomposites and the in situ formation of a gradient interface between the reinforcement and the matrix in SLM-processed tungsten carbide (WC/Inconel 718 composites were studied in the microscale. The laser absorption and melting/densification behaviors of AlSi10Mg and Inconel 718 alloy powder were disclosed in the mesoscale. Finally, the stress development during line-by-line localized laser scanning and the parameter-dependent control methods for the deformation of SLM-processed composites were proposed in the macroscale. Multiscale numerical simulation and experimental verification methods are beneficial in monitoring the complicated powder-laser interaction, heat and mass transfer behavior, and microstructural and mechanical properties development during the SLM AM process.

  11. Understanding the differing governance of EU emissions trading and renewable: feedback mechanisms and policy entrepreneurs

    Energy Technology Data Exchange (ETDEWEB)

    Boasson, Elin Lerum; Wettestad, Joergen

    2010-04-15

    This paper presents a comparative study of two central EU climate policies: the revised Emissions Trading System (ETS), and the revised Renewable Energy Directive (RES). Both were originally developed in the early 2000s and revised policies were adopted in December 2008. While the ETS from 2013 on will have a quite centralized and market-streamlined design, the revised RES stands forward as a more decentralized and technology-focused policy. Differing institutional feed-back mechanisms and related roles of policy entrepreneurs can shed considerable light on these policy differences. Due to member states' cautiousness and contrary to the preferences of the Commission, the initial ETS was designed as a rather decentralized and 'politicized' market system, creating a malfunctioning institutional dynamic. In the revision process, the Commission skillfully highlighted this ineffective dynamic to win support for a much more centralized and market-streamlined approach. In the case of RES, national technology-specific support schemes and the strong links between the renewable industry and member states promoted the converse outcome: decentralization and technology development. Members of the European Parliament utilized these mechanisms through policy networking, while the Commission successfully used developments within the global climate regime to induce some degree of centralization. (Author)

  12. Understanding the Mechanisms of Gold Shell Growth onto Polymer Microcapsules to Control Shell Thickness.

    Science.gov (United States)

    Tasker, Alison L; Hitchcock, James; Baxter, Elaine A; Cayre, Dr Olivier J; Biggs, Simon

    2017-07-04

    Polymer microcapsules have been used commercially for decades, however they have an inherent flaw which renders them impractical as a carrier of small, volatile molecules. The porous nature of the polymer shell allows for diffusion of the encapsulated molecules into the bulk. The use of metal shells is an innovative way to prevent undesired loss of small molecules from the core of microcapsules, however it is important, particularly when using expensive metals to ensure that the resulting shell is as thin as possible. Here we investigate the fundamental mechanisms controlling the gold shell thickness when a fragrance oil is encapsulated in a poly(methyl methacrylate) shell. We consider the distribution of the nanoparticles on the capsule surface, and from quantification of the adsorbed nanoparticle (NP) density and resulting shell thickness, we propose mechanisms to describe the gold shell growth for systems with high and low NP surface coverage. We suggest from our observations that the gold grows to fill in the gaps between NPs. At low NP concentrations, thicker metal shells form. We postulate that this is due to the low NP density on the surface, forcing the gold clusters to grow larger before they meet the adjacent ones. Thus, to grow the thinnest possible shells a densely packed monolayer of platinum nanoparticles is required on the capsule surface. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Understanding of carbon-based supercapacitors ageing mechanisms by electrochemical and analytical methods

    Science.gov (United States)

    Liu, Yinghui; Soucaze-Guillous, Benoît; Taberna, Pierre-Louis; Simon, Patrice

    2017-10-01

    In order to shed light on ageing mechanisms of Electrochemical Double Layer Capacitor (EDLC), two kinds of activated carbons are studied in tetraethyl ammonium tetrafluoroborate (Et4NBF4) in acetonitrile. In floating mode, it turns out that two different ageing mechanisms are observed, depending on the activated carbon electrode materials used. On one hand, carbon A exhibits a continuous capacitance and series resistance fall-off; on the other hand, for carbon B, only the series resistance degrades after ageing while the capacitance keeps unchanged. Additional electrochemical characterizations (Electrochemical Impedance Spectroscopy - EIS - and diffusion coefficient calculations) were carried out showing that carbon A's ageing behavior is suspected to be primarily related to the carbon degradation while for carbon B a passivation occurs leading to the formation of a Solid Electrolyte Interphase-Like (SEI-L) film. These hypotheses are supported by TG-IR and Raman spectroscopy analysis. The outcome forms the latter is an increase of carbon defects on carbon A on positive electrode.

  14. Atmospheric Compensation of Variations in Tropical Ocean Heat Transport: Understanding Mechanisms and Implications on Tectonic Timescales

    Science.gov (United States)

    Rencurrel, M. C.; Rose, B. E. J.

    2015-12-01

    The poleward transport of energy is a key aspect of the climate system, with surface ocean currents presently dominating the transport out of deep tropics. A classic study by Stone (1978) proposed that the total heat transport is determined by astronomical parameters and is highly insensitive to the detailed atmosphere-ocean dynamics. On the other hand, previous modeling work has shown that past continental configurations could have produced substantially different tropical ocean heat transport (OHT). How thoroughly does the atmosphere compensate for changes in ocean transport in terms of the top-of-atmosphere (TOA) radiative budget, what are the relevant mechanisms, and what are the consequences for surface temperature and climate on tectonic timescales? We examine these issues in a suite of aquaplanet GCM simulations subject to large prescribed variations in OHT. We find substantial but incomplete compensation, in which adjustment of the atmospheric Hadley circulation plays a key role. We then separate out the dynamical and thermodynamical components of the adjustment mechanism. Increased OHT tends to warm the mid- to high latitudes without cooling the tropics due asymmetries in radiative feedback processes. The warming is accompanied by hydrological cycle changes that are completely different from those driven by greenhouse gases, suggesting that drivers of past global change might be detectable from combinations of hydroclimate and temperature proxies.

  15. Psychosomatic medicine in the 21st century: understanding mechanisms and barriers to utilization.

    Science.gov (United States)

    Wise, Thomas N; Balon, Richard

    2015-01-01

    The psychosomatic approach arose in antiquity as mankind looked for explanations for illness and death. With the rise of modern medicine, the links between emotions and medical conditions, such as cardiac disease and diabetes, were described by astute clinical observers, but the mechanisms for these conditions were based on correlation from observations rather than on experimental design. Psychoanalytic theory was often utilized to explain many common diseases. For example, peptic ulcer disease was blamed upon anger and stress, but scientific methodology discovered Helicobacter pylori to be the significant causal factor of this disease and resulted in the development of more effective treatments. Nevertheless emotional factors are still linked to disease states and morbidity; for example, depression is a risk factor for mortality following myocardial infarction. Advances in neuroscience demonstrate that the reduction of telomere length by anxiety and stress leads to more rapid aging and potential disease vulnerability. Thus, neuroscientific probes may allow for the elucidation of psychosomatic mechanisms. Sadly, clinical barriers, in terms of time pressure upon physicians and the current separation of mental health services from primary care settings, continue the dualistic treatment of many conditions where psychological factors are important. It is not clear whether a mandate for the integration of behavioral health into primary care will remedy this partition and finally maximize a psychosomatic approach to medical care. © 2015 S. Karger AG, Basel.

  16. A New Alkali-Stable Phosphonium Cation Based on Fundamental Understanding of Degradation Mechanisms.

    Science.gov (United States)

    Zhang, Bingzi; Kaspar, Robert B; Gu, Shuang; Wang, Junhua; Zhuang, Zhongbin; Yan, Yushan

    2016-09-08

    Highly alkali-stable cationic groups are a critical component of hydroxide exchange membranes (HEMs). To search for such cations, we studied the degradation kinetics and mechanisms of a series of quaternary phosphonium (QP) cations. Benzyl tris(2,4,6-trimethoxyphenyl)phosphonium [BTPP-(2,4,6-MeO)] was determined to have higher alkaline stability than the benchmark cation, benzyl trimethylammonium (BTMA). A multi-step methoxy-triggered degradation mechanism for BTPP-(2,4,6-MeO) was proposed and verified. By replacing methoxy substituents with methyl groups, a superior QP cation, methyl tris(2,4,6-trimethylphenyl)phosphonium [MTPP-(2,4,6-Me)] was developed. MTPP-(2,4,6-Me) is one of the most stable cations reported to date, with <20 % degradation after 5000 h at 80 °C in a 1 m KOD in CD3 OD/D2 O (5:1 v/v) solution. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A vicious circle in chronic lymphoedema pathophysiology?

    DEFF Research Database (Denmark)

    Cucchi, F; Rossmeislova, L; Simonsen, L

    2017-01-01

    Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

  18. Understanding the evolution of the windlass mechanism of the human foot from comparative anatomy: Insights, obstacles, and future directions.

    Science.gov (United States)

    Griffin, Nicole L; Miller, Charlotte E; Schmitt, Daniel; D'Août, Kristiaan

    2015-01-01

    Humans stand alone from other primates in that we propel our bodies forward on a relatively stiff and arched foot and do so by employing an anatomical arrangement of bones and ligaments in the foot that can operate like a "windlass." This is a significant evolutionary innovation, but it is currently unknown when during hominin evolution this mechanism developed and within what genera or species it originated. The presence of recently discovered fossils along with novel research in the past two decades have improved our understanding of foot mechanics in humans and other apes, making it possible to consider this question more fully. Here we review the main elements thought to be involved in the production of an effective, modern human-like windlass mechanism. These elements are the triceps surae, plantar aponeurosis, medial longitudinal arch, and metatarsophalangeal joints. We discuss what is presently known about the evolution of these features and the challenges associated with identifying each of these specific components and/or their function in living and extinct primates for the purpose of predicting the presence of the windlass mechanism in our ancestors. In some cases we recommend alternative pathways for inferring foot mechanics and for testing the hypothesis that the windlass mechanism evolved to increase the speed and energetic efficiency of bipedal gait in hominins. © 2014 Wiley Periodicals, Inc.

  19. Understanding the mechanisms of thermal disintegrating treatment in the reduction of sludge production.

    Science.gov (United States)

    Camacho, P; Ginestet, P; Audic, J-M

    2005-01-01

    Among the technologies aimed at reducing sludge production, the combination of thermal treatment at 95 degrees C of sludge and the activated sludge process is a promising route. The feasibility of such a combined process is demonstrated (up to 60% sludge reduction) and the impacts of operating conditions on its efficiency are presented. Major emphasis was put on understanding the complex phenomena occurring within the thermal treatment: release and biodegradability of sludge organic matter, impact on the biological activity (decay, maintenance requirements, etc.). These effects were taken into account for the development of an ASM1-based model. Comparison between the modeling approach and experimental data (continuous and batch) showed that thermal treatment had three major issues partly explaining the reduction of sludge production: (i) a low release of organics; (ii) an immediate and reversible biological inactivation associated with additional maintenance energy requirements; and (iii) a potential inert production.

  20. Understanding mechanisms of solid-state phase transformations by probing nuclear materials

    Science.gov (United States)

    Banerjee, Srikumar; Donthula, Harish

    2018-04-01

    In this review a few examples will be cited to illustrate that a study on a specific nuclear material sometimes lead to a better understanding of scientific phenomena of broader interests. Zirconium alloys offer some unique opportunities in addressing fundamental issues such as (i) distinctive features between displacive and diffusional transformations, (ii) characteristics of shuffle and shear dominated displacive transformations and (iii) nature of mixed-mode transformations. Whether a transformation is of first or higher order?" is often raised while classifying it. There are rare examples, such as Ni-Mo alloys, in which during early stages of ordering the system experiences tendencies for both first order and second order transitions. Studies on the order-disorder transitions under a radiation environment have established the pathway for the evolution of ordering. These studies have also identified the temperature range over which the chemically ordered state remains stable in steady state under radiation.

  1. Understanding the desensitizing mechanism of olefin in explosives: shear slide of mixed HMX-olefin systems.

    Science.gov (United States)

    Zhang, Chaoyang; Cao, Xia; Xiang, Bin

    2012-04-01

    We simulated the shear slide behavior of typical mixed HMX-olefin systems and the effect of thickness of olefin layers (4-22 Å) on the behavior at a molecular level by considering two cases: bulk shear and interfacial shear. The results show that: (1) the addition of olefin into HMX can reduce greatly the shear sliding barriers relative to the pure HMX in the two cases, suggesting that the desensitizing mechanism of olefin is controlled dominantly by its good lubricating property; (2) the change of interaction energy in both systoles of shear slide is strongly dominated by van der Waals interaction; and (3) the thickness of olefin layers in the mixed explosives can influence its desensitizing efficiency. That is, the excessive thinness of olefin layers in the mixed explosive systems, for example, several angstroms, can lead to very high sliding barriers.

  2. Heat and mass transfer models to understand the drying mechanisms of a porous substrate.

    Science.gov (United States)

    Songok, Joel; Bousfield, Douglas W; Gane, Patrick A C; Toivakka, Martti

    2016-02-01

    While drying of paper and paper coatings is expensive, with significant energy requirements, the rate controlling mechanisms are not currently fully understood. Two two-dimensional models are used as a first approximation to predict the heat transfer during hot air drying and to evaluate the role of various parameters on the drying rates of porous coatings. The models help determine the structural limiting factors during the drying process, while applying for the first time the recently known values of coating thermal diffusivity. The results indicate that the thermal conductivity of the coating structure is not the controlling factor, but the drying rate is rather determined by the thermal transfer process at the structure surface. This underlines the need for ensuring an efficient thermal transfer from hot air to coating surface during drying, before considering further measures to increase the thermal conductivity of porous coatings.

  3. Understanding the neural mechanisms involved in sensory control of voice production.

    Science.gov (United States)

    Parkinson, Amy L; Flagmeier, Sabina G; Manes, Jordan L; Larson, Charles R; Rogers, Bill; Robin, Donald A

    2012-05-15

    Auditory feedback is important for the control of voice fundamental frequency (F0). In the present study we used neuroimaging to identify regions of the brain responsible for sensory control of the voice. We used a pitch-shift paradigm where subjects respond to an alteration, or shift, of voice pitch auditory feedback with a reflexive change in F0. To determine the neural substrates involved in these audio-vocal responses, subjects underwent fMRI scanning while vocalizing with or without pitch-shifted feedback. The comparison of shifted and unshifted vocalization revealed activation bilaterally in the superior temporal gyrus (STG) in response to the pitch shifted feedback. We hypothesize that the STG activity is related to error detection by auditory error cells located in the superior temporal cortex and efference copy mechanisms whereby this region is responsible for the coding of a mismatch between actual and predicted voice F0. Published by Elsevier Inc.

  4. The effects of bariatric surgery: will understanding its mechanism render the knife unnecessary?

    Science.gov (United States)

    Browning, Kirsteen N; Hajnal, Andras

    2014-01-01

    The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for morbid obesity with Roux-en-Y gastric bypass being the most commonly performed procedure, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From basic science as well as clinical standpoints, there are several areas of current interest that warrant continued investigation. Several major focus areas have also emerged in current research that may guide future efforts in this field, particularly with regards to using novel, non-surgical approaches to mimic the success of bariatric surgery while minimizing its adverse side effects.

  5. Metal Oxide Nanomaterial QNAR Models: Available Structural Descriptors and Understanding of Toxicity Mechanisms

    Directory of Open Access Journals (Sweden)

    Jiali Ying

    2015-10-01

    Full Text Available Metal oxide nanomaterials are widely used in various areas; however, the divergent published toxicology data makes it difficult to determine whether there is a risk associated with exposure to metal oxide nanomaterials. The application of quantitative structure activity relationship (QSAR modeling in metal oxide nanomaterials toxicity studies can reduce the need for time-consuming and resource-intensive nanotoxicity tests. The nanostructure and inorganic composition of metal oxide nanomaterials makes this approach different from classical QSAR study; this review lists and classifies some structural descriptors, such as size, cation charge, and band gap energy, in recent metal oxide nanomaterials quantitative nanostructure activity relationship (QNAR studies and discusses the mechanism of metal oxide nanomaterials toxicity based on these descriptors and traditional nanotoxicity tests.

  6. Oxide Nanoparticle EUV (ONE) Photoresists: Current Understanding of the Unusual Patterning Mechanism

    KAUST Repository

    Jiang, Jing

    2015-01-01

    © 2015 SPST. In the past few years, industry has made significant progress to deliver a stable high power EUV scanner and a 100 W light source is now being tested on the manufacuring scale. The success of a high power EUV source demands a fast and high resolution EUV resist. However, chemcially amplied resists encounter unprecedented challenges beyond the 22 nm node due to resolution, roughness and sensitivity tradeoffs. Unless novel solutions for EUV resists are proposed and further optimzed, breakthroughs can hardly be achieved. Oxide nanoparticle EUV (ONE) resists stablized by organic ligands were originally proposed by Ober et al. Recently this work attracts more and more attention due to its extraordinanry EUV sensitivity. This new class of photoresist utilizes ligand cleavage with a ligand exchange mechanism to switch its solubilty for dual-tone patterning. Therefore, ligand selection of the nanoparticles is extremely important to its EUV performance.

  7. Towards a better understanding of the therapeutic applications and corresponding mechanisms of action of honey.

    Science.gov (United States)

    Khan, Rifat Ullah; Naz, Shabana; Abudabos, Alaeldein M

    2017-12-01

    Honey is a bee-derived supersaturated solution composed of complex contents mainly glucose, fructose, amino acids, vitamins, and minerals. Composition of honey may vary due to the difference in nectar, season, geography, and storage condition. Honey has been used since times immemorial in folk medicine and has recently been rediscovered as an excellent therapeutic agent. In the past, honey was used for a variety of ailments without knowing the scientific background and active ingredients of honey. Today, honey has been scientifically proven for its antioxidant, regulation of glycemic response, antitumor, antimicrobial, anti-inflammatory, and cardiovascular potentiating agent. It can be used as a wound dressing and healing substance. Honey is different in color, flavor, sensory perception, and medical response. Apart from highlighting the nutritional facts of honey, we collected the finding of the published literature to know the mechanism of action of honey in different diseases. This review covers the composition, physiochemical characteristics, and some medical uses.

  8. Understanding Central Mechanisms of Acupuncture Analgesia Using Dynamic Quantitative Sensory Testing: A Review

    Directory of Open Access Journals (Sweden)

    Jiang-Ti Kong

    2013-01-01

    Full Text Available We discuss the emerging translational tools for the study of acupuncture analgesia with a focus on psychophysical methods. The gap between animal mechanistic studies and human clinical trials of acupuncture analgesia calls for effective translational tools that bridge neurophysiological data with meaningful clinical outcomes. Temporal summation (TS and conditioned pain modulation (CPM are two promising tools yet to be widely utilized. These psychophysical measures capture the state of the ascending facilitation and the descending inhibition of nociceptive transmission, respectively. We review the basic concepts and current methodologies underlying these measures in clinical pain research, and illustrate their application to research on acupuncture analgesia. Finally, we highlight the strengths and limitations of these research methods and make recommendations on future directions. The appropriate addition of TS and CPM to our current research armamentarium will facilitate our efforts to elucidate the central analgesic mechanisms of acupuncture in clinical populations.

  9. Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), steroid-induced diabetes (oral glucocorticoid-treated subjects), insulinopenic (f-P-C-peptide ... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333

  10. Hypertension in women--pathophysiological and clinical aspects.

    Science.gov (United States)

    Erdine, Serap; Arslan, Eren; Olszanecka, Agnieszka

    2012-01-01

    Hypertension is the most important risk factor, responsible for cardiovascular morbidity and mortality worldwide, both in men and women. Cardiovascular disorders in women are still underestimated, due to lower absolute risk calculations and the underdetection of classical risk factors. In recent years the differences in pathophysiology and the clinical presentation and treatment of cardiac diseases in women have become fields of interest and research. Several studies have examined gender-related differences in the pathophysiology of hypertension, its prevalence and control. The influence of menopause, obesity and salt-sensitivity on the pathogenesis of hypertension in women has been widely investigated. This article presents current data on differences in prevalence, control and mechanisms of hypertension in women.

  11. Different Pathophysiological Phenotypes among Newly Diagnosed Type 2 Diabetes Patients

    DEFF Research Database (Denmark)

    Stidsen, Jacob

    2013-01-01

    autoimmune diabetes (LADA) (GAD antibody titer >= 20 IE/ml and not T1D), secondary diabetes (recent history of pancreatitis, pancreatectomy or pancreas amylase > 65U/l, and GAD negativity), steroid-induced diabetes (oral glucocorticoid-treated subjects), insulinopenic (f-P-C-peptide ...Type 2 diabetes (T2D) can be considered a syndrome with several different pathophysiological mechanisms leading to hyperglycemia. Nonetheless, T2D is treated according to algorithms as if it was one disease entity. Methods: We investigated the prevalence of different pathophysiological phenotypes...... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333

  12. Understanding the Broad Substrate Repertoire of Nitroreductase Based on Its Kinetic Mechanism*

    Science.gov (United States)

    Pitsawong, Warintra; Hoben, John P.; Miller, Anne-Frances

    2014-01-01

    The oxygen-insensitive nitroreductase from Enterobacter cloacae (NR) catalyzes two-electron reduction of nitroaromatics to the corresponding nitroso compounds and, subsequently, to hydroxylamine products. NR has an unusually broad substrate repertoire, which may be related to protein dynamics (flexibility) and/or a simple non-selective kinetic mechanism. To investigate the possible role of mechanism in the broad substrate repertoire of NR, the kinetics of oxidation of NR by para-nitrobenzoic acid (p-NBA) were investigated using stopped-flow techniques at 4 °C. The results revealed a hyperbolic dependence on the p-NBA concentration with a limiting rate of 1.90 ± 0.09 s−1, indicating one-step binding before the flavin oxidation step. There is no evidence for a distinct binding step in which specificity might be enforced. The reduction of p-NBA is rate-limiting in steady-state turnover (1.7 ± 0.3 s−1). The pre-steady-state reduction kinetics of NR by NADH indicate that NADH reduces the enzyme with a rate constant of 700 ± 20 s−1 and a dissociation constant of 0.51 ± 0.04 mm. Thus, we demonstrate simple transient kinetics in both the reductive and oxidative half-reactions that help to explain the broad substrate repertoire of NR. Finally, we tested the ability of NR to reduce para-hydroxylaminobenzoic acid, demonstrating that the corresponding amine does not accumulate to significant levels even under anaerobic conditions. Thus E. cloacae NR is not a good candidate for enzymatic production of aromatic amines. PMID:24706760

  13. Functional anatomy and pathophysiologic principles in mitral regurgitation: Non-invasive assessment.

    Science.gov (United States)

    Maréchaux, Sylvestre; Illman, Jeffery E; Huynh, James; Michelena, Hector I; Nkomo, Vuyisile T; Tribouilloy, Christophe

    Mitral regurgitation (MR) is the most prevalent cause of valvular heart disease (VHD) in western countries. In the Euro Heart Survey on VHD, MR was the second most common heart VHD requiring surgery. It is also the most common form of VHD in community and population-based studies from the United States. The categorization of MR based on causes and mechanisms is a major determinant of clinical outcome, of possible therapies for the MR and of the effectiveness of these therapies. Surgical mitral valve (MV) repair has been shown to improve survival in patients with severe primary MR compared with MV replacement. In addition, new percutaneous repair and replacement procedures have been recently developed. Hence, accurate understanding of the functional anatomy of the MV and the pathophysiologic principles underlying MR is needed to appropriately target valve lesions. Recent advances in cardiac imaging have allowed to deeply strengthen the knowledge of the function of the MV. The present review aims at describing the functional anatomy and pathophysiology of MR through different cardiac imaging modalities. Copyright © 2017 Anesthesia History Association. Published by Elsevier Inc. All rights reserved.

  14. Refining and integrating schizophrenia pathophysiology - relevance of the allostatic load concept.

    Science.gov (United States)

    Misiak, Błażej; Frydecka, Dorota; Zawadzki, Marcin; Krefft, Maja; Kiejna, Andrzej

    2014-09-01

    Adaptation to stress leads to the activation of several biological systems that maintain homeostasis and enable effective coping with challenges. These adaptive processes have been designated as 'allostasis'. However, overactivation or aberrant performance of allostatic mechanisms due to chronic stress exposure may exert systemic deleterious effects. This condition has been called 'allostatic load' (AL). The AL concept is a useful framework allowing to understand the mulitisystem physiological dysregulation due to cumulative stressful demands over the lifespan. In the recent years, the AL paradigm has emerged as a novel concept explaining the morbidity and mortality with respect to several mental disorders. In this article, we suggest that AL provides a useful framework to describe schizophrenia - its etiology, course, outcome and comorbidities. Schizophrenia is a severe mental illness that is characterized by multidimensional psychopathology including positive and negative symptoms, affective symptoms and cognitive impairment with several known risk factors and accompanying pathophysiological correlates. However, there is a great need to refine and integrate the plethora of findings reported from various research perspectives. We propose that AL is a meaningful concept integrating findings on pathophysiological underpinnings, factors influencing course of the disorder and the development of co-occurring physical health impairments as well as substance use disorders in schizophrenia. Furthermore, there is an urgent necessity to investigate AL and its correlates in schizophrenia as no studies in this field have been performed so far. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control.

    Science.gov (United States)

    Reis, Janine; Swayne, Orlando B; Vandermeeren, Yves; Camus, Mickael; Dimyan, Michael A; Harris-Love, Michelle; Perez, Monica A; Ragert, Patrick; Rothwell, John C; Cohen, Leonardo G

    2008-01-15

    Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

  16. Accelerating Our Understanding of Supernova Explosion Mechanism via Simulations and Visualizations with GenASiS

    Energy Technology Data Exchange (ETDEWEB)

    Budiardja, R. D. [University of Tennessee, Knoxville (UTK); Cardall, Christian Y [ORNL; Endeve, Eirik [ORNL

    2015-01-01

    Core-collapse supernovae are among the most powerful explosions in the Universe, releasing about 1053 erg of energy on timescales of a few tens of seconds. These explosion events are also responsible for the production and dissemination of most of the heavy elements, making life as we know it possible. Yet exactly how they work is still unresolved. One reason for this is the sheer complexity and cost of a self-consistent, multi-physics, and multi-dimensional core-collapse supernova simulation, which is impractical, and often impossible, even on the largest supercomputers we have available today. To advance our understanding we instead must often use simplified models, teasing out the most important ingredients for successful explosions, while helping us to interpret results from higher fidelity multi-physics models. In this paper we investigate the role of instabilities in the core-collapse supernova environment. We present here simulation and visualization results produced by our code GenASiS.

  17. Pathophysiology and pathomorphology of osteoporosis; Pathophysiologie und Pathomorphologie der Osteoporose

    Energy Technology Data Exchange (ETDEWEB)

    Priemel, M.; Muench, C.; Beil, F.T.; Amling, M. [Universitaetsklinikum Hamburg-Eppendorf, Klinik und Poliklinik fuer Unfall-, Hand- und Wiederherstellungschirurgie, Hamburg (Germany); Klinik fuer Unfall-, Hand- und Wiederherstellungschirurgie am Universitaetsklinikum Hamburg-Eppendorf, Zentrum fuer Biomechanik und Skelettbiologie, Hamburg (Germany); Ritzel, H. [Klinikum Bamberg, Medizinische Klinik, Bamberg (Germany)

    2006-10-15

    Osteoporosis is a disease that leads to fragility fractures due to loss of bone mass and bone microstructure. This review presents an update on the fundamental pathophysiologic and pathomorphologic mechanisms of bone loss situations. Pathomorphologic characteristics such as perforations and microcallus formations are explained. The physiologic relevance of the remodeling process as well as its control by local-paracrine, systemic-endocrine and central-neural signaling pathways is discussed. Furthermore the role of hormones such as estrogen, FSH and leptin, of transcription-factors such as Runx2 and osterix and as well as that of the wnt signaling pathway for bone cell differentiation and function is presented. On the basis of current knowledge osteoporosis can be diagnosed, treated and fractures can be prevented. However, it is likely that new and even more effective diagnostic and therapeutic strategies will emerge as our understanding of the remodeling process that controls osteoblast and osteoclast function increases. (orig.) [German] Osteoporose ist eine Erkrankung, bei der es durch den Verlust an biomechanischer Stabilitaet des Knochens zu Frakturen ohne adaequates Trauma kommt. Diese Uebersichtsarbeit beleuchtet die grundlegenden pathophysiologischen Mechanismen und pathomorphologischen Besonderheiten der Osteoporose. Letztendlich kann jede Regulationsstoerung des Knochenremodelings zur Ausbildung eines Knochenmasseverlustsyndroms fuehren. Das Knochenremodeling wird durch verschiedene Mechanismen und Systeme reguliert, dazu gehoeren auf zellulaerer Ebene Osteoblasten, Osteoklasten. aber auch andere Knochenmarkzellen (z. B. Mastzellen, Adipozyten, Stammzellnichen); darueber hinaus wird die Funktion der Knochenzellen durch systemisch wirkende Hormone und neuronale Signale, lokal wirkende Zytokine und Wachstumsfaktoren sowie Transkriptionsfaktoren beeinflusst. Es ist heute moeglich, die Osteoporose zu diagnostizieren, das Frakturrisiko zu bestimmen und dieses

  18. Pompe disease: from pathophysiology to therapy and back again

    Directory of Open Access Journals (Sweden)

    Jeong-A eLim

    2014-07-01

    Full Text Available Pompe disease is a lysosomal storage disorder in which acid alpha-glucosidase is deficient or absent. Deficiency of this lysosomal enzyme results in progressive expansion of glycogen-filled lysosomes in multiple tissues, with cardiac and skeletal muscle being the most severely affected. The clinical spectrum ranges from fatal hypertrophic cardiomyopathy and skeletal muscle myopathy in infants to relatively attenuated forms, which manifest as a progressive myopathy without cardiac involvement. The currently available enzyme replacement therapy proved to be successful in reversing cardiac but not skeletal muscle abnormalities. Although the overall understanding of the disease has progressed, the pathophysiology of muscle damage remains poorly understood. Lysosomal enlargement/rupture has long been considered a mechanism of relentless muscle damage in Pompe disease. In past years, it became clear that this simple view of the pathology is inadequate; the pathological cascade involves dysfunctional autophagy, a major lysosome-dependent intracellular degradative pathway. The autophagic process in Pompe skeletal muscle is affected at the termination stage - impaired autophagosomal-lysosomal fusion. Yet another abnormality in the diseased muscle is the accelerated production of large, unrelated to ageing, lipofuscin deposits - a marker of cellular oxidative damage and a sign of mitochondrial dysfunction. The massive autophagic buildup and lipofuscin inclusions appear to cause a greater effect on muscle architecture than the enlarged lysosomes outside the autophagic regions. Furthermore, the dysfunctional autophagy affects the trafficking of the replacement enzyme and interferes with its delivery to the lysosomes. Several new therapeutic approaches have been tested in Pompe mouse models: substrate reduction therapy, lysosomal exocytosis following the overexpression of transcription factor EB and a closely related but distinct factor E3, and genetic

  19. Understanding the growth mechanism of graphene on Ge/Si(001) surfaces

    Science.gov (United States)

    Dabrowski, J.; Lippert, G.; Avila, J.; Baringhaus, J.; Colambo, I.; Dedkov, Yu S.; Herziger, F.; Lupina, G.; Maultzsch, J.; Schaffus, T.; Schroeder, T.; Kot, M.; Tegenkamp, C.; Vignaud, D.; Asensio, M.-C.

    2016-01-01

    The practical difficulties to use graphene in microelectronics and optoelectronics is that the available methods to grow graphene are not easily integrated in the mainstream technologies. A growth method that could overcome at least some of these problems is chemical vapour deposition (CVD) of graphene directly on semiconducting (Si or Ge) substrates. Here we report on the comparison of the CVD and molecular beam epitaxy (MBE) growth of graphene on the technologically relevant Ge(001)/Si(001) substrate from ethene (C2H4) precursor and describe the physical properties of the films as well as we discuss the surface reaction and diffusion processes that may be responsible for the observed behavior. Using nano angle resolved photoemission (nanoARPES) complemented by transport studies and Raman spectroscopy as well as density functional theory (DFT) calculations, we report the direct observation of massless Dirac particles in monolayer graphene, providing a comprehensive mapping of their low-hole doped Dirac electron bands. The micrometric graphene flakes are oriented along two predominant directions rotated by 30° with respect to each other. The growth mode is attributed to the mechanism when small graphene “molecules” nucleate on the Ge(001) surface and it is found that hydrogen plays a significant role in this process. PMID:27531322

  20. Study and understanding of the ageing mechanisms in lead-calcium alloys

    International Nuclear Information System (INIS)

    Rossi, F.

    2006-12-01

    The data available in the literature about ageing and over-ageing of lead-calcium alloys are often incomplete and inconsistent. It is undoubtedly due to the experimental difficulties encountered to observe the structure transformations which are numerous. As a result there is a certain confusion among the results of the different authors. Moreover, small variations in the process parameters and chemical composition may have some influence on the alloy behaviour. This work enabled us to obtain a set of TTT diagrams, more realistic and accurate than the ones available in the literature. Experimental techniques developed (particularly the preservation of the cold chain with is essential for the guaranty of the results repeatability), enabled particularly the study of the first transformations and better control the five stages of ageing and over-ageing. Our work have enabled to determine precisely the kinetics and the mechanisms of the transformations. This work constitutes a thorough analysis of the ageing and over-ageing of theses alloys. (author)

  1. ARHGEF9 mutations in epileptic encephalopathy/intellectual disability: toward understanding the mechanism underlying phenotypic variation.

    Science.gov (United States)

    Wang, Jing-Yang; Zhou, Peng; Wang, Jie; Tang, Bin; Su, Tao; Liu, Xiao-Rong; Li, Bing-Mei; Meng, Heng; Shi, Yi-Wu; Yi, Yong-Hong; He, Na; Liao, Wei-Ping

    2018-01-01

    ARHGEF9 resides on Xq11.1 and encodes collybistin, which is crucial in gephyrin clustering and GABA A receptor localization. ARHGEF9 mutations have been identified in patients with heterogeneous phenotypes, including epilepsy of variable severity and intellectual disability. However, the mechanism underlying phenotype variation is unknown. Using next-generation sequencing, we identified a novel mutation, c.868C > T/p.R290C, which co-segregated with epileptic encephalopathy, and validated its association with epileptic encephalopathy. Further analysis revealed that all ARHGEF9 mutations were associated with intellectual disability, suggesting its critical role in psychomotor development. Three missense mutations in the PH domain were not associated with epilepsy, suggesting that the co-occurrence of epilepsy depends on the affected functional domains. Missense mutations with severe molecular alteration in the DH domain, or located in the DH-gephyrin binding region, or adjacent to the SH3-NL2 binding site were associated with severe epilepsy, implying that the clinical severity was potentially determined by alteration of molecular structure and location of mutations. Male patients with ARHGEF9 mutations presented more severe phenotypes than female patients, which suggests a gene-dose effect and supports the pathogenic role of ARHGEF9 mutations. This study highlights the role of molecular alteration in phenotype expression and facilitates evaluation of the pathogenicity of ARHGEF9 mutations in clinical practice.

  2. Understanding physiological and degenerative natural vision mechanisms to define contrast and contour operators.

    Directory of Open Access Journals (Sweden)

    Jacques Demongeot

    Full Text Available BACKGROUND: Dynamical systems like neural networks based on lateral inhibition have a large field of applications in image processing, robotics and morphogenesis modeling. In this paper, we will propose some examples of dynamical flows used in image contrasting and contouring. METHODOLOGY: First we present the physiological basis of the retina function by showing the role of the lateral inhibition in the optical illusions and pathologic processes generation. Then, based on these biological considerations about the real vision mechanisms, we study an enhancement method for contrasting medical images, using either a discrete neural network approach, or its continuous version, i.e. a non-isotropic diffusion reaction partial differential system. Following this, we introduce other continuous operators based on similar biomimetic approaches: a chemotactic contrasting method, a viability contouring algorithm and an attentional focus operator. Then, we introduce the new notion of mixed potential Hamiltonian flows; we compare it with the watershed method and we use it for contouring. CONCLUSIONS: We conclude by showing the utility of these biomimetic methods with some examples of application in medical imaging and computed assisted surgery.

  3. Comprehensive Understanding of Ductility Loss Mechanisms in Various Steels with External and Internal Hydrogen

    Science.gov (United States)

    Takakuwa, Osamu; Yamabe, Junichiro; Matsunaga, Hisao; Furuya, Yoshiyuki; Matsuoka, Saburo

    2017-11-01

    Hydrogen-induced ductility loss and related fracture morphologies are comprehensively discussed in consideration of the hydrogen distribution in a specimen with external and internal hydrogen by using 300-series austenitic stainless steels (Types 304, 316, 316L), high-strength austenitic stainless steels (HP160, XM-19), precipitation-hardened iron-based super alloy (A286), low-alloy Cr-Mo steel (JIS-SCM435), and low-carbon steel (JIS-SM490B). External hydrogen is realized by a non-charged specimen tested in high-pressure gaseous hydrogen, and internal hydrogen is realized by a hydrogen-charged specimen tested in air or inert gas. Fracture morphologies obtained by slow-strain-rate tensile tests (SSRT) of the materials with external or internal hydrogen could be comprehensively categorized into five types: hydrogen-induced successive crack growth, ordinary void formation, small-sized void formation related to the void sheet, large-sized void formation, and facet formation. The mechanisms of hydrogen embrittlement are broadly classified into hydrogen-enhanced decohesion (HEDE) and hydrogen-enhanced localized plasticity (HELP). In the HEDE model, hydrogen weakens interatomic bonds, whereas in the HELP model, hydrogen enhances localized slip deformations. Although various fracture morphologies are produced by external or internal hydrogen, these morphologies can be explained by the HELP model rather than by the HEDE model.

  4. Understanding the mechanism of iron sulfide-induced fouling in upgrading

    Energy Technology Data Exchange (ETDEWEB)

    Panchal, C.B. [United States Dept. of Energy, Chicago, IL (United States). Argonne National Laboratory

    2006-07-01

    This presentation investigated the underlying mechanisms of iron sulfide-induced fouling and coking in upgrading processes. Experiments to determine the effects of dissolved metals on the rate of fouling were reviewed. It was noted that the presence of species such as active sulfur and diolefins can enhance the effect of dissolved metals. An investigation of a high temperature fouling unit was then conducted to investigate the effect of iron acetate and theiphenol additions to stable heavy gas oil. The deposition rate became strongly dependent on temperature in the presence of the dissolved metals. Fouling deposit analyses from various parts of the refining process consistently showed high concentrations of iron and sulfur. It was observed that the threshold tube-wall temperature corresponded to the decomposition temperature of iron salts. A review of current literature indicated that there is little information on the interactive effects of the thermal stability of dissolved organo-metallic compounds and the reactivity of organic species in generating fouling precursors. The creation of a predictive model of threshold fouling and coking conditions was recommended. It was suggested that the model should be used during the design phases of furnaces and heat exchangers. Other recommendations included the use of on-line sensors to detect iron sulfide formulation; and the monitoring of coking furnaces. Blending guidelines to minimize the interactive effects of dissolved metals and active sulfur compounds were also presented. refs., tabs., figs.

  5. Toward understanding the mechanics of hovering in insects, hummingbirds and bats

    Science.gov (United States)

    Vejdani, Hamid; Boerma, David; Swartz, Sharon; Breuer, Kenneth

    2016-11-01

    We present results on the dynamical characteristics of two different mechanisms of hovering, corresponding to the behavior of hummingbirds and bats. Using a Lagrangian formulation, we have developed a dynamical model of a body (trunk) and two rectangular wings. The trunk has 3 degrees of freedom (x, z and pitch angle) and each wing has 3 modes of actuation: flapping, pronation/supination, and wingspan extension/flexion (only present for bats). Wings can be effectively massless (hummingbird and insect wings) or relatively massive (important in the case of bats). The aerodynamic drag and lift forces are calculated using a quasi-steady blade-element model. The regions of state space in which hovering is possible are computed by over an exhaustive range of parameters. The effect of wing mass is to shrink the phase space available for viable hovering and, in general, to require higher wingbeat frequency. Moreover, by exploring hovering energy requirements, we find that the pronation angle of the wings also plays a critical role. For bats, who have relatively heavy wings, we show wing extension and flexion is critical in order to maintain a plausible hovering posture with reasonable power requirements. Comparisons with biological data show good agreement with our model predictions.

  6. Recent advances in understanding the molecular mechanism of chloroplast photorelocation movement.

    Science.gov (United States)

    Kong, Sam-Geun; Wada, Masamitsu

    2014-04-01

    Plants are photosynthetic organisms that have evolved unique systems to adapt fluctuating environmental light conditions. In addition to well-known movement responses such as phototropism, stomatal opening, and nastic leaf movements, chloroplast photorelocation movement is one of the essential cellular responses to optimize photosynthetic ability and avoid photodamage. For these adaptations, chloroplasts accumulate at the areas of cells illuminated with low light (called accumulation response), while they scatter from the area illuminated with strong light (called avoidance response). Plant-specific photoreceptors (phototropin, phytochrome, and/or neochrome) mediate these dynamic directional movements in response to incident light position and intensity. Several factors involved in the mechanisms underlying the processes from light perception to actin-based movements have also been identified through molecular genetic approach. This review aims to discuss recent findings in the field relating to how chloroplasts move at molecular levels. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases.

    Science.gov (United States)

    Torrão, Andréa S; Café-Mendes, Cecilia C; Real, Caroline C; Hernandes, Marina S; Ferreira, Ana F B; Santos, Taisa O; Chaves-Kirsten, Gabriela P; Mazucanti, Caio H Y; Ferro, Emer S; Scavone, Cristoforo; Britto, Luiz R G

    2012-10-01

    Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson's and Alzheimer's diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

  8. Final Report: Improving the understanding of the coupled thermal-mechanical-hydrologic behavior of consolidating granular salt

    Energy Technology Data Exchange (ETDEWEB)

    Stormont, John [Univ. of New Mexico, Albuquerque, NM (United States); Lampe, Brandon [Univ. of New Mexico, Albuquerque, NM (United States); Mills, Melissa [Univ. of New Mexico, Albuquerque, NM (United States); Paneru, Laxmi [Univ. of New Mexico, Albuquerque, NM (United States); Lynn, Timothy [Univ. of New Mexico, Albuquerque, NM (United States); Piya, Aayush [Univ. of New Mexico, Albuquerque, NM (United States)

    2017-09-09

    The goal of this project is to improve the understanding of key aspects of the coupled thermal-mechanical-hydrologic response of granular (or crushed) salt used as a seal material for shafts, drifts, and boreholes in mined repositories in salt. The project is organized into three tasks to accomplish this goal: laboratory measurements of granular salt consolidation (Task 1), microstructural observations on consolidated samples (Task 2), and constitutive model development and evaluation (Task 3). Task 1 involves laboratory measurements of salt consolidation along with thermal properties and permeability measurements conducted under a range of temperatures and stresses expected for potential mined repositories in salt. Testing focused on the role of moisture, temperature and stress state on the hydrologic (permeability) and thermal properties of consolidating granular salt at high fractional densities. Task 2 consists of microstructural observations made on samples after they have been consolidated to interpret deformation mechanisms and evaluate the ability of the constitutive model to predict operative mechanisms under different conditions. Task 3 concerns the development of the coupled thermal-mechanical-hydrologic constitutive model for granular salt consolidation. The measurements and observations in Tasks 1 and 2 were used to develop a thermal-mechanical constitutive model. Accomplishments and status from each of these efforts is reported in subsequent sections of this report

  9. Association of oxidative stress with the pathophysiology of depresion and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Lačković Maja

    2013-01-01

    Full Text Available The production of free radicals in an organism is under the control of various antioxidant mechanisms. If their production overcomes the capacity of antioxidant protection, oxidative stress occurs which is capable of damaging different cellular structures and biomolecules, leading to various diseases. The importance of oxidative stress was proven in many psychiatric diseases among which are depression and bipolar disorder. Different studies show the significant improvement of clinical presentation when antioxidant substances are administered, suggesting that redox imbalance can influence their symptoms appearance and severity. In addition, oxidative stress is intercrossed with the different comorbidities that appear among depressive and bipolar patients. Beside the clinical presentation, oxidative stress influences the chronicity of depression, which was demonstrated in patients with recurrent depressive disorder. Better understanding of oxidant/antioxidant imbalance and its role in the pathophysiology of depression and bipolar disorder could be useful for the development of a novel therapeutic approach to the management of these diseases.

  10. Partitioning CO2 fluxes with isotopologue measurements and modeling to understand mechanisms of forest carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Saleska, Scott [Univ. of Arizona, Tucson, AZ (United States); Davidson, Eric [Univ. of Arizona, Tucson, AZ (United States); Finzi, Adrien [Boston Univ., MA (United States); Wehr, Richdard [Harvard Univ., Cambridge, MA (United States); Moorcroft, Paul [Harvard Univ., Cambridge, MA (United States)

    2016-01-28

    1. Objectives This project combines automated in situ observations of the isotopologues of CO2 with root observations, novel experimental manipulations of belowground processes, and isotope-enabled ecosystem modeling to investigate mechanisms of below- vs. aboveground carbon sequestration at the Harvard Forest Environmental Measurements Site (EMS). The proposed objectives, which have now been largely accomplished, include: A. Partitioning of net ecosystem CO2 exchange (NEE) into photosynthesis and respiration using long-term continuous observations of the isotopic composition of NEE, and analysis of their dynamics ; B. Investigation of the influence of vegetation phenology on the timing and magnitude of carbon allocated belowground using measurements of root growth and indices of belowground autotrophic vs. heterotrophic respiration (via trenched plots and isotope measurements); C. Testing whether plant allocation of carbon belowground stimulates the microbial decomposition of soil organic matter, using in situ rhizosphere simulation experiments wherein realistic quantities of artificial isotopically-labeled exudates are released into the soil; and D. Synthesis and interpretation of the above data using the Ecosystem Demography Model 2 (ED2). 2. Highlights Accomplishments: • Our isotopic eddy flux record has completed its 5th full year and has been used to independently estimate ecosystem-scale respiration and photosynthesis. • Soil surface chamber isotopic flux measurements were carried out during three growing seasons, in conjunction with a trenching manipulation. Key findings to date (listed by objective): A. Partitioning of Net Ecosystem Exchange: 1. Ecosystem respiration is lower during the day than at night—the first robust evidence of the inhibition of leaf respiration by light (the “Kok effect”) at the ecosystem scale. 2. Because it neglects the Kok effect, the standard NEE partitioning approach overestimates ecosystem photosynthesis (by ~25%) and

  11. Pathophysiology of overuse tendon injury

    International Nuclear Information System (INIS)

    Kannus, P.; Paavola, M.; Paakkala, T.; Parkkari, J.; Jaervinen, T.; Jaervinen, M.

    2002-01-01

    Overuse tendon injury is one of the most common injuries in sports.The etiology as well as the pathophysilogical mechanisms leading to tendinopathy are of crucial medical importance.At the moment intrinsic and extrinsic factors are assumed as mechanisms of overuse tendon injury. Except for the acute, extrinsic trauma, the chronic overuse tendon injury is a multifactorial process. There are many other factors, such as local hypoxia, less of nutrition, impaired metabolism and local inflammatory that may also contribute to the development of tissue damage.The exact interaction of these factors cannot be explained entirely at the moment.Further studies will be necessary in order to get more information. (orig.) [de

  12. Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng

    2016-09-01

    Full Text Available The mammalian target of rapamycin (mTOR is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs, especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood. Classically, AAs activate mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1-4F2hc has dual transporter-receptor function that can sense extracellular AA availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9 and cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1 also participate in regulating mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, like G protein-coupled receptor (GPCR T1R1/T1R3, and regulate mTORC1 without being transported into the cells. Furthermore, AA-dependent mTORC1 activation also initiates within Golgi, which is regulated by Golgi-localized AA transporter PAT4. This review provides an overview of the research progress of the AA sensing mechanisms that regulate mTORC1 activity.

  13. Understanding the mechanisms of cobalt-catalyzed hydrogenation and dehydrogenation reactions.

    Science.gov (United States)

    Zhang, Guoqi; Vasudevan, Kalyan V; Scott, Brian L; Hanson, Susan K

    2013-06-12

    Cobalt(II) alkyl complexes of aliphatic PNP pincer ligands have been synthesized and characterized. The cationic cobalt(II) alkyl complex [(PNHP(Cy))Co(CH2SiMe3)]BAr(F)4 (4) (PNHP(Cy) = bis[(2-dicyclohexylphosphino)ethyl]amine) is an active precatalyst for the hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols. To elucidate the possible involvement of the N-H group on the pincer ligand in the catalysis via a metal-ligand cooperative interaction, the reactivities of 4 and [(PNMeP(Cy))Co(CH2SiMe3)]BAr(F)4 (7) were compared. Complex 7 was found to be an active precatalyst for the hydrogenation of olefins. In contrast, no catalytic activity was observed using 7 as a precatalyst for the hydrogenation of acetophenone under mild conditions. For the acceptorless dehydrogenation of 1-phenylethanol, complex 7 displayed similar activity to complex 4, affording acetophenone in high yield. When the acceptorless dehydrogenation of 1-phenylethanol with precatalyst 4 was monitored by NMR spectroscopy, the formation of the cobalt(III) acetylphenyl hydride complex [(PNHP(Cy))Co(III)(κ(2)-O,C-C6H4C(O)CH3)(H)]BAr(F)4 (13) was detected. Isolated complex 13 was found to be an effective catalyst for the acceptorless dehydrogenation of alcohols, implicating 13 as a catalyst resting state during the alcohol dehydrogenation reaction. Complex 13 catalyzed the hydrogenation of styrene but showed no catalytic activity for the room temperature hydrogenation of acetophenone. These results support the involvement of metal-ligand cooperativity in the room temperature hydrogenation of ketones but not the hydrogenation of olefins or the acceptorless dehydrogenation of alcohols. Mechanisms consistent with these observations are presented for the cobalt-catalyzed hydrogenation of olefins and ketones and the acceptorless dehydrogenation of alcohols.

  14. Understanding the mechanism of DNA deactivation in ion therapy of cancer cells: hydrogen peroxide action*

    Science.gov (United States)

    Piatnytskyi, Dmytro V.; Zdorevskyi, Oleksiy O.; Perepelytsya, Sergiy M.; Volkov, Sergey N.

    2015-11-01

    Changes in the medium of biological cells under ion beam irradiation has been considered as a possible cause of cell function disruption in the living body. The interaction of hydrogen peroxide, a long-lived molecular product of water radiolysis, with active sites of DNA macromolecule was studied, and the formation of stable DNA-peroxide complexes was considered. The phosphate groups of the macromolecule backbone were picked out among the atomic groups of DNA double helix as a probable target for interaction with hydrogen peroxide molecules. Complexes consisting of combinations including: the DNA phosphate group, H2O2 and H2O molecules, and Na+ counterion, were considered. The counterions have been taken into consideration insofar as under the natural conditions they neutralise DNA sugar-phosphate backbone. The energy of the complexes have been determined by considering the electrostatic and the Van der Waals interactions within the framework of atom-atom potential functions. As a result, the stability of various configurations of molecular complexes was estimated. It was shown that DNA phosphate groups and counterions can form stable complexes with hydrogen peroxide molecules, which are as stable as the complexes with water molecules. It has been demonstrated that the formation of stable complexes of H2O2-Na+-PO4- may be detected experimentally by observing specific vibrations in the low-frequency Raman spectra. The interaction of H2O2 molecule with phosphate group of the double helix backbone can disrupt DNA biological function and induce the deactivation of the cell genetic apparatus. Thus, the production of hydrogen peroxide molecules in the nucleus of living cells can be considered as an additional mechanism by which high-energy ion beams destroy tumour cells during ion beam therapy. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene

  15. Toward an understanding of the molecular mechanisms of barnacle larval settlement: A comparative transcriptomic approach

    KAUST Repository

    Chen, Zhang-Fan

    2011-07-29

    Background: The barnacle Balanus amphitrite is a globally distributed biofouler and a model species in intertidal ecology and larval settlement studies. However, a lack of genomic information has hindered the comprehensive elucidation of the molecular mechanisms coordinating its larval settlement. The pyrosequencing-based transcriptomic approach is thought to be useful to identify key molecular changes during larval settlement. Methodology and Principal Findings: Using 454 pyrosequencing, we collected totally 630,845 reads including 215,308 from the larval stages and 415,537 from the adults; 23,451 contigs were generated while 77,785 remained as singletons. We annotated 31,720 of the 92,322 predicted open reading frames, which matched hits in the NCBI NR database, and identified 7,954 putative genes that were differentially expressed between the larval and adult stages. Of these, several genes were further characterized with quantitative real-time PCR and in situ hybridization, revealing some key findings: 1) vitellogenin was uniquely expressed in late nauplius stage, suggesting it may be an energy source for the subsequent non-feeding cyprid stage; 2) the locations of mannose receptors suggested they may be involved in the sensory system of cyprids; 3) 20 kDa-cement protein homologues were expressed in the cyprid cement gland and probably function during attachment; and 4) receptor tyrosine kinases were expressed higher in cyprid stage and may be involved in signal perception during larval settlement. Conclusions: Our results provide not only the basis of several new hypotheses about gene functions during larval settlement, but also the availability of this large transcriptome dataset in B. amphitrite for further exploration of larval settlement and developmental pathways in this important marine species. © 2011 Chen et al.

  16. Obesity and asthma: Pathophysiology and implications for diagnosis and management in primary care

    OpenAIRE

    Mohanan, Sveta; Tapp, Hazel; McWilliams, Andrew; Dulin, Michael

    2014-01-01

    The effects of obesity on asthma diagnosis, control, and exacerbation severity are increasingly recognized; however, the underlying pathophysiology of this association is poorly understood. Mainstream clinical practice has yet to adopt aggressive management of obesity as a modifiable risk factor in asthma care, as is the case with a risk factor like tobacco or allergen exposure. This review summarizes existing data that support the pathophysiologic mechanisms underlying the association betwee...

  17. Pediatric Metabolic Syndrome: Pathophysiology and Laboratory Assessment.

    Science.gov (United States)

    Higgins, Victoria; Adeli, Khosrow

    2017-03-01

    Pediatric overweight and obesity is an emerging public health priority as rates have rapidly increased worldwide. Obesity is often clustered with other metabolic abnormalities including hypertension, dyslipidemia, and insulin resistance, leading to increased risk of cardiovascular disease. This cluster of risk factors, termed the metabolic syndrome, has traditionally been reported in adults. However, with the increased prevalence of pediatric obesity, the metabolic syndrome is now evident in children and adolescents. This complex cluster of risk factors is the result of the pathological interplay between several organs including adipose tissue, muscle, liver, and intestine with a common antecedent - insulin resistance. The association of the metabolic syndrome with several systemic alterations that involve numerous organs and tissues adds to the complexity and challenge of diagnosing the metabolic syndrome and identifying useful clinical indicators of the disease. The complex physiology of growing and developing children and adolescents further adds to the difficulties in standardizing laboratory assessment, diagnosis, and prognosis for the diverse pediatric population. However, establishing a consensus definition is critical to identifying and managing children and adolescents at high risk of developing the metabolic syndrome. As a result, the examination of novel metabolic syndrome biomarkers which can detect these metabolic abnormalities early with high specificity and sensitivity in the pediatric population has been of interest. Understanding this complex cluster of risk factors in the pediatric population is critical to ensure that this is not the first generation where children have a shorter life expectancy than their parents. This review will discuss the pathophysiology, consensus definitions and laboratory assessment of pediatric metabolic syndrome as well as potential novel biomarkers.

  18. Substrates for normal gait and pathophysiology of gait disturbances with respect to the basal ganglia dysfunction.

    Science.gov (United States)

    Takakusaki, Kaoru; Tomita, Nozomi; Yano, Masafumi

    2008-08-01

    In this review, we have tried to elucidate substrates for the execution of normal gait and to understand pathophysiological mechanisms of gait failure in basal ganglia dysfunctions. In Parkinson's disease, volitional and emotional expressions of movement processes are seriously affected in addition to the disturbance of automatic movement processes, such as adjustment of postural muscle tone before gait initiation and rhythmic limb movements during walking. These patients also suffer from muscle tone rigidity and postural instability, which may also cause reduced walking capabilities in adapting to various environments. Neurophysiological and clinical studies have suggested the importance of basal ganglia connections with the cerebral cortex and limbic system in the expression of volitional and emotional behaviors. Here we hypothesize a crucial role played by the basal ganglia-brainstem system in the integrative control of muscle tone and locomotion. The hypothetical model may provide a rational explanation for the role of the basal ganglia in the control of volitional and automatic aspects of movements. Moreover, it might also be beneficial for understanding pathophysiological mechanisms of basal ganglia movement disorders. A part of this hypothesis has been supported by studies utilizing a constructive simulation engineering technique that clearly shows that an appropriate level of postural muscle tone and proper acquisition and utilization of sensory information are essential to maintain adaptable bodily functions for the full execution of bipedal gait. In conclusion, we suggest that the major substrates for supporting bipedal posture and executing bipedal gait are 1) fine neural networks such as the cortico-basal ganglia loop and basal ganglia-brainstem system, 2) fine musculoskeletal structures with adequately developed (postural) muscle tone, and 3) proper sensory processing. It follows that any dysfunction of the above sensorimotor integration processes

  19. Understanding the mechanisms of solid-water reactions through analysis of surface topography.

    Science.gov (United States)

    Bandstra, Joel Z; Brantley, Susan L

    2015-12-01

    The topography of a reactive surface contains information about the reactions that form or modify the surface and, therefore, it should be possible to characterize reactivity using topography parameters such as surface area, roughness, or fractal dimension. As a test of this idea, we consider a two-dimensional (2D) lattice model for crystal dissolution and examine a suite of topography parameters to determine which may be useful for predicting rates and mechanisms of dissolution. The model is based on the assumption that the reactivity of a surface site decreases with the number of nearest neighbors. We show that the steady-state surface topography in our model system is a function of, at most, two variables: the ratio of the rate of loss of sites with two neighbors versus three neighbors (d(2)/d(3)) and the ratio of the rate of loss of sites with one neighbor versus three neighbors (d(1)/d(3)). This means that relative rates can be determined from two parameters characterizing the topography of a surface provided that the two parameters are independent of one another. It also means that absolute rates cannot be determined from measurements of surface topography alone. To identify independent sets of topography parameters, we simulated surfaces from a broad range of d(1)/d(3) and d(2)/d(3) and computed a suite of common topography parameters for each surface. Our results indicate that the fractal dimension D and the average spacing between steps, E[s], can serve to uniquely determine d(1)/d(3) and d(2)/d(3) provided that sufficiently strong correlations exist between the steps. Sufficiently strong correlations exist in our model system when D>1.5 (which corresponds to D>2.5 for real 3D reactive surfaces). When steps are uncorrelated, surface topography becomes independent of step retreat rate and D is equal to 1.5. Under these conditions, measures of surface topography are not independent and any single topography parameter contains all of the available mechanistic

  20. Pancreatitis in dogs and cats: definitions and pathophysiology.

    Science.gov (United States)

    Watson, P

    2015-01-01

    Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. © 2015 British Small Animal Veterinary Association.

  1. Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology.

    Science.gov (United States)

    Hintze, Justin M; Ludlow, Christy L; Bansberg, Stephen F; Adler, Charles H; Lott, David G

    2017-10-01

    Objective The purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task-specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia) and ( etiology, aetiology, diagnosis, pathogenesis, or pathophysiology). Conclusion The diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high-speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia. Implications for Practice A 3-tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

  2. Understanding dental CAD/CAM for restorations - dental milling machines from a mechanical engineering viewpoint. Part A: chairside milling machines.

    Science.gov (United States)

    Lebon, Nicolas; Tapie, Laurent; Duret, Francois; Attal, Jean-Pierre

    2016-01-01

    The dental milling machine is an important device in the dental CAD/CAM chain. Nowadays, dental numerical controlled (NC) milling machines are available for dental surgeries (chairside solution). This article provides a mechanical engineering approach to NC milling machines to help dentists understand the involvement of technology in digital dentistry practice. First, some technical concepts and definitions associated with NC milling machines are described from a mechanical engineering viewpoint. The technical and economic criteria of four chairside dental NC milling machines that are available on the market are then described. The technical criteria are focused on the capacities of the embedded technologies of these milling machines to mill both prosthetic materials and types of shape restorations. The economic criteria are focused on investment costs and interoperability with third-party software. The clinical relevance of the technology is assessed in terms of the accuracy and integrity of the restoration.

  3. Pathophysiology of salt sensitivity hypertension.

    Science.gov (United States)

    Ando, Katsuyuki; Fujita, Toshiro

    2012-06-01

    Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na(+) ). We recently identified two novel mechanisms that impair renal Na(+) -excreting function and result in an increase in BP. First, mineralocorticoid receptor (MR) activation in the kidney, which facilitates distal Na(+) reabsorption through epithelial Na(+) channel activation, causes salt-sensitive hypertension. This mechanism exists not only in models of high-aldosterone hypertension as seen in conditions of obesity or metabolic syndrome, but also in normal- or low-aldosterone type of salt-sensitive hypertension. In the latter, Rac1 activation by salt excess causes MR stimulation. Second, renospecific sympathoactivation may cause an increase in BP under conditions of salt excess. Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension. Abnormalities identified in these two pathways of Na(+) reabsorption in the distal nephron may present therapeutic targets for the treatment of salt-sensitive hypertension.

  4. Quantum interactive learning tutorial on the double-slit experiment to improve student understanding of quantum mechanics

    Directory of Open Access Journals (Sweden)

    Ryan Sayer

    2017-05-01

    Full Text Available Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students’ prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in various situations that appear to be counterintuitive and contradict classical notions of particles and waves. For example, if we send single electrons through the slits, they may behave as a “wave” in part of the experiment and as a “particle” in another part of the same experiment. Here we discuss the development and evaluation of a research-validated Quantum Interactive Learning Tutorial (QuILT which makes use of an interactive simulation to improve student understanding of the double-slit experiment and strives to help students develop a good grasp of foundational issues in quantum mechanics. We discuss common student difficulties identified during the development and evaluation of the QuILT and analyze the data from the pretest and post test administered to the upper-level undergraduate and first-year physics graduate students before and after they worked on the QuILT to assess its effectiveness. These data suggest that on average, the QuILT was effective in helping students develop a more robust understanding of foundational concepts in quantum mechanics that defy classical intuition using the context of the double-slit experiment. Moreover, upper-level undergraduates outperformed physics graduate students on the post test. One possible reason for this difference in performance may be the level of student engagement with the QuILT due to the grade incentive. In the undergraduate course, the post test was graded for correctness while in the graduate course, it was only graded for completeness.

  5. Quantum interactive learning tutorial on the double-slit experiment to improve student understanding of quantum mechanics

    Science.gov (United States)

    Sayer, Ryan; Maries, Alexandru; Singh, Chandralekha

    2017-06-01

    Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students' prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in various situations that appear to be counterintuitive and contradict classical notions of particles and waves. For example, if we send single electrons through the slits, they may behave as a "wave" in part of the experiment and as a "particle" in another part of the same experiment. Here we discuss the development and evaluation of a research-validated Quantum Interactive Learning Tutorial (QuILT) which makes use of an interactive simulation to improve student understanding of the double-slit experiment and strives to help students develop a good grasp of foundational issues in quantum mechanics. We discuss common student difficulties identified during the development and evaluation of the QuILT and analyze the data from the pretest and post test administered to the upper-level undergraduate and first-year physics graduate students before and after they worked on the QuILT to assess its effectiveness. These data suggest that on average, the QuILT was effective in helping students develop a more robust understanding of foundational concepts in quantum mechanics that defy classical intuition using the context of the double-slit experiment. Moreover, upper-level undergraduates outperformed physics graduate students on the post test. One possible reason for this difference in performance may be the level of student engagement with the QuILT due to the grade incentive. In the undergraduate course, the post test was graded for correctness while in the graduate course, it was only graded for completeness.

  6. Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

    Directory of Open Access Journals (Sweden)

    Jolene Michelle Helena

    2018-04-01

    Full Text Available Deoxyribonucleic acid (DNA is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.

  7. Fibromyalgia and Bipolar Disorder: Emerging Epidemiological Associations and Shared Pathophysiology.

    Science.gov (United States)

    Bortolato, B; Berk, M; Maes, M; McIntyre, R S; Carvalho, A F

    2016-01-01

    Fibromyalgia (FM) is a prevalent disorder defined by the presence of chronic widespread pain in association with fatigue, sleep disturbances and cognitive dysfunction. Recent studies indicate that bipolar spectrum disorders frequently co-occur in individuals with FM. Furthermore, shared pathophysiological mechanisms anticipate remarkable phenomenological similarities between FM and BD. A comprehensive search of the English literature was carried out in the Pubmed/MEDLINE database through May 10th, 2015 to identify unique references pertaining to the epidemiology and shared pathophysiology between FM and bipolar disorder (BD). Overlapping neural circuits may underpin parallel clinical manifestations of both disorders. Fibromyalgia and BD are both characterized by functional abnormalities in the hypothalamic-pituitary-adrenal axis, higher levels of inflammatory mediators, oxidative and nitrosative stress as well as mitochondrial dysfunction. An over-activation of the kynurenine pathway in both illnesses drives tryptophan away from the production of serotonin and melatonin, leading to affective symptoms, circadian rhythm disturbances and abnormalities in pain processing. In addition, both disorders are associated with impaired neuroplasticity (e.g., altered brain-derived neurotrophic factor signaling). The recognition of the symptomatic and pathophysiological overlapping between FM and bipolar spectrum disorders has relevant etiological, clinical and therapeutic implications that deserve future research consideration.

  8. Mechanical aberrations in hypetrophic cardiomyopathy: emerging concepts.

    Directory of Open Access Journals (Sweden)

    Dimitrios eNtelios

    2015-08-01

    Full Text Available Hypertrophic cardiomyopathy is the most common monogenic disorder in cardiology. Despite important advances in understanding disease pathogenesis, it is not clear how flaws in individual sarcomere components are responsible for the observed phenotype. The aim of this article is to provide a brief interpretative analysis of some currently proposed pathophysiological mechanisms of hypertrophic cardiomyopathy, with a special emphasis on alterations in the cardiac mechanical properties.

  9. Advances in cellular models to explore the pathophysiology of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Veyrat-Durebex, C; Corcia, P; Dangoumau, A; Laumonnier, F; Piver, E; Gordon, P H; Andres, C R; Vourc'h, P; Blasco, H

    2014-04-01

    Amyotrophic lateral sclerosis (ALS), the most common adult-onset motor neuron disorder, is fatal for most patients less than 3 years from when the first symptoms appear. The aetiologies for sporadic and most familial forms of ALS are unknown, but genetic factors are increasingly recognized as causal in a subset of patients. Studies of disease physiology suggest roles for oxidative stress, glutamate-mediated excitotoxicity or protein aggregation; how these pathways interact in the complex pathophysiology of ALS awaits elucidation. Cellular models are being used to examine disease mechanisms. Recent advances include the availability of expanded cell types, from neuronal or glial cell culture to motoneuron-astrocyte co-culture genetically or environmentally modified. Cell culture experiments confirmed the central role of glial cells in ALS. The recent adaptation of induced pluripotent stem cells (iPSC) for ALS modeling could allow a broader perspective and is expected to generate new hypotheses, related particularly to mechanisms underlying genetic factors. Cellular models have provided meaningful advances in the understanding of ALS, but, to date, complete characterization of in vitro models is only partially described. Consensus on methodological approaches, strategies for validation and techniques that allow rapid adaptation to new genetic or environmental influences is needed. In this article, we review the principal cellular models being employed in ALS and highlight their contribution to the understanding of disease mechanisms. We conclude with recommendations on means to enhance the robustness and generalizability of the different concepts for experimental ALS.

  10. Hemodynamic instability in the critically ill neonate: An approach to cardiovascular support based on disease pathophysiology.

    Science.gov (United States)

    Giesinger, Regan E; McNamara, Patrick J

    2016-04-01

    Hemodynamic disturbance in the sick neonate is common, highly diverse in underlying pathophysiology and dynamic. Dysregulated systemic and cerebral blood flow is hypothesized to have a negative impact on neurodevelopmental outcome and survival. An understanding of the physiology of the normal neonate, disease pathophysiology, and the properties of vasoactive medications may improve the quality of care and lead to an improvement in survival free from disability. In this review we present a modern approach to cardiovascular therapy in the sick neonate based on a more thoughtful approach to clinical assessment and actual pathophysiology. Targeted neonatal echocardiography offers a more detailed insight into disease processes and offers longitudinal assessment, particularly response to therapeutic intervention. The pathophysiology of common neonatal conditions and the properties of cardiovascular agents are described. In addition, we outline separate treatment algorithms for various hemodynamic disturbances that are tailored to clinical features, disease characteristics and echocardiographic findings. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  11. The pathophysiology of restless legs syndrome

    International Nuclear Information System (INIS)

    Miyamoto, Masayuki; Miyamoto, Tomoyuki; Iwanami, Masaoki; Suzuki, Keisuke; Hirata, Koichi

    2009-01-01

    Restless legs syndrome (RLS) is a sensorimotor disorder that is frequently associated with periodic leg movements (PLMS). RLS is generally considered to be a central nervous system (CNS)-related disorder although no specific lesion has been found to be associated with the syndrome. Reduced intracortical inhibition has been demonstrated in RLS by transcranial magnetic stimulation. Some MRI studies have revealed the presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter. The results of single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies showed that the limbic and opioid systems also play important roles in the pathophysiology of RLS. A functional MRI study revealed abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during PLMS. PLMS is likely to occur in patients with spinal cord lesions, and some patients with sensory polyneuropathy may exhibit RLS symptoms. RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing. PLMS appears to depend on increased excitability of the spinal cord and a decreased supraspinal inhibitory mechanism from the A11 diencephalic dopaminergic system. RLS symptoms respond very dramatically to dopaminergic therapy. The results of analysis by PET and SPECT studies of striatal D2 receptor binding in humans are inconclusive. However, studies in animal models suggest that the participation of the A11 dopaminergic system and the D3 receptor in RLS symptoms. The symptoms of RLS are aggravated in those with iron deficiency, and iron treatment ameliorates the symptoms in some patients. Neuroimaging studies, analysis of the cerebrospinal fluid, and studies on postmortem tissue and use of animal models have indicated that low brain iron concentrations and dysfunction of

  12. Pathophysiology, research challenges, and clinical management of smoke inhalation injury.

    Science.gov (United States)

    Enkhbaatar, Perenlei; Pruitt, Basil A; Suman, Oscar; Mlcak, Ronald; Wolf, Steven E; Sakurai, Hiroyuki; Herndon, David N

    2016-10-01

    Smoke inhalation injury is a serious medical problem that increases morbidity and mortality after severe burns. However, relatively little attention has been paid to this devastating condition, and the bulk of research is limited to preclinical basic science studies. Moreover, no worldwide consensus criteria exist for its diagnosis, severity grading, and prognosis. Therapeutic approaches are highly variable depending on the country and burn centre or hospital. In this Series paper, we discuss understanding of the pathophysiology of smoke inhalation injury, the best evidence-based treatments, and challenges and future directions in diagnostics and management. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Current approach to the treatment of human immunodeficiency virus-associated weight loss: pathophysiologic considerations and emerging management strategies.

    Science.gov (United States)

    Hellerstein, M K; Kahn, J; Mudie, H; Viteri, F

    1990-12-01

    Relationships between nutrition and infection are generally complex, bidirectional, and not perfectly worked out. Healthy people can adapt to simple decreases in intake or increases in expenditure. However, the imposition of infection with associated cytokines may impair such adaptations, resulting in wasting of lean tissue. In human immunodeficiency virus (HIV) infection, nutritional abnormalities are common. Lean body mass depletion is associated temporally with death in a subset of acquired immune deficiency syndrome (AIDS) patients. Weakness, fatigue, and anorexia are important symptomatic complaints affecting quality of life. Pathophysiologic mechanisms remain speculative, although there is reason to suspect four theoretic factors: decreased intake, malabsorption, hypermetabolism, and altered metabolism. More than one disturbance may be necessary for clinical wasting to develop; ie, a primary abnormality plus a failure of homeostatic adaptation. Excess cytokine production also may be involved, but this is uncertain. Therapeutics remain empiric in the absence of known mechanisms. Current options are restricted to diet adjustments or supplements, treatment of underlying diseases (where possible), and rarely, parenteral alimentation. Promising investigational possibilities include an appetite stimulant (megestrol acetate) and therapies to oppose cytokine production or actions, but definitive beneficial effects on nutritional status, subjective performance, disease activity, or survival have not yet been demonstrated. Advances in clinical therapeutics await an improved understanding of pathophysiologic mechanisms and carefully designed clinical trials testing proposed interventions.

  14. Understanding the Mechanism of the Hydrogen Abstraction from Arachidonic Acid Catalyzed by the Human Enzyme 15-Lipoxygenase-2. A Quantum Mechanics/Molecular Mechanics Free Energy Simulation.

    Science.gov (United States)

    Suardíaz, Reynier; Jambrina, Pablo G; Masgrau, Laura; González-Lafont, Àngels; Rosta, Edina; Lluch, José M

    2016-04-12

    . Overall, a different binding mode from the one accepted for 15-LOX-1 is proposed, which provides a molecular basis for 15-LOX-2 exclusive 15-HPETE production in front of the double (although highly 15-) 12/15 regiospecificity of 15-LOX-1. Understanding how these different isoenzymes achieve their regiospecificity is expected to help in specific inhibitor design.

  15. The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome.

    Science.gov (United States)

    El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

    2017-02-01

    The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

  16. From observation to understanding: Approach to analysis of wear mechanisms, Case of RCCAs and CRDM latch arms

    International Nuclear Information System (INIS)

    Hertz, D.

    2004-01-01

    Component wear can affect the ability of a component to fulfill its required function. For a designer or user, it is reasonable to expect possible wear occurrence as soon as parts are in relative motion. It is less obvious to extend this possibility to motions with small or very small amplitudes and loads. However, it has to be admitted that such cases exist. It then becomes imperative to determine the wear mechanisms so that the lifetime of the components and the optimum date of their replacement can be predicted or the degradation can be remedied. For this purpose, standard and widely accepted practice is to carry out simulator tests. Through examples of wear from nuclear reactor components such as the RCCAs (Rod Cluster Control Assembly) and the CRDM (Control Rod Drive Mechanism) latch arms, an approach for understanding the wear mechanisms and controlling their effects can be undertaken. Cases of wear have been observed on real-life parts, but the first simulator tests have shown deviations from in-reactor behaviour. Comparative examination of the wear facies of actual parts which have operated in reactor or simulators, both control rods and CRDM latch arms, was the key starting point for a new analytical approach, incorporating the formulation of wear mechanism hypotheses which can account for the observed facies. Expert assessment thus highlighted the importance of the environment by revealing that the wear featured a large component linked to friction-assisted corrosion. By including this tribo-corrosion aspect, it became possible to reach understanding of the mechanisms and account for the wear observed in reactor and on simulators. Further well-controlled simulator tests then made it possible to verify the importance of the tribo-corrosion processes in a pressurized water medium. Analysis of the physical chemical behaviour of the original materials (austenitic stainless steel) also explains why these surface modifications limit or remedy wear

  17. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-12-16

    Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  18. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-12-01

    Full Text Available Metabolic syndrome (MS is becoming a worldwide health problem. Wendan decoction (WDD—a famous traditional Chinese medicine formula—has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  19. Understanding the mechanical properties of DNA origami tiles and controlling the kinetics of their folding and unfolding reconfiguration.

    Science.gov (United States)

    Chen, Haorong; Weng, Te-Wei; Riccitelli, Molly M; Cui, Yi; Irudayaraj, Joseph; Choi, Jong Hyun

    2014-05-14

    DNA origami represents a class of highly programmable macromolecules that can go through conformational changes in response to external signals. Here we show that a two-dimensional origami rectangle can be effectively folded into a short, cylindrical tube by connecting the two opposite edges through the hybridization of linker strands and that this process can be efficiently reversed via toehold-mediated strand displacement. The reconfiguration kinetics was experimentally studied as a function of incubation temperature, initial origami concentration, missing staples, and origami geometry. A kinetic model was developed by introducing the j factor to describe the reaction rates in the cyclization process. We found that the cyclization efficiency (j factor) increases sharply with temperature and depends strongly on the structural flexibility and geometry. A simple mechanical model was used to correlate the observed cyclization efficiency with origami structure details. The mechanical analysis suggests two sources of the energy barrier for DNA origami folding: overcoming global twisting and bending the structure into a circular conformation. It also provides the first semiquantitative estimation of the rigidity of DNA interhelix crossovers, an essential element in structural DNA nanotechnology. This work demonstrates efficient DNA origami reconfiguration, advances our understanding of the dynamics and mechanical properties of self-assembled DNA structures, and should be valuable to the field of DNA nanotechnology.

  20. Acute colonic pseudo-obstruction: A systematic review of aetiology and mechanisms

    Science.gov (United States)

    Wells, Cameron I; O’Grady, Gregory; Bissett, Ian P

    2017-01-01

    AIM To critically review the literature addressing the definition, epidemiology, aetiology and pathophysiology of acute colonic pseudo-obstruction (ACPO). METHODS A systematic search was performed to identify articles investigating the aetiology and pathophysiology of ACPO. A narrative synthesis of the evidence was undertaken. RESULTS No consistent approach to the definition or reporting of ACPO has been developed, which has led to overlapping investigation with other conditions. A vast array of risk factors has been identified, supporting a multifactorial aetiology. The pathophysiological mechanisms remain unclear, but are likely related to altered autonomic regulation of colonic motility, in the setting of other predisposing factors. CONCLUSION Future research should aim to establish a clear and consistent definition of ACPO, and elucidate the pathophysiological mechanisms leading to altered colonic function. An improved understanding of the aetiology of ACPO may facilitate the development of targeted strategies for its prevention and treatment. PMID:28852322

  1. Heavy metal poisoning: clinical presentations and pathophysiology.

    Science.gov (United States)

    Ibrahim, Danyal; Froberg, Blake; Wolf, Andrea; Rusyniak, Daniel E

    2006-03-01

    Humans have had a long and tumultuous relationship with heavy metals. Their ubiquitous nature and our reliance on them for manufacturing have resulted at times in exposures sufficient to cause systemic toxicity. Their easy acquisition and potent toxicity have also made them popular choices for criminal poisonings. This article examines the clinical manifestation and pathophysiology of poisoning from lead, mercury, arsenic, and thallium.

  2. Pathophysiology of Increased Fetal Nuchal Translucency Thickness

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2010-06-01

    Full Text Available Increased fetal nuchal translucency thickness is associated with trisomy 13, trisomy 18, trisomy 21, Turner syndrome, other sex chromosome abnormalities, as well as many fetal anomalies and genetic syndromes. This article provides a comprehensive review of the cardinal proposed pathophysiology including altered composition of the extracellular matrix, abnormalities of the heart and great arteries, and disturbed or delayed lymphatic development.

  3. Pathophysiology of diurnal drooling in Parkinson's disease

    NARCIS (Netherlands)

    Kalf, J.G.; Munneke, M.; Engel-Hoek, L. van den; Swart, B.J.M. de; Borm, G.F.; Bloem, B.R.; Zwarts, M.J.

    2011-01-01

    Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

  4. Insights into Pathophysiology from Medication-induced Tremor

    Directory of Open Access Journals (Sweden)

    John C. Morgan

    2017-10-01

    Full Text Available Background: Medication-induced tremor (MIT is common in clinical practice and there are many medications/drugs that can cause or exacerbate tremors. MIT typically occurs by enhancement of physiological tremor (EPT, but not all drugs cause tremor in this way. In this manuscript, we review how some common examples of MIT have informed us about the pathophysiology of tremor.Methods: We performed a PubMed literature search for published articles dealing with MIT and attempted to identify articles that especially dealt with the medication’s mechanism of inducing tremor.Results: There is a paucity of literature that deals with the mechanisms of MIT, with most manuscripts only describing the frequency and clinical settings where MIT is observed. That being said, MIT emanates from multiple mechanisms depending on the drug and it often takes an individualized approach to manage MIT in a given patient.Discussion: MIT has provided some insight into the mechanisms of tremors we see in clinical practice. The exact mechanism of MIT is unknown for most medications that cause tremor, but it is assumed that in most cases physiological tremor is influenced by these medications. Some medications (epinephrine that cause EPT likely lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists, but others may influence the central component (amitriptyline. Other drugs can cause tremor, presumably by blockade of dopamine receptors in the basal ganglia (dopamine-blocking agents, by secondary effects such as causing hyperthyroidism (amiodarone, or by other mechanisms. We will attempt to discuss what is known and unknown about the pathophysiology of the most common MITs.

  5. Ferrous archaeological analogues for the understanding of the multi-secular corrosion mechanisms in an anoxic environment

    International Nuclear Information System (INIS)

    Saheb-Djahromi, M.

    2009-12-01

    Understanding the long term corrosion mechanisms of iron in an anoxic environment is essential in the field of the radioactive waste storage. In France, it is planned to store high level nuclear wastes in a multi-barrier system containing a glassy matrix surrounded by a stainless steel container, embedded in a low-carbon steel over-container. This system would be placed in a deep geological repository, which would impose anoxic conditions. As it must be efficient for a period of several thousands of years, one should understand the alteration mechanisms that are expected to occur in such a long time. To this purpose, a specific approach is developed on ferrous archaeological analogues with thick corrosion layer formed in natural conditions. In this study, the corrosion mechanisms have been assessed by examining nails aged of 400 years coming from the archaeological site of Glinet, selected as a reference site. The first point was a fine characterisation of the entire corrosion system metal / corrosion products / medium, through the use of coupled multi-scale analytical tools. The first results showed that the samples were corroded in an anoxic calco-carbonated environment. Moreover, the coupling of X-ray micro-diffraction, Raman microspectroscopy and dispersive energy spectroscopy has enabled to identify three corrosion systems composed of iron carbonates, siderite and chukanovite, and magnetite. Depending on the phase's layout in the system, the electronic resistance of the corrosion layers has been established, from resistive to conductive. In a second stage, re-corroding experiments in laboratory were performed. Firstly, the electrochemical behaviour of the corrosion system has shown that water reduction at the metallic interface is negligible. Furthermore, reaction tracing with copper and deuterium has allowed identifying the electron consumptions sites mainly localised on the external part, and the precipitation sites on the internal part of the corrosion

  6. Toward understanding the anticorrosive mechanism of some thiourea derivatives for carbon steel corrosion: A combined DFT and molecular dynamics investigation.

    Science.gov (United States)

    Guo, Lei; Kaya, Savaş; Obot, Ime Bassey; Zheng, Xingwen; Qiang, Yujie

    2017-11-15

    The mutually corroborated density functional theory (DFT) and molecular dynamics (MD) simulation methodology were employed to evaluate the inhibition performance of three thiourea derivatives (Inh1, Inh2, and Inh3) on carbon steel corrosion. Experimental results have shown that the corrosion rate follows the order: Inh3>Inh2>Inh1. Quantum chemical descriptors such as the frontier orbital energies (E HOMO and E LUMO ), the energy gap between E LUMO and E HOMO (ΔE), dipole moment (μ), and Fukui index have been calculated and discussed. Some significant factors such as solvent, temperature, and coverage have been considered when investigating the adsorption of aforementioned thiourea derivatives on Fe(110) surface. Our results provide important atomic/molecular insights into the anticorrosive mechanism of inhibitor molecules, which could help in understanding the organic-metal interface and designing more appropriate organic corrosion inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Understanding the Mechanisms behind Changing People’s Recycling Behavior at Work by Applying a Comprehensive Action Determination Model

    Directory of Open Access Journals (Sweden)

    Sunita Prugsamatz Ofstad

    2017-02-01

    Full Text Available This study moves toward a better understanding of the mechanisms behind changing people’s recycling behavior at work by mapping out which pathways and variables change in recycling behavior as triggered by interventions. A questionnaire was designed based on the theory of planned behaviour, the norm-activation model, habits, and a comprehensive action determination model (CADM. The data was collected in two rounds: before the intervention and after a three-month pilot period with implemented interventions using a sample of n = 1269 students and employees. The CADM model appears to be a good fit with the data. The results from the structural equation modelling indicate the pathways to influencing behavioural change. The most important psychological variables accounting for waste separation behaviour are intentions, perceived behavioural control, personal norms, social norms and habits. No difference in waste separation behaviour was observed in the control building. Interventions targeting the increase in waste separation raised participants’ intentions to engage in such behaviour. Results indicate that waste separation at work must go beyond technical aspects to include various key elements of sustainability to ensure success. Furthermore, understanding human behavior is key in determining the performance and success of an integrated and effective recycling intervention strategy.

  8. Pathophysiological aspects of cystocele with a 3D finite elements model.

    Science.gov (United States)

    Lamblin, Géry; Mayeur, Olivier; Giraudet, Géraldine; Jean Dit Gautier, Estelle; Chene, Gautier; Brieu, Mathias; Rubod, Chrystèle; Cosson, Michel

    2016-11-01

    The objective of this study is to design a 3D biomechanical model of the female pelvic system to assess pelvic organ suspension theories and understand cystocele mechanisms. A finite elements (FE) model was constructed to calculate the impact of suspension structure geometry on cystocele. The sample was a geometric model of a control patient's pelvic organs. The method used geometric reconstruction, implemented by the biomechanical properties of each anatomic structure. Various geometric configurations were simulated on the FE method to analyse the role of each structure and compare the two main anatomic theories. The main outcome measure was a 3D biomechanical model of the female pelvic system. The various configurations of bladder displacement simulated mechanisms underlying medial, lateral and apical cystocele. FE simulation revealed that pubocervical fascia is the most influential structure in the onset of median cystocele (essentially after 40 % impairment). Lateral cystocele showed a stronger influence of arcus tendineus fasciae pelvis (ATFP) on vaginal wall displacement under short ATFP lengthening. In apical cystocele, the uterosacral ligament showed greater influence than the cardinal ligament. Suspension system elongation increased displacement by 25 % in each type of cystocele. A 3D digital model enabled simulations of anatomic structures underlying cystocele to better understand cystocele pathophysiology. The model could be used to predict cystocele surgery results and personalising technique by preoperative simulation.

  9. The Pathophysiology and Care of Exercise Related Muscle Cramps

    Directory of Open Access Journals (Sweden)

    Abhay Kumar Pandey

    2015-01-01

    Full Text Available Cramps are major concerns to competing athletes occurring during or after exercise, are common yet, poorly understood phenomena. Pain alone is not object of treatment as serious musculophysiologic and metabolic disturbance of fluid and electrolyte deserve correction. Acute muscle pain and stiffness may cause soreness for longer time. Based on observations, two etiological theories are construed, i.e. the muscle fatigue theory and sodium-water deficit theory. Either has supporting and contradicting facts, but these are relevant to guide prevention and management interventions. Cramps may be different in kind based on different local and/or general causes. Occurrence of cramps in varied situations, environmental conditions and populations, suggests of pleural causal determinents. These include neuromuscular and fluid-electrolyte disturbance factors directly responsible under specific circumstances of individual sports person. Degree of conditioning to particular kind of physical exertion appears most significant factor. Prevention exercises target theorised physiology of muscle tendon and golgi organ receptors, toward delaying fatigability and cramp risk. Occurrence of cramps mostly in hot environments emphasizes support to dehydration-electrolyte imbalance theory. Maintenance of hydration and adequate electrolyte levels in cramp-prone individuals thus makes sense. Worth of variety of measures empirically employed for cramp relief can be judged by scientific understanding. Drugs found useful may not be the best match to pathophysiologic proprieties and thus irrational. The pathophysiological details and relevant clinical information is presented and discussed as first hand understanding for the sports persons and their care givers.

  10. Computational Design of a pH Stable Enzyme: Understanding Molecular Mechanism of Penicillin Acylase's Adaptation to Alkaline Conditions

    Science.gov (United States)

    Suplatov, Dmitry; Panin, Nikolay; Kirilin, Evgeny; Shcherbakova, Tatyana; Kudryavtsev, Pavel; Švedas, Vytas

    2014-01-01

    Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties. PMID:24959852

  11. Multiple stressor effects in Chlamydomonas reinhardtii--toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants.

    Science.gov (United States)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B; Junghans, Marion; Eggen, Rik I L

    2015-05-01

    The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Computational design of a pH stable enzyme: understanding molecular mechanism of penicillin acylase's adaptation to alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Dmitry Suplatov

    Full Text Available Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties.

  13. Scanning electron microscopy-based approach to understand the mechanism underlying the adhesion of dengue viruses on ceramic hydroxyapatite columns.

    Directory of Open Access Journals (Sweden)

    Maiko Saito

    Full Text Available Although ceramic hydroxyapatite (HAp chromatography has been used as an alternative method ultracentrifugation for the production of vaccines, the mechanism of virus separation is still obscure. In order to begin to understand the mechanisms of virus separation, HAp surfaces were observed by scanning electron microscopy after chromatography with dengue viruses. When these processes were performed without elution and with a 10-207 mM sodium phosphate buffer gradient elution, dengue viruses that were adsorbed to HAp were disproportionately located in the columns. However, when eluted with a 10-600 mM sodium phosphate buffer gradient, few viruses were observed on the HAp surface. After incubating the dengue viruses that were adsorbed on HAp beads at 37°C and 2°C, the sphericity of the dengue viruses were reduced with an increase in incubation temperature. These results suggested that dengue virus was adsorbed to the HAp surface by electronic interactions and could be eluted by high-salt concentration buffers, which are commonly used in protein purification. Furthermore, virus fusion was thought to occur with increasing temperature, which implied that virus-HAp adhesion was similar to virus-cell adhesion.

  14. Severe bullous hypersensitivity reactions after exposure to carbamazepine in a Han-Chinese child with a positive HLA-B*1502 and negative in vitro toxicity assays: evidence for different pathophysiological mechanisms.

    Science.gov (United States)

    Elzagallaai, Abdelbaset A; Garcia-Bournissen, Facundo; Finkelstein, Yaron; Bend, John R; Rieder, Michael J; Koren, Gideon

    2011-01-01

    Drug hypersensitivity syndrome (DHS) can present in several clinical forms ranging from simple maculopapular skin rash to severe bullous reactions and multi-system dysfunction. Genetic analysis of DHS patients has revealed a striking association between carbamazepine (CBZ)-induced severe bullous reactions, such as Steven-Johnson Syndrome, and toxic epidermal necrolysis in individuals from Southeast Asia who carry a specific HLA allele (HLA-B*1502). This ethnic-specific relationship with a disease phenotype has raised the question of the commonality of the pathogenesis mechanisms of these diseases. The aim of this study was to investigate the genetic and metabolic bases of DHS development to help predict patient susceptibility. A case of carbamazepine-induced Steven-Johnson Syndrome reaction in a HLA-B*1502 positive child of Han Chinese origin, a carbamazepine-induced DHS case in a Caucasian patient and 3 healthy controls were investigated. We performed two types of in vitro toxicity assay, the lymphocyte toxicity assay (LTA) and the novel in vitro platelet toxicity assay (iPTA) on cells taken from the Chinese child 3 and 9 months after recovery from the reaction and from two healthy volunteers. We also tested the Caucasian patient, who developed CBZ-induced DHS, 3 months after the reaction. Both LTA and iPTA tests were negative 3 and 9 months after the reaction on samples from the Chinese child whereas the tests were positive in the Caucasian patient. These results strongly suggest more than one mechanistic pathway for different CBZ-induced hypersensitivity reactions in patients with different ethnic backgrounds.

  15. Pathophysiology of increased intestinal permeability in obstructive jaundice

    Science.gov (United States)

    Assimakopoulos, Stelios F; Scopa, Chrisoula D; Vagianos, Constantine E

    2007-01-01

    Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome. PMID:18161914

  16. Clinical, Cellular, and Molecular Aspects in the Pathophysiology of Rosacea

    Science.gov (United States)

    Steinhoff, Martin; Buddenkotte, Jörg; Aubert, Jerome; Sulk, Mathias; Novak, Pawel; Schwab, Verena D.; Mess, Christian; Cevikbas, Ferda; Rivier, Michel; Carlavan, Isabelle; Déret, Sophie; Rosignoli, Carine; Metze, Dieter; Luger, Thomas A.; Voegel, Johannes J.

    2013-01-01

    Rosacea is a chronic inflammatory skin disease of unknown etiology. Although described centuries ago, the pathophysiology of this disease is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been identified yet. Four subtypes and several variants of rosacea have been described. It is still unclear whether these subtypes represent a “developmental march” of different stages or are merely part of a syndrome that develops independently but overlaps clinically. Clinical and histopathological characteristics of rosacea make it a fascinating “human disease model” for learning about the connection between the cutaneous vascular, nervous, and immune systems. Innate immune mechanisms and dysregulation of the neurovascular system are involved in rosacea initiation and perpetuation, although the complex network of primary induction and secondary reaction of neuroimmune communication is still unclear. Later, rosacea may result in fibrotic facial changes, suggesting a strong connection between chronic inflammatory processes and skin fibrosis development. This review highlights recent molecular (gene array) and cellular findings and aims to integrate the different body defense mechanisms into a modern concept of rosacea pathophysiology. PMID:22076321

  17. Postoperative ileus: Recent developments in pathophysiology and management.

    Science.gov (United States)

    Bragg, Damian; El-Sharkawy, Ahmed M; Psaltis, Emmanouil; Maxwell-Armstrong, Charles A; Lobo, Dileep N

    2015-06-01

    Postoperative ileus (POI) is a frequent occurrence after abdominal and other types of surgery, and is associated with significant morbidity and costs to health care providers. The aims of this narrative review were to provide an update of classification systems, preventive techniques, pathophysiological mechanisms, and treatment options for established POI. The Web of Science, MEDLINE, PubMed and Google Scholar databases were searched using the key phrases 'ileus', 'postoperative ileus' and 'definition', for relevant studies published in English from January 1997 to August 2014. POI is still a problematic and frequent complication of surgery. Fluid overload, exogenous opioids, neurohormonal dysfunction, and gastrointestinal stretch and inflammation are key mechanisms in the pathophysiology of POI. Evidence is supportive of thoracic epidural analgesia, avoidance of salt and water overload, alvimopan and gum chewing as measures for the prevention of POI, and should be incorporated into perioperative care protocols. Minimal access surgery and avoidance of nasogastric tubes may also help. Novel strategies are emerging, but further studies are required for the treatment of prolonged POI, where evidence is still lacking. Although POI is often inevitable, methods to reduce its duration and facilitate recovery of postoperative gastrointestinal function are evolving rapidly. Utilisation of standardised diagnostic classification systems will help improve applicability of future studies. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  18. [Physiology and pathophysiology of wound healing of wound defects].

    Science.gov (United States)

    Mutschler, W

    2012-09-01

    Understanding wound healing involves more than simply stating that there are the three phases of inflammation, proliferation and maturation. Wound healing is a complex series of actions, reactions and interactions among cells and mediators in a sequential and simultaneously ongoing temporal process within a spatial frame. At first this article will attempt to provide a concise summary of the events, cellular components and main influential mediators of wound healing over time. Secondly, the pathophysiology of chronic non-healing wounds is described where an imbalance of stimulating and inhibiting factors causes failure of healing. The most relevant extrinsic and intrinsic determinants are described and related to the cellular and molecular level of disturbed wound healing. A basic understanding of wound healing is a prerequisite for any prophylactic or therapeutic maneuver to maintain or re-establish wound equilibrium to give a satisfactory healing trajectory.

  19. Multimodal approach to control postoperative pathophysiology and rehabilitation

    DEFF Research Database (Denmark)

    Kehlet, H

    1997-01-01

    , complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc). To understand postoperative morbidity it is therefore necessary to understand the pathophysiological role of the various components of the surgical stress response and to determine if modification of such responses may......Major surgery is still associated with undesirable sequelae such as pain, cardiopulmonary, infective and thromboembolic complications, cerebral dysfunction, nausea and gastrointestinal paralysis, fatigue and prolonged convalescence. The key pathogenic factor in postoperative morbidity, excluding...... failures of surgical and anaesthetic technique, is the surgical stress response with subsequent increased demands on organ function. These changes in organ function are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biological cascade systems (cytokines...

  20. Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management.

    Science.gov (United States)

    Baruteau, Alban-Elouen; Pass, Robert H; Thambo, Jean-Benoit; Behaghel, Albin; Le Pennec, Solène; Perdreau, Elodie; Combes, Nicolas; Liberman, Leonardo; McLeod, Christopher J

    2016-09-01

    Atrioventricular block is classified as congenital if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental passage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive cardiac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe permanent cardiac pacing in almost all patients, including those with structural heart abnormalities. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current understanding of the pathogenetic mechanisms, clinical course, and optimal management of congenital and childhood AV block. • Prevalence of congenital heart block of 1 per 15,000 to 20,000 live births. AV block is defined as congenital if diagnosed in utero, at birth, or within the first month of life, whereas childhood AV block is diagnosed between the first month and the 18th year of life. As a result of several different etiologies, congenital and childhood atrioventricular block may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Cardiac pacing is indicated in symptomatic patients and has several prophylactic indications in asymptomatic patients to prevent sudden death. • Autoimmune, congenital AV block is associated with a high neonatal mortality rate and development of dilated cardiomyopathy in 5 to 30 % cases. What is New: • Several genes including SCN5A have been implicated in autosomal dominant forms of familial progressive cardiac conduction disorders. • Leadless pacemaker technology and gene therapy for

  1. Otosclerosis update (1). Pathophysiology and diagnosis

    International Nuclear Information System (INIS)

    Ogawa, Kaoru; Inoue, Yasuhiro; Saito, Hideyuki; Kanzaki, Sho; Okamoto, Yasuhide; Mizutari, Kunio; Suzuki, Takashi; Oishi, Naoki

    2009-01-01

    Otosclerosis is an otological disease that typicaly causes conductive hearing loss. This disease is an important clinical entity since hearing impairment in these case can be dramatically improved by surgery. In this review paper, we review recent research into the pathophysiology of otosclerosis and summarize clinical features, audiometry and diagnostic imaging examinations in 160 ears with otosclerosis that we treated surgically in our department. (author)

  2. Teachers' Beliefs about the Role of Interaction in Teaching Newtonian Mechanics and Its Influence on Students' Conceptual Understanding of Newton's Third Law

    Science.gov (United States)

    Jauhiainen, Johanna; Koponen, Ismo T.; Lavonen, Jari

    2006-01-01

    Students' conceptual understanding of Newton's third law has been the subject of numerous studies. These studies have often pointed out the importance of addressing the concept of interaction in teaching Newtonian mechanics. In this study, teachers were interviewed in order to examine how they understand interaction and use it in their…

  3. [Chronic daily headache: I. Diagnosis and pathophysiology].

    Science.gov (United States)

    Volcy-Gómez, M

    Chronic daily headache (CDH), or headache more than 15 days/month or over 180 days/year, is one of the main reasons for visits to specialised headache centres and accounts for up to 5% of primary headaches. Our objective was to determine the classification, epidemiology, risk factors and pathophysiology of CDH by reviewing the literature. CDH has a prevalence of 2 to 3% in the general population and is subdivided into two groups according to the headache duration. The first group (more than four hours) represents over 90% patients; includes chronic migraine (60 to 87.4%), chronic tension-type headache (0.9 to 28.8%), new daily persistent headache (0.8 to 20%) and hemicrania continua (2.2%), which represents over 90% of patients. The second group (less than four hours) is made up of cluster, chronic paroxysmal hemicranial, idiopathic stabbing-type headache and cranial neuralgias. The pathophysiology of CDH is multifactorial; it has been suggested that genetic factors, peripheral and central neuronal dysfunction derived from the alteration of protein and receptor synthesis, inadequate release of inhibitory and excitatory neuropeptides, imbalance, excitatory and inhibitory neuropeptides concentration imbalance, in association with abuse of analgesics, high comorbidity with psychiatric disorders (anxiety, depression and panic) and sleep disorders may all be involved. CDH is a frequent cause of headache and chronic migraine is the main presenting symptom. Pathophysiology is multifactorial; there is a strong association with analgesic abuse, high comorbidity with psychiatric disorders and sleep disorders.

  4. Understanding mechanisms of rarity in pteridophytes: competition and climate change threaten the rare fern Asplenium scolopendrium var. americanum (Aspleniaceae).

    Science.gov (United States)

    Testo, Weston L; Watkins, James E

    2013-11-01

    Understanding the ecology of rare species can inform aspects of conservation strategies; however, the mechanisms of rarity remain elusive for most pteridophytes, which possess independent and ecologically distinct gametophyte and sporophyte generations. To elucidate factors contributing to recent declines of the rare fern Asplenium scolopendrium var. americanum, we studied the ecology and ecophysiology of its gametophyte generation, focusing on responses to competition, temperature, and water stress. Gametophytes of A. scolopendrium var. americanum, its widespread European relative A. scolopendrium var. scolopendrium, and five co-occurring fern species were grown from spores. Gametophytes were grown at 20°C and 25°C, and germination rates, intra- and interspecific competition, desiccation tolerance, and sporophyte production were determined for all species. Gametophytes of A. scolopendrium var. americanum had the lowest rates of germination and sporophyte production among all species studied and exhibited the greatest sensitivity to interspecific competition, temperature increases, and desiccation. Mature gametophytes of A. scolopendrium var. americanum grown at 25°C were 84.6% smaller than those grown at 20°C, and only 1.5% produced sporophytes after 200 d in culture. Similar responses were not observed in other species studied. The recent declines and current status of populations of A. scolopendrium var. americanum are linked to its gametophyte's limited capacity to tolerate competition and physiological stress linked to climate change. This is the first study to develop a mechanistic understanding of rarity and decline in a fern and demonstrates the importance of considering the ecology of the gametophyte in plants with independent sporophyte and gametophyte generations.

  5. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Korkaric, Muris [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata; Fischer, Beat B. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); Junghans, Marion [Swiss Center for Applied Ecotoxicology Eawag-EPFL, 8600, Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

    2015-05-15

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  6. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    International Nuclear Information System (INIS)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B.; Junghans, Marion; Eggen, Rik I.L.

    2015-01-01

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  7. Negative pressure pulmonary edema revisited: Pathophysiology and review of management

    Directory of Open Access Journals (Sweden)

    Balu Bhaskar

    2011-01-01

    Full Text Available Negative pressure pulmonary edema (NPPE is a dangerous and potentially fatal condition with a multifactorial pathogenesis. Frequently, NPPE is a manifestation of upper airway obstruction, the large negative intrathoracic pressure generated by forced inspiration against an obstructed airway is thought to be the principal mechanism involved. This negative pressure leads to an increase in pulmonary vascular volume and pulmonary capillary transmural pressure, creating a risk of disruption of the alveolar-capillary membrane. The early detection of the signs of this syndrome is vital to the treatment and to patient outcome. The purpose of this review is to highlight the available literature on NPPE, while probing the pathophysiological mechanisms relevant in both the development of this condition and that involved in its resolution.

  8. Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea.

    Science.gov (United States)

    Camilleri, Michael; Sellin, Joseph H; Barrett, Kim E

    2017-02-01

    Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (>4 weeks in duration) are more elusive. We review the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extraepithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in the assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

    Science.gov (United States)

    Camilleri, Michael; Sellin, Joseph H.; Barrett, Kim E.

    2016-01-01

    Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (more than 4 weeks in duration) are more elusive. We review on the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extra-epithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. PMID:27773805

  10. A new application of the phase-field method for understanding the mechanisms of nuclear architecture reorganization.

    Science.gov (United States)

    Lee, S Seirin; Tashiro, S; Awazu, A; Kobayashi, R

    2017-01-01

    Specific features of nuclear architecture are important for the functional organization of the nucleus, and chromatin consists of two forms, heterochromatin and euchromatin. Conventional nuclear architecture is observed when heterochromatin is enriched at nuclear periphery, and it represents the primary structure in the majority of eukaryotic cells, including the rod cells of diurnal mammals. In contrast to this, inverted nuclear architecture is observed when the heterochromatin is distributed at the center of the nucleus, which occurs in the rod cells of nocturnal mammals. The inverted architecture found in the rod cells of the adult mouse is formed through the reorganization of conventional architecture during terminal differentiation. Although a previous experimental approach has demonstrated the relationship between these two nuclear architecture types at the molecular level, the mechanisms underlying long-range reorganization processes remain unknown. The details of nuclear structures and their spatial and temporal dynamics remain to be elucidated. Therefore, a comprehensive approach, using mathematical modeling, is required, in order to address these questions. Here, we propose a new mathematical approach to the understanding of nuclear architecture dynamics using the phase-field method. We successfully recreated the process of nuclear architecture reorganization, and showed that it is robustly induced by physical features, independent of a specific genotype. Our study demonstrates the potential of phase-field method application in the life science fields.

  11. Contribution of proteomics of Leishmania spp. to the understanding of differentiation, drug resistance mechanisms, vaccine and drug development.

    Science.gov (United States)

    Paape, Daniel; Aebischer, Toni

    2011-08-24

    Leishmania spp., protozoan parasites with a digenetic life cycle, cause a spectrum of diseases in humans. Recently several Leishmania spp. have been sequenced which significantly boosted the number and quality of proteomic studies conducted. Here a historic review will summarize work of the pre-genomic era and then focus on studies after genome information became available. Firstly works comparing the different life cycle stages, in order to identify stage specific proteins, will be discussed. Identifying post-translational modifications by proteomics especially phosphorylation events will be discussed. Further the contribution of proteomics to the understanding of the molecular mechanism of drug resistance and the investigation of immunogenic proteins for the identification of vaccine candidates will be summarized. Approaches of how potentially secreted proteins were identified are discussed. So far 30-35% of the total predicted proteome of Leishmania spp. have been identified. This comprises mainly the abundant proteins, therefore the last section will look into technological approaches on how this coverage may be increased and what the gel-free and gel-based proteomics have to offer will be compared. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Adult and juvenile dermatomyositis: are the distinct clinical features explained by our current understanding of serological subgroups and pathogenic mechanisms?

    Science.gov (United States)

    2013-01-01

    Adult and juvenile dermatomyositis share the hallmark features of pathognomic skin rash and muscle inflammation, but are heterogeneous disorders with a range of additional disease features and complications. The frequency of important clinical features such as calcinosis, interstitial lung disease and malignancy varies markedly between adult and juvenile disease. These differences may reflect different disease triggers between children and adults, but whilst various viral and other environmental triggers have been implicated, results are so far conflicting. Myositis-specific autoantibodies can be detected in both adults and children with idiopathic inflammatory myopathies. They are associated with specific disease phenotypes and complications, and divide patients into clinically homogenous subgroups. Interestingly, whilst the same autoantibodies are found in both adults and children, the disease features remain different within autoantibody subgroups, particularly with regard to life-threatening disease associations, such as malignancy and rapidly progressive interstitial lung disease. Our understanding of the mechanisms that underlie these differences is limited by a lack of studies directly comparing adults and children. Dermatomyositis is an autoimmune disease, which is believed to develop as a result of an environmental trigger in a genetically predisposed individual. Age-specific host immune responses and muscle physiology may be additional complicating factors that have significant impact on disease presentation. Further study into this area may produce new insights into disease pathogenesis. PMID:23566358

  13. Copper-based opaque red glasses - Understanding the colouring mechanism of copper nanoparticles in archaeological glass samples

    Science.gov (United States)

    Drünert, F.; Blanz, M.; Pollok, K.; Pan, Z.; Wondraczek, L.; Möncke, D.

    2018-02-01

    Red opaque glasses of two different sites in central Germany, a medieval glassworks in Glashütten, Taunus Mountains, and an early modern glassworks in Wieda, Harz Mountains, were analysed with regard to their optical appearance. By scanning electron microscopy and X-ray diffraction, metallic copper nanoparticles were identified as a conspicuous constituent in these glasses. In addition, similar opaque red glasses were reproduced in the laboratory in order to better understand the manufacturing process. Detailed analysis of the optical scattering was conducted in order to evaluate the role of Cu0 nanoparticles in the colouring mechanism relative to other possible reasons of colouration. We find clear differences between the possible contributions of Cu2O (cuprite) particles and metallic copper (Cu0) nanoparticles. Through simulated backscattering spectra we were able to calculate an average copper particle radius in the archaeological glass samples resulting in a value of up to 95 nm, which matches well the results of SEM investigation (minimum 65 nm). Using the methods we applied in this study, it becomes possible to reconstruct various processing conditions as they were applied in medieval manufacture of these particular materials.

  14. Toward a better understanding of the mechanisms of symbiosis: a comprehensive proteome map of a nascent insect symbiont

    Directory of Open Access Journals (Sweden)

    François Renoz

    2017-05-01

    Full Text Available Symbiotic bacteria are common in insects and can affect various aspects of their hosts’ biology. Although the effects of insect symbionts have been clarified for various insect symbiosis models, due to the difficulty of cultivating them in vitro, there is still limited knowledge available on the molecular features that drive symbiosis. Serratia symbiotica is one of the most common symbionts found in aphids. The recent findings of free-living strains that are considered as nascent partners of aphids provide the opportunity to examine the molecular mechanisms that a symbiont can deploy at the early stages of the symbiosis (i.e., symbiotic factors. In this work, a proteomic approach was used to establish a comprehensive proteome map of the free-living S. symbiotica strain CWBI-2.3T. Most of the 720 proteins identified are related to housekeeping or primary metabolism. Of these, 76 were identified as candidate proteins possibly promoting host colonization. Our results provide strong evidence that S. symbiotica CWBI-2.3T is well-armed for invading insect host tissues, and suggest that certain molecular features usually harbored by pathogenic bacteria are no longer present. This comprehensive proteome map provides a series of candidate genes for further studies to understand the molecular cross-talk between insects and symbiotic bacteria.

  15. Imaging of multi-step hepatocarcinogenesis. Imaging, pathophysiologic and molecular correlation

    International Nuclear Information System (INIS)

    Matsui, Osamu; Kitao, Azusa; Kobayashi, Satoshi

    2011-01-01

    For the diagnosis of early hepatocellular carcinoma (HCC), it is essential to understand the correlation between its pathophysiology and concomitant image changes during multi-step hepatocarcinogenesis (MS-HCG). For this, authors explain about the circulatory alteration inside/outside of the nodule at MS-HCG and its pathophysiologic base, and imaging mechanics of HCC in gadolinium ethoxybenzyl-diethylene-triamine-pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and its molecular base. Imaging diagnosis of early HCC has been difficult as the ordinary images only give the presence of dysplastic nodules (DN) while pathologic diagnosis can decide the disease with observed focus (or foci) of HCC within DN. The important diagnostic imaging involves CT during hepatic arteriography (CTHA) and CT during arterial portography (CTAP), which can show blood flow changes within and around DN along the progression of early to well/moderately differentiated HCC. That is, it has been shown that, with the progression of malignancy of DN in MS-HCG, the portal blood flow decreases to zero finally at the moderate phase, and arterial flow is once reduced, and due to angiogenesis, is increased to the far higher level than normal at well/moderate phases. Recently, Gd-EOB-DTPA enhanced MRI is suggested to be a useful imaging for HCC diagnosis as, not only blood flow imaging, but also the function of hepatocytes are evaluable with the agent. It is taken up in normal hepatocytes from sinusoidal blood via the organic anion transporting polypeptide (OATP) and excluded in bile via multidrug resistance associated protein 2 (Mrp2). Alteration of expression of the transporters in HCC can be reflected by the enhanced MRI. The circulatory alteration by CT detection around the nodule and Gd-EOB-DTPA enhanced MRI will be the most important imaging means of early HCC diagnosis. (T.T.)

  16. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

    Science.gov (United States)

    Keay, Susan K.; Birder, Lori A.; Chai, Toby C.

    2014-01-01

    Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC), feline interstitial cystitis (FIC), and nonneurogenic idiopathic overactive bladder (OAB). These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology. PMID:24900993

  17. Jaundice associated pruritis: a review of pathophysiology and treatment.

    Science.gov (United States)

    Bassari, Ramez; Koea, Jonathan B

    2015-02-07

    To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and clinicaltrials.gov for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective.

  18. Evidence for Bladder Urothelial Pathophysiology in Functional Bladder Disorders

    Directory of Open Access Journals (Sweden)

    Susan K. Keay

    2014-01-01

    Full Text Available Understanding of the role of urothelium in regulating bladder function is continuing to evolve. While the urothelium is thought to function primarily as a barrier for preventing injurious substances and microorganisms from gaining access to bladder stroma and upper urinary tract, studies indicate it may also function in cell signaling events relating to voiding function. This review highlights urothelial abnormalities in bladder pain syndrome/interstitial cystitis (BPS/IC, feline interstitial cystitis (FIC, and nonneurogenic idiopathic overactive bladder (OAB. These bladder conditions are typified by lower urinary tract symptoms including urinary frequency, urgency, urgency incontinence, nocturia, and bladder discomfort or pain. Urothelial tissues and cells from affected clinical subjects and asymptomatic controls have been compared for expression of proteins and mRNA. Animal models have also been used to probe urothelial responses to injuries of the urothelium, urethra, or central nervous system, and transgenic techniques are being used to test specific urothelial abnormalities on bladder function. BPS/IC, FIC, and OAB appear to share some common pathophysiology including increased purinergic, TRPV1, and muscarinic signaling, increased urothelial permeability, and aberrant urothelial differentiation. One challenge is to determine which of several abnormally regulated signaling pathways is most important for mediating bladder dysfunction in these syndromes, with a goal of treating these conditions by targeting specific pathophysiology.

  19. Pathophysiology, diagnosis, and treatment of canine hip dysplasia

    International Nuclear Information System (INIS)

    Cook, J.L.; Tomlinson, J.L.; Constantinescu, G.M.

    1996-01-01

    Dogs with hip dysplasia are commonly presented to veterinarians for evaluation. Although many causes of the condition have been proposed, a definitive cause has not been established. The multifactorial nature of canine hip dysplasia can confuse client education and management ofthe disease. The basic concept involved is the biomechanical imbalance between the forces on the coxofemoral joint and the associated muscle mass; the result is joint laxity in young, growing dogs. This laxity leads to incongruity; the eventual result is degenerative joint disease. Canine hip dysplasia can affect any breed but is most often reported in large and giant breeds. Understanding the pathophysiology and biomechanics involved with this developmental disease is important in providing clients with diagnostic, therapeutic, and prognostic information. The selection of treatment is influenced by the following factors:the age, health, and intended use of the patient; clinical signs; diagnostic findings; the availability of treatment; and the financial constraints of the owner. This article discusses the current concepts concerning the pathophysiology and biomechanics of canine hip dysplasia and outlines diagnostic and therapeutic options. The objective of the article is to provide practitioners with a reference for decision making and client education

  20. From genomes to metabolomes: Understanding mechanisms of symbiosis and cell-cell signaling using the archaeal system Ignicoccus-Nanoarchaeum

    Energy Technology Data Exchange (ETDEWEB)

    Podar, Mircea [Univ. of Tennessee, Knoxville, TN (United States). Biosciences Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hettich, Robert [Univ. of Tennessee, Knoxville, TN (United States). Biosciences Division; Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Copie, Valerie [Montana State Univ., Bozeman, MT (United States). Dept. of Chemistry and Biochemistry; Bothner, Brian [Montana State Univ., Bozeman, MT (United States). Dept. of Chemistry and Biochemistry

    2016-12-16

    The main objective of this project was to use symbiotic Nanoarchaeaota, a group of thermophilic Archaea that are obligate symbionts/parasites on other Archaea, to develop an integrated multi-omic approach to study inter-species interactions as well as to understand fundamental mechanism that enable such relationships. As part of this grant we have achieved a number of important milestone on both technical and scientific levels. On the technical side, we developed immunofluorescence labeling and tracking methods to follow Nanoarchaeota in cultures and in environmental samples, we applied such methods in conjunction with flow cytometry to quantify and isolate uncultured representatives from the environment and characterized them by single cell genomics. On the proteomics side, we developed a more efficient and sensitive method to recover and semi-quantitatively measure membrane proteins, while achieving high total cellular proteome coverage (70-80% of the predicted proteome). Metabolomic analyses used complementary NMR and LC/GC mass spectrometry and led to the identification of novel lipids in these organisms as well as quantification of some of the major metabolites. Importantly, using several informatics approaches we were also able to integrate the transcriptomic, proteomic and metabolomic datasets, revealing aspects of the interspecies interaction that were not evident in the single omic analyses (manuscript in review). On the science side we determined that N. equitans and I. hospitalis are metabolically coupled and that N. equitans is strictly dependent on its host both for metabolic precursors and energetic needs. The actual mechanism by which small molecules move across the cell membrane remains unknown. The Ignicoccus host responds to the metabolic and energetic burned by upregulating of key primary metabolism steps and ATP synthesis. The two species have co-evolved, aspect that we determined by comparative genomics with other species of Ignicoccus

  1. Mechanisms related to the pathophysiology and management of central hypothyroidism.

    Science.gov (United States)

    Yamada, Masanobu; Mori, Masatomo

    2008-12-01

    Central hypothyroidism (CH) is defined as hypothyroidism due to insufficient stimulation of the thyroid gland by TSH, for which secretion or activity can be impaired at the hypothalamic or pituitary levels. Patients with CH frequently present with multiple other pituitary hormone deficiencies. In addition to classic CH induced by hypothalamic-pituitary tumors or Sheehan syndrome, novel causes include traumatic brain injury or subarachnoid hemorrhage, bexarotene (a retinoid X receptor agonist) therapy, neonates being born to mothers with insufficiently controlled Graves disease, and lymphocytic hypophysitis. Growth hormone therapy, which may be used in children and adults, is now also recognized as a possible cause of unmasking CH in susceptible individuals. In addition, mutations in genes, such as TRHR, POU1F1, PROP1, HESX1, SOX3, LHX3, LHX4 and TSHB, have been associated with CH. The difficulty in making a clear diagnosis of CH is that the serum TSH levels can vary; values are normal in most cases, but in some might be low or slightly elevated. Levels of endogenous T(4) in serum might also be subnormal. Appropriate doses of levothyroxine for T(4) replacement therapy have not been confirmed, but might need to be higher than presently used empirically in patients with CH and should be adjusted according to age and other hormone deficiencies, to achieve free T(4) concentrations in the upper end of the normal range.

  2. Immunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Sven Francque

    2013-10-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue.

  3. Complement in immune and inflammatory disorders: pathophysiological mechanisms

    Science.gov (United States)

    Ricklin, Daniel; Lambris, John D.

    2013-01-01

    While acute or chronic inflammation is a common component of many clinical disorders, the underlying processes can be highly distinct. In recent years, the complement system has been associated with a growing number of immunological and inflammatory conditions that include degenerative diseases, cancer and transplant rejection. It becomes evident that excessive activation or insufficient control of complement activation on host cells can cause an immune imbalance that may fuel a vicious cycle between complement, inflammatory cells and tissue damage that exacerbates clinical complications. Although the exact involvement of complement needs to be carefully investigated for each disease, therapeutic modulation of complement activity emerges as attractive target for upstream inhibition of inflammatory processes. This review provides an update about the functional and collaborative capabilities of complement, highlights major disease areas with known complement contribution, and indicates the potential for complement as focal point in immunomodulatory strategies for treating inflammatory diseases. PMID:23564577

  4. Cytomegalovirus: pathophysiological mechanisms of the cytomegalovirus-induced cellular responses

    International Nuclear Information System (INIS)

    Nokta, M.A.

    1986-01-01

    Cytomegalovirus (CMV) infection of fibroblasts of human origin is associated with a cascade of morphologic cellular responses which in other systems have been associated with regulation of intracellular free (IF) [Ca ++ ]. In the present study, the relationship of specific ion fluxes (Ca ++ , Na + ) to the development of cytomegalovirus (CMV)-induced morphologic cellular responses was investigated. An influx of Ca ++ was observed by the first hour after CMV infection (PI), and total calcium sequestered by infected cells was enhanced by 5 hr Pl. A gradual rise in intracellular free (IF) [Ca ++ ] was observed that continued through 48 hour postinfection (hr Pl). The IF [Ca ++ ] response to CMV infection was shown to be multiplicity dependent, require viable virus, and occur under conditions consistent with the expression of immediate early CMV genes. Development and progression of cytomegaly was found to be independent of CMV DNA synthesis and appeared to be dependent on the IF [Ca ++ ] response. Ca ++ influx blockers (e.g. verapamil) and cyclic nucleotide modulators (e.g. papaverine) inhibited both Ca ++ responses and cytomegaly. Quabain-sensitive 86 Rb uptake and sequestering of Ca ++ increased in parallel with development of cytomegaly. There may be a relationship between Ca ++ influx, IF [Ca ++ ], activation of the Na + /H + exchanger, induction of Na + , Cl - , HCO 3 cotransport, Na + entry, Na + /K + ATPase activity and development of CMV-induced morphologic cellular responses including cytomegaly

  5. A Comprehensive Pathophysiology of Dandruff and Seborrheic Dermatitis - Towards a More Precise Definition of Scalp Health

    DEFF Research Database (Denmark)

    Schwartz, James R; Messenger, Andrew G; Tosti, Antonella

    2012-01-01

    Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published...

  6. Pathophysiology of placentation abnormalities in pregnancy-induced hypertension

    Directory of Open Access Journals (Sweden)

    Mitsuko Furuya

    2008-12-01

    Full Text Available Mitsuko Furuya1, Junji Ishida2,3, Ichiro Aoki1, Akiyoshi Fukamizu2,31Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; 2Graduate School of Life and Environmental Sciences; 3Center for Tsukuba Advanced Research Alliance (TARA, University of Tsukuba, Tsukuba 305-8577, JapanAbstract: During embryogenesis and development, the fetus obtains oxygen and nutrients from the mother through placental microcirculation. The placenta is a distinctive organ that develops and differentiates per se, and that organizes fetal growth and maternal condition in the entire course of gestation. Several life-threatening diseases during pregnancy, such as pregnancy-induced hypertension (PIH and eclampsia, are closely associated with placental dysfunction. Genetic susceptibilities and poor placentation have been investigated intensively to understand the pathophysiology of PIH. It is currently thought that “poor placentation hypothesis”, in which extravillous trophoblasts fail to invade sufficiently the placental bed, explains in part maternal predisposition to this disease. Cumulative studies have suggested that hypoxic micromilieu of fetoplacental site, shear stress of uteroplacental blood flow, and aberrantly secreted proinflammatory substances into maternal circulation synergistically contribute to the progression of PIH. For example, soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1 and soluble form of CD105 are elevated in circulation of PIH mothers. However, it remains to be poorly understood the pathological events in the placenta during the last half of gestation as maternal systemic disorders get worse. For better understanding and effective therapeutic approaches to PIH, it is important to clarify pathological course of PIH-associated changes in the placenta. In this review, current understanding of placental development and the pathophysiology of PIH placenta are summarized. In

  7. Involvement of tumor acidification in brain cancer pathophysiology

    Directory of Open Access Journals (Sweden)

    Avinash eHonasoge

    2013-11-01

    Full Text Available Gliomas, primary brain cancers, are characterized by remarkable invasiveness and fast growth. While they share many qualities with other solid tumors, gliomas have developed special mechanisms to convert the cramped brain space and other limitations afforded by the privileged central nervous system into pathophysiological advantages. In this review we discuss gliomas and other primary brain cancers in the context of acid-base regulation and interstitial acidification; namely, how the altered proton (H+ content surrounding these brain tumors influences tumor development in both autocrine and paracrine manners. As proton movement is directly coupled to movement of other ions, pH serves as both a regulator of cell activity as well as an indirect readout of other cellular functions. In the case of brain tumors, these processes result in pathophysiology unique to the central nervous system. We will highlight what is known about pH-sensitive processes in brain tumors in addition to gleaning insight from other solid tumors.

  8. Pathophysiology of X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Berger, J; Forss-Petter, S; Eichler, F S

    2014-03-01

    Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype-phenotype correlation in X-ALD. The default manifestation of mutations in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in childhood (35-40%) or in adulthood (20%), an initial, clinically silent, myelin destabilization results in conversion to a devastating, rapidly progressive form of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility gene, necessary but not sufficient for inflammatory demyelination to occur. Although the accumulation of very long-chain fatty acids appears to be essential for the pathomechanism of all phenotypes, the molecular mechanisms underlying these phenotypes are fundamentally different. Cell autonomous processes such as oxidative stress and energy shortage in axons as well as non-cell autonomous processes involving axon-glial interactions seem pertinent to the dying-back axonopathy. Various dynamic mechanisms may underlie the initiation of inflammation, the altered immune reactivity, the propagation of inflammation, as well as the mechanisms leading to the arrest of inflammation after hematopoietic stem cell transplantation. An improved understanding of the

  9. Pathophysiology of X-linked adrenoleukodystrophy☆

    Science.gov (United States)

    Berger, J.; Forss-Petter, S.; Eichler, F.S.

    2014-01-01

    Currently the molecular basis for the clinical heterogeneity of X-linked adrenoleukodystrophy (X-ALD) is poorly understood. The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype–phenotype correlation in X-ALD. The default manifestation of mutations in ABCD1 is adrenomyeloneuropathy, a slowly progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, a peripheral neuropathy. In about 60% of male X-ALD patients, either in childhood (35–40%) or in adulthood (20%), an initial, clinically silent, myelin destabilization results in conversion to a devastating, rapidly progressive form of cerebral inflammatory demyelination. Here, ABCD1 remains a susceptibility gene, necessary but not sufficient for inflammatory demyelination to occur. Although the accumulation of very long-chain fatty acids appears to be essential for the pathomechanism of all phenotypes, the molecular mechanisms underlying these phenotypes are fundamentally different. Cell autonomous processes such as oxidative stress and energy shortage in axons as well as non-cell autonomous processes involving axon–glial interactions seem pertinent to the dying-back axonopathy. Various dynamic mechanisms may underlie the initiation of inflammation, the altered immune reactivity, the propagation of inflammation, as well as the mechanisms leading to the arrest of inflammation after hematopoietic stem cell transplantation. An improved understanding of

  10. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  11. Pathophysiologic response to severe burn injury.

    Science.gov (United States)

    Jeschke, Marc G; Chinkes, David L; Finnerty, Celeste C; Kulp, Gabriela; Suman, Oscar E; Norbury, William B; Branski, Ludwik K; Gauglitz, Gerd G; Mlcak, Ronald P; Herndon, David N

    2008-09-01

    To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial. A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated. Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course. Average age was 8 +/- 0.2 years, and average burn size was 56 +/- 1% TBSA with 43 +/- 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (-0.05% +/- 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (-4.1% +/- 1.9%); P < 0.05. Patients lost 3% +/- 1% of their bone mineral content (BMC) and 2 +/- 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 +/- 0.2 infections and 17% sepsis. In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with

  12. Advances in the Evaluation of Respiratory Pathophysiology during Exercise in Chronic Lung Diseases

    Science.gov (United States)

    O'Donnell, Denis E.; Elbehairy, Amany F.; Berton, Danilo C.; Domnik, Nicolle J.; Neder, J. Alberto

    2017-01-01

    Dyspnea and exercise limitation are among the most common symptoms experienced by patients with various chronic lung diseases and are linked to poor quality of life. Our understanding of the source and nature of perceived respiratory discomfort and exercise intolerance in chronic lung diseases has increased substantially in recent years. These new mechanistic insights are the primary focus of the current review. Cardiopulmonary exercise testing (CPET) provides a unique opportunity to objectively evaluate the ability of the respiratory system to respond to imposed incremental physiological stress. In addition to measuring aerobic capacity and quantifying an individual's cardiac and ventilatory reserves, we have expanded the role of CPET to include evaluation of symptom intensity, together with a simple “non-invasive” assessment of relevant ventilatory control parameters and dynamic respiratory mechanics during standardized incremental tests to tolerance. This review explores the application of the new advances in the clinical evaluation of the pathophysiology of exercise intolerance in chronic obstructive pulmonary disease (COPD), chronic asthma, interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). We hope to demonstrate how this novel approach to CPET interpretation, which includes a quantification of activity-related dyspnea and evaluation of its underlying mechanisms, enhances our ability to meaningfully intervene to improve quality of life in these pathologically-distinct conditions. PMID:28275353

  13. The Pathophysiology and Treatment of Osteoporosis.

    Science.gov (United States)

    Drake, Matthew T; Clarke, Bart L; Lewiecki, E Michael

    2015-08-01

    The objectives of this article are to review the pathophysiology of bone loss associated with aging and to review current pharmacologic approaches for the treatment of osteoporosis. A literature search with PubMed was performed with the terms osteoporosis and pathophysiology and osteoporosis and treatment and limited to studies written in English that were published within the preceding 10 years. Given the large number of studies identified, we selectively reviewed those studies that contained primary data related to osteoporosis pathophysiology or osteoporosis pharmacologic treatments and references included within selected studies identified from abstract review. Published studies have consistently reported that osteoporosis in older adults is caused by an imbalance of bone resorption in excess of bone formation. The dominant factor leading to bone loss in older adults appears to be gonadal sex steroid deficiency, with multiple genetic and biochemical factors, such as vitamin D deficiency or hyperparathyroidism, that may accelerate bone loss. Conditions that adversely affect growth and development may limit development of peak bone mass and accelerate subsequent bone loss. Studies of bone microarchitecture have shown that trabecular bone loss begins in the third decade of life, before gonadal sex steroid deficiency develops, whereas cortical loss typically begins in the sixth decade, about the time of menopause in women and about the same age in men. Antiresorptive agents for the treatment of osteoporosis act primarily by limiting osteoclast activity, whereas osteoanabolic agents, such as teriparatide, act primarily by stimulating osteoblastic bone formation. Clinical investigation of new compounds for the treatment of osteoporosis is mainly directed to those that stimulate bone formation or differentially decrease bone resorption more than bone formation. Therapies for osteoporosis are associated with adverse effects, but in patients at high risk of fracture

  14. Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.

    Science.gov (United States)

    Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E

    2017-06-01

    Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

  15. Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Saito, Hiroyuki

    2018-01-01

    Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Application of isotope exchange based mass spectrometry to understand the mechanism of inhibition of sickle hemoglobin polymerization upon oxygenation.

    Science.gov (United States)

    Das, Rajdeep; Mitra, Amrita; Bhat, Vijay; Mandal, Amit Kumar

    2017-07-01

    Sickle hemoglobin (HbS) polymerization initiates in the deoxy state with the binding of hydrophobic patch formed by the isopropyl group of βVal6 residue of a hemoglobin tetramer with the hydrophobic pocket of another tetramer, whose hydrophobic patch binds to the hydrophobic groove of a third molecule. Subsequent elongation of a single stranded polymer followed by the formation of a double strand and finally combination of seven such pairs of double strands results in a fourteen stranded fibrous polymer. Precipitation of this fiber inside the erythrocytes results in sickling of red blood cells. Surprisingly, the polymerization does not occur in the oxy state of HbS. Due to the unavailability of crystal structure of oxy form of HbS, the molecular basis of inhibition of polymerization in the oxy state is unknown to date. In the present study, we have attempted to understand the molecular mechanism of inhibition of polymerization by exploiting the exchange of backbone amide hydrogens of HbS with deuterated solvent. Hydrogen/deuterium exchange kinetics of peptide amide hydrogens of both oxy and deoxy form of HbS were monitored through ESI mass spectrometry. Upon oxygenation changes in the conformational flexibility across different regions of α and β globin chains in the tetrameric HbS molecule were investigated. It was observed that oxygenation led to perturbation in the conformation of several residues around the hydrophobic patch, groove of a tetramer and axial, lateral contacts across the double strands that are involved in HbS polymerization. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Understanding the undelaying mechanism of HA-subtyping in the level of physic-chemical characteristics of protein.

    Science.gov (United States)

    Ebrahimi, Mansour; Aghagolzadeh, Parisa; Shamabadi, Narges; Tahmasebi, Ahmad; Alsharifi, Mohammed; Adelson, David L; Hemmatzadeh, Farhid; Ebrahimie, Esmaeil

    2014-01-01

    The evolution of the influenza A virus to increase its host range is a major concern worldwide. Molecular mechanisms of increasing host range are largely unknown. Influenza surface proteins play determining roles in reorganization of host-sialic acid receptors and host range. In an attempt to uncover the physic-chemical attributes which govern HA subtyping, we performed a large scale functional analysis of over 7000 sequences of 16 different HA subtypes. Large number (896) of physic-chemical protein characteristics were calculated for each HA sequence. Then, 10 different attribute weighting algorithms were used to find the key characteristics distinguishing HA subtypes. Furthermore, to discover machine leaning models which can predict HA subtypes, various Decision Tree, Support Vector Machine, Naïve Bayes, and Neural Network models were trained on calculated protein characteristics dataset as well as 10 trimmed datasets generated by attribute weighting algorithms. The prediction accuracies of the machine learning methods were evaluated by 10-fold cross validation. The results highlighted the frequency of Gln (selected by 80% of attribute weighting algorithms), percentage/frequency of Tyr, percentage of Cys, and frequencies of Try and Glu (selected by 70% of attribute weighting algorithms) as the key features that are associated with HA subtyping. Random Forest tree induction algorithm and RBF kernel function of SVM (scaled by grid search) showed high accuracy of 98% in clustering and predicting HA subtypes based on protein attributes. Decision tree models were successful in monitoring the short mutation/reassortment paths by which influenza virus can gain the key protein structure of another HA subtype and increase its host range in a short period of time with less energy consumption. Extracting and mining a large number of amino acid attributes of HA subtypes of influenza A virus through supervised algorithms represent a new avenue for understanding and

  18. Use of rheometry and {sup 1}H NMR spectroscopy for understanding the mechanisms behind the generation of coking pressure

    Energy Technology Data Exchange (ETDEWEB)

    Karen M. Steel; Miguel Castro Diaz; John W. Patrick; Colin E. Snape [Nottingham University, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre, School of Chemical, Environmental and Mining Engineering

    2004-10-01

    The fluid phase which forms during carbonization of a range of coals was studied using rheometry and {sup 1}H NMR spectroscopy to study the mechanisms behind the generation of excessive wall pressures during coking. It is proposed that high coking pressures are generated for low volatile matter coals when the temperature of maximum fluidity (T{sub mf}) is {gt} 465{degree}C, the minimum complex viscosity ({eta}{asterisk}) is {gt} 10{sup 5} Pa s, the percentage of mobile 1H (fluid phase) is {lt} 40%, and the {sup 1}H mobility in the fluid phase is {lt} 65 {mu}s. It is suggested for these coals that the particles fuse to form a rigid network containing pockets of fluid material which have a low fluidity and do not link up. This arrangement could present an impermeable barrier for gas flow and force the gas to the coal side where it builds up in a diminishing region to a critical level, causing pressure on the walls. The magnitude of the pressure generated may be proportional to T{sub mf} and {eta}{asterisk} and inversely proportional to the percentage and mobility of mobile {sup 1}H. It was also found that a high volatile coal which formed a highly fluid phase over a broad temperature range gave rise to a significant coking pressure. In this case, it is proposed that the sheer expansion of the coal charge as it converts to gas and liquid phases is the reason for pressure on the oven walls. These proposals agree with current thinking on the generation of coking pressure. This work is based on the testing of only nine samples and further work is planned to gain a greater fundamental understanding of fluidity development from which models for predicting coking pressure and coke quality for coal blends may be developed. 20 refs., 10 figs., 5 tabs.

  19. Understanding the undelaying mechanism of HA-subtyping in the level of physic-chemical characteristics of protein.

    Directory of Open Access Journals (Sweden)

    Mansour Ebrahimi

    Full Text Available The evolution of the influenza A virus to increase its host range is a major concern worldwide. Molecular mechanisms of increasing host range are largely unknown. Influenza surface proteins play determining roles in reorganization of host-sialic acid receptors and host range. In an attempt to uncover the physic-chemical attributes which govern HA subtyping, we performed a large scale functional analysis of over 7000 sequences of 16 different HA subtypes. Large number (896 of physic-chemical protein characteristics were calculated for each HA sequence. Then, 10 different attribute weighting algorithms were used to find the key characteristics distinguishing HA subtypes. Furthermore, to discover machine leaning models which can predict HA subtypes, various Decision Tree, Support Vector Machine, Naïve Bayes, and Neural Network models were trained on calculated protein characteristics dataset as well as 10 trimmed datasets generated by attribute weighting algorithms. The prediction accuracies of the machine learning methods were evaluated by 10-fold cross validation. The results highlighted the frequency of Gln (selected by 80% of attribute weighting algorithms, percentage/frequency of Tyr, percentage of Cys, and frequencies of Try and Glu (selected by 70% of attribute weighting algorithms as the key features that are associated with HA subtyping. Random Forest tree induction algorithm and RBF kernel function of SVM (scaled by grid search showed high accuracy of 98% in clustering and predicting HA subtypes based on protein attributes. Decision tree models were successful in monitoring the short mutation/reassortment paths by which influenza virus can gain the key protein structure of another HA subtype and increase its host range in a short period of time with less energy consumption. Extracting and mining a large number of amino acid attributes of HA subtypes of influenza A virus through supervised algorithms represent a new avenue for

  20. 95thAnniversary of Pathophysiology in Croatia.

    Science.gov (United States)

    Kovač, Zdenko

    2017-12-01

    lasting legacy on generations to come. Professor Stjepan Gamulin made molecular medicine the working reality at Rebro. Both in clinical research, and in health system as diagnostic service and tool for all centers in Croatia, molecular measurement in tissue samples came into usage in daily physicians reasoning and therapy prescriptions. Macromolecular aspects of disease have come of age and became clinimetric signs of patients' condition. Professor Gamulin with his group and associated authors wrote the textbook of pathophysiology, which in upcoming 30 years had 7 editions, has become the bestseller in medicine. The textbook was translated and published in English and Albanian. In the most recent book professor Gamulin turned the focus of medical community to clinical epidemiology and a need for retrospective insights into medical efficiency. Medical performance can be improved with the improvement of understanding of underlying etiopathogenetic relations as the foundation of therapy-is the main message. Following the academic legacy and spirit of three charismatic authorities we established two methods of teaching/learning in medicine. The two methods opened up a new avenue, so important for the era of postgenomic plethora of information and demands of precision/personalized medicine. Methodology has been introduced timely. It is student-friendly and usable for advanced types of education. Problem based algorhytmic matrices stimulate analysis and resynthesis of etiopathogenetic pathways. Graphic presentation of the solution integrates horizontal, vertical and longitudinal aspects of the problem. The companion textbook in the form of problem solver has been published in 3 editions, and contains 128 study solved cases. It was published in English, as well. Out of algorhythmic analysis the etiopathogenetic clusters (EPCs) are composed of etiopathogenetic pathway analysis. EPCs are natural units of disease development, the crossing points of processes. They are integrative

  1. Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

    Science.gov (United States)

    Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

    2014-06-28

    Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

  2. Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee.

    Science.gov (United States)

    Gallo, Richard L; Granstein, Richard D; Kang, Sewon; Mannis, Mark; Steinhoff, Martin; Tan, Jerry; Thiboutot, Diane

    2018-01-01

    In 2002, the National Rosacea Society assembled an expert committee to develop the first standard classification of rosacea. This original classification was intended to be updated as scientific knowledge and clinical experience increased. Over the last 15 years, significant new insights into rosacea's pathogenesis and pathophysiology have emerged, and the disorder is now widely addressed in clinical practice. Growing knowledge of rosacea's pathophysiology has established that a consistent multivariate disease process underlies the various clinical manifestations of this disorder, and the clinical significance of each of these elements is increasing as more is understood. This review proposes an updated standard classification of rosacea that is based on phenotypes linked to our increased understanding of disease pathophysiology. This updated classification is intended to provide clearer parameters to conduct investigations, guide diagnosis, and improve treatment. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  3. Sexual and gonadal dysfunction in chronic kidney disease: Pathophysiology

    Directory of Open Access Journals (Sweden)

    Manish Rathi

    2012-01-01

    Full Text Available Sexual and gonadal dysfunction/infertility are quite common in patients with chronic kidney disease. Forty percent of male and 55% of female dialysis patients do not achieve orgasm. The pathophysiology of gonadal dysfunction is multifactorial. It is usually a combination of psychological, physiological, and other comorbid factors. Erectile dysfunction in males is mainly due to arterial factors, venous leakage, psychological factors, neurogenic factors, endocrine factors, and drugs. Sexual dysfunction in females is mainly due to hormonal factors and manifests mainly as menstrual irregularities, amenorrhea, lack of vaginal lubrication, and failure to conceive. Treatment of gonadal dysfunction in chronic kidney disease is multipronged and an exact understanding of underlying pathology is essential in proper management of these patients.

  4. Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology?

    Directory of Open Access Journals (Sweden)

    Anne Marie Morse

    2018-02-01

    Full Text Available Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to the protracted time to accurate diagnosis and treatment. Narcolepsy is a disabling neurodegenerative condition that carries a high risk for development of social and occupational dysfunction. Deterioration in function may lead to the secondary development of psychiatric symptoms. Inversely, the development of psychiatric symptoms can lead to the deterioration in function and quality of life. The overlap in pharmaceutical intervention may further enhance the difficulty to distinguish between diagnoses. Comprehensive care for patients with narcolepsy should include surveillance for psychiatric illness and appropriate treatment when necessary. Further research is necessary to better understand the underlying pathophysiology between psychiatric disease and narcolepsy.

  5. Pathophysiology, evaluation, and management of sleep disorders in the mucopolysaccharidoses.

    Science.gov (United States)

    Rapoport, David M; Mitchell, John J

    2017-12-01

    The mucopolysaccharidoses (MPS) represent a heterogeneous group of lysosomal storage disorders, each one associated with a deficiency in one of the enzymes involved in glycosaminoglycan degradation. Sleep disorders are a frequent manifestation of all types of MPS. Underlying causes are diverse and comprised of both respiratory and central nervous system (CNS) abnormalities. Sleep disordered breathing such as obstructive sleep apnea and nocturnal hypoventilation can arise in patients with upper airway obstruction and/or with alterations in respiratory mechanics, causing restrictive pulmonary disease. MPS patients with CNS disease can also develop sleep disturbances unrelated to ventilatory impairments, often associated with severe behavioral problems or night-time epileptic seizures. The present review discusses the pathophysiology, evaluation, and management of sleep disorders in MPS based on information from a meeting on the brain in MPS, attended by an international group of experts (April 28-30, 2016, Stockholm, Sweden), and additional literature searches. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Main theoretical, pathophysiological and practical aspects of neuroplasticity

    Directory of Open Access Journals (Sweden)

    Pogorelov А.V.

    2017-04-01

    Full Text Available Results of the state-of-the-art review of the "neuroplasticity" term development and new data about the sanogenetic, pathophysiological, neurophysiological, bio - and neurochemical bases of the nervous system recovery processes are given in this article. Key mechanisms of adaptive, desadaptive, responsive and cross modal forms of neuroplasticity within primary and secondary neuroplasticity are distinguished. The specific character of neurogenesis and functional reorganization of neuronets in specific regulatory structures of the brain in the norm and pathogenesis are outlined. Controversies about functional and morphological aspects of neuroplastic processes are presented. Application-oriented methods of neuroplasticity study are considered and systemically classified. Clinical diagnostics with the specified neu­rovisualization, neurochemical, neurophysiological criteria and coefficients is considered also. Specific methods of neurorehabilitation and perspective urgent directions of neuro- sanogenesis are designated using physical, reflex, neuropsychological, behavioural brain stimulation methods and pharmacological therapy.

  7. Obesity-Related Digestive Diseases and Their Pathophysiology.

    Science.gov (United States)

    Nam, Su Youn

    2017-05-15

    Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects.

  8. Pathology and pathophysiology of pulmonary manifestations in leptospirosis

    Directory of Open Access Journals (Sweden)

    Marisa Dolhnikoff

    Full Text Available Leptospirosis is a re-emerging zoonosis occurring as large outbreaks throughout the world caused by Leptospira interrogans. The incidence of pulmonary involvement in leptospirosis has been reported to be increasing in the last years, affecting up to 70% of the patients. Alveolar hemorrhage presented as dyspnea and hemoptysis is the main pulmonary manifestation. The emergence of massive hemoptysis and acute respiratory distress syndrome has characterized the recent changes reported in the clinical patterns of leptospirosis. The pulmonary involvement has been emerged as a serious life threat, becoming the main cause of death due to leptospirosis in some countries. In this review we present the main clinical and pathological manifestations of pulmonary involvement in leptospirosis, with special focus on recent data concerning the pathophysiological mechanisms underlying lung injury.

  9. Proteomics studies in inner ear disorders: pathophysiology and biomarkers.

    Science.gov (United States)

    Alawieh, Ali; Mondello, Stefania; Kobeissy, Firas; Shibbani, Kamel; Bassim, Marc

    2015-04-01

    Although proteomics has been exploited in a wide range of diseases for identification of biomarkers and pathophysiological mechanisms, there are still biomedical disciplines such as otology where proteomics platforms are underused due to technical challenges and/or complex features of the disease. Thus, in the past few years, healthcare and scientific agencies have advocated the development and adoption of proteomic technologies in otological research. However, few studies have been conducted and limited literature is available in this area. Here, we present the state of the art of proteomics in otology, discussing the substantial evidence from recent experimental models and clinical studies in inner-ear conditions. We also delineate a series of critical issues including minute size of the inner ear, delicacy and poor accessibility of tissue that researchers face while undertaking otology proteomics research. Furthermore, we provide perspective to enhance the impact and lead to the clinical implementation of these proteomics-based strategies.

  10. NEMS Oscillators as Sensors and Actuators: Understanding the Mechanical Properties of Nanoresonators and Their Applications for Molecular Sensing

    Data.gov (United States)

    National Aeronautics and Space Administration — Development of nanotechnology and enhancement of nanostructures for future applications requires a good understanding of a material's behavior at the nanoscale, as...

  11. Frontiers in the bioarchaeology of stress and disease: cross-disciplinary perspectives from pathophysiology, human biology, and epidemiology.

    Science.gov (United States)

    Klaus, Haagen D

    2014-10-01

    Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science. Copyright © 2014 Wiley Periodicals, Inc.

  12. The bitter barricading of prostaglandin biosynthesis pathway: understanding the molecular mechanism of selective cyclooxygenase-2 inhibition by amarogentin, a secoiridoid glycoside from Swertia chirayita.

    Directory of Open Access Journals (Sweden)

    Shantanu Shukla

    Full Text Available Swertia chirayita, a medicinal herb inhabiting the challenging terrains and high altitudes of the Himalayas, is a rich source of essential phytochemical isolates. Amarogentin, a bitter secoiridoid glycoside from S. chirayita, shows varied activity in several patho-physiological conditions, predominantly in leishmaniasis and carcinogenesis. Experimental analysis has revealed that amarogentin downregulates the cyclooxygenase-2 (COX-2 activity and helps to curtail skin carcinogenesis in mouse models; however, there exists no account on selective inhibition of the inducible cyclooxygenase (COX isoform by amarogentin. Hence the computer-aided drug discovery methods were used to unravel the COX-2 inhibitory mechanism of amarogentin and to check its selectivity for the inducible isoform over the constitutive one. The generated theoretical models of both isoforms were subjected to molecular docking analysis with amarogentin and twenty-one other Food and Drug Authority (FDA approved lead molecules. The post-docking binding energy profile of amarogentin was comparable to the binding energy profiles of the FDA approved selective COX-2 inhibitors. Subsequent molecular dynamics simulation analysis delineated the difference in the stability of both complexes, with amarogentin-COX-2 complex being more stable after 40ns simulation. The total binding free energy calculated by MMGBSA for the amarogentin-COX-2 complex was -52.35 KCal/mol against a binding free energy of -8.57 KCal/mol for amarogentin-COX-1 complex, suggesting a possible selective inhibition of the COX-2 protein by the natural inhibitor. Amarogentin achieves this potential selectivity by small, yet significant, structural differences inherent to the binding cavities of the two isoforms. Hypothetically, it might block the entry of the natural substrates in the hydrophobic binding channel of the COX-2, inhibiting the cyclooxygenation step. To sum up briefly, this work highlights the mechanism of the

  13. Pathophysiology of septic shock: From bench to bedside.

    Science.gov (United States)

    McConnell, Kevin W; Coopersmith, Craig M

    2016-04-01

    Our understanding of sepsis and its resultant outcomes remains a paradox. On the one hand, we know more about the pathophysiology of sepsis than ever before. However, this knowledge has not been successfully translated to the bedside, as the vast majority of clinical trials for sepsis have been negative. Yet even in the general absence of positive clinical trials, mortality from sepsis has fallen to its lowest point in history, in large part due to educational campaigns that stress timely antibiotics and hemodynamic support. While additional improvements in outcome will assuredly result from further compliance with evidence based practices, a deeper understanding of the science that underlies the host response in sepsis is critical to the development of novel therapeutics. In this review, we outline immunopathologic abnormalities in sepsis, and then look at potential approaches to therapeutically modulate them. Ultimately, an understanding of the science underlying sepsis should allow the critical care community to utilize precision medicine to combat this devastating disease on an individual basis leading to improved outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Quantum Interactive Learning Tutorial on the Double-Slit Experiment to Improve Student Understanding of Quantum Mechanics

    Science.gov (United States)

    Sayer, Ryan; Maries, Alexandru; Singh, Chandralekha

    2017-01-01

    Learning quantum mechanics is challenging, even for upper-level undergraduate and graduate students. Research-validated interactive tutorials that build on students' prior knowledge can be useful tools to enhance student learning. We have been investigating student difficulties with quantum mechanics pertaining to the double-slit experiment in…

  15. Pathophysiological implications of the chemical messengers

    International Nuclear Information System (INIS)

    Blazquez Fernandez, E.

    2009-01-01

    To maintain a physical organization and a different composition of its surroundings environment, living beings use a great part of the energy that they produce. Vital processes require an elevated number of reactions which are regulated and integrated by chemical messengers. They use autocrine, paracrine, endocrine and synaptic signals through receptors of cell surface, nuclear or associated with ionic channels, enzymes, trim eric G proteins and to intracellular kinases. Through these mechanisms pheromones play an important role in the relationships between different individuals, and hormones are able to regulate the integrative functions of our organism. In the nervous system, neurotransmitters, neuromodulators, sensors and receptors between other messengers, play functions of great relevance, while growth factors stimulate cell proliferation and cytokines have many effects but the most important is the ones related with the control of the immflamatory process. Alterations of these messengers permit us a better understanding of the diseases and possibly of its treatments in a near future. Modifications of the expression of genes from the nuclear and mitochondrial genomes are responsible of monogenic, polygenic and mitochondrial diseases, while alterations in the activities of dopamine and serotonin neurotransmitters are related with schizophrenia, Parkinson disease and depression, respectively. Other example is the hyperthyroidism of the Graves-Bassedow disease due to the competitive interference of the LATS immunoglobulin with TSH at the level of the follicular cells producing thyroid hormones Twenty five years ago in the reviews on the mechanisms of insulin action, there was presentations in which the insulin receptor was located in the plasma membrane of the target cells while in the cytoplasm only a big interrogative was observed, that at present is replaced by chemical mediators cascades responsible of the multiple effects of insulin. This finding is similar

  16. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    obvious targets for therapy. These cysteinyl leukotrienes, previously known as the slow-reacting substance of anaphylaxis (SRS-A), mediate many of the features of asthma, including bronchial constriction, bronchial hyperreactivity, edema, and eosinophilia. Data show that selective cysteinyl leukotriene......Inflammation is an essential component of asthma pathophysiology. While beta(2)-agonists are often used for short-term relief of acute bronchospasm, anti-inflammatory agents are required for the long-term management of chronic inflammation in this disease. Corticosteroids have emerged as the first......-line anti-inflammatory therapy for asthma management. However, in some patients, especially children, the high doses of corticosteroids that may be required to control features of hyperresponsiveness, including exercise-induced asthma, raise safety concerns. Thus, there is a need for complementary anti...

  17. [Pathophysiology of myopia: nature versus nurture].

    Science.gov (United States)

    Cassagne, M; Malecaze, F; Soler, V

    2014-05-01

    Myopia is the most frequent refractive disorder in the world. It has become a real Public Health problem, due to its frequency and to high myopia-related blinding complications. Myopic progression depends on genetic and environmental factors. Genetic studies have identified more than forty candidate genes that take part in pathophysiological pathways, from retinal phototransduction to axial lengthening via scleral remodelling. Environmental factors also influence scleral remodelling by way of visual perception. In the case of predominant attention to near tasks, a physiological feedback loop leads to axial growth. This phenomenon, called active emmetropization, is particularly obvious in animal models and in some human populations. To date, research has failed to identify a molecule common to all the implicated metabolic pathways which could be a target for an effective preventive treatment against myopic progression. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Somnambulism: clinical aspects and pathophysiological hypotheses.

    Science.gov (United States)

    Zadra, Antonio; Desautels, Alex; Petit, Dominique; Montplaisir, Jacques

    2013-03-01

    Somnambulism, or sleepwalking, can give rise to a wide range of adverse consequences and is one of the leading causes of sleep-related injury. Accurate diagnosis is crucial for proper management and imperative in an ever-increasing number of medicolegal cases implicating sleep-related violence. Unfortunately, several widely held views of sleepwalking are characterised by key misconceptions, and some established diagnostic criteria are inconsistent with research findings. The traditional idea of somnambulism as a disorder of arousal might be too restrictive and a comprehensive view should include the idea of simultaneous interplay between states of sleep and wakefulness. Abnormal sleep physiology, state dissociation, and genetic factors might explain the pathophysiology of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Pathophysiology and Current Clinical Management of Preeclampsia.

    Science.gov (United States)

    Amaral, Lorena M; Wallace, Kedra; Owens, Michelle; LaMarca, Babbette

    2017-08-01

    Preeclampsia is characterized by blood pressure greater than 140/90 mmHg in the second half of pregnancy. This disease is a major contributor to preterm and low birth weight babies. The early delivery of the baby, which becomes necessary for maintaining maternal well-being, makes preeclampsia the leading cause for preterm labor and infant mortality and morbidity. Currently, there is no cure for this pregnancy disorder. The current clinical management of PE is hydralazine with labetalol and magnesium sulfate to slow disease progression and prevent maternal seizure, and hopefully prolong the pregnancy. This review will highlight factors implicated in the pathophysiology of preeclampsia and current treatments for the management of this disease.

  20. Atypical odontalgia - pathophysiology and clinical management.

    Science.gov (United States)

    Baad-Hansen, L

    2008-01-01

    Atypical odontalgia (AO) is a chronic form of dental pain without signs of pathology. Several hypotheses have been put forward regarding the pathophysiology. AO has been proposed to be psychogenic, vascular, neuropathic or idiopathic. The scientific evidence supporting or rejecting these hypotheses are reviewed in this paper. At this time, the best supported hypothesis is that AO is a neuropathic pain condition. Relevant differential diagnoses, such as odontogenic pain, sinusitis, trigeminal neuralgia among others, are presented and the evidence regarding possible management strategies is reviewed. A treatment algorithm for AO is proposed based on the rather scarce scientific evidence available and inspired by a similar treatment algorithm for peripheral neuropathic pain. The proposed strategy involves an interdisciplinary approach including patient education, psychological counselling, topical and systemic medication and, importantly, avoidance of invasive treatments like surgery and endodontics. Two illustrative cases are presented.

  1. The role of ADAMs in disease pathophysiology.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    The ADAMs are a family of multidomain transmembrane and secreted proteins involved in both proteolysis and cell adhesion. Altered expression of specific ADAMs is implicated in the pathophysiology of several diseases including rheumatoid arthritis, Alzheimer\\'s disease, cardiac hypertrophy, asthma and cancer. Of these different diseases, it is in cancer where most research has been carried out. Multiple ADAMs, including ADAM-9, ADAM-10, ADAM-12, ADAM-15 and ADAM-17, have been shown to play a role in either cancer formation or progression. Consistent with these findings, increased expression of specific ADAMs in several cancer types was found to correlate with features of aggressive disease and poor prognosis. Currently, selective ADAM inhibitors against ADAM-10 and ADAM-17 are undergoing clinical trials for the treatment of cancer. Further work is required in order to establish a causative role for ADAMs in rheumatoid arthritis, Alzheimer\\'s disease, cardiac hypertrophy and asthma.

  2. Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

    Science.gov (United States)

    Robinson, Shenandoah

    2013-01-01

    Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is

  3. Circadian molecular clock in lung pathophysiology

    Science.gov (United States)

    Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.

    2015-01-01

    Disrupted daily or circadian rhythms of lung function and inflammatory responses are common features of chronic airway diseases. At the molecular level these circadian rhythms depend on the activity of an autoregulatory feedback loop oscillator of clock gene transcription factors, including the BMAL1:CLOCK activator complex and the repressors PERIOD and CRYPTOCHROME. The key nuclear receptors and transcription factors REV-ERBα and RORα regulate Bmal1 expression and provide stability to the oscillator. Circadian clock dysfunction is implicated in both immune and inflammatory responses to environmental, inflammatory, and infectious agents. Molecular clock function is altered by exposomes, tobacco smoke, lipopolysaccharide, hyperoxia, allergens, bleomycin, as well as bacterial and viral infections. The deacetylase Sirtuin 1 (SIRT1) regulates the timing of the clock through acetylation of BMAL1 and PER2 and controls the clock-dependent functions, which can also be affected by environmental stressors. Environmental agents and redox modulation may alter the levels of REV-ERBα and RORα in lung tissue in association with a heightened DNA damage response, cellular senescence, and inflammation. A reciprocal relationship exists between the molecular clock and immune/inflammatory responses in the lungs. Molecular clock function in lung cells may be used as a biomarker of disease severity and exacerbations or for assessing the efficacy of chronotherapy for disease management. Here, we provide a comprehensive overview of clock-controlled cellular and molecular functions in the lungs and highlight the repercussions of clock disruption on the pathophysiology of chronic airway diseases and their exacerbations. Furthermore, we highlight the potential for the molecular clock as a novel chronopharmacological target for the management of lung pathophysiology. PMID:26361874

  4. Spectrum of Visual Impairment in Cerebral Venous Thrombosis: Importance of Tailoring Therapies Based on Pathophysiology.

    Science.gov (United States)

    Aaron, Sanjith; Arthur, Anupriya; Prabakhar, A T; Mannam, Pavitra; Shyamkumar, N K; Mani, Sunithi; Mathew, Vivek; Peter, Jeyanthi; Sivadasan, Ajith; Alexander, Anika; Karthik, M; Benjamin, Rohith Ninan; Alexander, Mathew

    2017-01-01

    Visual impairment can complicate cerebral venous thrombosis (CVT). Here, we describe the various pathophysiological mechanisms and treatments available. A retrospective chart review of all patients treated for CVT in a large quaternary teaching hospital was done, and cases with visual impairment due to CVT were identified. The various mechanisms causing visual impairment in CVT were (1) raised intracranial pressure (ICP) caused by venous thrombosis without venous infarcts resulting in a benign intracranial hypertension-like presentation of CVT, (2) venous infarcts involving the occipital cortex, (3) raised ICP following the development of a secondary dural arteriovenous (AV) fistula, and (4) arterial occipital infarcts due to posterior cerebral artery compression secondary to herniation in large venous infarcts. Apart from using systemic anticoagulants to attempt recanalization and drugs with carbonic anhydrase inhibitor activity to reduce the ICPs, treatment modalities employed to save vision were (1) recanalization by local thrombolysis, stenting, or mechanical devices; (2) cerebrospinal fluid diversion procedures such as theco-periotoneal shunting; (3) optic nerve sheath fenestration; and (4) specific treatment for conditions such as dural AV fistula occurring as a late complication. CVT can cause visual impairment through different pathophysiological mechanisms. Depending on the mechanism, treatment strategies need to be tailored. Furthermore, very close monitoring is needed both in the acute and in the follow-up period, as new pathophysiological mechanisms can arise, compromising the vision. This may require a different treatment approach. Literature on this aspect of CVT is lacking.

  5. Addressing the Don't Ask, Don't Tell Practice in Observational Studies: Using Interviews to Understand the Assignment Mechanism

    Science.gov (United States)

    Rickles, Jordan H.

    2010-01-01

    This paper illustrates how information collected through interviews can develop a richer understanding of the assignment mechanism, which can result in more plausible causal effect estimates from observational studies and provides a roadmap for sensitivity analysis. Focusing on the issue of assignment to algebra in 8th grade, the author shows how…

  6. Biophysics, Pathophysiology and Pharmacology of Ion Channel Gating Pores

    Directory of Open Access Journals (Sweden)

    Adrien eMoreau

    2014-04-01

    Full Text Available Voltage sensor domain (VSDs are a feature of voltage gated ion channel (VGICs and voltage sensitive proteins. They are composed of four transmembrane (TM segments (S1 to S4. Currents leaking through VSDs are called omega or gating pore currents.Gating pores are caused by mutations of the highly conserved positively charged amino acids in the S4 segment that disrupt interactions between the S4 segment and the gating charge transfer center (GCTC. The GCTC separates the intracellular and extracellular water crevices. The disruption of S4–GCTC interactions allows these crevices to communicate and create a fast activating and non-inactivating alternative cation-selective permeation pathway of low conductance, or a gating pore.Gating pore currents have recently been shown to cause periodic paralysis phenotypes. There is also increasing evidence that gating pores are linked to several other familial diseases. For example, gating pores in Nav1.5 and Kv7.2 channels may underlie mixed arrhythmias associated with dilated cardiomyopathy (DCM phenotypes and peripheral nerve hyperexcitability (PNH respectively. There is little evidence for the existence of gating pore blockers. Moreover, it is known that a number of toxins bind to the VSD of a specific domain of Na+ channels. These toxins may thus modulate gating pore currents. This focus on the VSD motif opens up a new area of research centered on developing molecules to treat a number of cell excitability disorders such as epilepsy, cardiac arrhythmias, and pain.The purpose of the present review is to summarize existing knowledge of the pathophysiology, biophysics, and pharmacology of gating pore currents and to serve as a guide for future studies aimed at improving our understanding of gating pores and their pathophysiological roles.

  7. Stress corrosion cracking of alloy 600 in water at high temperature: contribution to a phenomenological approach to the understanding of mechanisms

    International Nuclear Information System (INIS)

    Abadie, Pascale

    1998-01-01

    This research thesis aims at being a contribution to the understanding of mechanisms of stress corrosion cracking of an alloy 600 in water at high temperature. More precisely, it aimed at determining, by using quantitative data characterizing cracking phenomenology, which mechanism(s) is (are) able to explain crack initiation and crack growth. These data concern quantitative characterization of crack initiation, of crack growth and of the influence of two cracking parameters (strain rate, medium hydrogen content). They have been obtained by quantifying cracking through the application of a morphological model. More precisely, these data are: evolution of crack density during a tensile test at slow rate, value of initial crack width with respect to grain boundary length, and relationship between crack density and medium hydrogen content. It appears that hydrogen absorption seems to be involved in the crack initiation mechanism. Crack growth mechanisms and crack growth rates are also discussed [fr

  8. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective.

    Science.gov (United States)

    Zaccardi, Francesco; Webb, David R; Yates, Thomas; Davies, Melanie J

    2016-02-01

    Diabetes mellitus is a complex metabolic disorder associated with an increased risk of microvascular and macrovascular disease; its main clinical characteristic is hyperglycaemia. The last century has been characterised by remarkable advances in our understanding of the mechanisms leading to hyperglycaemia. The central role of insulin in glucose metabolism regulation was clearly demonstrated during the early 1920s, when Banting, Best, Collip and Macleod successfully reduced blood glucose levels and glycosuria in a patient treated with a substance purified from bovine pancreata. Later, during the mid-1930s, clinical observations suggested a possible distinction between 'insulin-sensitive' and 'insulin-insensitive' diabetes. Only during the 1950s, when a reliable measure of circulating insulin was available, was it possible to translate these clinical observations into pathophysiological and biochemical differences, and the terms 'insulin-dependent' (indicating undetectable insulin levels) and 'non-insulin-dependent' (normal or high insulin levels) started to emerge. The next 30 years were characterised by pivotal progress in the field of immunology that were instrumental in demonstrating an immune-mediated loss of insulin-secreting β-cells in subjects with 'insulin-dependent' diabetes. At the same time, new experimental techniques allowing measurement of insulin 'impedance' showed a reduced peripheral effect of insulin in subjects with 'non-insulin-dependent' diabetes (insulin resistance). The difference between the two types of diabetes emerging from decades of observations and experiments was further formally recognised in 1979, when the definitions 'type I' and 'type II' diabetes were introduced to replace the former 'insulin-dependent' and 'non-insulin-dependent' terms. In the following years, many studies elucidated the natural history and temporal contribution of insulin resistance and β-cell insulin secretion in 'type II' diabetes. Furthermore, a central

  9. Glial cells as key elements in the pathophysiology and treatment of bipolar disorder.

    Science.gov (United States)

    Keshavarz, Mojtaba

    2017-06-01

    The exact pathophysiology of bipolar disorder (BD) is not yet fully understood, and there are many questions in this area which should be answered. This review aims to discuss the roles of glial cells in the pathophysiology of BD and their contribution to the mechanism of action of mood-stabilising drugs. We critically reviewed the most recent advances regarding glial cell roles in the pathophysiology and treatment of BD and the neuroprotective and neurotrophic effects of these cells. Postmortem studies revealed a decrease in the glial cell number or density in the specific layers of prefrontal and anterior cingulate cortex in the patients with BD, whereas there was no difference in other brain regions, such as entorhinal cortex, amygdala and hippocampus. Astrocytes and oligodendrocytes were the most important glial types that were responsible for the glial reduction, but microglia activation rather than loss may be implicated in BD. The decreased number or density of glial cells may contribute to the pathological changes observed in neurons in the patients with BD. Alteration of specific neurotrophic factors such as glial cell line-derived neurotrophic factor and S100B may be an important feature of BD. Glial cells mediate the therapeutic effects of mood-stabilising agents in the treatment of BD. Recent studies provide important evidence on the impairment of glial cells in the pathophysiology and treatment of BD. However, future controlled studies are necessary to elucidate different aspects of glial cells contribution to BD, and the mechanism of action of mood-stabilising drugs.

  10. Understanding mechanisms of raveling to extend open graded friction course (OGFC) service life : Florida Department of Transportation Research.

    Science.gov (United States)

    2016-04-01

    Texas A&M Transportation Institute researchers, working with the Universidad de los Andes in Bogot, Colombia, studied the mechanisms of raveling in OGFCs through experimental analysis and finite element modeling.

  11. The role of estrogens at men. Part 2. Private clinical endocrinology and pathophysiology of estrogens at men

    Directory of Open Access Journals (Sweden)

    I. A. Tyuzikov

    2015-01-01

    Full Text Available Until now, estrogens are traditionally considered primarily as key hormones that perform critical functions in females, however, their role in males is not less important, although it remains understudied. However, a deep understanding of male physiology and endocrinology, it is imperative to solve practical problems of gender pathogenetic therapy of men,s diseases, is impossible today without taking into account the key role of testosterone in males, and without rethinking the role of estrogens, 80 % of which in males formed as a result of testosterone aromatisation. Thus, the violation of the synthesis and metabolism of testosterone in men naturally lead to disorder of the synthesis and metabolism of estrogen, which allows to express the idea that without estrogens, testosterone alone can not provide the entire range of the male body physiological effects. The second part of the literature review highlights exactly the Private Endocrinology and Pathophysiology of estrogens in men, which prove this assertion. The most important systems in which the regulation of the primary role of estrogens is presented in both sexes are central nervous system and bones, and possible mechanisms of these pathophysiological effects of estrogen in males are reviewed in detail. In addition, issues of influence of estrogens at the state of the male breast (gynecomastia, and shows close interaction of estrogens and androgens in providing function of male reproductive and cardiovascular systems. Today we know that the pathogenesis of such common disease in men as benign prostatic hyperplasia (BPH, is closely associated with the pathophysiology of both androgens and estrogens, so mechanisms of estrogens participation in the processes of prostatic proliferation (BPH are examined in detail in this review. Urgent problem of men,s health is prostate cancer, which has a hormonal nature, so current data available on the hormonal mechanisms of this disease with estrogens are

  12. The role of estrogens at men. Part 2. Private clinical endocrinology and pathophysiology of estrogens at men

    Directory of Open Access Journals (Sweden)

    I. A. Tyuzikov

    2015-04-01

    Full Text Available Until now, estrogens are traditionally considered primarily as key hormones that perform critical functions in females, however, their role in males is not less important, although it remains understudied. However, a deep understanding of male physiology and endocrinology, it is imperative to solve practical problems of gender pathogenetic therapy of men,s diseases, is impossible today without taking into account the key role of testosterone in males, and without rethinking the role of estrogens, 80 % of which in males formed as a result of testosterone aromatisation. Thus, the violation of the synthesis and metabolism of testosterone in men naturally lead to disorder of the synthesis and metabolism of estrogen, which allows to express the idea that without estrogens, testosterone alone can not provide the entire range of the male body physiological effects. The second part of the literature review highlights exactly the Private Endocrinology and Pathophysiology of estrogens in men, which prove this assertion. The most important systems in which the regulation of the primary role of estrogens is presented in both sexes are central nervous system and bones, and possible mechanisms of these pathophysiological effects of estrogen in males are reviewed in detail. In addition, issues of influence of estrogens at the state of the male breast (gynecomastia, and shows close interaction of estrogens and androgens in providing function of male reproductive and cardiovascular systems. Today we know that the pathogenesis of such common disease in men as benign prostatic hyperplasia (BPH, is closely associated with the pathophysiology of both androgens and estrogens, so mechanisms of estrogens participation in the processes of prostatic proliferation (BPH are examined in detail in this review. Urgent problem of men,s health is prostate cancer, which has a hormonal nature, so current data available on the hormonal mechanisms of this disease with estrogens are

  13. Colony Collapse Disorder (CCD and bee age impact honey bee pathophysiology.

    Directory of Open Access Journals (Sweden)

    Dennis vanEngelsdorp

    Full Text Available Honey bee (Apis mellifera colonies continue to experience high annual losses that remain poorly explained. Numerous interacting factors have been linked to colony declines. Understanding the pathways linking pathophysiology with symptoms is an important step in understanding the mechanisms of disease. In this study we examined the specific pathologies associated with honey bees collected from colonies suffering from Colony Collapse Disorder (CCD and compared these with bees collected from apparently healthy colonies. We identified a set of pathological physical characteristics that occurred at different rates in CCD diagnosed colonies prior to their collapse: rectum distension, Malpighian tubule iridescence, fecal matter consistency, rectal enteroliths (hard concretions, and venom sac color. The multiple differences in rectum symptomology in bees from CCD apiaries and colonies suggest effected bees had trouble regulating water. To ensure that pathologies we found associated with CCD were indeed pathologies and not due to normal changes in physical appearances that occur as an adult bee ages (CCD colonies are assumed to be composed mostly of young bees, we documented the changes in bees of different ages taken from healthy colonies. We found that young bees had much greater incidences of white nodules than older cohorts. Prevalent in newly-emerged bees, these white nodules or cellular encapsulations indicate an active immune response. Comparing the two sets of characteristics, we determined a subset of pathologies that reliably predict CCD status rather than bee age (fecal matter consistency, rectal distension size, rectal enteroliths and Malpighian tubule iridescence and that may serve as biomarkers for colony health. In addition, these pathologies suggest that CCD bees are experiencing disrupted excretory physiology. Our identification of these symptoms is an important first step in understanding the physiological pathways that underlie CCD and

  14. Colony Collapse Disorder (CCD) and bee age impact honey bee pathophysiology.

    Science.gov (United States)

    vanEngelsdorp, Dennis; Traynor, Kirsten S; Andree, Michael; Lichtenberg, Elinor M; Chen, Yanping; Saegerman, Claude; Cox-Foster, Diana L

    2017-01-01

    Honey bee (Apis mellifera) colonies continue to experience high annual losses that remain poorly explained. Numerous interacting factors have been linked to colony declines. Understanding the pathways linking pathophysiology with symptoms is an important step in understanding the mechanisms of disease. In this study we examined the specific pathologies associated with honey bees collected from colonies suffering from Colony Collapse Disorder (CCD) and compared these with bees collected from apparently healthy colonies. We identified a set of pathological physical characteristics that occurred at different rates in CCD diagnosed colonies prior to their collapse: rectum distension, Malpighian tubule iridescence, fecal matter consistency, rectal enteroliths (hard concretions), and venom sac color. The multiple differences in rectum symptomology in bees from CCD apiaries and colonies suggest effected bees had trouble regulating water. To ensure that pathologies we found associated with CCD were indeed pathologies and not due to normal changes in physical appearances that occur as an adult bee ages (CCD colonies are assumed to be composed mostly of young bees), we documented the changes in bees of different ages taken from healthy colonies. We found that young bees had much greater incidences of white nodules than older cohorts. Prevalent in newly-emerged bees, these white nodules or cellular encapsulations indicate an active immune response. Comparing the two sets of characteristics, we determined a subset of pathologies that reliably predict CCD status rather than bee age (fecal matter consistency, rectal distension size, rectal enteroliths and Malpighian tubule iridescence) and that may serve as biomarkers for colony health. In addition, these pathologies suggest that CCD bees are experiencing disrupted excretory physiology. Our identification of these symptoms is an important first step in understanding the physiological pathways that underlie CCD and factors

  15. The role of stress in heart failure – ground for sex specific pathophysiology

    Directory of Open Access Journals (Sweden)

    Viljetic B.

    2011-04-01

    Full Text Available In the last hundred years modern society went through numerous changes in life style, dietary habits, work load, physical activity and other environmental factors. As a species we are not well adapted to new de- mands. Higher levels of stress hormones provoke various effects, especially gradual change in the sensitivity of adrenergic, glucocorticoid and insulin receptors. All these changes are mutually associated and they gradually lead to metabolic syndrome, obesity, diabetes, heart failure and other types of pathology depending on genetic makeup and environmental factors. The aim of this paper is to summarize current knowledge concerning the impact of stress on cardiac function. Whereas stress response is sex specific we would emphasize a potential difference in pathophysiology of ischemic heart failure in men and women. Modern medicine has misinterpreted autonomous nervous system functions for years and this was reflected in heart failure (HF and arterial hypertension therapy. Stress before the onset of menopause has a lesser effect on cardiac function compared to stress after menopause. Postmenopausal women have a significantly higher risk of heart disease, which is related to the diminished protection of the female hormonal cycle, but low doses of estrogen have not proven protective in postmenopausal women. Potential new targets of sex- specific cardiac therapy would come from better understanding of the molecular mechanisms exerted by nuclear receptors for steroid hormones, transcription factors involved in heart remodeling, cross-talk in adrenergic signaling pathways and their down-stream molecules.

  16. Psychomotor Retardation in Depression: A Systematic Review of Diagnostic, Pathophysiologic, and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Djamila Bennabi

    2013-01-01

    Full Text Available Psychomotor retardation is a central feature of depression which includes motor and cognitive impairments. Effective management may be useful to improve the classification of depressive subtypes and treatment selection, as well as prediction of outcome in patients with depression. The aim of this paper was to review the current status of knowledge regarding psychomotor retardation in depression, in order to clarify its role in the diagnostic management of mood disorders. Retardation modifies all the actions of the individual, including motility, mental activity, and speech. Objective assessments can highlight the diagnostic importance of psychomotor retardation, especially in melancholic and bipolar depression. Psychomotor retardation is also related to depression severity and therapeutic change and could be considered a good criterion for the prediction of therapeutic effect. The neurobiological process underlying the inhibition of activity includes functional deficits in the prefrontal cortex and abnormalities in dopamine neurotransmission. Future investigations of psychomotor retardation should help improve the understanding of the pathophysiological mechanisms underlying mood disorders and contribute to improving their therapeutic management.

  17. Headache attributed to airplane travel: diagnosis, pathophysiology, and treatment - a systematic review.

    Science.gov (United States)

    Bui, Sebastian Bao Dinh; Gazerani, Parisa

    2017-08-16

    Headache attributed to airplane travel, also named "airplane headache" (AH) is a headache that occurs during take-off and landing. Today, there are still uncertainties about the pathophysiology and treatment of AH. This systematic review was performed to facilitate identification of the existing literature on AH in order to discuss the current evidence and areas that remain to be investigated in AH. The systematic literature search was performed in 3 relevant medical databases; PubMed, Scopus, and Embase. The search yielded 220 papers and the papers were sorted based on inclusion and exclusion criteria established for this study. This systematic review included 39 papers. Main findings revealed that AH attacks are clinically stereotyped and appear mostly during landing phases. The headache presents as a severe painful headache that often disappears within 30 min. The pain is unilateral and localized in the fronto-orbital region. Sinus barotrauma has been considered as the main cause of AH. Nonsteroidal anti-inflammatory drugs and triptans have been taken by passengers with AH, to relieve the headache. Based on this systematic review, further studies seem required to investigate underlying mechanisms in AH and also to investigate the biological effects of nonsteroidal anti-inflammatory drugs and triptans for alleviating of AH. These studies would advance our understanding of AH pathogenesis and potential use of treatments that are not yet established.

  18. Biofilms in chronic rhinosinusitis: Pathophysiology and therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Judd H. Fastenberg

    2016-12-01

    Full Text Available Background: There is increasing evidence that biofilms are critical to the pathophysiology of chronic infections including chronic rhinosinusitis (CRS. Until relatively recently, our understanding of biofilms was limited. Recent advances in methods for biofilm identification and molecular biology have offered new insights into the role of biofilms in CRS. With these insights, investigators have begun to investigate novel therapeutic strategies that may disrupt or eradicate biofilms in CRS. Objective: This review seeks to explore the evidence implicating biofilms in CRS, discuss potential anti-biofilm therapeutic strategies, and suggest future directions for research. Results: The existing evidence strongly supports the role of biofilms in the pathogenesis of CRS. Several anti-biofilm therapies have been investigated for use in CRS and these are at variable stages of development. Generally, these strategies: 1 neutralize biofilm microbes; 2 disperse existing biofilms; or 3 disrupt quorum sensing. Several of the most promising anti-biofilm therapeutic strategies are reviewed. Conclusions: A better understanding of biofilm function and their contribution to the CRS disease process will be pivotal to the development of novel treatments that may augment and, potentially, redefine the CRS treatment paradigm. There is tremendous potential for future research. Keywords: Sinusitis, Biofilms, Anti-bacterial agents, Quorum sensing, Surface-active agents, Active immune response, Innate immune response

  19. Pathophysiological basis of syncope and neurological conditions that mimic syncope

    NARCIS (Netherlands)

    van Dijk, J. Gert; Wieling, Wouter

    2013-01-01

    The definition of syncope has clinical and pathophysiological parts. The clinical part is that syncope is a form of transient loss of consciousness (TLOC), while the pathophysiological element is that syncope differs from other forms of TLOC by virtue of the basis of true syncope - specifically

  20. Understanding and modelling of the aniso-thermal cyclic mechanical behaviour of the AISI 316LN austenitic stainless steel

    International Nuclear Information System (INIS)

    Gentet, D.

    2009-11-01

    The main subject of this report consists in proposing a mechanical model of the viscoplastic behaviour of an austenitic stainless steel under isothermal and aniso-thermal low cycle fatigue loadings at high temperatures (550-900 K). In this domain, numerous phenomena linked to dynamic strain ageing (DSA) and to dipolar dislocation structure formation may appear. Isothermal and aniso-thermal low cycle fatigue tension-compression tests were performed in order to verify some aspects about the effect of temperature on the mechanical behaviour. The study of the hysteresis loops and the observation of dislocation structures carried on transmission electron microscopy establish two different DSA mechanisms during isothermal tests. The effect of temperature history is shown for for particular temperature sequences. It is demonstrated that the stress amplitude increase when the sample is submitted to cycles at 'high temperature' is linked to the second mechanism of DSA. It comes from the increase of short range interaction between dislocations (chromium segregation), but it is also the consequence of the lack of dipolar structure annihilation at low temperature. From the experimental analysis of DSA mechanisms and dipolar restoration, a macroscopic aniso-thermal model is developed using physical internal variables (densities of dislocations). The equations of a polycrystalline model are rewritten with the aim of getting a simple multi-scale approach which can be used on finite elements analysis software. Between 550 and 873 K, the simulation results are in good accordance with the macroscopic and microscopic observations of low cycle fatigue, relaxation, and 2D-ratchetting tests. (author)