WorldWideScience

Sample records for understand pathophysiological mechanisms

  1. Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

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    Kaustav Majumder

    2014-12-01

    Full Text Available There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE, are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

  2. 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

  3. Pathophysiologic mechanisms of biomedical nanomaterials

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    Wang, Liming, E-mail: wangliming@ihep.ac.cn; Chen, Chunying, E-mail: chenchy@nanoctr.cn

    2016-05-15

    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.

  4. 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

  5. Understanding changes in cardiovascular pathophysiology.

    Science.gov (United States)

    Chummun, Harry

    Cardiovascular pathophysiological changes, such as hypertension and enlarged ventricles, reflect the altered functions of the heart and its circulation during ill-health. This article examines the normal and altered anatomy of the cardiac valves, the contractile elements and enzymes of the myocardium, the significance of the different factors associated with cardiac output, and the role of the autonomic nervous system in the heart beat. It also explores how certain diseases alter these functions and result in cardiac symptoms. Nurses can benefit from knowledge of these specific changes, for example, by being able to ask relevant questions in order to ascertain the nature of a patients condition, by being able to take an effective patient history and by being able to read diagnostic results, such as electrocardiograms and cardiac enzyme results. All this will help nurses to promote sound cardiac care based on a physiological rationale.

  6. Diagnosing the pathophysiologic mechanisms of nocturnal polyuria.

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    Goessaert, An-Sofie; Krott, Louise; Hoebeke, Piet; Vande Walle, Johan; Everaert, Karel

    2015-02-01

    Diagnosis of nocturnal polyuria (NP) is based on a bladder diary. Addition of a renal function profile (RFP) for analysis of concentrating and solute-conserving capacity allows differentiation of NP pathophysiology and could facilitate individualized treatment. To map circadian rhythms of water and solute diuresis by comparing participants with and without NP. This prospective observational study was carried out in Ghent University Hospital between 2011 and 2013. Participants with and without NP completed a 72-h bladder dairy. RFP, free water clearance (FWC), and creatinine, solute, sodium, and urea clearance were measured for all participants. The study participants were divided into those with (n=77) and those without (n=35) NP. The mean age was 57 yr (SD 16 yr) and 41% of the participants were female. Compared to participants without NP, the NP group exhibited a higher diuresis rate throughout the night (p=0.015); higher FWC (p=0.013) and lower osmolality (p=0.030) at the start of the night; and persistently higher sodium clearance during the night (p<0.001). The pathophysiologic mechanism of NP was identified as water diuresis alone in 22%, sodium diuresis alone in 19%, and a combination of water and sodium diuresis in 47% of the NP group. RFP measurement in first-line NP screening to discriminate between water and solute diuresis as pathophysiologic mechanisms complements the bladder diary and could facilitate optimal individualized treatment of patients with NP. We evaluated eight urine samples collected over 24h to detect the underlying problem in NP. We found that NP can be attributed to water or sodium diuresis or a combination of both. This urinalysis can be used to adapt treatment according to the underlying mechanism in patients with bothersome consequences of NP, such as nocturia and urinary incontinence. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  7. 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

  8. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

    Science.gov (United States)

    Alexandre, Leo; Long, Elizabeth; Beales, Ian LP

    2014-01-01

    In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits. PMID:25400997

  9. Neurological complications of drug abuse: pathophysiological mechanisms.

    Science.gov (United States)

    Neiman, J; Haapaniemi, H M; Hillbom, M

    2000-11-01

    Drug abuse is associated with a variety of neurological complications. The use of certain recreational drugs shows a marked temporal association with the onset of both haemorrhagic and ischaemic strokes, the majority of which develop within minutes to 1 h after the administration of the index drug. Delayed onset of stroke has also been observed. Acute, severe elevation of blood pressure, cardiac dysrhythmias, cerebral vasospasm, vasculitis, embolization due to infective endocarditis or dilated cardiomyopathy, embolization due to foreign material injected with the diluents under non-sterile conditions and 'street drug' contaminants with cardiovascular effects have been suggested as possible underlying mechanisms. Rupture of aneurysms and arteriovenous malformations have been detected in up to half of the patients with haemorrhagic stroke due to cocaine abuse. The less common findings reported have included a mycotic cerebrovascular aneurysm in a patient with infective endocarditis and haemorrhagic stroke. In addition to stroke, cocaine seems to provoke vascular headache. Seizures precipitated by recreational drug abuse are usually caused by acute intoxication in contrast to the withdrawal seizures encountered in subjects with alcohol abuse. Movement disorders and cerebral atrophy correlating with the duration of abuse have been described. Snorting of organic solvents may cause encephalopathy. Cases of spongiform leukoencephalopathy in heroin addicts have also been reported. Peripheral neuropathy is occasionally precipitated by drug poisoning after intravenous administration. Impurities of the drug, risky administration techniques, and the use of mixtures of various drugs, frequently with simultaneous alcohol drinking, should be taken into account when assessing the background of the adverse event as well as the overall lifestyle of the addicted subjects.

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

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    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.

  11. Pathophysiological Mechanisms of Laser Correction in Critical Conditions

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    V. L. Kozhura

    2006-01-01

    Full Text Available The paper provides the generalized results of studies dealing with the use of low-intensive laser irradiation in blood loss-induced critical conditions in an experiment and in patients with severe mechanical injury. In the light of recent data and the data available in the literature, the authors consider some pathophysiological mechanisms of action of laser radiation at all living matter organization levels: molecular, cellular, organ, and systemic. The feasibilities of laser correction of hemostastic disorders are defined in relation to the volume of blood loss and the functional state of compensatory systems. 

  12. Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle.

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    Rech, Monika; Barandiarán Aizpurua, Arantxa; van Empel, Vanessa; van Bilsen, Marc; Schroen, Blanche

    2018-05-01

    Half of all heart failure patients have preserved ejection fraction (HFpEF). Comorbidities associated with and contributing to HFpEF include obesity, diabetes and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF are unknown. A preliminary consensus proposes that the multi-morbidity triggers a state of systemic, chronic low-grade inflammation, and microvascular dysfunction, causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a result, the cardiomyocyte remodels its contractile elements and fails to relax properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex syndrome for which currently no efficient therapies exist. This is notably due to the current one-size-fits-all therapy approach that ignores individual patient differences. MicroRNAs have been studied in relation to pathophysiological mechanisms and comorbidities underlying and contributing to HFpEF. As regulators of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In addition, secreted circulating microRNAs are potential biomarkers and as such, they could help stratify the HFpEF population and open new ways for individualized therapies. In this review, we provide an overview of the ever-expanding world of non-coding RNAs and their contribution to the molecular mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying the HFpEF population. MicroRNAs add a new level of complexity to the regulatory network controlling cardiac function and hence the understanding of gene regulation becomes a fundamental piece in solving the HFpEF puzzle.

  13. Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms.

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    Campos, Derbis; Monaga, Madelyn

    2012-06-01

    Mucopolysaccharidosis type I is one of the most frequent lysosomal storage diseases. It has a high morbidity and mortality, causing in many cases severe neurological and somatic damage in the first years of life. Although the clinical phenotypes have been described for decades, and the enzymatic deficiency and many of the mutations that cause this disease are well known, the underlying pathophysiological mechanisms that lead to its development are not completely understood. In this review we describe and discuss the different pathogenic mechanisms currently proposed for this disease regarding its neurological damage. Deficiency in the lysosomal degradation of heparan sulfate and dermatan sulfate, as well as its primary accumulation, may disrupt a variety of physiological and biochemical processes: the intracellular and extracellular homeostasis of these macromolecules, the pathways related to gangliosides metabolism, mechanisms related to the activation of inflammation, receptor-mediated signaling, oxidative stress and permeability of the lysosomal membrane, as well as alterations in intracellular ionic homeostasis and the endosomal pathway. Many of the pathogenic mechanisms proposed for mucopolysaccharidosis type I are also present in other lysosomal storage diseases with neurological implications. Results from the use of methods that allow the analysis of multiple genes and proteins, in both patients and animal models, will shed light on the role of each of these mechanisms and their combination in the development of different phenotypes due to the same deficiency.

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

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    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.

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

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    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.

  16. Pathophysiological mechanisms of severe anaemia in Malawian children.

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    Michaël Boele van Hensbroek

    2010-09-01

    Full Text Available Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success.We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl] studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%. Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis.RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome.

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

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    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.

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

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    Sibmooh, Nathawut; Fucharoen, Suthat

    2017-01-01

    Abstract Significance: 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 βE-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. Critical Issues: 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. Future Directions: 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. PMID:27650096

  19. Understand quantum mechanics

    International Nuclear Information System (INIS)

    Omnes, R.

    2000-01-01

    The author presents the interpretation of quantum mechanics in a simple and direct way. This book may be considered as a complement of specialized books whose aim is to present the mathematical developments of quantum mechanics. As early as the beginning of quantum theory, Bohr, Heisenberg and Pauli proposed the basis of what is today called the interpretation of Copenhagen. This interpretation is still valid but 2 important discoveries have led to renew some aspects of the interpretation of Copenhagen. The first one was the discovery of the decoherence phenomenon which is responsible for the absence of quantum interferences in the macroscopic world. The second discovery was the achievement of the complete derivation of classical physics from quantum physics, it means that the classical determinism fits in the framework of quantum probabilism. A short summary ends each chapter. (A.C.)

  20. Understanding mechanical ventilators.

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    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.

  1. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

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    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.

  2. Endocrine Tumors Causing Arterial Hypertension: Pathophysiological Mechanisms and Clinical Implications.

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    Buonacera, Agata; Stancanelli, Benedetta; Malatino, Lorenzo

    2017-09-01

    Some tumors are a relatively rare and amendable cause of hypertension, often associated with a higher cardiovascular morbidity and mortality, as compared with that of both general population and patients with essential hypertension. This worse prognosis is not entirely related to blood pressure increase, because the release of substances from the tumor can directly influence blood pressure behavior. Diagnostic approach is challenging and needs a deep knowledge of the different neuro-hormonal and genetic mechanisms determining blood pressure increase. Surgical tumor removal can, but not always, cause blood pressure normalization, depending on how early was tumor detection, since a long-standing history of hypertension is often associated with a much weaker effect on blood pressure. Moreover, target organ damage can be affected by the substances themselves released by the tumors as well as by tumor removal. In this review we consider the phenotype and genetic features of patients with tumor-induced hypertension and focus on their diagnostic work-up.

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

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    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. PATHO-PHYSIOLOGICAL MECHANISMS OF TOBACCO SMOKING EFFECT ON THE CARDIOVASCULAR SYSTEM

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    V.F. Kirichuk

    2007-09-01

    Full Text Available Modern patho-physiological mechanisms with the help of which tobacco smoking contributes to the development of cardiovascular pathology are represented in the review. The most significant of them are endothelial dysfunction, progressing of atherosclerotic processes, alteration of rheologic properties of blood, increase of carboxyhemoglobin levels, activation of sympathetic nervous system of the heart.

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

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    Simona-Adriana Manea

    2015-08-01

    Full Text Available 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.

  6. 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.

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

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    Figueiredo, Andre A., E-mail: andreavaresef@gmail.com [Department of Morphology and Division of Urology, Federal University of Juiz de Fora, Minas Gerais (Brazil); Division of Urology, Medical School, University of Sao Paulo, Sao Paulo (Brazil); Lucon, Antonio M. [Division of Urology, Medical School, University of Sao Paulo, Sao Paulo (Brazil); Arvellos, Andre N.; Ramos, Claudio O.P.; Toledo, Antonio C.T. [Department of Morphology and Division of Urology, Federal University of Juiz de Fora, Minas Gerais (Brazil); Falci, Renato; Gomes, Cristiano M. [Division of Urology, Medical School, University of Sao Paulo, Sao Paulo (Brazil); Recaverren, Fernando E.Q.; Netto, Jose Murillo B. [Department of Morphology and Division of Urology, Federal University of Juiz de Fora, Minas Gerais (Brazil); Srougi, Miguel [Division of Urology, Medical School, University of Sao Paulo, Sao Paulo (Brazil)

    2010-11-15

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

    Science.gov (United States)

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

    2015-09-29

    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 disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

  9. How to understand quantum mechanics

    CERN Document Server

    Ralston, John P

    2018-01-01

    How to Understand Quantum Mechanics presents an accessible introduction to understanding quantum mechanics in a natural and intuitive way, which was advocated by Erwin Schroedinger and Albert Einstein. A theoretical physicist reveals dozens of easy tricks that avoid long calculations, makes complicated things simple, and bypasses the worthless anguish of famous scientists who died in angst. The author's approach is light-hearted, and the book is written to be read without equations, however all relevant equations still appear with explanations as to what they mean. The book entertainingly rejects quantum disinformation, the MKS unit system (obsolete), pompous non-explanations, pompous people, the hoax of the 'uncertainty principle' (it is just a math relation), and the accumulated junk-DNA that got into the quantum operating system by misreporting it. The order of presentation is new and also unique by warning about traps to be avoided, while separating topics such as quantum probability to let the Schroeding...

  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 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.

  12. 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.

  13. 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.

  14. Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities

    Science.gov (United States)

    Cavalera, Michele; Wang, Junhong; Frangogiannis, Nikolaos G

    2014-01-01

    Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients. PMID:24880146

  15. 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.

  16. Placebo analgesia: understanding the mechanisms

    OpenAIRE

    Medoff, Zev M; Colloca, Luana

    2015-01-01

    Expectations of pain relief drive placebo analgesia. Understanding how expectations of improvement trigger distinct biological systems to shape therapeutic analgesic outcomes has been the focus of recent pharmacologic and neuroimaging studies in the field of pain. Recent findings indicate that placebo effects can imitate the actions of real painkillers and promote the endogenous release of opioids and nonopioids in humans. Social support and observational learning also contribute to placebo a...

  17. 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.

  18. 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.

  19. 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.

  20. Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

    Science.gov (United States)

    Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

    2016-01-01

    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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

    Pan, Ying; Kong, Ling-Dong

    2018-04-01

    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

  4. Pathophysiology of cervical myelopathy.

    Science.gov (United States)

    Baptiste, Darryl C; Fehlings, Michael G

    2006-01-01

    Cervical myelopathy is a group of closely related disorders usually caused by spondylosis or by ossification of the posterior longitudinal ligament and is characterized by compression of the cervical spinal cord or nerve roots by varying degrees and number of levels. The decrease in diameter of the vertebral canal secondary to disc degeneration and osteophytic spurs compresses the spinal cord and nerve roots at one or several levels, producing direct damage and often secondary ischemic changes. Clinicians who treat cervical myelopathy cord injuries should have a basic understanding of the pathophysiology and the processes that are initiated after the spinal cord has been injured. Literature review. Literature review of human cervical myelopathy and clinically relevant animal models to further our understanding of the pathological mechanisms involved. The pathophysiology of cervical myelopathy involves static factors, which result in acquired or developmental stenosis of the cervical canal and dynamic factors, which involve repetitive injury to the cervical cord. These mechanical factors in turn result in direct injury to neurons and glia as well as a secondary cascade of events including ischemia, excitotoxicity, and apoptosis; a pathobiology similar to that occurring in traumatic spinal cord injury. This review summarizes some of the significant pathophysiological processes involved in cervical myelopathy.

  5. PTSD in the military: special considerations for understanding prevalence, pathophysiology and treatment following deployment

    Science.gov (United States)

    Yehuda, Rachel; Vermetten, Eric; McFarlane, Alexander C.; Lehrner, Amy

    2014-01-01

    Given the unique context of warzone engagement, which may include chronic threat, multiple and lengthy deployments, and loss, there is a need to understand whether and to what extent knowledge about PTSD derived from studies of civilian trauma exposure is generalizeable to the military. This special issue on PTSD in the military addresses a range of issues and debates related to mental health in military personnel and combat veterans. This article provides an overview of the issues covered in selected contributions that have been assembled for a special volume to consider issues unique to the military. Several leading scholars and military experts have contributed papers regarding: 1) prevalence rates of PTSD and other post-deployment mental health problems in different NATO countries, 2) the search for biomarkers of PTSD and the potential applications of such findings, and 3) prevention and intervention approaches for service members and veterans. The volume includes studies that highlight the divergence in prevalence rates of PTSD and other post-deployment mental health problems across nations and that discuss potential causes and implications. Included studies also provide an overview of research conducted in military or Veteran's Affairs settings, and overarching reviews of military-wide approaches to research, promotion of resilience, and mental health interventions in the Unites States and across NATO and allied ISAF partners. PMID:25206950

  6. 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.

  7. 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.

  8. 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

  9. Comorbidity between Type 2 Diabetes and Depression in the Adult Population: Directions of the Association and Its Possible Pathophysiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Line Iden Berge

    2015-01-01

    Full Text Available Type 2 diabetes and depression are regarded as comorbid conditions, and three possible directions of the association between the diseases can underlie this observation of comorbidity. First, common etiology can increase a person’s risk of both diseases; second, persons with type 2 diabetes have increased prevalence or risk of future development of depression; or third, persons with depression have increased prevalence or risk of development of type 2 diabetes. This review gives an overview over possible pathophysiological mechanisms for each of the directions of the association between type 2 diabetes and depression and further discusses epigenetics as an additional, direction independent approach. We argue that unspecific pathophysiological mechanisms involved in the stress response might, at least to some extent, explain each of the directions of the association between type 2 diabetes and depression, while changes in brain structure and function among persons with diabetes and possible increased risk of development of type 2 diabetes after use of antidepressant agents could represent more disease specific mechanisms underlying the comorbidity.

  10. Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.

    Science.gov (United States)

    Robinson, Antwon D; Ramanathan, Kodangudi B; McGee, Jesse E; Newman, Kevin P; Weber, Karl T

    2011-08-01

    The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

  11. Respiratory mechanics to understand ARDS and guide mechanical ventilation.

    Science.gov (United States)

    Mauri, Tommaso; Lazzeri, Marta; Bellani, Giacomo; Zanella, Alberto; Grasselli, Giacomo

    2017-11-30

    As precision medicine is becoming a standard of care in selecting tailored rather than average treatments, physiological measurements might represent the first step in applying personalized therapy in the intensive care unit (ICU). A systematic assessment of respiratory mechanics in patients with the acute respiratory distress syndrome (ARDS) could represent a step in this direction, for two main reasons. Approach and Main results: On the one hand, respiratory mechanics are a powerful physiological method to understand the severity of this syndrome in each single patient. Decreased respiratory system compliance, for example, is associated with low end expiratory lung volume and more severe lung injury. On the other hand, respiratory mechanics might guide protective mechanical ventilation settings. Improved gravitationally dependent regional lung compliance could support the selection of positive end-expiratory pressure and maximize alveolar recruitment. Moreover, the association between driving airway pressure and mortality in ARDS patients potentially underlines the importance of sizing tidal volume on respiratory system compliance rather than on predicted body weight. The present review article aims to describe the main alterations of respiratory mechanics in ARDS as a potent bedside tool to understand severity and guide mechanical ventilation settings, thus representing a readily available clinical resource for ICU physicians.

  12. 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.

  13. Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms, therapeutic opportunities, and clinical investigation challenges

    NARCIS (Netherlands)

    Zannad, F.; Stough, W.G.; Regnault, V.; Gheorghiade, M.; Deliargyris, E.; Gibson, C.M.; Agewall, S.; Berkowitz, S.D.; Burton, P.; Calvo, G.; Goldstein, S.; Verheugt, F.W.A.; Koglin, J.; O'Connor, C.M.

    2013-01-01

    Thrombotic events (coronary thrombosis, venous thromboembolism, intraventricular thrombosis, intracranial and systemic thromboembolism) occur frequently in patients with heart failure. These events may be precipitated by several mechanisms including hypercoagulability through enhancement of

  14. The metabolic syndrome, depression, and cardiovascular disease : Interrelated conditions that share pathophysiologic mechanisms

    NARCIS (Netherlands)

    Gans, Rijk O. B.

    This article introduces the metabolic syndrome as a clinical phenotype with consequences for diagnosis and treatment that go beyond the different clinical specialties involved. A life-course approach is suggested as a means of understanding the complex interrelations between the metabolic syndrome,

  15. 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.

  16. 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.

  17. 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.

  18. Pathophysiology of acute small bowel disease with CT correlation

    International Nuclear Information System (INIS)

    Sarwani, N.; Tappouni, R.; Tice, J.

    2011-01-01

    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.

  19. 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.

  20. 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.

  1. 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

  2. Quantum mechanics - a key to understanding magnetism

    International Nuclear Information System (INIS)

    Van Vleck, J.H.

    1978-01-01

    A translation is presented of J.H. van Vleck's lecture read at the 1977 Nobel Prize avarding ceremony. The basic results obtained using quantum mechanics in solving the problems of magnetism and especially paramagnetism are chronologically arranged. (Z.J.)

  3. Evolution in the understanding of the pathophysiological basis of portal hypertension: How changes in paradigm are leading to successful new treatments

    Science.gov (United States)

    Bosch, Jaume; Groszmann, Roberto J.; Shah, Vijay H.

    2015-01-01

    Summary Among the common complication of cirrhosis portal hypertension witnessed a major improvement of prognosis during the past decades. Principally due to the introduction of rational treatments based on new pathophysiological paradigms (concepts of thought) developed in the 1980s. The best example being the use of non-selective beta-blockers and of vasopressin analogs, somatostatin, and its analogs. Further refinement in the knowledge of the molecular mechanisms involved in the regulation of both the splanchnic and hepatic circulation has led to the emergence of new treatments, which are based on evidence that show not only structural but also vasoactive components increase the hepatic vascular resistance, as well as of angiogenesis. This knowledge and future improvements will most likely result in more effective treatment of portal hypertension and effective prevention of its complications in early stages. PMID:25920081

  4. 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.

  5. Understanding gene functions and disease mechanisms

    DEFF Research Database (Denmark)

    Fuchs, Helmut; Aguilar-Pimentel, Juan Antonio; Amarie, Oana V.

    2018-01-01

    Since decades, model organisms have provided an important approach for understanding the mechanistic basis of human diseases. The German Mouse Clinic (GMC) was the first phenotyping facility that established a collaboration-based platform for phenotype characterization of mouse lines. In order...... to address individual projects by a tailor-made phenotyping strategy, the GMC advanced in developing a series of pipelines with tests for the analysis of specific disease areas. For a general broad analysis, there is a screening pipeline that covers the key parameters for the most relevant disease areas...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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…

  12. 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…

  13. 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...

  14. Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38

    DEFF Research Database (Denmark)

    Amin, Faisal Mohammad; Hougaard, Anders; Schytz, Henrik W

    2014-01-01

    Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the ...

  15. 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...... 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....... 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...

  16. 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.

  17. The pathophysiology of heart failure.

    Science.gov (United States)

    Kemp, Clinton D; Conte, John V

    2012-01-01

    Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. 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.

  19. 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.

  20. Toward a quantitative understanding of mechanical behavior of nanocrystalline metals

    International Nuclear Information System (INIS)

    Dao, M.; Lu, L.; Asaro, R.J.; Hosson, J.T.M. de; Ma, E.

    2007-01-01

    Focusing on nanocrystalline (nc) pure face-centered cubic metals, where systematic experimental data are available, this paper presents a brief overview of the recent progress made in improving mechanical properties of nc materials, and in quantitatively and mechanistically understanding the underlying mechanisms. The mechanical properties reviewed include strength, ductility, strain rate and temperature dependence, fatigue and tribological properties. The highlighted examples include recent experimental studies in obtaining both high strength and considerable ductility, the compromise between enhanced fatigue limit and reduced crack growth resistance, the stress-assisted dynamic grain growth during deformation, and the relation between rate sensitivity and possible deformation mechanisms. The recent advances in obtaining quantitative and mechanics-based models, developed in line with the related transmission electron microscopy and relevant molecular dynamics observations, are discussed with particular attention to mechanistic models of partial/perfect-dislocation or deformation-twin-mediated deformation processes interacting with grain boundaries, constitutive modeling and simulations of grain size distribution and dynamic grain growth, and physically motivated crystal plasticity modeling of pure Cu with nanoscale growth twins. Sustained research efforts have established a group of nanocrystalline and nanostructured metals that exhibit a combination of high strength and considerable ductility in tension. Accompanying the gradually deepening understanding of the deformation mechanisms and their relative importance, quantitative and mechanisms-based constitutive models that can realistically capture experimentally measured and grain-size-dependent stress-strain behavior, strain-rate sensitivity and even ductility limit are becoming available. Some outstanding issues and future opportunities are listed and discussed

  1. Pathophysiology of gastroesophageal reflux disease

    NARCIS (Netherlands)

    Boeckxstaens, Guy E.; Rohof, Wout O.

    2014-01-01

    Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in the Western world, with typical symptoms, such as heartburn, regurgitation, or retrosternal pain, reported by 15% to 20% of the general population. The pathophysiology of GERD is multifactorial. Our understanding

  2. 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...... 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....

  3. Intact and Impaired Mechanisms of Action Understanding in Autism

    Science.gov (United States)

    Vivanti, Giacomo; McCormick, Carolyn; Young, Gregory S.; Abucayan, Floridette; Hatt, Naomi; Nadig, Aparna; Ozonoff, Sally; Rogers, Sally J.

    2016-01-01

    Typically developing children understand and predict others’ behavior by extracting and processing relevant information such as the logic of their actions within the situational constraints and the intentions conveyed by their gaze direction and emotional expressions. Children with autism have difficulties understanding and predicting others’ actions. With the use of eye tracking and behavioral measures, we investigated action understanding mechanisms used by 18 children with autism and a well-matched group of 18 typically developing children. Results showed that children with autism (a) consider situational constraints in order to understand the logic of an agent’s action and (b) show typical usage of the agent’s emotional expressions to infer his or her intentions. We found (c) subtle atypicalities in the way children with autism respond to an agent’s direct gaze and (d) marked impairments in their ability to attend to and interpret referential cues such as a head turn for understanding an agent’s intentions. PMID:21401220

  4. A case of hypoglycemiainduced QT prolongation leading to torsade de pointes and a review of pathophysiological mechanisms

    Directory of Open Access Journals (Sweden)

    Faris Hannoodi

    2017-06-01

    Full Text Available Torsades de pointes is a life-threatening cardiac arrhythmia. Occurrence of this arrhythmia as a result of hypoglycemia has not been reported in the literature. We describe an interesting case of an insulindependent diabetic patient presenting with torsades de pointes resulting from hypoglycemia. A 62-year-old male was admitted to the hospital following an episode of severe insulin-induced hypoglycemia and a cardiac arrest. He was found to unresponsive at home after taking insulin. His serum glucose was found to be 18. He was given juice initially to normalize his glucose and was then transferred by EMS to ER where he was given 5% dextrose infusion. Analysis of the LifeVest rhythm recording showed torsades de pointes that was terminated by defibrillation of the LifeVest. Several mechanisms are responsible for torsade, including QT interval prolongation, adrenalin secretion and calcium overload leading to intracellular calcium oscillations. These mechanisms are a trigger to torsade de pointes. Predisposing factors were present leading torsade to occur.

  5. 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.

  6. 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

  7. Pathophysiology of nocturnal enuresis

    DEFF Research Database (Denmark)

    Rittig, Søren; Kamperis, Konstantinos

    2015-01-01

    The perception of the pathogenesis of enuresis has undergone marked changes over the past 30 years from a psychiatric/psychological background to a more somatic model where nighttime urine production and bladder capacity are main components together with an arousal dysfunction that prevents...... that dysfunction of the intrinsic circadian regulation located in the suprachiasmatic nucleus results in dysfunction of one or more of the brainstem centers involved in AVP secretion, arousal function, bladder control, and blood pressure regulation. Furthermore, nocturnal enuresis has a strong genetic influence...... that in some families present as autosomal dominant inheritance with high degree of penetrance. Linkage to several chromosomal areas have been confirmed in such families although a specific causative enuresis gene has not yet been identified. In conclusion, our understanding of enuresis pathophysiology has...

  8. An update on the mechanisms and pathophysiological consequences of genomic instability with a focus on ionizing radiation

    Directory of Open Access Journals (Sweden)

    Streffer C

    2015-12-01

    Full Text Available Christian Streffer Institute for Medical Radiobiology, University Clinics Essen, Essen, Germany Abstract: The genome of eukaryotic cells is generally instable. DNA damage occurs by endogenous processes and exogenous toxic agents. The efficient DNA repair pathways conserve the genetic information to a large extent throughout the life. However, exposure to genotoxic agents can increase the genomic instability. This phenomenon develops in a delayed manner after approximately 20 and more cell generations. It is comparatively thoroughly investigated after the exposure to ionizing radiation. The increase of genomic instability has been observed after exposures to ionizing radiation in vitro and in vivo as well as with many different types of radiation. The effect is induced over a wide dose range, and it has been found with cell death, chromosomal damage, cell transformations, mutations, double-strand breaks, malformations, and cancers. No specific chromosomes or genomic sites have been observed for such events. The increased genomic instability can be transmitted to the next generation. Possible mechanisms such as oxidative stress (mitochondria may be involved, reduced DNA repair, changes in telomeres, epigenetic effects are discussed. A second wave of oxidative stress has been observed after radiation exposures with considerably high doses as well as with cytotoxic agents at time periods when an increased genomic instability was seen. However, the increase of genomic instability also happens to much lower radiation doses. Hypoxia induces an increase of genomic instability. This effect is apparently connected with a reduction of DNA repair. Changes of telomeres appear as the most probable mechanisms for the increase of genomic instability. Syndromes have been described with a genetic predisposition for high radiosensitivity. These individuals show an increase of cancer, a deficient DNA repair, a disturbed regulation of the cell cycle, and an

  9. Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.

    Science.gov (United States)

    Strahler, Jana; Skoluda, Nadine; Rohleder, Nicolas; Nater, Urs M

    2016-09-01

    Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Student understanding of time dependence in quantum mechanics

    Directory of Open Access Journals (Sweden)

    Paul J. Emigh

    2015-09-01

    Full Text Available [This paper is part of the Focused Collection on Upper Division Physics Courses.] 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 the key role of the energy eigenbasis in determining the time dependence of wave functions. Through analysis of student responses to a set of four interrelated tasks, we categorize some of the difficulties that underlie common errors. The conceptual and reasoning difficulties that have been identified are illustrated through student responses to four sets of questions administered at different points in a junior-level course on quantum mechanics. Evidence is also given that the problems persist throughout undergraduate instruction and into the graduate level.

  11. From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process: Respiratory and Cardiovascular Effects in COPD (KOLIN).

    Science.gov (United States)

    Lindberg, Anne; Linder, Robert; Backman, Helena; Eriksson Ström, Jonas; Frølich, Andreas; Nilsson, Ulf; Rönmark, Eva; Johansson Strandkvist, Viktor; Behndig, Annelie F; Blomberg, Anders

    2017-01-01

    Background : Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study. Method : The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002-04 ( n  = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002-2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2-3 with rapid decline in FEV 1 and group B) COPD grade 2-3 without rapid decline in FEV 1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A-C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D. Results : From the database groups A-D were identified; group A n  = 37, group B n  = 29, group C n  = 41, and group D n  = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A ( n  = 12) and B ( n  = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome. Conclusion : The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.

  12. 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.

  13. Recent progress on understanding the mechanisms of amyloid nucleation.

    Science.gov (United States)

    Chatani, Eri; Yamamoto, Naoki

    2018-04-01

    Amyloid fibrils are supramolecular protein assemblies with a fibrous morphology and cross-β structure. The formation of amyloid fibrils typically follows a nucleation-dependent polymerization mechanism, in which a one-step nucleation scheme has widely been accepted. However, a variety of oligomers have been identified in early stages of fibrillation, and a nucleated conformational conversion (NCC) mechanism, in which oligomers serve as a precursor of amyloid nucleation and convert to amyloid nuclei, has been proposed. This development has raised the need to consider more complicated multi-step nucleation processes in addition to the simplest one-step process, and evidence for the direct involvement of oligomers as nucleation precursors has been obtained both experimentally and theoretically. Interestingly, the NCC mechanism has some analogy with the two-step nucleation mechanism proposed for inorganic and organic crystals and protein crystals, although a more dramatic conformational conversion of proteins should be considered in amyloid nucleation. Clarifying the properties of the nucleation precursors of amyloid fibrils in detail, in comparison with those of crystals, will allow a better understanding of the nucleation of amyloid fibrils and pave the way to develop techniques to regulate it.

  14. [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.

  15. 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

  16. 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.

  17. Mechanisms influencing student understanding on an outdoor guided field trip

    Science.gov (United States)

    Caskey, Nourah Al-Rashid

    Field trips are a basic and important, yet often overlooked part of the student experience. They provide the opportunity to integrate real world knowledge with classroom learning and student previous personal experiences. Outdoor guided field trips leave students with an increased understanding, awareness and interest and in science. However, the benefits of this experience are ambiguous at best (Falk and Balling, 1982; Falk and Dierking, 1992; Kisiel, 2006.) Students on an outdoor guided field trip to a local nature park experienced a significant increase in their understanding of the rock cycle. The changes in the pre-field trip test and the post-field trip test as well as their answers in interviews showed a profound change in the students' understanding and in their interest in the subject matter. The use of the "student's voice" (Bamberger and Tal, 2008) was the motivation for data analysis. By using the students' voice, I was able to determine the mechanisms that might influence their understanding of a subject. The central concepts emerging from the data were: the outdoor setting; the students' interest; the social interaction. From these central concepts, a conceptual model was developed. The outdoor setting allows for the freedom to explore, touch, smell and movement. This, in turn, leads to an increased interest in subject matter. As the students are exploring, they are enjoying themselves and become more open to learning. Interest leads to a desire to learn (Dewey, 1975). In addition to allowing the freedom to explore and move, the outdoor setting creates the condition for social interaction. The students talk to each other as they walk; they have in-depth discourse regarding the subject matter---with the teachers, each other and with the guides. The guides have an extremely important role in the students' learning. The more successful guides not only act as experts, but also adjust to the students' needs and act or speak accordingly. The

  18. 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.

  19. Floppy mitral valve (FMV)/mitral valve prolapse (MVP) and the FMV/MVP syndrome: pathophysiologic mechanisms and pathogenesis of symptoms.

    Science.gov (United States)

    Boudoulas, Konstantinos Dean; Boudoulas, Harisios

    2013-01-01

    Mitral valve prolapse (MVP) results from the systolic movement of a portion or segments of the mitral valve leaflets into the left atrium during left ventricular systole. It is well appreciated today that floppy mitral valve (FMV) is the central issue in the MVP and mitral valve regurgitation (MVR) story. The term FMV refers to the expansion of the area of the mitral valve leaflets with elongated chordae tendineae, chordae rupture and mitral annular dilation. FMV/MVP occurs in a heterogeneous group of patients with a wide spectrum of mitral valve involvement from mild to severe. Two types of symptoms can be defined in FMV/MVP patients. In one group of patients, symptoms are directly related to progressive MVR. In the other group, symptoms cannot be explained by the degree of MVR alone; activation of the autonomic nervous system has been implicated for the explanation of symptoms in this group of patients which is referred to as the FMV/MVP syndrome. In this brief review, the natural history, pathophysiologic mechanisms and management of patients with FMV/MVP/MVR and FMV/MVP syndrome are discussed. © 2013 S. Karger AG, Basel.

  20. 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

  1. In SilicoModel-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology.

    Science.gov (United States)

    Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

    2017-05-31

    Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current

  2. Understanding quantum mechanics by measuring the properties of mesoscopic devices

    International Nuclear Information System (INIS)

    Webb, R.

    1993-01-01

    Measurements of the electrical transport and magnetic properties of micron-size scale insulators, metals, semi-metals, and semiconductors at low temperatures have uncovered a wealth of unexpected phenomena. The only way to understand these new properties is by invoking many of the postulates of quantum mechanics. The author has confirmed that the electron acts as a long-range phase-coherent wave and conventional classical forces are not as important as scalar and vector potentials in determining the response of the electron as it moves through its environment. This talk will focus on the measurement of the Aharonov-Bohm self-interference effects, nonlocal transport phenomena, and persistent currents in normal metal ring structures that have been observed in these nanostructures

  3. Our Evolving Understanding of the Mechanism of Quinolones

    Directory of Open Access Journals (Sweden)

    Arnaud Gutierrez

    2018-04-01

    Full Text Available The maintenance of DNA supercoiling is essential for the proper regulation of a plethora of biological processes. As a consequence of this mode of regulation, ahead of the replication fork, DNA replication machinery is prone to introducing supercoiled regions into the DNA double helix. Resolution of DNA supercoiling is essential to maintain DNA replication rates that are amenable to life. This resolution is handled by evolutionarily conserved enzymes known as topoisomerases. The activity of topoisomerases is essential, and therefore constitutes a prime candidate for targeting by antibiotics. In this review, we present hallmark investigations describing the mode of action of quinolones, one of the antibacterial classes targeting the function of topoisomerases in bacteria. By chronologically analyzing data gathered on the mode of action of this imperative antibiotic class, we highlight the necessity to look beyond primary drug-target interactions towards thoroughly understanding the mechanism of quinolones at the level of the cell.

  4. 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.

  5. Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Hana Starobova

    2017-05-01

    Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

  6. 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.

  7. The pathophysiology of lifelong premature ejaculation

    Science.gov (United States)

    2016-01-01

    For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

  8. 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.

    Science.gov (United States)

    Hadrup, Niels

    2014-08-01

    Mathematical models have been developed for the toxicological risk assessment of chemical mixtures. However, exposure data as well as single chemical toxicological data are required for these models. When addressing this data need, it could be attractive to focus on chemicals with similar mechanisms of action, similar modes of action or with common target organs. In the European Union, efforts are currently being made to subgroup chemicals according to this need. However, it remains to be determined whether this is the best strategy to obtain data for risk assessment. In conditions 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 concomitantly contribute to the pathophysiology, suggesting that a grouping based on common target organs may also be inefficient. A better option may be to prioritise chemicals on the basis of potency and risk of exposure. In conclusion, there are arguments to suggest that we should concomitantly consider all targets that a chemical can affect in the human body and not merely a subset. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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

  10. The pathophysiology of Peyronie's disease.

    Science.gov (United States)

    El-Sakka, Ahmed I; Salabas, Emre; Dinçer, Murat; Kadioglu, Ates

    2013-09-01

    To review the contemporary knowledge of the pathophysiology of Peyronie's disease (PD). Medline was searched for papers published in English from 2000 to March 2013, using the keywords 'Peyronie's disease' and 'pathophysiology'. More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease.

  11. 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

  12. 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)

  13. Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

    Science.gov (United States)

    Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

    2015-09-01

    The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

  14. 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.

  15. A challenge to the striking genotypic heterogeneity of retinitis pigmentosa: a better understanding of the pathophysiology using the newest genetic strategies

    Science.gov (United States)

    Sorrentino, F S; Gallenga, C E; Bonifazzi, C; Perri, P

    2016-01-01

    Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by a complex association between tremendous genotypic multiplicity and great phenotypic heterogeneity. The severity of the clinical manifestation depends on penetrance and expressivity of the disease-gene. Also, various interactions between gene expression and environmental factors have been hypothesized. More than 250 genes with ~4500 causative mutations have been reported to be involved in different RP-related mechanisms. Nowadays, not more than the 50% of RPs are attributable to identified genes, whereas the rest of molecular defects are still undetectable, especially in populations where few genetic screenings have been performed. Therefore, new genetic strategies can be a remarkably useful tool to aid clinical diagnosis, potentially modifying treatment options, and family counseling. Genome-wide analytical techniques (array comparative genomic hybridization and single-nucleotide polymorphism genotyping) and DNA sequencing strategies (arrayed primer extension, Sanger sequencing, and ultra high-throughput sequencing) are successfully used to early make molecular diagnosis detecting single or multiple mutations in the huge heterogeneity of RPs. To date, further research needs to be carried out to better investigate the genotype/phenotype correlation, putting together genetic and clinical findings to provide detailed information concerning the risk of RP development and novel effective treatments. PMID:27564722

  16. Molecular pathophysiology of cerebral edema

    Science.gov (United States)

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    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. PMID:26661240

  17. 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.

  18. Pathophysiology of Cushing's disease.

    Science.gov (United States)

    Fehm, H L; Voigt, K H

    1979-01-01

    The term Cushing's disease is applied to those cases of Cushing's syndrome in which hypercortisolism is secondary to inappropriate secretion of ACTH by the pituitary. Studies on control of ACTH secretion in these patients reveal: (a) that the episodic secretion of ACTH is similar to the normal; however, frequency and amplitude of the secretory episodes lack the normal circadian rhythm; (b) that ACTH release can be stimulated by vasopressin and metyrapone in a normal or above-normal manner; and (c) that it can be suppressed by large doses of corticosteroids. When the dynamic aspects of the ACTH response to corticosteroid administration are studied, it appears that the normally negative differential feedback mechanism is converted into a positive one, whereas the delayed, integral mechanism is undisturbed. Patients with Cushing's disease in the presence of obvious pituitary tumors cannot be distinguished from those without pituitary tumors by studying only the pituitary function. All these and other well-known facts would favor the concept that ACTH secretion in Cushing's disease is under hypothalamic control whether or not a pituitary tumor is present. Moreover, there are observations that suggest that brain centers superior to the hypophysiotropic area of the hypothalamus are involved in the pathophysiology of Cushing's disease. This concept has led to the discovery of neurotropic drugs that are able to induce complete remission of Cushing's syndrome in a cerain percentage of patients. In some patients with severe psychiatric diseases, neuroendocrine abnormalities are present that resemble closely those characteristic for Cushing's disease. With the most refined neuroradiological methods, pituitary microadenomas are demonstrable in approximately 70% of patients with Cushing's disease, and this number compares well with those of earlier autopsy findings (70 to 80%). In a small number of patients (4 to 10%), these tumors are large and can easily be detected by

  19. Etiology of lumbar lordosis and its pathophysiology: a review of the evolution of lumbar lordosis, and the mechanics and biology of lumbar degeneration.

    Science.gov (United States)

    Sparrey, Carolyn J; Bailey, Jeannie F; Safaee, Michael; Clark, Aaron J; Lafage, Virginie; Schwab, Frank; Smith, Justin S; Ames, Christopher P

    2014-05-01

    The goal of this review is to discuss the mechanisms of postural degeneration, particularly the loss of lumbar lordosis commonly observed in the elderly in the context of evolution, mechanical, and biological studies of the human spine and to synthesize recent research findings to clinical management of postural malalignment. Lumbar lordosis is unique to the human spine and is necessary to facilitate our upright posture. However, decreased lumbar lordosis and increased thoracic kyphosis are hallmarks of an aging human spinal column. The unique upright posture and lordotic lumbar curvature of the human spine suggest that an understanding of the evolution of the human spinal column, and the unique anatomical features that support lumbar lordosis may provide insight into spine health and degeneration. Considering evolution of the skeleton in isolation from other scientific studies provides a limited picture for clinicians. The evolution and development of human lumbar lordosis highlight the interdependence of pelvic structure and lumbar lordosis. Studies of fossils of human lineage demonstrate a convergence on the degree of lumbar lordosis and the number of lumbar vertebrae in modern Homo sapiens. Evolution and spine mechanics research show that lumbar lordosis is dictated by pelvic incidence, spinal musculature, vertebral wedging, and disc health. The evolution, mechanics, and biology research all point to the importance of spinal posture and flexibility in supporting optimal health. However, surgical management of postural deformity has focused on restoring posture at the expense of flexibility. It is possible that the need for complex and costly spinal fixation can be eliminated by developing tools for early identification of patients at risk for postural deformities through patient history (genetics, mechanics, and environmental exposure) and tracking postural changes over time.

  20. 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…

  1. 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 ...

  2. 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...

  3. 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

  4. Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

    Science.gov (United States)

    Makris, Konstantinos; Spanou, Loukia

    2016-05-01

    Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

  5. Orthostatic intolerance: potential pathophysiology and therapy.

    Science.gov (United States)

    Lu, Chih-Cherng; Tseng, Ching-Jiunn; Tang, Hung-Shang; Tung, Che-Se

    2004-09-30

    Orthostatic intolerance affects an estimated 1 in 500 persons and causes a wide range of disabilities. After essential hypertension, it is the most frequently encountered dysautonomia, accounting for the majority of patients referred to centers specializing in autonomic disorders. Patients are typically young females with symptoms such as dizziness, visual changes, head and neck discomfort, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, syncope. Syncope is the most hazardous symptom of orthostatic intolerance, presumably occurring because of impaired cerebral perfusion and in part to compensatory autonomic mechanisms. The etiology of this syndrome is still unclear but is heterogeneous. Orthostatic intolerance used to be characterized by an overall enhancement of noradrenergic tone at rest in some patients and by a patchy dysautonomia of postganglionic sympathetic fibers with a compensatory cardiac sympathetic activation in others. However, recent advances in molecular genetics are improving our understanding of orthostatic intolerance, such as several genetic diseases (such as Ehler-Danlos syndrome and norepinephrine transporter deficiency) presenting with symptoms typical of orthostatic intolerance. Future work will include investigation of genetic functional mutations underlying interindividual differences in autonomic cardiovascular control, body fluid regulation, and vascular regulation in orthostatic intolerance patients. The goal of this review article is to describe recent advances in understanding the pathophysiological mechanisms of orthostatic intolerance and their clinical significance.

  6. 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

  7. Understanding mechanisms to predict and optimize biochar for agrochemical sorption

    Science.gov (United States)

    Hall, Kathleen; Gámiz, Beatriz; Cox, Lucia; Spokas, Kurt; Koskinen, William

    2017-04-01

    The ability of biochars to bind various organic compounds has been widely studied due to the potential effects on pesticide fate in soil and interest in the adoption of biochar as a "low-cost" filter material. However, the sorptive behaviors of biochars are extremely variable and much of the reported data is limited to specific biochar-chemical interactions. The lack of knowledge regarding biochar sorption mechanisms limits our current ability to predict and optimize biochar's use. This work unveils mechanistic drivers of organic pesticide sorption on biochars through targeted alteration of biochar surface chemistry. Changes in the quantity and type of functional groups on biochars and other black carbon materials were achieved through treatments with H2O2, and CO2, and characterized using Fourier transform infrared spectroscopy and scanning electron microscope (SEM/EDX). The sorption capacities of these treated biochars were subsequently measured to evaluate the effects of different surface moieties on the binding of target herbicides cyhalofop acid ((R)-2-[4-(4-cyano-2-fluorophenoxy)phenoxy]propionic acid) and clomazone (2-[(2-chlorophenyl)methyl]-4,4-dimethyl-1,2-oxazolidin-3-one). Sorption of both herbicides on the studied biochars increased following H2O2 activation; however, the influence of the H2O2 activation on sorption was more pronounced for cyhalofop acid (pKa = 3.9) than clomazone, which is non-ionizable. Increased cyhalofop acid sorption on H2O2 treated biochars can be attributed to the increase in oxygen containing functional groups as well as the decrease in biochar pH. In contrast, CO2 activation reduced the sorption of cyhalofop acid compared to untreated biochar. FTIR data suggest the reduced sorption on CO2 -treated biochar was due to the removal of surface carboxyl groups, further supporting the role of specific functionality in the sorption of ionizable herbicides. Results from this work offer insight into the mechanisms of sorption and

  8. Understanding the mechanisms of amorphous creep through molecular simulation.

    Science.gov (United States)

    Cao, Penghui; Short, Michael P; Yip, Sidney

    2017-12-26

    Molecular processes of creep in metallic glass thin films are simulated at experimental timescales using a metadynamics-based atomistic method. Space-time evolutions of the atomic strains and nonaffine atom displacements are analyzed to reveal details of the atomic-level deformation and flow processes of amorphous creep in response to stress and thermal activations. From the simulation results, resolved spatially on the nanoscale and temporally over time increments of fractions of a second, we derive a mechanistic explanation of the well-known variation of creep rate with stress. We also construct a deformation map delineating the predominant regimes of diffusional creep at low stress and high temperature and deformational creep at high stress. Our findings validate the relevance of two original models of the mechanisms of amorphous plasticity: one focusing on atomic diffusion via free volume and the other focusing on stress-induced shear deformation. These processes are found to be nonlinearly coupled through dynamically heterogeneous fluctuations that characterize the slow dynamics of systems out of equilibrium.

  9. 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

  10. 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

  11. Pathophysiology of Manganese-Associated Neurotoxicity

    Science.gov (United States)

    Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei

    2012-01-01

    Conference Summary Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms.(Rodier J, 1955) Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures.(Rodier J, 1955; Hobson et al., 2011) The clinical syndrome associated with Mn neurotoxicity has been called manganism. Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers.(Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011) Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers,(Huang et al., 2003) many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system.(Jankovic, 2005) The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from C. elegans

  12. 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…

  13. 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.

  14. 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

  15. Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

    African Journals Online (AJOL)

    The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

  16. 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.

  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. 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

  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. 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…

  1. Unit mechanisms of fission gas release: Current understanding and future needs

    Science.gov (United States)

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

    2018-06-01

    Gaseous fission product transport and release has a large impact on fuel performance, degrading fuel and gap properties. 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 beginning to reveal new understanding of the unit mechanisms that define fission product behavior. Here, existing research on the basic mechanisms of fission gas release during normal reactor operation are summarized and critical areas where 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 and to design fuels with improved performance. 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.

  2. Understanding the Growth Mechanism of GaN Epitaxial Layers on Mechanically Exfoliated Graphite.

    Science.gov (United States)

    Li, Tianbao; Liu, Chenyang; Zhang, Zhe; Yu, Bin; Dong, Hailiang; Jia, Wei; Jia, Zhigang; Yu, Chunyan; Gan, Lin; Xu, Bingshe; Jiang, Haiwei

    2018-04-27

    The growth mechanism of GaN epitaxial layers on mechanically exfoliated graphite is explained in detail based on classic nucleation theory. The number of defects on the graphite surface can be increased via O-plasma treatment, leading to increased nucleation density on the graphite surface. The addition of elemental Al can effectively improve the nucleation rate, which can promote the formation of dense nucleation layers and the lateral growth of GaN epitaxial layers. The surface morphologies of the nucleation layers, annealed layers and epitaxial layers were characterized by field-emission scanning electron microscopy, where the evolution of the surface morphology coincided with a 3D-to-2D growth mechanism. High-resolution transmission electron microscopy was used to characterize the microstructure of GaN. Fast Fourier transform diffraction patterns showed that cubic phase (zinc-blend structure) GaN grains were obtained using conventional GaN nucleation layers, while the hexagonal phase (wurtzite structure) GaN films were formed using AlGaN nucleation layers. Our work opens new avenues for using highly oriented pyrolytic graphite as a substrate to fabricate transferable optoelectronic devices.

  3. 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....

  4. The pathophysiology of migraine: implications for clinical management.

    Science.gov (United States)

    Charles, Andrew

    2018-02-01

    The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Pompili, Cecilia; Miserocchi, Giuseppe

    2016-02-01

    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.

  6. 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

  7. Pathophysiology of Glucocorticoid Signaling.

    Science.gov (United States)

    Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

    2018-06-01

    Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. 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

    Mathematical models have been developed for the toxicological risk assessment of chemical mixtures. However, exposure data as well as single chemical toxicological data are required for these models. When addressing this data need, it could be attractive to focus on chemicals with similar...... concomitantly contribute to the pathophysiology, suggesting that a grouping based on common target organs may also be inefficient. A better option may be to prioritise chemicals on the basis of potency and risk of exposure. In conclusion, there are arguments to suggest that we should concomitantly consider all...... targets that a chemical can affect in the human body and not merely a subset....

  9. 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.

  10. Atherosclerotic Plaque Destabilization Mechanisms, Models, and Therapeutic Strategies

    NARCIS (Netherlands)

    Silvestre-Roig, Carlos; de Winther, Menno P.; Weber, Christian; Daemen, Mat J.; Lutgens, Esther; Soehnlein, Oliver

    2014-01-01

    Understanding the pathophysiology of atherogenesis and the progression of atherosclerosis have been major goals of cardiovascular research during the previous decades. However, the complex molecular and cellular mechanisms underlying plaque destabilization remain largely obscure. Here, we review how

  11. 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.

  12. 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

  13. Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

    Science.gov (United States)

    Qashqari, Hanadi; Al-Mars, Amany; Chaudhary, Adeel; Abuzenadah, Adel; Damanhouri, Ghazi; Alqahtani, Mohammed; Mahmoud, Maged; El Sayed Zaki, Maysaa; Fatima, Kaneez; Qadri, Ishtiaq

    2013-10-01

    Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Investigating and Improving Student Understanding of Key Ideas in Quantum Mechanics throughout Instruction

    Science.gov (United States)

    Emigh, Paul Jeffrey

    This dissertation describes research on student understanding of quantum mechanics across multiple levels of instruction. The primary focus has been to identify patterns in student reasoning related to key concepts in quantum mechanics. The specific topics include quantum measurements, time dependence, vector spaces, and angular momentum. The research has spanned a variety of different quantum courses intended for introductory physics students, upper-division physics majors, and graduate students in physics. The results of this research have been used to develop a set of curriculum, Tutorials in Physics: Quantum Mechanics, for addressing the most persistent student difficulties. We document both the development of this curriculum and how it has impacted and improved student understanding of quantum mechanics.

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

    Science.gov (United States)

    Singh, Chandralekha

    2015-04-01

    Compared with introductory physics, relatively little is known about the development of expertise in advanced physics courses, especially in the case of quantum mechanics. We describe a theoretical framework for understanding the patterns of student reasoning difficulties and how students develop expertise in quantum mechanics. The framework posits that the challenges many students face in developing expertise in quantum mechanics are analogous to the challenges introductory students face in developing expertise in introductory classical mechanics. This framework incorporates the effects of diversity in students' prior preparation, goals and motivation for taking upper-level physics courses in general as well as the ``paradigm shift'' from classical mechanics to quantum mechanics. The framework is based on empirical investigations demonstrating that the patterns of reasoning, problem-solving, and self-monitoring difficulties in quantum mechanics bear a striking resemblance to those found in introductory classical mechanics. Examples from research in quantum mechanics and introductory classical mechanics will be discussed to illustrate how the patterns of difficulties are analogous as students learn to unpack the respective principles and grasp the formalism in each knowledge domain during the development of expertise. Embracing such a theoretical framework and contemplating the parallels between the difficulties in these two knowledge domains can enable researchers to leverage the extensive literature for introductory physics education research to guide the design of teaching and learning tools for helping students develop expertise in quantum mechanics. Support from the National Science Foundation is gratefully acknowledged.

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

    International Nuclear Information System (INIS)

    2014-01-01

    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.

  17. 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.

  18. 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.

  19. 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.

  20. [Functional pathophysiology of consciousness].

    Science.gov (United States)

    Jellinger, Kurt A

    2009-01-01

    from important somatic and sensory pathways and acts as a control system of neuronal activities of the cerebral cortex. The principal function of the ARAS is to focus our alertness on specific stimuli or internal processes, which run via complex neuronal cell groups and numerous neurotransmitters that influence various aspects of consciousness and wakefulness. Stimulation of the ARAS produces an arousal reaction as the electric correlate of consciousness; its destruction causes coma and related states. The highest level are cortical (prefrontal and association) networks for recognition, motor activity, longterm memory and attention, the left hemisphere being considered as the dominant one. Different levels of consciousness are distinguished: 1. hyperalertness, 2. alertness (normal state of wakefulness), 3. somnolence or lethargy, 4. obtundation with tendency to fall asleep, 5. stupor, 6. coma and its subtypes, like akinetic mutism, apallic syndrome or persistent vegative state, locked-in syndrome, delirium, and catatonia. They are caused by damages in various functional levels of the brain, by psychogenic factors or experimentally, and are accompanied by characteristic neurological and psychiatric disorders. The relevant morphological lesions can be detected by electrophysiological and imaging studies. The bases of functional anatomy and pathophysiology of consciousness, its cognitive aspects and its major disorders, their causes and functional substrates with reference to sleep and both spontaneous and iatrogenic disorders of consciousness are critically summarized.

  1. 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.

  2. Pathophysiology of osteoarthritis: perspectives

    Directory of Open Access Journals (Sweden)

    O. Viapiana

    2011-09-01

    Full Text Available Osteoarthritis is generally considered a degenerative disorder driven by mechanical alteration of joint cartilage, with the bone changes being reactive to cartilage changes. According to this pathogenetic mechanism the only strategy to prevent osteoarthritis should be based on the so-called “chondro-protective agents”. However, a number of recent finding suggests that both the initiation and the progression of the disease is driven by subchondral bone changes reactive to mechanical microdamages. These increase osteoblastic activity at the “tide-mark” with consequent enlargement of the epiphyses and osteophyte formation. The increased bone turnover is secondary to overproduction of cytokines that diffuse to cartilage tissue, where they suppress condrocyte activity and activate metallo-proteases. Preliminary observational finding and experimental data showed that inhibitors of bone turnover might slow osteoarthritis progression. The pathogenetic hypothesis for osteoarthritis illustrated here provides the rational for a new therapeutic approach to the disease.

  3. Understanding the molecular mechanisms involved in the interfacial self-healing of supramolecular rubbers

    NARCIS (Netherlands)

    Bose, R.K.; Garcia Espallargas, S.J.; Van der Zwaag, S.

    2013-01-01

    Supramolecular rubbers based on 2-aminoethylimidazolidone and fatty acids with epoxy crosslinks have been shown to self-heal via multiple hydrogen bonding sites. In this work, several tools are used to investigate the molecular mechanisms taking place at the interface to understand cohesive healing

  4. 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...

  5. 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.

  6. Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.

    Science.gov (United States)

    Antoine, Clemence; Mantovani, Francesca; Benfari, Giovanni; Mankad, Sunil V; Maalouf, Joseph F; Michelena, Hector I; Enriquez-Sarano, Maurice

    2018-01-01

    Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology. © 2018 American Heart Association, Inc.

  7. 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.

  8. 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 ...

  9. 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

  10. 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.

  11. 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; Freyss, Michel; Iglesias, Fernando; Kulacsy, Katalin; Pastore, Giovanni; Phillpot, Simon R.; Welland, Michael

    2018-06-01

    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.

  12. Framework for understanding the patterns of student difficulties in quantum mechanics

    Directory of Open Access Journals (Sweden)

    Emily Marshman

    2015-09-01

    Full Text Available [This paper is part of the Focused Collection on Upper Division Physics Courses.] 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 the challenges many students face in developing expertise in quantum mechanics are analogous to the challenges introductory students face in developing expertise in introductory classical mechanics. This framework incorporates both the effects of diversity in upper-level students’ prior preparation, goals, and motivation in general (i.e., the facts that even in upper-level courses, students may be inadequately prepared, have unclear goals, and have insufficient motivation to excel as well as the “paradigm shift” from classical mechanics to quantum mechanics. The framework is based on empirical investigations demonstrating that the patterns of reasoning, problem-solving, and self-monitoring difficulties in quantum mechanics bear a striking resemblance to those found in introductory classical mechanics. Examples from research in quantum mechanics and introductory classical mechanics are discussed to illustrate how the patterns of difficulties are analogous as students learn to unpack the respective principles and grasp the formalism in each knowledge domain during the development of expertise. Embracing such a framework and contemplating the parallels between the difficulties in these two knowledge domains can enable researchers to leverage the extensive literature for introductory physics education research to guide the design of teaching and learning tools for helping students develop expertise in quantum mechanics.

  13. Framework for understanding the patterns of student difficulties in quantum mechanics

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2015-12-01

    [This paper is part of the Focused Collection on Upper Division Physics Courses.] 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 the challenges many students face in developing expertise in quantum mechanics are analogous to the challenges introductory students face in developing expertise in introductory classical mechanics. This framework incorporates both the effects of diversity in upper-level students' prior preparation, goals, and motivation in general (i.e., the facts that even in upper-level courses, students may be inadequately prepared, have unclear goals, and have insufficient motivation to excel) as well as the "paradigm shift" from classical mechanics to quantum mechanics. The framework is based on empirical investigations demonstrating that the patterns of reasoning, problem-solving, and self-monitoring difficulties in quantum mechanics bear a striking resemblance to those found in introductory classical mechanics. Examples from research in quantum mechanics and introductory classical mechanics are discussed to illustrate how the patterns of difficulties are analogous as students learn to unpack the respective principles and grasp the formalism in each knowledge domain during the development of expertise. Embracing such a framework and contemplating the parallels between the difficulties in these two knowledge domains can enable researchers to leverage the extensive literature for introductory physics education research to guide the design of teaching and learning tools for helping students develop expertise in quantum mechanics.

  14. 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.

  15. 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.

  16. 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

  17. Contribution of local probes in the understanding of mechanical effect on localized corrosion

    International Nuclear Information System (INIS)

    Vignal, Vincent; Oltra, Roland; Mary, Nicolas

    2004-01-01

    Understanding the actual effects of mechanical stresses on the processes leading to pitting corrosion necessitates to develop both a mechanical approach and electrochemical experiments at a microscopic scale. Typical embrittlement can be observed after straining around MnS inclusions on a re-sulfurized 316 stainless steels and their corrosion sensitivity have been classified using the micro-capillary electrochemical cell technique. It has been shown that the numerical simulation of the location of stress gradients is possible before the local electrochemical analysis and could be a very interesting way to define the pitting susceptibility of micro-cracked areas during straining. (authors)

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. RI: Rheology as a Tool for Understanding the Mechanics of Live Ant Aggregations, Part 2

    Science.gov (United States)

    2016-11-04

    earwax of pigs, dogs , cows, and humans. We find that earwax is shear-thinning for all these animals. This ability enables it to cling to the ear in low...self-cleaning.” Society for Integrative and Comparative Biology annual meeting, 2017.  P. Yang, D. Dao, R. Lehner, D. Hu, “ The hydrodynamics of...RI: Rheology as a Tool for Understanding the Mechanics of Live Ant Aggregations, Part 2 An Anton Paarr MCR 501 rheometer was purchased in order to

  4. An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).

    Science.gov (United States)

    Hammer, Heinz F

    2014-02-01

    This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

  5. 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].

  6. 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.

  7. 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.

  8. Gas embolism: pathophysiology and treatment

    NARCIS (Netherlands)

    van Hulst, Robert A.; Klein, Jan; Lachmann, Burkhard

    2003-01-01

    Based on a literature search, an overview is presented of the pathophysiology of venous and arterial gas embolism in the experimental and clinical environment, as well as the relevance and aims of diagnostics and treatment of gas embolism. The review starts with a few historical observations and

  9. [Bacterial Translocation from Intestine: Microbiological, Immunological and Pathophysiological Aspects].

    Science.gov (United States)

    Podoprigora, G I; Kafarskaya, L I; Bainov, N A; Shkoporov, A N

    2015-01-01

    Bacterial translocation (BT) is both pathology and physiology phenomenon. In healthy newborns it accompanies the process of establishing the autochthonous intestinal microbiota and the host microbiome. In immunodeficiency it can be an aethio-pathogenetic link and a manifestation of infection or septic complications. The host colonization resistance to exogenous microbic colonizers is provided by gastrointestinal microbiota in concert with complex constitutional and adaptive defense mechanisms. BT may be result of barrier dysfunction and self-purification mechanisms involving the host myeloid cell phagocytic system and opsonins. Dynamic cell humoral response to microbial molecular patterns that occurs on the mucous membranes initiates receptorsignalingpathways and cascade ofreactions. Their vector and results are largely determined by cross-reactivity between microbiome and the host genome. Enterocyte barriers interacting with microbiota play leading role in providing adaptive, homeostatic and stress host reactivity. Microcirculatory ischemic tissue alterations and inflammatory reactions increase the intestinal barrier permeability and BT These processes a well as mechanisms for apoptotic cells and bacteria clearance are justified to be of prospective research interest. The inflammatory and related diseases caused by alteration and dysfunction of the intestinal barrier are reasonably considered as diseases of single origin. Maternal microbiota affects theformation of the innate immune system and the microbiota of the newborn, including intestinal commensal translocation during lactation. Deeper understanding of intestinal barrier mechanisms needs complex microbiological, immunological, pathophysiological, etc. investigations using adequate biomodels, including gnotobiotic animals.

  10. [Pathophysiology and treatment of orofacial pain.

    Science.gov (United States)

    Shinoda, Masamichi; Noma, Noboru

    "Pain" is one of body defense mechanisms and crucial for the life support. However, orofacial pain such as myofascial pain syndrome, burning mouth syndrome and trigeminal neuralgia plays no part in body defense mechanisms and requires therapeutic intervention. Recent studies have indicated that plastic changes in the activities of trigeminal neurons, satellite glial cells in trigeminal ganglion, secondary neurons, microglia and astrocytes in trigeminal spinal subnucleus following orofacial inflammation and trigeminal nerve injury are responsible for orofacial pain mechanisms. Clinically, it is well known that the etiologic differential diagnosis which consists of careful history-taking and physical examination is essential for therapeutic decision in patients with orofacial pain. This report outlines the current knowledge on the pathophysiology, diagnosis, treatment of orofacial pain.

  11. Reactive Molecular Dynamics Simulations to Understand Mechanical Response of Thaumasite under Temperature and Strain Rate Effects.

    Science.gov (United States)

    Hajilar, Shahin; Shafei, Behrouz; Cheng, Tao; Jaramillo-Botero, Andres

    2017-06-22

    Understanding the structural, thermal, and mechanical properties of thaumasite is of great interest to the cement industry, mainly because it is the phase responsible for the aging and deterioration of civil infrastructures made of cementitious materials attacked by external sources of sulfate. Despite the importance, effects of temperature and strain rate on the mechanical response of thaumasite had remained unexplored prior to the current study, in which the mechanical properties of thaumasite are fully characterized using the reactive molecular dynamics (RMD) method. With employing a first-principles based reactive force field, the RMD simulations enable the description of bond dissociation and formation under realistic conditions. From the stress-strain curves of thaumasite generated in the x, y, and z directions, the tensile strength, Young's modulus, and fracture strain are determined for the three orthogonal directions. During the course of each simulation, the chemical bonds undergoing tensile deformations are monitored to reveal the bonds responsible for the mechanical strength of thaumasite. The temperature increase is found to accelerate the bond breaking rate and consequently the degradation of mechanical properties of thaumasite, while the strain rate only leads to a slight enhancement of them for the ranges considered in this study.

  12. 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.

  13. 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.

  14. [Current concepts in pathophysiology of CRPS I].

    Science.gov (United States)

    Nickel, F T; Maihöfner, C

    2010-02-01

    Knowledge about the pathophysiology underlying the complex regional pain syndrome (CRPS) has increased over the last years. Classically, CRPS has been considered to be mainly driven by sympathetic dysfunction with sympathetically maintained pain being its major pathogenetic mechanism. Currently, the disease is understood as result of a complex interplay between altered somatosensory, motor, autonomic and inflammatory systems. Peripheral and central sensitization is a common feature in CRPS as in other neuropathic pain syndromes. One important mechanism is the sensitization of spinal dorsal horn cells via activation of postsynaptic NMDA-receptors by chronic C-fiber input. Differential activity of endogenous pain modulating systems may play a pivotal role in the development of CRPS, too. Neuronal plasticity of the somatosensory cortex accounts for central sensory signs. Also the motor system is subject to central adaptive changes in patients with CRPS. Calcitonin-gene related peptide (CGRP) and substance P mediate neurogenic inflammation. Additionally other proinflammatory cytokines involved in the inflammatory response in CRPS have been identified. In terms of the sympathetic nervous system, recent evidence rather points to a sensitization of adrenergic receptors than to increased efferent sympathetic activity. Particularly the expression of alpha (1)-adrenoceptors on nociceptive C-fibers may play a major role. These pathophysiological ideas do not exclude each other. In fact they complement one another. The variety of the involved systems may explain the versatile clinical picture of CRPS. Georg Thieme Verlag KG Stuttgart, New York.

  15. 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.

  16. A Unified Pathophysiological Construct of Diabetes and its Complications.

    Science.gov (United States)

    Schwartz, Stanley S; Epstein, Solomon; Corkey, Barbara E; Grant, Struan F A; Gavin Iii, James R; Aguilar, Richard B; Herman, Mary E

    2017-09-01

    Advances in understanding diabetes mellitus (DM) through basic and clinical research have helped clarify and reunify a disease state fragmented into numerous etiologies and subtypes. It is now understood that a common pathophysiology drives the diabetic state throughout its natural history and across its varied clinical presentations, a pathophysiology involving metabolic insults, oxidative damage, and vicious cycles that aggravate and intensify organ dysfunction and damage. This new understanding of the disease requires that we revisit existing diagnostics and treatment approaches, which were built upon outmoded assumptions. 'The Common Pathophysiologic Origins of Diabetes Mellitus and its Complications Construct' is presented as a more accurate, foundational, and translatable construct of DM that helps make sense of the hitherto ambiguous findings of long-term outcome studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Assessing pathophysiology of cancer anorexia.

    Science.gov (United States)

    Laviano, Alessandro; Koverech, Angela; Seelaender, Marilia

    2017-09-01

    Cancer anorexia is a negative prognostic factor and is broadly defined as the loss of the interest in food. However, multiple clinical domains contribute to the phenotype of cancer anorexia. The characterization of the clinical and molecular pathophysiology of cancer anorexia may enhance the efficacy of preventive and therapeutic strategies. Clinical trials showed that cancer anorexia should be considered as an umbrella encompassing different signs and symptoms contributing to appetite disruption in cancer patients. Loss of appetite, early satiety, changes in taste and smell are determinants of cancer anorexia, whose presence should be assessed in cancer patients. Interestingly, neuronal correlates of cancer anorexia-related symptoms have been revealed by brain imaging techniques. The pathophysiology of cancer anorexia is complex and involves different domains influencing eating behavior. Limiting the assessment of cancer anorexia to questions investigating changes in appetite may impede correct identification of the targets to address.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, Vickie S., E-mail: wilson.vickie@epa.gov [National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Keshava, Nagalakshmi [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Hester, Susan [National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Segal, Deborah; Chiu, Weihsueh [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States); Thompson, Chad M. [ToxStrategies, Inc., 23501 Cinco Ranch Blvd., Suite G265, Katy, TX 77494 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW, Washington, DC 20460 (United States)

    2013-09-15

    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.

  19. 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

  20. New elements to understand hydrogen diffusion and trapping mechanisms in quenched and tempered HSLA martensitic steels

    International Nuclear Information System (INIS)

    Frappart, S.

    2011-01-01

    Hydrogen Embrittlement is a complex phenomenon responsible of metal degradation. It mainly depends on the material (chemical composition, heat treatment), the environment or the mechanical state. The main goal of this study is to give new elements to understand hydrogen diffusion and trapping mechanisms in High Strength Low Alloy martensitic steels used in the field of 'Oil and Gas' applications and nuclear industry. In this way, the purpose is to identify hydrogen trapping sites related to microstructural features as a basis for a better knowledge concerning hydrogen embrittlement. Thus, accurate electrochemical permeation set-up (with or without a mechanical state) were developed as well as a procedure to thoroughly analyze experimental data. An original approach on how to interpret electrochemical permeation results has been therefore performed. Afterward, the effect of different critical parameters has been assessed i.e. the membrane thickness, the surface state of the detection side as well as the microstructure and the mechanical state. The relationship between physical parameters associated to diffusion and trapping with the microstructure evolution will give rise to a first thought 'toward the embrittlement'

  1. 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

  2. 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; Manolagas, Stavros C

    2017-01-01

    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. Copyright © 2017 the American Physiological Society.

  3. 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.

  4. 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.

  5. 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.

  6. [Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

    Science.gov (United States)

    Watanabe, Ken

    2009-01-01

    The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation

  7. Statistical grand rounds: understanding the mechanism: mediation analysis in randomized and nonrandomized studies.

    Science.gov (United States)

    Mascha, Edward J; Dalton, Jarrod E; Kurz, Andrea; Saager, Leif

    2013-10-01

    In comparative clinical studies, a common goal is to assess whether an exposure, or intervention, affects the outcome of interest. However, just as important is to understand the mechanism(s) for how the intervention affects outcome. For example, if preoperative anemia was shown to increase the risk of postoperative complications by 15%, it would be important to quantify how much of that effect was due to patients receiving intraoperative transfusions. Mediation analysis attempts to quantify how much, if any, of the effect of an intervention on outcome goes though prespecified mediator, or "mechanism" variable(s), that is, variables sitting on the causal pathway between exposure and outcome. Effects of an exposure on outcome can thus be divided into direct and indirect, or mediated, effects. Mediation is claimed when 2 conditions are true: the exposure affects the mediator and the mediator (adjusting for the exposure) affects the outcome. Understanding how an intervention affects outcome can validate or invalidate one's original hypothesis and also facilitate further research to modify the responsible factors, and thus improve patient outcome. We discuss the proper design and analysis of studies investigating mediation, including the importance of distinguishing mediator variables from confounding variables, the challenge of identifying potential mediators when the exposure is chronic versus acute, and the requirements for claiming mediation. Simple designs are considered, as well as those containing multiple mediators, multiple outcomes, and mixed data types. Methods are illustrated with data collected by the National Surgical Quality Improvement Project (NSQIP) and utilized in a companion paper which assessed the effects of preoperative anemic status on postoperative outcomes.

  8. 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.

  9. 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

  10. Pathophysiology and Treatment of Alien Hand Syndrome

    Directory of Open Access Journals (Sweden)

    Harini Sarva

    2014-12-01

    Full Text Available Background: Alien hand syndrome (AHS is a disorder of involuntary, yet purposeful, hand movements that may be accompanied by agnosia, aphasia, weakness, or sensory loss. We herein review the most reported cases, current understanding of the pathophysiology, and treatments.Methods: We performed a PubMed search in July of 2014 using the phrases “alien hand syndrome,” “alien hand syndrome pathophysiology,” “alien hand syndrome treatment,” and “anarchic hand syndrome.” The search yielded 141 papers (reviews, case reports, case series, and clinical studies, of which we reviewed 109. Non‐English reports without English abstracts were excluded.Results: Accumulating evidence indicates that there are three AHS variants: frontal, callosal, and posterior. Patients may demonstrate symptoms of multiple types; there is a lack of correlation between phenomenology and neuroimaging findings. Most pathologic and functional imaging studies suggest network disruption causing loss of inhibition as the likely cause. Successful interventions include botulinum toxin injections, clonazepam, visuospatial coaching techniques, distracting the affected hand, and cognitive behavioral therapy.Discussion: The available literature suggests that overlap between AHS subtypes is common. The evidence for effective treatments remains anecdotal, and, given the rarity of AHS, the possibility of performing randomized, placebo‐controlled trials seems unlikely. As with many other interventions for movement disorders, identifying the specific functional impairments caused by AHS may provide the best guidance towards individualized supportive care.

  11. Similar verbal memory impairments in schizophrenia and healthy aging. Implications for understanding of neural mechanisms.

    Science.gov (United States)

    Silver, Henry; Bilker, Warren B

    2015-03-30

    Memory is impaired in schizophrenia patients but it is not clear whether this is specific to the illness and whether different types of memory (verbal and nonverbal) or memories in different cognitive domains (executive, object recognition) are similarly affected. To study relationships between memory impairments and schizophrenia we compared memory functions in 77 schizophrenia patients, 58 elderly healthy individuals and 41 young healthy individuals. Tests included verbal associative and logical memory and memory in executive and object recognition domains. We compared relationships of memory functions to each other and to other cognitive functions including psychomotor speed and verbal and spatial working memory. Compared to the young healthy group, schizophrenia patients and elderly healthy individuals showed similar severe impairment in logical memory and in the ability to learn new associations (NAL), and similar but less severe impairment in spatial working memory and executive and object memory. Verbal working memory was significantly more impaired in schizophrenia patients than in the healthy elderly. Verbal episodic memory impairment in schizophrenia may share common mechanisms with similar impairment in healthy aging. Impairment in verbal working memory in contrast may reflect mechanisms specific to schizophrenia. Study of verbal explicit memory impairment tapped by the NAL index may advance understanding of abnormal hippocampus dependent mechanisms common to schizophrenia and aging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. 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

  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. PMID:26931398

  14. 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.

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

    KAUST Repository

    Mateker, William R.; McGehee, Michael D.

    2016-01-01

    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.

  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. 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.

  18. The adverse pathophysiological effects of outdoor air pollution on the body tissues

    Directory of Open Access Journals (Sweden)

    Simona Perčič

    2018-04-01

    Full Text Available Long-term exposure to outdoor air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. There are many published studies about the pathophysiological mechanisms involved in response of the body tissues to outdoor air pollution exposure. The aim of our review was to investigate the problem of outdoor air pollution and health effects of pathological mechanisms, with specific goal to point out public health intervention strategies based upon a clearer understanding of pathophysiological mechanisms of outdoor air pollution. A systematic literature review was carried out in two bibliographic databases, Science Direct and PubMed, in the period from January 1995 to December 2015. We conducted a systematic analysis of 95 studies, 43 of them being review studies and 52 original studies. The systematic analysis was done in three steps, for each body tissue separately (respiratory diseases, cardiovascular diseases, neurologic diseases and diabetes mellitus. This insight into literature review may help foster more effective preventive measures at the public health level as well as potential intervention strategies based upon a clearer understanding of the involved pathways.

  19. Novel Tissue Models of Junctional Epidermolysis Bullosa to Characterize Functional Mechanisms of Sulfur Mustard Injury to Human Skin

    National Research Council Canada - National Science Library

    Garlick, Joanthan

    2003-01-01

    In the second year of our research, our laboratory has extensively studied skin pathophysiology in response to SM by adapting in vivo, human skin/nude mouse chimera to further understand mechanisms...

  20. Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    Jessica Y. Lee

    2018-03-01

    Full Text Available Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD. The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestinal tissue integrity which will have a significant impact on the development of novel therapies targeting the intestinal mucosa.

  1. 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)

  2. 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

  3. 95th Anniversary 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

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

    International Nuclear Information System (INIS)

    Marshman, Emily; Singh, Chandralekha

    2017-01-01

    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. (paper)

  9. 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.

  10. 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

  11. 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)

  12. Understanding deformation mechanisms during powder compaction using principal component analysis of compression data.

    Science.gov (United States)

    Roopwani, Rahul; Buckner, Ira S

    2011-10-14

    Principal component analysis (PCA) was applied to pharmaceutical powder compaction. A solid fraction parameter (SF(c/d)) and a mechanical work parameter (W(c/d)) representing irreversible compression behavior were determined as functions of applied load. Multivariate analysis of the compression data was carried out using PCA. The first principal component (PC1) showed loadings for the solid fraction and work values that agreed with changes in the relative significance of plastic deformation to consolidation at different pressures. The PC1 scores showed the same rank order as the relative plasticity ranking derived from the literature for common pharmaceutical materials. The utility of PC1 in understanding deformation was extended to binary mixtures using a subset of the original materials. Combinations of brittle and plastic materials were characterized using the PCA method. The relationships between PC1 scores and the weight fractions of the mixtures were typically linear showing ideal mixing in their deformation behaviors. The mixture consisting of two plastic materials was the only combination to show a consistent positive deviation from ideality. The application of PCA to solid fraction and mechanical work data appears to be an effective means of predicting deformation behavior during compaction of simple powder mixtures. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. 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.

  14. 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).

  15. 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 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Priapism: etiology, pathophysiology and management

    Directory of Open Access Journals (Sweden)

    Van Der Horst C.

    2003-01-01

    Full Text Available The understanding of erectile physiology has improved the prompt diagnosis and treatment of priapism. Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation and failure to subside despite orgasm. Numerous etiologies of this condition are considered. Among others a disturbed detumescence mechanism, which may due to excess release of contractile neurotransmitters, obstruction of draining venules, malfunction of the intrinsic detumescence mechanism or prolonged relaxation of intracavernosal smooth muscle are postulated. Treatment of priapism varies from a conservative medical to a drastic surgical approach. Two main types of priapism; veno-occlusive low flow (ischemic and arterial high flow (non-ischemic, must be distinguished to choose the correct treatment option for each type. Patient history, physical examination, penile hemodynamics and corporeal metabolic blood quality provides distinction between a static or dynamic pathology. Priapism can be treated effectively with intracavernous vasoconstrictive agents or surgical shunting. Alternative options, such as intracavernous injection of methylene blue (MB or selective penile arterial embolization (SPEA, for the management of high and low flow priapism are described and a survey on current treatment modalities is given.

  18. Does knowledge of seat design and whiplash injury mechanisms translate to understanding outcomes?

    Science.gov (United States)

    Ivancic, Paul C

    2011-12-01

    Review of whiplash injury mechanisms and effects of anti-whiplash systems including active head restraint (AHR) and Whiplash Protection System (WHIPS). This article provides an overview of previous biomechanical and epidemiological studies of AHR and WHIPS and investigates whether seat design and biomechanical knowledge of proposed whiplash injury mechanisms translates to understanding outcomes of rear crash occupants. In attempt to reduce whiplash injuries, some newer automobiles incorporate anti-whiplash systems such as AHR or WHIPS. During a rear crash, mechanically based systems activate by occupant momentum pressing into the seatback whereas electronically based systems activate using crash sensors and an electronic control unit linked to the head restraint. To investigate the effects of AHR and WHIPS on occupant responses including head and neck loads and motions, biomechanical studies of simulated rear crashes have been performed using human volunteers, mathematical models, crash dummies, whole cadavers, and hybrid cadaveric/surrogate models. Epidemiological studies have evaluated the effects of AHR and WHIPS on reducing whiplash injury claims and lessening subjective complaints of neck pain after rear crashes. RESULTS.: Biomechanical studies indicate that AHR and WHIPS reduced the potential for some whiplash injuries but did not completely eliminate the injury risk. Epidemiological outcomes indicate reduced whiplash injury claims or subjective complaints of crash-related neck pain between 43 and 75% due to AHR and between 21% and 49% due to WHIPS as compared to conventional seats and head restraints. Yielding energy-absorbing seats aim to reduce occupant loads and accelerations whereas AHRs aim to provide early head support to minimize head and neck motions. Continued objective biomechanical and epidemiological studies of anti-whiplash systems together with industry, governmental, and clinical initiatives will ultimately lead to reduced whiplash injuries

  19. 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.

  20. A full understanding of oxygen reduction reaction mechanism on Au(1 1 1) surface

    Science.gov (United States)

    Yang, Yang; Dai, Changqing; Fisher, Adrian; Shen, Yanchun; Cheng, Daojian

    2017-09-01

    Oxygen reduction and hydrogen peroxide reduction are technologically important reactions in energy-conversion devices. In this work, a full understanding of oxygen reduction reaction (ORR) mechanism on Au(1 1 1) surface is investigated by density functional theory (DFT) calculations, including the reaction mechanisms of O2 dissociation, OOH dissociation, and H2O2 dissociation. Among these ORR mechanisms on Au(1 1 1), the activation energy of \\text{O}2* hydrogenation reaction is much lower than that of \\text{O}2* dissociation, indicating that \\text{O}2* hydrogenation reaction is more appropriate at the first step than \\text{O}2* dissociation. In the following, H2O2 can be formed with the lower activation energy compared with the OOH dissociation reaction, and finally H2O2 could be generated as a detectable product due to the high activation energy of H2O2 dissociation reaction. Furthermore, the potential dependent free energy study suggests that the H2O2 formation is thermodynamically favorable up to 0.4 V on Au(1 1 1), reducing the overpotential for 2e - ORR process. And the elementary step of first H2O formation becomes non-spontaneous at 0.4 V, indicating the difficulty of 4e - reduction pathway. Our DFT calculations show that H2O2 can be generated on Au(1 1 1) and the first electron transfer is the rate determining step. Our results show that gold surface could be used as a good catalyst for small-scale manufacture and on-site production of H2O2.

  1. 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).

  2. Understanding the mechanical and acoustical characteristics of sand aggregates compacting under triaxial conditions

    Science.gov (United States)

    Hangx, Suzanne; Brantut, Nicolas

    2016-04-01

    failure being present but occurring to a relatively limited extent. Acoustic emission localization showed that failure was focussed along a broad shear plane. At higher confining pressure pervasive grain failure clearly accommodated compaction, though no strain localization was observed and failure appeared to be through cataclastic flow. Chemical environment, i.e. chemically inert decane vs. water as a pore fluid, had no significant effect on compaction in the strain rate range tested. Grain size distribution or grain shape also appeared to not affect the observed mechanical behaviour. Our results can be used to better understand the compaction behaviour of poorly consolidated sandstones. Future research will focus on understanding the effect of cementation on strain localization in deforming artificial Ottawa sandstone.

  3. 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...... haemodynamics, regional hypoxia, auto-, and paracrine factors (adenosine, endothelin, reactive oxygen species) to direct cytotoxic effects. Although these potential mediators of CIN will be discussed separately, several factors may act in concert to perturb kidney function after exposure to contrast media. From...... 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...

  4. Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus

    Science.gov (United States)

    Abell, Sally K.; De Courten, Barbora; Boyle, Jacqueline A.; Teede, Helena J.

    2015-01-01

    Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM. PMID:26110385

  5. A theoretical framework informing research about the role of stress in the pathophysiology of bipolar disorder.

    Science.gov (United States)

    Brietzke, Elisa; Mansur, Rodrigo Barbachan; Soczynska, Joanna; Powell, Alissa M; McIntyre, Roger S

    2012-10-01

    The staggering illness burden associated with Bipolar Disorder (BD) invites the need for primary prevention strategies. Before preventative strategies can be considered in individuals during a pre-symptomatic period (i.e., at risk), unraveling the mechanistic steps wherein external stress is transduced and interacts with genetic vulnerability in the early stages of BD will be a critical conceptual necessity. Herein we comprehensively review extant studies reporting on stress and bipolar disorder. The overarching aim is to propose a conceptual framework to inform research about the role of stress in the pathophysiology of BD. Computerized databases i.e. PubMed, PsychInfo, Cochrane Library and Scielo were searched using the following terms: "bipolar disorder" cross-referenced with "stress", "general reaction to stress", "resilience", "resistance", "recovery" "stress-diathesis", "allostasis", and "hormesis". Data from literature indicate the existence of some theoretical models to understand the influence of stress in the pathophysiology of BD, including classical stress-diathesis model and new models such as allostasis and hormesis. In addition, molecular mechanisms involved in stress adaptation (resistance, resilience and recovery) can also be translated in research strategies to investigate the impact of stress in the pathophysiology of BD. Most studies are retrospective and/or cross sectional, do not consider the period of development, assess brain function with only one or few methodologies, and use animal models which are not always similar to human phenotypes. The interaction between stress and brain development is dynamic and complex. In this article we proposed a theoretical model for investigation about the role of stress in the pathophysiology of BD, based on the different kinds of stress adaptation response and their putative neurobiological underpinnings. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. 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.

  7. Fisiopatologia da enxaqueca Migraine pathophysiology

    Directory of Open Access Journals (Sweden)

    MAURICE B. VINCENT

    1998-12-01

    Full Text Available A fisiopatologia da enxaqueca ainda não foi completamente elucidada. As principais estruturas envolvidas parecem ser o sistema nervoso central (córtex e tronco cerebral, o sistema trigeminovascular e os vasos correspondentes, outras fibras autonômicas que inervam estes vasos, e os vários agentes vasoativos locais, como a SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, entre outros. A depressão alastrante é o fenômeno neurológico que provavelmente justifica achados experimenais e clínicos na enxaqueca. Ela tem velocidade de propagação semelhante à aura, ativa o núcleo espinhal do trigêmeo e está relacionada à liberação de CGRP e NO. Alterações circulatórias detectadas por métodos complementares reforçam o papel da depressão alastrante. A identificação de anormalidades em pelo menos três loci (cromossomas 19 e 1 na enxaqueca hemiplégica familiar ocorreu recentemente. Elas estão relacionadas a anormalidades nos canais de cálcio voltagem dependentes tipo P/Q, específicos do sistema nervoso central, que regulam a liberação de vários neurotransmissores, incluindo possivelmente a serotonina. A exemplo de outras anormalidades neurológicas paroxísticas que resultam da hiperexcitabilidade da membrana plasmática, é possível que a enxaqueca ocorra devido a uma desordem de canais iônicos.The pathophysiology of migraine is not yet fully understood. The most important structures involved seem to be the central nervous system (cortex and brain stem, the trigeminovascular system and related cranial arteries, other autonomic fibres innervating such vessels, and various local vasoactive agents, including SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, among others. The spreading depression phenomenon may explain clinical as well experimental findings in migraine. Its propagation velocity mirrors what is found in clinical aura, it may activate the spinal trigeminal nucleus and may induce CGRP and NO release. Circulatory changes detected with

  8. 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

    2017-01-01

    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. PMID:28776039

  9. 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.

  10. The pathophysiology of trauma-induced coagulopathy.

    Science.gov (United States)

    Frith, Daniel; Brohi, Karim

    2012-12-01

    Transfusion paradigms and protocols have evolved at a rapid pace in the last few years to ameliorate the adverse effects of trauma-induced coagulopathy (TIC). This has occurred despite fragmented and inadequate knowledge of the underlying pathophysiology that they are supposed to treat. This review will collate and assimilate the most recent data about TIC in order to present our state-of-the-art understanding of this condition. TIC was conventionally construed simply as depletion, dysfunction or dilution of procoagulant factors. However, contemporary understanding recognizes it as an imbalance of the dynamic equilibrium between procoagulant factors, anticoagulant factors, platelets, endothelium and fibrinolysis. The endogenous component of TIC (acute traumatic coagulopathy) is not merely a consumptive coagulopathy, but is characterized by isolated factor V inhibition, dysfibrinogenaemia, systemic anticoagulation, impaired platelet function and hyperfibrinolysis. Acute traumatic coagulopathy then becomes exacerbated by hypothermia, acidosis and resuscitation with hypocoagulable fluids. Further improvement in the outcome from trauma-haemorrhage is possible with more refined and tailored haemostatic resuscitation. Achieving this will depend upon a better understanding of the haemostatic defects that develop after injury.

  11. 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.

  12. 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

  13. 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.

  14. Understanding gas production mechanism and effectiveness of well stimulation in the Haynesville shale through reservoir simulation

    Energy Technology Data Exchange (ETDEWEB)

    Fan, L.; Thompson, J.W.; Robinson, J.R. [Schlumberger, Houston, TX (United States)

    2010-07-01

    The Haynesville Shale Basin is one of the large and most active shale gas plays in the United States, with 185 horizontal rigs currently in place. The Haynesville Shale is a very tight source rock and resource play. The gas resources are being converted into gas reserves with horizontal wells and hydraulic fracture treatments. A complex fracture network created during well stimulation is the main factor in generating superior early well performance in the area. The key to making better wells in all the gas shale plays is to understand how to create more surface area during hydraulic stimulation jobs and preserve the surface area for as long as possible. This paper presented a unique workflow and methodology that has enabled analysis of production data using reservoir simulation to explain the shale gas production mechanism and the effectiveness of stimulation treatments along laterals. Since 2008, this methodology has been used to analyze production data from more than 30 horizontal wells in the Haynesville Shale. Factors and parameters relating to short and long term well performance were investigated, including pore pressure, rock matrix quality, natural fractures, hydraulic fractures, and complex fracture networks. Operators can use the simulation results to determine where and how to spend resources to produce better wells and to reduce the uncertainties of developing these properties. 19 refs., 1 tab., 17 figs.

  15. Does an Emphasis on the Concept of Quantum States Enhance Students' Understanding of Quantum Mechanics?

    Science.gov (United States)

    Greca, Ileana Maria; Freire, Olival

    Teaching physics implies making choices. In the case of teaching quantum physics, besides an educational choice - the didactic strategy - another choice must be made, an epistemological one, concerning the interpretation of quantum theory itself. These two choices are closely connected. We have chosen a didactic strategy that privileges the phenomenological-conceptual approach, with emphasis upon quantum features of the systems, instead of searching for classical analogies. This choice has led us to present quantum theory associated with an orthodox, yet realistic, interpretation of the concept of quantum state, considered as the key concept of quantum theory, representing the physical reality of a system, independent of measurement processes. The results of the mplementation of this strategy, with three groups of engineering students, showed that more than a half of them attained a reasonable understanding of the basics of quantum mechanics (QM) for this level. In addition, a high degree of satisfaction was attained with the classes as 80% of the students of the experimental groups claimed to have liked it and to be interested in learning more about QM.

  16. Application of microscopy methods to the understanding of mechanisms involved in ilmenite reduction by hydrogen

    International Nuclear Information System (INIS)

    De Vries, M.; Grey, I.; Fitzgerald, J.

    2003-01-01

    Full text: Titania pigment is one of the major drivers of the mineral sands industry with production of over 4 million tpa in 2002 for paints, plastics, paper and ceramics applications. The main feedstock for titania pigment production is ilmenite, FeTiO 3 . It is used either directly or after it has been upgraded to a higher titania content. The major commercial upgrading processes are electro smelting (titania slag) or high temperature char reduction followed by iron removal (synthetic rutile SR). Future ilmenite upgrading processes are likely to use low temperature hydrogen reduction according to reaction, followed by aeration of the metallic iron and acid leaching to produce a high grade SR (Nicholson et al, 2000). The commercial application of such a process requires a detailed knowledge of the kinetics of reaction. FeTiO 3 + H 2 = Fe(m) + TiO 2 + H 2 O. The kinetics of ilmenite reduction has been studied at CSIRO Minerals using a specially designed thermogravimetric apparatus built around a Cahn pressurised symmetrical beam balance. The kinetics have been measured as a function of different operating parameters such as temperature, gas velocity and pressure. The parameters were set so as to minimise mass transport effects and increase chemical reaction control and to ensure the reduction kinetics are outside the gas starvation region. Small samples were used that had been sintered at close to melting point to form large grains with low unconnected porosity. High flow rates of reactant gas were also used. The application of a range of microscopy techniques to the reduced samples at various stages of reaction conversion has been critical to the development of an understanding of the reaction mechanisms. From analysis of TEM, IFESEM and optical microscopy results it appears that initially, chemical reaction is rate controlling at the surface and as the reaction proceeds topochemically inwards then diffusion mechanisms increase their control. Reaction proceeds

  17. 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, ...

  18. 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.

  19. Improvised explosive devices: pathophysiology, injury profiles and current medical management.

    Science.gov (United States)

    Ramasamy, A; Hill, A M; Clasper, J C

    2009-12-01

    The improvised explosive device (IED), in all its forms, has become the most significant threat to troops operating in Afghanistan and Iraq. These devices range from rudimentary home made explosives to sophisticated weapon systems containing high-grade explosives. Within this broad definition they may be classified as roadside explosives and blast mines, explosive formed pojectile (EFP) devices and suicide bombings. Each of these groups causeinjury through a number of different mechanisms and can result in vastly different injury profiles. The "Global War on Terror" has meant that incidents which were previously exclusively seen in conflict areas, can occur anywhere, and clinicians who are involved in emergency trauma care may be required to manage casualties from similar terrorist attacks. An understanding of the types of devices and their pathophysiological effects is necessary to allow proper planning of mass casualty events and to allow appropriate management of the complex poly-trauma casualties they invariably cause. The aim of this review article is to firstly describe the physics and injury profile from these different devices and secondly to present the current clinical evidence that underpins their medical management.

  20. 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

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

    Science.gov (United States)

    Mao, Huiting; Cheng, Irene; Zhang, Leiming

    2016-10-01

    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/GEM increasing from the

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

    KAUST Repository

    Nasr Saleh, Mohamed; Lubineau, Gilles

    2014-01-01

    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

  3. 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.

  4. 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.

  5. Neutron reflectivity study of critical adsorption. Application to the understanding of environmental mechanisms

    International Nuclear Information System (INIS)

    Jestin, Jacques

    2001-01-01

    This study is within the scope of fundamental knowledge transfer to a field case-study, i.e. the understanding of the adsorption properties of binary mixtures against a wall in the case of soil pollution by liquid hydrocarbons. From the theoretical study of critical adsorption, which has been well described in the literature, we carried out experiments on model systems by using neutron techniques. Neutron reflectivity was then applied to the liquid-vapor interface of three different binary mixtures: perfluorohexane-hexane, deuterated methanol-cyclohexane and methanol-deuterated cyclohexane. The experimental data were analysed according to the theoretical prediction of Fisher and De Gennes, along with Liu and Fisher that suggested a power law decrease of the concentration profile (with an exponent equal to 0.52) followed by an exponential function. The characteristic exponent and the amplitude ratios for the methanol-cyclohexane mixtures were found fitted well with theoretical values for the three systems. Only the perfluorohexane-hexane mixture exhibited a particular behavior in the adsorption process that affected the power law amplitude value. This step allowed us to study non critical adsorption and to apply neutrons techniques, e.g. reflectivity and small angles neutrons scattering, to a water-2,5 dimethylpyridine mixture against silica, which is a model system for soils polluted by water/hydrocarbon mixtures. These experiments highlighted new experimental difficulties, which were not fully solved over this study, together with some problems in the analysis that would require specific modelling. Nevertheless, this study shows the capabilities of neutrons techniques to investigate some environmental mechanisms. Moreover, some of the results reported here can be used as a basis for future experiments. (author)

  6. 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.

  7. Pathophysiology of valvular heart disease.

    Science.gov (United States)

    Zeng, Y I; Sun, Rongrong; Li, Xianchi; Liu, Min; Chen, Shuang; Zhang, Peiying

    2016-04-01

    Valvular heart disease (VHD) is caused by either damage or defect in one of the four heart valves, aortic, mitral, tricuspid or pulmonary. Defects in these valves can be congenital or acquired. Age, gender, tobacco use, hypercholesterolemia, hypertension, and type II diabetes contribute to the risk of disease. VHD is an escalating health issue with a prevalence of 2.5% in the United States alone. Considering the likely increase of the aging population worldwide, the incidence of acquired VHD is expected to increase. Technological advances are instrumental in identifying congenital heart defects in infants, thereby adding to the growing VHD population. Almost one-third of elderly individuals have echocardiographic or radiological evidence of calcific aortic valve (CAV) sclerosis, an early and subclinical form of CAV disease (CAVD). Of individuals ages >60, ~2% suffer from disease progression to its most severe form, calcific aortic stenosis. Surgical intervention is therefore required in these patients as no effective pharmacotherapies exist. Valvular calcium load and valve biomineralization are orchestrated by the concerted action of diverse cell-dependent mechanisms. Signaling pathways important in skeletal morphogenesis are also involved in the regulation of cardiac valve morphogenesis, CAVD and the pathobiology of cardiovascular calcification. CAVD usually occurs without any obvious symptoms in early stages over a long period of time and symptoms are identified at advanced stages of the disease, leading to a high rate of mortality. Aortic valve replacement is the only primary treatment of choice. Biomarkers such as asymmetric dimethylarginine, fetuin-A, calcium phosphate product, natriuretic peptides and osteopontin have been useful in improving outcomes among various disease states. This review, highlights the current understanding of the biology of VHD, with particular reference to molecular and cellular aspects of its regulation. Current clinical questions

  8. 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.

  9. 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.

  10. 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.

  11. 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 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 triaxial deformation test on such cracked granites

  12. 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

  13. Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

    Science.gov (United States)

    Hanson, M. A.; Gluckman, P. D.

    2014-01-01

    Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

  14. Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.

    Science.gov (United States)

    Matsumoto, Naoyuki; Kobayashi, Naoki; Uda, Natsu; Hirota, Miwako; Kawasaki, Hiroshi

    2018-03-15

    Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

  15. Using interviews to understand the assignment mechanism in a nonexperimental study: the case of eighth grade algebra.

    Science.gov (United States)

    Rickles, Jordan H

    2011-10-01

    Many inquiries regarding the causal effects of policies or programs are based on research designs where the treatment assignment process is unknown, and thus valid inferences depend on tenuous assumptions about the assignment mechanism. This article draws attention to the importance of understanding the assignment mechanism in policy and program evaluation studies, and illustrates how information collected through interviews can develop a richer understanding of the assignment mechanism. Focusing on the issue of student assignment to algebra in 8th grade, I show how a preliminary data collection effort aimed at understanding the assignment mechanism is particularly beneficial in multisite observational studies in education. The findings, based on ten interviews and administrative data from a large school district, draw attention to the often ignored heterogeneity in the assignment mechanism across schools. These findings likely extend beyond the current research project in question to related educational policy issues such as ability grouping, tracking, differential course taking, and curricular intensity, as well as other social programs in which the assignment mechanism can differ across sites.

  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. How Do Students in an Innovative Principle-Based Mechanics Course Understand Energy Concepts?

    Science.gov (United States)

    Ding, Lin; Chabay, Ruth; Sherwood, Bruce

    2013-01-01

    We investigated students' conceptual learning of energy topics in an innovative college-level introductory mechanics course, entitled Matter & Interactions (M&I) Modern Mechanics. This course differs from traditional curricula in that it emphasizes application of a small number of fundamental principles across various scales, involving…

  18. 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.

  19. Stroke MRI: pathophysiology, potential and perspectives

    International Nuclear Information System (INIS)

    Fiehler, J.; Kucinski, T.; Zeumer, H.

    2004-01-01

    Magnetic resonance imaging (MRT) is increasingly utilized as the primary imaging modality in major stroke centers. The ability to depict several aspects of individual pathophysiology makes the use of MRI in stroke both attractive and complex. Profound knowledge of the pathophysiology of the imaging findings is crucial for a rational diagnostic workup. The pathophysiology of MRI in stroke will be reviewed considering recent experiences in clinical application, and the potential of stroke MRI will be assessed. Further perspectives like application of 'blood oxygen level dependent' (BOLD) and the use of multiparametric prediction maps will be discussed. (orig.) [de

  20. 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

  1. Understanding the mechanism of sweet taste: synthesis of tritium labeled guanidineacetic acids

    Energy Technology Data Exchange (ETDEWEB)

    Nagarajan, S.; Kellogg, M.S.; DuBois, G.E. (NutraSweet Company, Mt. Prospect, IL (United States)); Williams, D.S. (Amersham International plc, Cardiff (United Kingdom). Cardiff Labs.); Gresk, C.J.; Markos, C.S. (Searle Research and Development, Skokie, IL (United States))

    1992-08-01

    Syntheses of tritium labeled guanidineacetic acid sweetener and a tritiated photoaffinity labeling reagent via the catalytic hydrogenation of the dibromo intermediates are described. These labeled compounds were required for the investigation of sweet taste mechanism. (author).

  2. Understanding the mechanism of sweet taste: synthesis of tritium labeled guanidineacetic acids

    International Nuclear Information System (INIS)

    Nagarajan, S.; Kellogg, M.S.; DuBois, G.E.; Williams, D.S.

    1992-01-01

    Syntheses of tritium labeled guanidineacetic acid sweetener and a tritiated photoaffinity labeling reagent via the catalytic hydrogenation of the dibromo intermediates are described. These labeled compounds were required for the investigation of sweet taste mechanism. (author)

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

    KAUST Repository

    Chakrabarty, Souvik; Ouyang, Christine; Krysak, Marie; Trikeriotis, Markos; Cho, Kyoungyoung; Giannelis, Emmanuel P.; Ober, Christopher K.

    2013-01-01

    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.

  4. 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.

  5. 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.

  6. Analysis of multiple instructional techniques on the understanding and retention of select mechanical topics

    Science.gov (United States)

    Fetsco, Sara Elizabeth

    There are several topics that introductory physics students typically have difficulty understanding. The purpose of this thesis is to investigate if multiple instructional techniques will help students to better understand and retain the material. The three units analyzed in this study are graphing motion, projectile motion, and conservation of momentum. For each unit students were taught using new or altered instructional methods including online laboratory simulations, inquiry labs, and interactive demonstrations. Additionally, traditional instructional methods such as lecture and problem sets were retained. Effectiveness was measured through pre- and post-tests and student opinion surveys. Results suggest that incorporating multiple instructional techniques into teaching will improve student understanding and retention. Students stated that they learned well from all of the instructional methods used except the online simulations.

  7. 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

  8. Pathophysiological relationships between heart failure and depression and anxiety.

    Science.gov (United States)

    Chapa, Deborah W; Akintade, Bimbola; Son, Heesook; Woltz, Patricia; Hunt, Dennis; Friedmann, Erika; Hartung, Mary Kay; Thomas, Sue Ann

    2014-04-01

    Depression and anxiety are common comorbid conditions in patients with heart failure. Patients with heart failure and depression have increased mortality. The association of anxiety with increased mortality in patients with heart failure is not established. The purpose of this article is to illustrate the similarities of the underlying pathophysiology of heart failure, depression, and anxiety by using the Biopsychosocial Holistic Model of Cardiovascular Health. Depression and anxiety affect biological processes of cardiovascular function in patients with heart failure by altering neurohormonal function via activation of the hypothalamic-pituitary-adrenal axis, autonomic dysregulation, and activation of cytokine cascades and platelets. Patients with heart failure and depression or anxiety may exhibit a continued cycle of heart failure progression, increased depression, and increased anxiety. Understanding the underlying pathophysiological relationships in patients with heart failure who experience comorbid depression and/or anxiety is critical in order to implement appropriate treatments, educate patients and caregivers, and educate other health professionals.

  9. 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....

  10. Understanding Irreversible Degradation of Nb3Sn Wires with Fundamental Fracture Mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Yuhu [PPPL; Calzolaio, Ciro [Univ of Geneva; Senatore, Carmine [Univ of Geneva

    2014-08-01

    Irreversible performance degradation of advanced Nb3Sn superconducting wires subjected to transverse or axial mechanical loading is a critical issue for the design of large-scale fusion and accelerator magnets such as ITER and LHC. Recent SULTAN tests indicate that most cable-in-conduit conductors for ITER coils made of Nb3Sn wires processed by various fabrication techniques show similar performance degradation under cyclic loading. The irreversible degradation due to filament fracture and local strain accumulation in Nb3Sn wires cannot be described by the existing strand scaling law. Fracture mechanic modeling combined with X-ray diffraction imaging of filament micro-crack formation inside the wires under mechanical loading may reveal exciting insights to the wire degradation mechanisms. We apply fundamental fracture mechanics with a singularity approach to study influence of wire filament microstructure of initial void size and distribution to local stress concentration and potential crack propagation. We report impact of the scale and density of the void structure on stress concentration in the composite wire materials for crack initiation. These initial defects result in an irreversible degradation of the critical current beyond certain applied stress. We also discuss options to minimize stress concentration in the design of the material microstructure for enhanced wire performance for future applications.

  11. 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

  12. 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

  13. 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.

  14. [Neural pathophysiology of cancer anorexia].

    Science.gov (United States)

    Sánchez-Lara, K; Sosa-Sánchez, R; Green-Renner, D; Méndez-Sánchez, N

    2011-01-01

    Approximately two thirds of cancer patients at advanced stages of the disease suffer from anorexia. Defined as the loss of the desire to eat, anorexia lower the energy intake which further exacerbates a progressive deterioration of the patient nutritional status. Malnutrition has a large impact on morbidity and mortality affecting the quality of life. Cancer anorexia etiology is multifactorial including complex interactions among the tumor, host metabolism and antineoplastic treatment. New related theories include peripheral and brain mechanisms affecting hypothalamic pathways; inducing behavioral and metabolic failure of responses to energy balance. The aim of this review is to describe actual concepts involved in the pathogenesis of cancer anorexia with special interest in brain mechanisms. Anorexia and reduced food intake are important issues in the management of cancer patients, more knowledge about pathogenic mechanism is needed to improve therapeutic options, prognosis and quality of life in cancer patients.

  15. 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...... or secondary diabetes), classic obesity-associated insulin resistant diabetes ( f-P-C-peptide >= 568 pmol/l) and a normoinsulinopenic group (333 age of our new T2D patients was 61 years (range 21-95 years), 57% were men. We found that 3.0% newly diagnosed T2D patients...... suffered from LADA, 3.9% from secondary diabetes, 6.0% from steroid induced diabetes 5.9% had insulinopenic diabetes, whereas 56.7% presented the classic obesity-associated insulin-resistant phenotype. 24.6% was classified as normoinsulinopenic patients. Conclusion: We conclude that newly diagnosed T2D...

  16. 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.

  17. 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…

  18. Investigating and Improving Student Understanding of Quantum Mechanics in the Context of Single Photon Interference

    Science.gov (United States)

    Marshman, Emily; Singh, Chandralekha

    2017-01-01

    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…

  19. 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

  20. Massage therapy: understanding the mechanisms of action on blood pressure. A scoping review.

    Science.gov (United States)

    Nelson, Nicole L

    2015-10-01

    Massage therapy (MT) has shown potential in reducing blood pressure (BP); however, the psychophysiological pathways and structures involved in this outcome are unclear. The aims of this scoping review were twofold. (1) To summarize the current knowledge of the mechanisms of action of MT on BP. (2) To highlight the research gaps and challenges that researchers must overcome to further elucidate how MT attenuates BP. A scoping review was conducted to examine the evidence regarding the mechanisms of action of MT on BP. This review included the thematic analysis of 27 publications that considered the influence of MT on BP. Based on this analysis, six potential BP mediating pathways were identified Current theories suggest that MT exerts sympatholytic effects through physiologic and psychological mechanisms, improves hypothalamus-pituitary-adrenocortical axis function, and increases in blood flow, which, in turn, may improve endothelial function. Future study is needed, using more scientifically rigorous methodology, to fully elucidate the mechanism of action of MT. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  1. 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…

  2. 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

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

    Science.gov (United States)

    Estili, Mehdi; Sakka, Yoshio

    2014-12-01

    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

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

    Science.gov (United States)

    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

  5. 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.

  6. 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

  7. New Insight in Understanding the mechanical responses of polymer glasses using molecular dynamic simulation

    Science.gov (United States)

    Zheng, Yexin; Wang, Shi-Qing; Tsige, Mesfin

    The Kremer-Grest bead-spring model has been the standard model in molecular dynamics simulation of polymer glasses. However, due to current computational limitations in accessing relevant time scales in polymer glasses in a reasonable amount of CPU time, simulation of mechanical response of polymer glasses in molecular dynamic simulations requires a much higher quenching rate and deformation rate than used in experiments. Despite several orders of magnitude difference in time scale between simulation and experiment, previous studies have shown that simulations can produce meaningful results that can be directly compared with experimental results. In this work we show that by tuning the quenching rate and deformation rate relative to the segmental relaxation times, a reasonable mechanical response shows up in the glassy state. Specifically, we show a younger glass prepared with a faster quenching rate shows glassy responses only when the imposed deformation rate is proportionally higher. the National Science Foundation (DMR-1444859 and DMR-1609977).

  8. An investigation and understanding of the mechanical response of Palmyrah timber

    International Nuclear Information System (INIS)

    Sobier, Hatim; Menzemer, C.C.; Srivatsan, T.S.

    2003-01-01

    The Palmyrah tree flourishes in tropical areas around South East Asia, and particularly in Sri Lanka. Palmyrah is an important economic resource for the region, and has found use in structural applications for both residential dwellings and commercial buildings. While there is a great deal of local field experience with Palmyrah, the mechanical properties have not been well characterized or understood. In an effort to assist engineers with the design and efficient use of the timber, a study was undertaken to evaluate the mechanical response of Palmyrah and develop estimates of design allowable properties. Properties evaluated include static bending strength, modulus, compression parallel and perpendicular to the grain, shear parallel to the grain and tensile strength parallel and perpendicular to the grain. In order to gain insight into the behavior of the wood, samples were examined using standard optical microscopy techniques. In addition, available fracture surfaces were examined using scanning electron microscopy

  9. [Use of laws of interelement interactions for understanding of mechanisms of various human diseases].

    Science.gov (United States)

    Barashkov, G K; Zaĭtseva, L I

    2008-01-01

    The review considers the basic laws of interaction of elements in real physiological conditions of metabolism. The law of replacement and two it consequences have been formulated taking into account a major principle of cybernetics, the feedback principle. A rule of a fractional threshold and the law of toxicity based on the Mertz's rules have been formulated. These laws have been used here for consideration of mechanisms of occurrence and development of apoptosis and also side-effects of statins. Study of bioinorganic mechanisms of different diseases is a erspective way for search of complex connections of metals and ligands, capable to interaction with initiators of chain reactions, and for a finding of substances--inhibitors these reactions.

  10. Understanding of mechanical properties of graphite on the basis of mesoscopic microstructure (review)

    International Nuclear Information System (INIS)

    Ishihara, M.; Shibata, T.; Takahashi, T.; Baba, S.; Hoshiya, T.

    2002-01-01

    With the aim of nuclear application of ceramics in the high-temperature engineering field, the authors have investigated the mesoscopic microstructure related to the mechanical and thermal properties of ceramics. In this paper, recent activities concerning mechanical properties, strength and Young's modulus are presented. In the strength research field, the brittle fracture model considering pore/grain mesoscopic microstructure was expanded so as to render possible an estimation of the strength under stress gradient conditions. Furthermore, the model was expanded to treat the pore/crack interaction effect. The performance of the developed model was investigated from a comparison with experimental data and the Weibull strength theory. In the field of Young's modulus research, ultrasonic wave propagation was investigated using the pore/wave interaction model. Three kinds of interaction modes are treated in the model. The model was applied to the graphite, and its applicability was investigated through comparison with experimental data. (authors)

  11. 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

  12. A numerical toolkit to understand the mechanics of partially saturated granular materials

    OpenAIRE

    Roux , Jean-Noël

    2015-01-01

    ``Focus on Fluids'' section; International audience; The mechanisms by which a wetting, non-saturating liquid bestows macroscopic cohesion and strength to a granular material are usually not accessible to micromechanical investigations for saturations exceeding the pendular regime of isolated menisci, easily studied by discrete element models. The " JFM-Rapids " paper (vol. 762, R5, 2015) by Delenne, Richefeu and Radja¨ıRadja¨ı, exploiting a multiphase Lattice Boltzmann approach, pioneers the...

  13. 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

  14. 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

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

    OpenAIRE

    Epel, Elissa S.; Lithgow, Gordon J.

    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 str...

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

    Directory of Open Access Journals (Sweden)

    Jérémy Roque

    2018-01-01

    Full Text Available 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

  17. 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.

  18. Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems

    Science.gov (United States)

    Rivera-Jacquez, Hector J.; Masunov, Artëm E.

    2018-06-01

    Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications.

  19. 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

  20. 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.

  1. Pathophysiological characterization of asthma transitions across adolescence.

    Science.gov (United States)

    Arshad, Syed Hasan; Raza, Abid; Lau, Laurie; Bawakid, Khalid; Karmaus, Wilfried; Zhang, Hongmei; Ewart, Susan; Patil, Veersh; Roberts, Graham; Kurukulaaratchy, Ramesh

    2014-11-29

    Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of transitional adolescent asthma phenotypes in a longitudinal birth cohort. The Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterization included questionnaires, skin tests, spirometry, exhaled nitric oxide, bronchial challenge and (in a subset of 100 at 18-years) induced sputum. Asthma groups were "never asthma" (no asthma since birth), "persistent asthma" (asthma at age 10 and 18), "remission asthma" (asthma at age 10 but not at 18) and "adolescent-onset asthma" (asthma at age 18 but not at age 10). Participants whose asthma remitted during adolescence had lower bronchial reactivity (odds ratio (OR) 0.30; CI 0.10 -0.90; p = 0.03) at age 10 plus greater improvement in lung function (forced expiratory flow 25-75% gain: 1.7 L; 1.0-2.9; p = 0.04) compared to persistent asthma by age 18. Male sex (0.3; 0.1-0.7; p adolescent-onset asthma showed eosinophilic airway inflammation (3.0%, 0.7-6.6), not seen in persistent asthma (1.0%, 0-3.9), while remission group had the lowest sputum eosinophil count (0.3%, 0-1.4) and lowest eosinophils/neutrophils ratio of 0.0 (Interquartile range: 0.1). Asthma remission during adolescence is associated with lower initial BHR and greater gain in small airways function, while adolescent-onset asthma is primarily eosinophilic.

  2. 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

  3. Understanding mobility degeneration mechanism in organic thin-film transistors (OTFT)

    Science.gov (United States)

    Wang, Wei; Wang, Long; Xu, Guangwei; Gao, Nan; Wang, Lingfei; Ji, Zhuoyu; Lu, Congyan; Lu, Nianduan; Li, Ling; Liu, Miwng

    2017-08-01

    Mobility degradation at high gate bias is often observed in organic thin film transistors. We propose a mechanism for this confusing phenomenon, based on the percolation theory with the presence of disordered energy landscape with an exponential density of states. Within a simple model we show how the surface states at insulator/organic interface trap a portion of channel carriers, and result in decrease of mobility as well as source/drain current with gate voltage. Depending on the competition between the carrier accumulation and surface trapping effect, two different carrier density dependences of mobility are obtained, in excellent agreement with experiment data.

  4. 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

  5. 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.

  6. Understanding the Mechanical forces of Self-Expandable Metal Stents in the Biliary Ducts.

    Science.gov (United States)

    Isayama, Hiroyuki; Nakai, Yousuke; Hamada, Tsuyoshi; Matsubara, Saburo; Kogure, Hirofumi; Koike, Kazuhiko

    2016-12-01

    Self-expandable metallic stent (SEMS) was an effective biliary endoprosthesis. Mechanical properties of SEMS, radial and axial force (RF, AF), may play important roles in the bile duct after placement. RF was well known dilation force and influenced on the occurrence of migration. AF, newly proposed by this author, was defined as the recovery force when the SEMS vended. AF was related with the cause of bile duct kinking, pancreatitis, and cholecystitis due to the compression of the bile duct, orifice of the cystic duct, and pancreatic orifice. Ideal SEMS may show high RF and low AF.

  7. 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.

  8. 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.

  9. 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.

  10. Understanding the Cognitive and Affective Mechanisms that Underlie Proxy Risk Perceptions among Caregivers of Asthmatic Children.

    Science.gov (United States)

    Shepperd, James A; Lipsey, Nikolette P; Pachur, Thorsten; Waters, Erika A

    2018-07-01

    Medical decisions made on behalf of another person-particularly those made by adult caregivers for their minor children-are often informed by the decision maker's beliefs about the treatment's risks and benefits. However, we know little about the cognitive and affective mechanisms influencing such "proxy" risk perceptions and about how proxy risk perceptions are related to prominent judgment phenomena. Adult caregivers of minor children with asthma ( N = 132) completed an online, cross-sectional survey assessing 1) cognitions and affects that form the basis of the availability, representativeness, and affect heuristics; 2) endorsement of the absent-exempt and the better-than-average effect; and 3) proxy perceived risk and unrealistic comparative optimism of an asthma exacerbation. We used the Pediatric Asthma Control and Communication Instrument (PACCI) to assess asthma severity. Respondents with higher scores on availability, representativeness, and negative affect indicated higher proxy risk perceptions and (for representativeness only) lower unrealistic optimism, irrespective of asthma severity. Conversely, respondents who showed a stronger display of the better-than-average effect indicated lower proxy risk perceptions but did not differ in unrealistic optimism. The absent-exempt effect was unrelated to proxy risk perceptions and unrealistic optimism. Heuristic judgment processes appear to contribute to caregivers' proxy risk perceptions of their child's asthma exacerbation risk. Moreover, the display of other, possibly erroneous, judgment phenomena is associated with lower caregiver risk perceptions. Designing interventions that target these mechanisms may help caregivers work with their children to reduce exacerbation risk.

  11. 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.

  12. 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)

  13. Biomineralization of gold by Mucor plumbeus: The progress in understanding the mechanism of nanoparticles' formation.

    Science.gov (United States)

    Maliszewska, Irena; Tylus, Włodzimierz; Chęcmanowski, Jacek; Szczygieł, Bogdan; Pawlaczyk-Graja, Izabela; Pusz, Wojciech; Baturo-Cieśniewska, Anna

    2017-09-01

    This contribution describes the deposition of gold nanoparticles by microbial reduction of Au(III) ions using the mycelium of Mucor plumbeus. Biosorption as the major mechanism of Au(III) ions binding by the fungal cells and the reduction of them to the form of Au(0) on/in the cell wall, followed by the transportation of the synthesized gold nanoparticles to the cytoplasm, is postulated. The probable mechanism behind the reduction of Au(III) ions is discussed, leading to the conclusion that this process is nonenzymatic one. Chitosan of the fungal cell wall is most likely to be the major molecule involved in biomineralization of gold by the mycelium of M. plumbeus. Separation of gold nanoparticles from the cells has been carried out by the ultrasonic disintegration and the obtained nanostructures were characterized by UV-vis spectroscopy and transmission electron micrograph analysis. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1381-1392, 2017. © 2017 American Institute of Chemical Engineers.

  14. 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.

  15. Getting the phenotypes right: an essential ingredient for understanding aetiological mechanisms underlying persistent violence and developing effective treatments

    Directory of Open Access Journals (Sweden)

    Sheilagh Hodgins

    2009-11-01

    Full Text Available In order to reduce societal levels of violence, it is essential to advance understanding of the neurobiological mechanisms involved in initiating and maintaining individual patterns of physical aggression. New technologies such as Magnetic Resonance Imagining and analyses of DNA provide tools for identifying these mechanisms. The reliability and validity of the results of studies using these tools depend not only on aspects of the technology, but also on the methodological rigour with which the studies are conducted, particularly with respect to characterizing the phenotype. The present article discusses five challenges confronting scientists who aim to advance understanding of the neurobiological mechanisms associated with persistent violence. These challenges are: (1 to develop evidence-based hypotheses and to design studies that test alternate hypotheses; (2 to recruit samples that are homogeneous with respect to variables that may be linked to neurobiological mechanisms underpinning violent behaviour; (3 to use reliable and valid measures in order to fully characterize participants so that the external validity of the results is evident; (4 to restrict the range of age of participants so as not to confuse developmental change with group differences; and (5 to take account of sex. Our goal is to contribute to elevating methodological standards in this new field of research and to thereby improve the validity of results and move closer to finding effective ways to reduce violence

  16. Understanding the crystallization mechanism of delafossite CuGaO2 for controlled hydrothermal synthesis of nanoparticles and nanoplates.

    Science.gov (United States)

    Yu, Mingzhe; Draskovic, Thomas I; Wu, Yiying

    2014-06-02

    The delafossite CuGaO2 is an important p-type transparent conducting oxide for both fundamental science and industrial applications. An emerging application is for p-type dye-sensitized solar cells. Obtaining delafossite CuGaO2 nanoparticles is challenging but desirable for efficient dye loading. In this work, the phase formation and crystal growth mechanism of delafossite CuGaO2 under low-temperature (mechanism to explain the formation of large CuGaO2 nanoplates. Importantly, by suppressing this OA process, delafossite CuGaO2 nanoparticles that are 20 nm in size were successfully synthesized for the first time. Moreover, considering the structural and chemical similarities between the Cu-based delafossite series compounds, the understanding of the hydrothermal chemistry and crystallization mechanism of CuGaO2 should also benefit syntheses of other similar delafossites such as CuAlO2 and CuScO2.

  17. 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

    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......There is a growing interest in using marine phospholipids (PL) as ingredient for food fortification due to their numerous health benefits. However, the use of marine PL for food fortification is a challenge due to the complex nature of the degradation products that are formed during the handling...... 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...

  18. 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.

  19. Integrated Approach for Understanding Impurity Adsorption on Calcite: Mechanisms for Micro-scale Surface Phenomena

    Science.gov (United States)

    Vinson, M. D.; Arvidson, R. S.; Luttge, A.

    2004-12-01

    A longstanding goal within the field of environmental geochemistry has been the development of a fundamental understanding of the kinetics that governs the interactions of solution-borne impurities with the calcite mineral surface. Recent dissolution experiments using Mg2+, Mn2+, and Sr2+ have shown distinct differences in the interaction of these three impurity ions with the calcite crystal surface. Because the dissolution of carbonate minerals in soils and sediments influences the uptake and migration of groundwater contaminants, a rigorous understanding of the basic processes that occur at the mineral-fluid interface is necessary. We have used vertical scanning interferometry (VSI) coupled with scanning probe microscopy (SPM) to examine calcite crystal dissolution in the presence of Mg2+, Mn2+, and Sr2+, all known dissolution inhibitors and possible groundwater contaminants. We have studied the kinetics of impurity-crystal interactions at a pH 8.8, and in the presence or absence of dissolved inorganic carbon. Our data show that, when individually introduced into undersaturated solutions, Mg2+ and Mn2+ are shown to activate the calcite crystal surface, resulting in enhanced etch pit nucleation rates and step density. Conversely, Sr2+ is shown to cause passivation of the calcite surface. The effect is intensified when solutions are saturated with respect to atmospheric CO2. Results indicate that aqueous CO32- (or HCO3-) may influence how aqueous metal ionic complexes interact with the crystal surface. Furthermore, the influence is differently exhibited, and passivation or activation ultimately depends on the properties of the diffusing metal ion or metal-hydroxide complex. These properties include for example, differences in hydration enthalpy, the effective ionic radius, and electron shell configuration.

  20. Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

    Science.gov (United States)

    Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi

    2017-03-15

    Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Understanding the ordering mechanisms of self-assembled nanostructures of block copolymers during zone annealing

    Energy Technology Data Exchange (ETDEWEB)

    Cong, Zhinan; Zhang, Liangshun, E-mail: zhangls@ecust.edu.cn, E-mail: jlin@ecust.edu.cn; Wang, Liquan; Lin, Jiaping, E-mail: zhangls@ecust.edu.cn, E-mail: jlin@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2016-03-21

    A theoretical method based on dynamic version of self-consistent field theory is extended to investigate directed self-assembly behaviors of block copolymers subjected to zone annealing. The ordering mechanisms and orientation modulation of microphase-separated nanostructures of block copolymers are discussed in terms of sweep velocity, wall preference, and Flory-Huggins interaction parameter. The simulated results demonstrate that the long-range ordered nanopatterns are achieved by lowering the sweep velocity of zone annealing due to the incorporation of templated ordering of block copolymers. The surface enrichment by one of the two polymer species induces the orientation modulation of defect-free nanostructures through finely tuning the composition of block copolymers and the preference of walls. Additionally, the Flory-Huggins interaction parameters of block copolymers in the distinct regions are main factors to design the zone annealing process for creating the highly ordered nanostructures with single orientation.

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

    KAUST Repository

    Jiang, Jing; Zhang, Ben; Yu, Mufei; Li, Li; Neisser, Mark; Sung Chun, Jun; Giannelis, Emmanuel P.; Ober, Christopher K.

    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.

  4. 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.

  5. Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells.

    Science.gov (United States)

    Armstrong, Christine A; Tomita, Kazunori

    2017-03-01

    Aberrant activation of telomerase occurs in 85-90% of all cancers and underpins the ability of cancer cells to bypass their proliferative limit, rendering them immortal. The activity of telomerase is tightly controlled at multiple levels, from transcriptional regulation of the telomerase components to holoenzyme biogenesis and recruitment to the telomere, and finally activation and processivity. However, studies using cancer cell lines and other model systems have begun to reveal features of telomeres and telomerase that are unique to cancer. This review summarizes our current knowledge on the mechanisms of telomerase recruitment and activation using insights from studies in mammals and budding and fission yeasts. Finally, we discuss the differences in telomere homeostasis between normal cells and cancer cells, which may provide a foundation for telomere/telomerase targeted cancer treatments. © 2017 The Authors.

  6. 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.

  7. 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.

  8. Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells.

    Science.gov (United States)

    Benameur, Laila; Charif, Naceur; Li, Yueying; Stoltz, Jean-François; de Isla, Natalia

    2015-01-01

    Under physiological conditions, there is a production of limited range of free radicals. However, when the cellular antioxidant defence systems, overwhelm and fail to reverse back the free radicals to their normal basal levels, there is a creation of a condition of redox disequilibrium termed "oxidative stress", which is implicated in a very wide spectrum of genetic, metabolic, and cellular responses. The excess of free radicals can, cause unfavourable molecular alterations to biomolecules through oxidation of lipids, proteins, RNA and DNA, that can in turn lead to mutagenesis, carcinogenesis, and aging. Mesenchymal stem cells (MSCs) have been proven to be a promising source of cells for regenerative medicine, and to be useful in the treatment of pathologies in which tissue damage is linked to oxidative stress. Moreover, MSCs appeared to efficiently manage oxidative stress and to be more resistant to oxidative insult than normal somatic cells, making them an interesting and testable model for the role of oxidative stress in the aging process. In addition, aging is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Also, there is an obvious link between intracellular reactive oxygen species levels and cellular senescence. To date, few studies have investigated the promotion of aging by oxidative stress on human MSCs, and the mechanism by which oxidative stress induce stem cell aging is poorly understood. In this context, the aim of this review is to gain insight the current knowledge about the molecular mechanisms of aging-induced oxidative stress in human MSCs.

  9. 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

  10. Imaging Alzheimer's disease pathophysiology with PET

    Directory of Open Access Journals (Sweden)

    Lucas Porcello Schilling

    Full Text Available ABSTRACT Alzheimer's disease (AD has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI, and dementia stages. Positron emission tomography (PET associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD.

  11. Engagement in Training as a Mechanism to Understanding Fidelity of Implementation of the Responsive Classroom Approach.

    Science.gov (United States)

    Wanless, Shannon B; Rimm-Kaufman, Sara E; Abry, Tashia; Larsen, Ross A; Patton, Christine L

    2015-11-01

    Fidelity of implementation of classroom interventions varies greatly, a reality that is concerning because higher fidelity of implementation relates to greater effectiveness of the intervention. We analyzed 126 fourth and fifth grade teachers from the treatment group of a randomized controlled trial of the Responsive Classroom® (RC) approach. Prior to training in the intervention, we assessed factors that had the potential to represent a teacher's readiness to implement with fidelity. These included teachers' observed emotional support, teacher-rated use of intervention practices, teacher-rated self-efficacy, teacher-rated collective responsibility, education level, and years of experience, and they were not directly related to observed fidelity of implementation 2 years later. Further analyses indicated, however, that RC trainers' ratings of teachers' engagement in the initial weeklong RC training mediated the relation between initial observed emotional support and later observed fidelity of implementation. We discuss these findings as a way to advance understanding of teachers' readiness to implement new interventions with fidelity.

  12. 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.

  13. 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.

  14. Modeling TH 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma.

    Science.gov (United States)

    Foster, Paul S; Maltby, Steven; Rosenberg, Helene F; Tay, Hock L; Hogan, Simon P; Collison, Adam M; Yang, Ming; Kaiko, Gerard E; Hansbro, Philip M; Kumar, Rakesh K; Mattes, Joerg

    2017-07-01

    In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4 + T-helper type-2 lymphocytes (T H 2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical T H 2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of T H 2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote T H 2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of T H 2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. 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.

  16. Structural Understanding of the Glutathione-dependent Reduction Mechanism of Glutathionyl-Hydroquinone Reductases*

    Science.gov (United States)

    Green, Abigail R.; Hayes, Robert P.; Xun, Luying; Kang, ChulHee

    2012-01-01

    Glutathionyl-hydroquinone reductases (GS- HQRs) are a newly identified group of glutathione transferases, and they are widely distributed in bacteria, halobacteria, fungi, and plants. GS-HQRs catalyze glutathione (GSH)-dependent reduction of glutathionyl-hydroquinones (GS-hydroquinones) to hydroquinones. GS-hydroquinones can be spontaneously formed from benzoquinones reacting with reduced GSH via Michael addition, and GS-HQRs convert the conjugates to hydroquinones. In this report we have determined the structures of two bacterial GS-HQRs, PcpF of Sphingobium chlorophenolicum and YqjG of Escherichia coli. The two structures and the previously reported structure of a fungal GS-HQR shared many features and displayed complete conservation for all the critical residues. Furthermore, we obtained the binary complex structures with GS-menadione, which in its reduced form, GS-menadiol, is a substrate. The structure revealed a large H-site that could accommodate various substituted hydroquinones and a hydrogen network of three Tyr residues that could provide the proton for reductive deglutathionylation. Mutation of the Tyr residues and the position of two GSH molecules confirmed the proposed mechanism of GS-HQRs. The conservation of GS-HQRs across bacteria, halobacteria, fungi, and plants potentiates the physiological role of these enzymes in quinone metabolism. PMID:22955277

  17. 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

    2016-08-17

    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.

  18. Towards a Better Understanding of the Molecular Mechanisms Involved in Sunlight-Induced Melanoma

    Directory of Open Access Journals (Sweden)

    Williams Mandy

    2005-01-01

    Full Text Available Although much less prevalent than its nonmelanoma skin cancer counterparts, cutaneous malignant melanoma (CMM is the most lethal human skin cancer. Epidemiological and biological studies have established a strong link between lifetime exposure to ultraviolet (UV light, particularly sunburn in childhood, and the development of melanoma. However, the specific molecular targets of this environmental carcinogen are not known. Data obtained from genetic and molecular studies over the last few years have identified the INK4a/ARF locus as the “gatekeeper” melanoma suppressor, encoding two tumour suppressor proteins in human, p16 INK4a and p14 ARF . Recent developments in molecular biotechnology and research using laboratory animals have made a significant gene breakthrough identifying the components of the p16 INK4a /Rb pathway as the principal and rate-limiting targets of UV radiation actions in melanoma formation. This review summarizes the current knowledge of the molecular mechanisms involved in melanoma development and its relationship to sunlight UV radiation.

  19. Investigating and improving student understanding of the probability distributions for measuring physical observables in quantum mechanics

    International Nuclear Information System (INIS)

    Marshman, Emily; Singh, Chandralekha

    2017-01-01

    A solid grasp of the probability distributions for measuring physical observables is central to connecting the quantum formalism to measurements. However, students often struggle with the probability distributions of measurement outcomes for an observable and have difficulty expressing this concept in different representations. Here we first describe the difficulties that upper-level undergraduate and PhD students have with the probability distributions for measuring physical observables in quantum mechanics. We then discuss how student difficulties found in 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 probability distributions of measurement outcomes for physical observables. The QuILT strives to help students become proficient in expressing the probability distributions for the measurement of physical observables in Dirac notation and in the position representation and be able to convert from Dirac notation to position representation and vice versa. We describe the development and evaluation of the QuILT and findings about the effectiveness of the QuILT from in-class evaluations. (paper)

  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. GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia.

    Science.gov (United States)

    Gonzalez-Burgos, Guillermo; Lewis, David A

    2008-09-01

    Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and thus is critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Here we review the data suggesting that phasic synaptic inhibition mediated by specific subtypes of cortical gamma-aminobutyric acid (GABA) neurons is essential for the production of synchronized network oscillations. We also discuss evidence indicating that GABA neurotransmission is altered in schizophrenia and propose mechanisms by which such alterations can decrease the strength of inhibitory connections in a cell-type-specific manner. We suggest that some alterations observed in the neocortex of schizophrenia subjects may be compensatory responses that partially restore inhibitory synaptic efficacy. The findings of altered neural synchrony and impaired cognitive function in schizophrenia suggest that such compensatory responses are insufficient and that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value.

  2. Understanding Physiological and Degenerative Natural Vision Mechanisms to Define Contrast and Contour Operators

    Science.gov (United States)

    Demongeot, Jacques; Fouquet, Yannick; Tayyab, Muhammad; Vuillerme, Nicolas

    2009-01-01

    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. PMID:19547712

  3. 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.

  4. 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.

  5. The rise of pathophysiologic research in the United States: the role of two Harvard hospitals.

    Science.gov (United States)

    Tishler, Peter V

    2013-01-01

    Pathophysiologic research, the major approach to understanding and treating disease, was created in the 20th century, and two Harvard-affiliated hospitals, the Peter Bent Brigham Hospital and Boston City Hospital, played a key role in its development. After the Flexner Report of 1910, medical students were assigned clinical clerkships in teaching hospitals. Rockefeller-trained Francis Weld Peabody, who was committed to investigative, pathophysiologic research, was a critical leader in these efforts. At the Brigham, Harvard medical students observed patients closely and asked provocative questions about their diseases. Additionally, physicians returned from World War I with questions concerning the pathophysiology of wartime injuries. At the Boston City Hospital's new Thorndike Memorial Laboratory, Peabody fostered investigative question-based research by physicians. These physicians expanded pathophysiologic investigation from the 1920s. Post-war, Watson and Crick's formulation of the structure of DNA led shortly to modern molecular biology and new research approaches that are being furthered at the Boston Hospitals.

  6. Dry eye disease: pathophysiology, classification, and diagnosis.

    Science.gov (United States)

    Perry, Henry D

    2008-04-01

    Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.

  7. Pathophysiology, Evaluation, and Treatment of Bloating

    Science.gov (United States)

    Gabbard, Scott L.; Crowell, Michael D.

    2011-01-01

    Abdominal bloating is commonly reported by men and women of all ages. Bloating occurs in nearly all patients with irritable bowel syndrome, and it also occurs in patients with other functional and organic disorders. Bloating is frequently disturbing to patients and frustrating to clinicians, as effective treatments are limited and are not universally successful. Although the terms bloating and abdominal distention are often used interchangeably, these symptoms likely involve different pathophysiologic processes, both of which are still not completely understood. The goal of this paper is to review the pathophysiology, evaluation, and treatment of bloating and abdominal distention. PMID:22298969

  8. 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

  9. 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

  10. Diabetic retinopathy: Proteomic approaches to help the differential diagnosis and to understand the underlying molecular mechanisms.

    Science.gov (United States)

    Csősz, Éva; Deák, Eszter; Kalló, Gergő; Csutak, Adrienne; Tőzsér, József

    2017-01-06

    Diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness among patients with diabetes. The appearance and the severity of the symptoms correlate with the duration of diabetes and poor blood glucose level management. Diabetic retinopathy is also categorized as a chronic low-level inflammatory disease; the high blood glucose level promotes the accumulation of the advanced glycation end products and leads to the stimulation of monocytes and macrophages. Examination of protein level alterations in tears using state-of the art proteomics techniques have identified several proteins as possible biomarkers for the different stages of the diabetic retinopathy. Some of the differentially expressed tear proteins have a role in the barrier function of tears linking the diabetic retinopathy with another eye complication of diabetes, namely the diabetic keratopathy resulting in impaired wound healing. Understanding the molecular events leading to the eye complications caused by hyperglycemia may help the identification of novel biomarkers as well as therapeutic targets in order to improve quality of life of diabetic patients. Diabetic retinopathy (DR), the leading cause of blindness among diabetic patients can develop without any serious symptoms therefore the early detection is crucial. Because of the increasing prevalence there is a high need for improved screening methods able to diagnose DR as soon as possible. The non-invasive collection and the relatively high protein concentration make the tear fluid a good source for biomarker discovery helping the early diagnosis. In this work we have reviewed the administration of advanced proteomics techniques used in tear biomarker studies and the identified biomarkers with potential to improve the already existing screening methods for DR detection. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Understanding Evapotranspiration Trends and their Driving Mechanisms: An investigation across CONUS based on numerical modeling

    Science.gov (United States)

    Parr, D.; Wang, G.; Fu, C.

    2015-12-01

    As shown by climate models, increasing global temperatures and enhanced greenhouse gas concentration such as CO2 have had major effects on the dynamics of the hydrologic cycle and the surface energy budget, in particular, on evapotranspiration (ET). ET has significant decadal variations whether it be regionally or globally and variations of ET have major environmental and socioeconomic impacts. A number of recent studies have found a global increase in annual mean ET around 7mm per year per decade from about 1982 to the late 1990s. These results correspond with what is expected from an intensification of the hydrological cycle. However, the increasing ET trend did not continue after 1998 and from 1998-2008 this global trend was replaced with a decreasing trend of similar magnitude. This study uses numerical modeling to investigate if similar changing ET trends emerge in the continental U.S and part of northern Mexico. After validating model simulated evaporative fluxes and comparing spatial patterns to the aforementioned studies, various changing trends of different signs are identified across the U.S., and specific regions with strong signals of change are chosen for further examination with the purpose of identifying the root causes of these changing trends and which variables are most influential towards change. Experimental simulations conducted to isolate the most influential factors towards ET reveal that precipitation amount as well as its characteristics have the greatest impact on the ET trends discovered, with other factors like wind and air temperatures displaying less influence over inter-annual trends. This study helps better understand terrestrial ET and it's interactions which will help facilitate better predictions of change in surface climate such as heatwaves and droughts as well as impacts on water resources.

  12. 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

  13. 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.

  14. Understanding pea resistance mechanisms in response to Fusarium oxysporum through proteomic analysis.

    Science.gov (United States)

    Castillejo, María Ángeles; Bani, Moustafa; Rubiales, Diego

    2015-07-01

    Fusarium oxysporum f. sp. pisi (Fop) is an important and destructive pathogen affecting pea crop (Pisum sativum) throughout the world. Control of this disease is achieved mainly by integration of different disease management procedures. However, the constant evolution of the pathogen drives the necessity to broaden the molecular basis of resistance to Fop. Our proteomic study was performed on pea with the aim of identifying proteins involved in different resistance mechanisms operating during F. oxysporum infection. For such purpose, we used a two-dimensional electrophoresis (2-DE) coupled to mass spectrometry (MALDI-TOF/TOF) analysis to study the root proteome of three pea genotypes showing different resistance response to Fop race 2. Multivariate statistical analysis identified 132 differential protein spots under the experimental conditions (genotypes/treatments). All of these protein spots were subjected to mass spectrometry analysis to deduce their possible functions. A total of 53 proteins were identified using a combination of peptide mass fingerprinting (PMF) and MSMS fragmentation. The following main functional categories were assigned to the identified proteins: carbohydrate and energy metabolism, nucleotides and aminoacid metabolism, signal transduction and cellular process, folding and degradation, redox and homeostasis, defense, biosynthetic process and transcription/translation. Results obtained in this work suggest that the most susceptible genotypes have increased levels of enzymes involved in the production of reducing power which could then be used as cofactor for enzymes of the redox reactions. This is in concordance with the fact that a ROS burst occurred in the same genotypes, as well as an increase of PR proteins. Conversely, in the resistant genotype proteins responsible to induce changes in the membrane and cell wall composition related to reinforcement were identified. Results are discussed in terms of the differential response to Fop

  15. The importance of DNA superstructure units for the understanding of the radiation action mechanism

    International Nuclear Information System (INIS)

    Regel, K.

    1985-04-01

    A molecular radiation action model is presented. It relates the physical parameters of the radiation interaction in tissue and of the DNA structure in mammalian cells to their dose survival curves. Using this model it is possible to explain many of the radiation effects in cells, including such ones which were not clearly understood as yet. Both the kind of the basic parameters and the 'efficiency' of the model suggest that it describes real properties of mammalian cells. However, in finding out the radiation action mechanism we had to fill up two gaps in our knowledge concerning the radiation action in organisms. The first gap is characterized by the question: Are there any DNA structures (sites) in mammalian cells on the basis of which a radiation action model can be established which is valid in all the cell cycle stages. This question is answered by comparisons of the magnitude of DNA parameters measured in suitable experiments with those calculated from a hypothetical model of DNA organization in mammalian cells. The second gap in knowledge is filled up by testing the hypothesis that certain patterns of double-strand breaks (DSBs) in the membrane attached superstructure units (MASSUs) of a cell cause its inactivation. The dependence of the dose survival curves on the cell cycle can be explained in the following way: Dose survival curves of G1, G2 and mitotic cells are changed because of the cyclically altering volume of the MASSU compartments. Its change during the S stage is mainly determined by the growing fraction of replicated MASSUs. The high radiation resistance of late S cells probably results from the ability of mammalian cells to establish one intact sister genome from both sister genomes containing heavily damaged MASSUs joint in the attachment points. This ability is explained by the interference of DSB repair, sister chromatid exchange and DNA degradation. (author)

  16. 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

  17. Experimental study on tissue phantoms to understand the effect of injury and suturing on human skin mechanical properties.

    Science.gov (United States)

    Chanda, Arnab; Unnikrishnan, Vinu; Flynn, Zachary; Lackey, Kim

    2017-01-01

    Skin injuries are the most common type of injuries occurring in day-to-day life. A skin injury usually manifests itself in the form of a wound or a cut. While a shallow wound may heal by itself within a short time, deep wounds require surgical interventions such as suturing for timely healing. To date, suturing practices are based on a surgeon's experience and may vary widely from one situation to another. Understanding the mechanics of wound closure and suturing of the skin is crucial to improve clinical suturing practices and also to plan automated robotic surgeries. In the literature, phenomenological two-dimensional computational skin models have been developed to study the mechanics of wound closure. Additionally, the effect of skin pre-stress (due to the natural tension of the skin) on wound closure mechanics has been studied. However, in most of these analyses, idealistic two-dimensional skin geometries, materials and loads have been assumed, which are far from reality, and would clearly generate inaccurate quantitative results. In this work, for the first time, a biofidelic human skin tissue phantom was developed using a two-part silicone material. A wound was created on the phantom material and sutures were placed to close the wound. Uniaxial mechanical tests were carried out on the phantom specimens to study the effect of varying wound size, quantity, suture and pre-stress on the mechanical behavior of human skin. Also, the average mechanical behavior of the human skin surrogate was characterized using hyperelastic material models, in the presence of a wound and sutures. To date, such a robust experimental study on the effect of injury and sutures on human skin mechanics has not been attempted. The results of this novel investigation will provide important guidelines for surgical planning and validation of results from computational models in the future.

  18. 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.

  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. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?

    DEFF Research Database (Denmark)

    Faerch, K; Borch-Johnsen, K; Holst, Jens Juul

    2009-01-01

    Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology and pathophysiology of the prediabetic states...... might give a basis for the development of individualised prevention and treatment strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the development of the different prediabetic states. The pathophysiology of i-IFG seems to include...... the following key defects: reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised by reduced peripheral insulin...

  1. Melatonin plays a protective role in postburn rodent gut pathophysiology.

    Science.gov (United States)

    Al-Ghoul, Walid M; Abu-Shaqra, Steven; Park, Byeong Gyu; Fazal, Nadeem

    2010-05-17

    Melatonin is a possible protective agent in postburn gut pathophysiological dynamics. We investigated the role of endogenously-produced versus exogenously-administered melatonin in a major thermal injury rat model with well-characterized gut inflammatory complications. Our rationale is that understanding in vivo melatonin mechanisms in control and inflamed tissues will improve our understanding of its potential as a safe anti-inflammatory/antioxidant therapeutic alternative. Towards this end, we tested the hypothesis that the gut is both a source and a target for melatonin and that mesenteric melatonin plays an anti-inflammatory role following major thermal injury in rats with 3rd degree hot water scald over 30% TBSA. Our methods for assessing the gut as a source of melatonin included plasma melatonin ELISA measurements in systemic and mesenteric circulation as well as rtPCR measurement of jejunum and terminal ileum expression of the melatonin synthesizing enzymes arylalkylamine N-acetyltransferase (AA-NAT) and 5-hydroxyindole-O-methyltransferase (HIOMT) in sham versus day-3 postburn rats. Our melatonin ELISA results revealed that mesenteric circulation has much higher melatonin than systemic circulation and that both mesenteric and systemic melatonin levels are increased three days following major thermal injury. Our rtPCR results complemented the ELISA data in showing that the melatonin synthesizing enzymes AA-NAT and HIOMT are expressed in the ileum and jejunum and that this expression is increased three days following major thermal injury. Interestingly, the rtPCR data also revealed negative feedback by melatonin as exogenous melatonin supplementation at a dose of 7.43 mg (32 micromole/kg), but not 1.86 mg/kg (8 micromole/kg) drastically suppressed AA-NAT mRNA expression. Our methods also included an assessment of the gut as a target for melatonin utilizing computerized immunohistochemical measurements to quantify the effects of exogenous melatonin

  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. Retinal vein occlusion: pathophysiology and treatment options

    OpenAIRE

    Karia, Niral

    2010-01-01

    Niral KariaDepartment of Ophthalmology, Southend Hospital, Prittlewell Chase, Westcliff on Sea, Essex, United KingdomAbstract: This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.Keywords: central, hemispheric, branch, retinal vein occlusion, visual loss

  4. 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

  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. 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.

  7. 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.

  8. 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.

  9. Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects

    International Nuclear Information System (INIS)

    Lerch, H.; Franke, W.G.; Templin, A.

    1990-01-01

    The sensitivity in the diagnosis of cerebrovascular diseases using radiotracers can be enhanced by the use of the acetazolamide test. In this paper we present and discuss some physiological and pathophysiological aspects of its mechanism. The physiological action of the carboanhydrase inhibitor is like the action of enhanced pCO 2 in the tissue, thus acting at the site of metabolic regulation. The reaction of the vascular bed is influenced in part by subcortical structures. Pathologically the reaction can be disturbed at first by an altered regulation with the vessels being mechanically intact, e.g. in hypoxia or transient ischemia. Secondly, the mechanics of the vessels may be not intact e.g., in atherosclerosis or surrounding edema. Lastly, the vessels have already dilated, e.g. poststenotically. All these facts have to be taken into consideration interpreting an acetazolamid test. (orig.) [de

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Multimodal approach to control postoperative pathophysiology and rehabilitation

    DEFF Research Database (Denmark)

    Kehlet, H

    1997-01-01

    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......, 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...

  17. 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

  18. Pathophysiology of spontaneous venous gas embolism

    Science.gov (United States)

    Lambertsen, C. J.; Albertine, K. H.; Pisarello, J. B.; Flores, N. D.

    1991-01-01

    The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

  19. 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)

  20. 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

    /osteolysis development. Only studies analysing periprosthetic tissues retrieved from failed implants in humans were included. Data from 101 studies (5532 patients with failure of THA implants) published in English or German between 1974 and 2013 were included. "Control" samples were reported in 45 of the 101 studies...... 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....

  1. 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

  2. An investigation of student understanding of classical ideas related to quantum mechanics: Potential energy diagrams and spatial probability density

    Science.gov (United States)

    Stephanik, Brian Michael

    This dissertation describes the results of two related investigations into introductory student understanding of ideas from classical physics that are key elements of quantum mechanics. One investigation probes the extent to which students are able to interpret and apply potential energy diagrams (i.e., graphs of potential energy versus position). The other probes the extent to which students are able to reason classically about probability and spatial probability density. The results of these investigations revealed significant conceptual and reasoning difficulties that students encounter with these topics. The findings guided the design of instructional materials to address the major problems. Results from post-instructional assessments are presented that illustrate the impact of the curricula on student learning.

  3. Towards a molecular understanding of cellulose dissolution in ionic liquids: anion/cation effect, synergistic mechanism and physicochemical aspects.

    Science.gov (United States)

    Li, Yao; Wang, Jianji; Liu, Xiaomin; Zhang, Suojiang

    2018-05-07

    Cellulose is one of the most abundant bio-renewable materials on the earth and its conversion to biofuels provides an appealing way to satisfy the increasing global energy demand. However, before carrying out the process of enzymolysis to glucose or polysaccharides, cellulose needs to be pretreated to overcome its recalcitrance. In recent years, a variety of ionic liquids (ILs) have been found to be effective solvents for cellulose, providing a new, feasible pretreatment strategy. A lot of experimental and computational studies have been carried out to investigate the dissolution mechanism. However, many details are not fully understood, which highlights the necessity to overview the current knowledge of cellulose dissolution and identify the research trend in the future. This perspective summarizes the mechanistic studies and microscopic insights of cellulose dissolution in ILs. Recent investigations of the synergistic effect of cations/anions and the distinctive structural changes of cellulose microfibril in ILs are also reviewed. Besides, understanding the factors controlling the dissolution process, such as the structure of anions/cations, viscosity of ILs, pretreatment temperature, heating rate, etc. , has been discussed from a structural and physicochemical viewpoint. At the end, the existing problems are discussed and future prospects are given. We hope this article would be helpful for deeper understanding of the cellulose dissolution process in ILs and the rational design of more efficient and recyclable ILs.

  4. 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

  5. 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.

  6. Effects of biological sex on the pathophysiology of the heart.

    Science.gov (United States)

    Fazal, Loubina; Azibani, Feriel; Vodovar, Nicolas; Cohen Solal, Alain; Delcayre, Claude; Samuel, Jane-Lise

    2014-02-01

    Cardiovascular diseases are the leading causes of death in men and women in industrialized countries. While the effects of biological sex on cardiovascular pathophysiology have long been known, the sex-specific mechanisms mediating these processes have been further elucidated over recent years. This review aims at analysing the sex-based differences in cardiac structure and function in adult mammals, and the sex-based differences in the main molecular mechanisms involved in the response of the heart to pathological situations. It emerged from this review that the sex-based difference is a variable that should be dealt with, not only in basic science or clinical research, but also with regards to therapeutic approaches. © 2013 The British Pharmacological Society.

  7. 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.

  8. Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts.

    Science.gov (United States)

    Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; Patterson, Natalie L; McMullen, Julie R

    2018-01-01

    The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

  9. Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Pedro M.; Fadeel, Bengt, E-mail: Bengt.Fadeel@ki.se

    2016-05-15

    Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.

  10. Emerging systems biology approaches in nanotoxicology: Towards a mechanism-based understanding of nanomaterial hazard and risk

    International Nuclear Information System (INIS)

    Costa, Pedro M.; Fadeel, Bengt

    2016-01-01

    Engineered nanomaterials are being developed for a variety of technological applications. However, the increasing use of nanomaterials in society has led to concerns about their potential adverse effects on human health and the environment. During the first decade of nanotoxicological research, the realization has emerged that effective risk assessment of the multitudes of new nanomaterials would benefit from a comprehensive understanding of their toxicological mechanisms, which is difficult to achieve with traditional, low-throughput, single end-point oriented approaches. Therefore, systems biology approaches are being progressively applied within the nano(eco)toxicological sciences. This novel paradigm implies that the study of biological systems should be integrative resulting in quantitative and predictive models of nanomaterial behaviour in a biological system. To this end, global ‘omics’ approaches with which to assess changes in genes, proteins, metabolites, etc. are deployed allowing for computational modelling of the biological effects of nanomaterials. Here, we highlight omics and systems biology studies in nanotoxicology, aiming towards the implementation of a systems nanotoxicology and mechanism-based risk assessment of nanomaterials. - Highlights: • Systems nanotoxicology is a multi-disciplinary approach to quantitative modelling. • Transcriptomics, proteomics and metabolomics remain the most common methods. • Global “omics” techniques should be coupled to computational modelling approaches. • The discovery of nano-specific toxicity pathways and biomarkers is a prioritized goal. • Overall, experimental nanosafety research must endeavour reproducibility and relevance.

  11. R7T7 glass alteration mechanism in an aqueous closed system: understanding and modelling the long term alteration kinetic

    International Nuclear Information System (INIS)

    Chave, T.

    2007-10-01

    The long term alteration rate of the French R7T7 nuclear glass has been investigated since many years because it will define the overall resistance of the radionuclide containment matrix. Recent studies have shown that the final rate remains constant or is slightly decreasing with time. It never reaches zero. Though this residual rate is very low, only 5 nm per year at 50 C, it would be the dominant alteration phenomenon in a geological repository. Two mechanisms are suggested for explaining such behaviour: diffusion in solution of elements from glass through an amorphous altered layer and precipitation of neo-formed phases. The diffusion processes are in agreement with a solid state diffusion mechanism and can lead to secondary phase precipitation due to solution concentration increases. Observed phases are mainly phyllosilicates and zeolites, in specific conditions. Phyllosilicates are expected to maintain the residual kinetic rate whereas alteration resumption could be observed in presence of zeolites at very high pH or temperature (10.5 at 90 C or temperature above 150 C). Both diffusion and neo-formed phase precipitation have been investigated in order to better understand their impact on the residual alteration rate and have then been modelled by a calculation code, coupling chemistry and transport, in order to be able to better anticipate the long term behaviour of the glass R7T7 in an aqueous closed system. (author)

  12. Toward an understanding of the neural mechanisms underlying dual-task performance: Contribution of comparative approaches using animal models.

    Science.gov (United States)

    Watanabe, Kei; Funahashi, Shintaro

    2018-01-01

    The study of dual-task performance in human subjects has received considerable interest in cognitive neuroscience because it can provide detailed insights into the neural mechanisms underlying higher-order cognitive control. Despite many decades of research, our understanding of the neurobiological basis of dual-task performance is still limited, and some critical questions are still under debate. Recently, behavioral and neurophysiological studies of dual-task performance in animals have begun to provide intriguing evidence regarding how dual-task information is processed in the brain. In this review, we first summarize key evidence in neuroimaging and neuropsychological studies in humans and discuss possible reasons for discrepancies across studies. We then provide a comprehensive review of the literature on dual-task studies in animals and provide a novel working hypothesis that may reconcile the divergent results in human studies toward a unified view of the mechanisms underlying dual-task processing. Finally, we propose possible directions for future dual-task experiments in the framework of comparative cognitive neuroscience. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Understanding abiotic stress tolerance mechanisms in soybean: a comparative evaluation of soybean response to drought and flooding stress.

    Science.gov (United States)

    Mutava, Raymond N; Prince, Silvas Jebakumar K; Syed, Naeem Hasan; Song, Li; Valliyodan, Babu; Chen, Wei; Nguyen, Henry T

    2015-01-01

    Many sources of drought and flooding tolerance have been identified in soybean, however underlying molecular and physiological mechanisms are poorly understood. Therefore, it is important to illuminate different plant responses to these abiotic stresses and understand the mechanisms that confer tolerance. Towards this goal we used four contrasting soybean (Glycine max) genotypes (PI 567690--drought tolerant, Pana--drought susceptible, PI 408105A--flooding tolerant, S99-2281--flooding susceptible) grown under greenhouse conditions and compared genotypic responses to drought and flooding at the physiological, biochemical, and cellular level. We also quantified these variations and tried to infer their role in drought and flooding tolerance in soybean. Our results revealed that different mechanisms contribute to reduction in net photosynthesis under drought and flooding stress. Under drought stress, ABA and stomatal conductance are responsible for reduced photosynthetic rate; while under flooding stress, accumulation of starch granules played a major role. Drought tolerant genotypes PI 567690 and PI 408105A had higher plastoglobule numbers than the susceptible Pana and S99-2281. Drought stress increased the number and size of plastoglobules in most of the genotypes pointing to a possible role in stress tolerance. Interestingly, there were seven fibrillin proteins localized within the plastoglobules that were up-regulated in the drought and flooding tolerant genotypes PI 567690 and PI 408105A, respectively, but down-regulated in the drought susceptible genotype Pana. These results suggest a potential role of Fibrillin proteins, FBN1a, 1b and 7a in soybean response to drought and flooding stress. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. A theoretical understanding on the CO-tolerance mechanism of the WC(0001) supported Pt monolayer: Some improvement strategies

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xilin [College of Physics and Materials Science, Henan Normal University, Xinxiang, 453007 (China); Lu, Zhansheng [College of Physics and Materials Science, Henan Normal University, Xinxiang, 453007 (China); Collaborative Innovation Center of Nano Functional Materials and Applications, Henan Province (China); Yang, Zongxian, E-mail: yzx@henannu.edu.cn [College of Physics and Materials Science, Henan Normal University, Xinxiang, 453007 (China); Collaborative Innovation Center of Nano Functional Materials and Applications, Henan Province (China)

    2016-12-15

    Highlights: • The mechanism of CO tolerance and oxidation on Pt{sub ML}/WC(0001) is clarified. • The high tolerance of Pt{sub ML}/WC(0001) to CO originate from the weak adsorption. • The minimum energy path and the rate-determining step are identified. • The activity of Pt{sub ML}/WC(0001) to CO oxidation is comparable to that of Pt(111). • Some probable strategies are proposed to improve the activity of Pt{sub ML}/WC(0001). - Abstract: The deposition of platinum on the tungsten carbide (Pt/WC) have been achieved and proved with high stability, activity and CO-tolerance toward some reactions in experiments. Although a lot of experimental efforts have been focused on understanding the activity, stability and CO-tolerance of Pt/WC, the relevant theoretical works related to the CO-tolerance mechanism are still scarce. In current study, the adsorption and oxidation of CO on the Pt monolayer supported on WC(0001) surface (Pt{sub ML}/WC(0001)) are investigated using density functional theory calculations. It is found that the oxidation of CO on Pt{sub ML}/WC(0001) proceeds preferably along the Langmuir-Hinshelwood mechanism. The energy barrier of 1.06 eV for the rate-determining step of OOCO formation is almost equal to that (1.05 eV) for CO oxidation by atomic O on Pt(111), while the adsorption energy of 1.59 eV for CO on Pt{sub ML}/WC(0001) is smaller than that on Pt(111) (1.85 eV), indicating that the high resistance to CO poisoning of Pt{sub ML}/WC(0001) may originate from the weak interaction between them. To further improve the CO tolerance, some probable strategies are proposed based on the relevant kinetics results. The current results are helpful to understanding the origin of the highly resistant to CO poisoning of Pt{sub ML}/WC(0001) and rationally designing catalysts to improve the CO oxidation activity.

  15. The control of independent students’ work effectiveness during pathophysiology study

    Directory of Open Access Journals (Sweden)

    О. V. Melnikova

    2013-06-01

    Full Text Available The course of Pathophysiology study includes both auditoria hours (lectures and practical classes and independent work of students. The latter makes up 38% of total hours given for Pathophysiology study. Independent work of students includes the following items: preparation for practical classes, writing reviews on different topics, preparation for current and final computer testing, study of the topics which are not discussed during lectures and practical classes. In order to assimilate the course of Pathophysiology completely students should effectively use their hours given for independent work. Unfortunately, the level of students’ independent individual work is low; it includes only learning of single facts, that is not enough for higher medical education. THE AIM OF STUDY: To propose the method of control of the effectiveness of students’ independent work. The most important part of student’s individual work is preparation for study in auditoria, because it determines the qualitative level of study during practical classes. The student should enter the class not only with the knowledge of basic sciences (Anatomy, Histology, Biochemistry, Normal Physiology etc. but also with the understanding of key items of the topic of the practical class. The problem consists in the following: the teacher can’t check the level of basic knowledge in each student – there is not enough time during practical class for this procedure. In order to increase the effectiveness of individual students’ work a special workbook for the practical classes was developed at the Pathophysiology department. While preparing for practical classes students write down basic items of the topic, refresh some questions from Normal Physiology, Biochemistry and other subjects. In the beginning of the practical class the teacher controls the level of student’s preparation to the topic by checking the fulfillment of tasks in the workbook. It takes a little time, but it

  16. 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.

  17. SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.

    Science.gov (United States)

    Shimano, Hitoshi; Sato, Ryuichiro

    2017-12-01

    Cellular lipid metabolism and homeostasis are controlled by sterol regulatory-element binding proteins (SREBPs). In addition to performing canonical functions in the transcriptional regulation of genes involved in the biosynthesis and uptake of lipids, genome-wide system analyses have revealed that these versatile transcription factors act as important nodes of convergence and divergence within biological signalling networks. Thus, they are involved in myriad physiological and pathophysiological processes, highlighting the importance of lipid metabolism in biology. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signalling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. In addition, SREBPs are implicated in numerous pathogenic processes such as endoplasmic reticulum stress, inflammation, autophagy and apoptosis, and in this way, they contribute to obesity, dyslipidaemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, chronic kidney disease, neurodegenerative diseases and cancers. This Review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ and organism levels.

  18. 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

  19. 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 publish...

  20. Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

    Science.gov (United States)

    Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

    2018-01-01

    An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

  1. Neuropeptides in Alzheimer's Disease : From Pathophysiological Mechanisms to Therapeutic Opportunities

    NARCIS (Netherlands)

    Van Dam, Debby; Van Dijck, Annemie; Janssen, Leen; De Deyn, Peter Paul

    Neuropeptides are found throughout the entire nervous system where they can act as neurotransmitter, neuromodulator or neurohormone. In those functions, they play important roles in the regulation of cognition and behavior. In brain disorders like Alzheimer's disease (AD), where abnormal cognition

  2. Orofacial complex regional pain syndrome: pathophysiologic mechanisms and functional MRI.

    Science.gov (United States)

    Lee, Yeon-Hee; Lee, Kyung Mi; Kim, Hyug-Gi; Kang, Soo-Kyung; Auh, Q-Schick; Hong, Jyung-Pyo; Chun, Yang-Hyun

    2017-08-01

    Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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.

  4. Reflex reticular myoclonus: relationship to some brainstem pathophysiological mechanisms.

    Science.gov (United States)

    Rektor, I; Kadanka, Z; Bednarik, J

    1991-04-01

    Two patients with reflex reticular myoclonus [RRM] were tested electrophysiologically and pharmacologically. In one of the cases the underlying disease was chronic Lyme borreliosis. In the other, the RRM attacks may have been associated with procarbazine therapy applied for Hodgkin's disease. No cortical lesion could be demonstrated either clinically or electrophysiologically [EEG, averaged EEg preceeding the jerks, SSEP]. An EMG analysis of the jerks revealed the shortest latency in the muscles innervated by the accessory nerve. The latencies became longer in a more rostral muscle [masseter], as well as in a more caudal one, the muscles innervated by the facial nerve were spared. it is presumed that the complete movement pattern of the myoclonus residues in the jerk generating structure. RRM in the described cases differs from the startle by sparing the facial nerve and from the Papio papio baboon non-epileptic myoclonus by the activating effect of physostigmine. A partial therapeutic effect was achieved with a serotonine precursor, but a GABAergic therapy proved to be the most effective.

  5. Analysis of DNA replication associated chromatin decondensation: in vivo assay for understanding chromatin remodeling mechanisms of selected proteins.

    Science.gov (United States)

    Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G

    2015-01-01

    mechanisms underlying DNA replication associated chromatin accessibility, this unique and powerful experimental system has the propensity to be a valuable tool for understanding chromatin remodeling mechanisms orchestrated by other cellular processes such as DNA repair, recombination, mitotic chromosome condensation, or other chromosome dynamics involving chromatin alterations and accessibility.

  6. 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…

  7. 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.

  8. 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.

  9. Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.

    Science.gov (United States)

    Kortlever, Joost T P; Janssen, Stein J; Molleman, Jeroen; Hageman, Michiel G J S; Ring, David

    2016-06-01

    Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms? We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain. There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms. Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.

  10. Understanding the Oxygen Evolution Reaction Mechanism on CoOx using Operando Ambient-Pressure X-ray Photoelectron Spectroscopy

    International Nuclear Information System (INIS)

    Favaro, Marco; Yang, Jinhui; Nappini, Silvia; Magnano, Elena

    2017-01-01

    Photoelectrochemical water splitting is a promising approach for renewable production of hydrogen from solar energy and requires interfacing advanced water-splitting catalysts with semiconductors. Understanding the mechanism of function of such electrocatalysts at the atomic scale and under realistic working conditions is a challenging, yet important, task for advancing efficient and stable function. This is particularly true for the case of oxygen evolution catalysts and, here, we study a highly active Co 3 O 4 /Co(OH) 2 biphasic electrocatalyst on Si by means of operando ambient-pressure X-ray photoelectron spectroscopy performed at the solid/liquid electrified interface. Spectral simulation and multiplet fitting reveal that the catalyst undergoes chemical-structural transformations as a function of the applied anodic potential, with complete conversion of the Co(OH) 2 and partial conversion of the spinel Co 3 O 4 phases to CoO(OH) under precatalytic electrochemical conditions. Furthermore, we observe new spectral features in both Co 2p and O 1s core-level regions to emerge under oxygen evolution reaction conditions on CoO(OH). The operando photoelectron spectra support assignment of these newly observed features to highly active Co 4+ centers under catalytic conditions. Comparison of these results to those from a pure phase spinel Co 3 O 4 catalyst supports this interpretation and reveals that the presence of Co(OH) 2 enhances catalytic activity by promoting transformations to CoO(OH). The direct investigation of electrified interfaces presented in this work can be extended to different materials under realistic catalytic conditions, thereby providing a powerful tool for mechanism discovery and an enabling capability for catalyst design.

  11. 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

  12. 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

  13. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity

    DEFF Research Database (Denmark)

    Polk, Anne; Vistisen, Kirsten; Vaage-Nilsen, Merete

    2014-01-01

    BACKGROUND: Cardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic review was to evaluate the pathophysiology of 5-FU- induced cardiotoxicity. METHODS: We systematically searched Pub...

  14. Cervical spondylosis anatomy: pathophysiology and biomechanics.

    Science.gov (United States)

    Shedid, Daniel; Benzel, Edward C

    2007-01-01

    Cervical spondylosis is the most common progressive disorder in the aging cervical spine. It results from the process of degeneration of the intervertebral discs and facet joints of the cervical spine. Biomechanically, the disc and the facets are the connecting structures between the vertebrae for the transmission of external forces. They also facilitate cervical spine mobility. Symptoms related to myelopathy and radiculopathy are caused by the formation of osteophytes, which compromise the diameter of the spinal canal. This compromise may also be partially developmental. The developmental process, together with the degenerative process, may cause mechanical pressure on the spinal cord at one or multiple levels. This pressure may produce direct neurological damage or ischemic changes and, thus, lead to spinal cord disturbances. A thorough understanding of the biomechanics, the pathology, the clinical presentation, the radiological evaluation, as well as the surgical indications of cervical spondylosis, is essential for the management of patients with cervical spondylosis.

  15. Pathophysiology and biology of peritoneal carcinomatosis.

    Science.gov (United States)

    Kusamura, Shigeki; Baratti, Dario; Zaffaroni, Nadia; Villa, Raffaella; Laterza, Barbara; Balestra, Maria Rosaria; Deraco, Marcello

    2010-01-15

    Peritoneal carcinomatosis represents a devastating form of cancer progression with a very poor prognosis. Its complex pathogenesis is represented by a dynamic process comprising several steps. To the best of our knowledge pathogenesis can be partly explained by 3 major molecular pathways: (1) dissemination from the primary tumor; (2) primary tumor of peritoneum; and (3) independent origins of the primary tumor and peritoneal implants. These are not mutually exclusive and combinations of different mechanisms could occur inside a single case. There are still several aspects which need explanation by future studies. A comprehensive understanding of molecular events involved in peritoneal carcinomatosis is of paramount importance and should be systematically pursued not only to identify novel strategies for the prevention of the condition, but also to obtain therapeutic advances, through the identification of surrogate markers of prognosis and development of future molecular targeted therapies.

  16. 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.

  17. 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.

  18. 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.

  19. Pathophysiology-based phenotyping in type 2 diabetes

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Henriksen, Jan E; Olsen, Michael H

    2018-01-01

    clinically diagnosed type 2 diabetes. METHODS: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients......BACKGROUND: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new...... into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. RESULTS: Among 5813 patients diagnosed with incident type 2 diabetes in the community...

  20. The Postural Tachycardia Syndrome (POTS: Pathophysiology, Diagnosis & Management

    Directory of Open Access Journals (Sweden)

    Satish R Raj

    2006-04-01

    Full Text Available Postural tachycardia syndrome (POTS, characterized by orthostatic tachycardia in the absence of orthostatic hypotension, has been the focus of increasing clinical interest over the last 15 years 1. Patients with POTS complain of symptoms of tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache and mental clouding. Patients with POTS demonstrate a heart rate increase of ≥30 bpm with prolonged standing (5-30 minutes, often have high levels of upright plasma norepinephrine (reflecting sympathetic nervous system activation, and many patients have a low blood volume. POTS can be associated with a high degree of functional disability. Therapies aimed at correcting the hypovolemia and the autonomic imbalance may help relieve the severity of the symptoms. This review outlines the present understanding of the pathophysiology, diagnosis, and management of POTS.

  1. Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.

    Science.gov (United States)

    Azaña, J M; Torrelo, A; Matito, A

    2016-01-01

    Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  2. Molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Meruelo, D; Rossomando, A

    1986-01-01

    The authors laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to fractionated x-irradiation-(FXI) induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. Not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. It is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help clone and characterize this locus. Currently chromosomal ''walking'' and ''hopping'' techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and substraction hybridization analysis is being used in the search for Ril-1.

  3. The INHANCE consortium: toward a better understanding of the causes and mechanisms of head and neck cancer.

    Science.gov (United States)

    Winn, D M; Lee, Y-C A; Hashibe, M; Boffetta, P

    2015-09-01

    The International Head and Neck Cancer Epidemiology (INHANCE) consortium is a collaboration of research groups leading large epidemiology studies to improve the understanding of the causes and mechanisms of head and neck cancer. The consortium includes investigators of 35 studies who have pooled their data on 25 500 patients with head and neck cancer (i.e., cancers of the oral cavity, oropharynx, hypopharynx, and larynx) and 37 100 controls. The INHANCE analyses have confirmed that tobacco use and alcohol intake are key risk factors of these diseases and have provided precise estimates of risk and dose response, the benefit of quitting, and the hazard of smoking even a few cigarettes per day. Other risk factors include short height, lean body mass, low education and income, and a family history of head and neck cancer. Risk factors are generally similar for oral cavity, pharynx, and larynx, although the magnitude of risk may vary. Some major strengths of pooling data across studies include more precise estimates of risk and the ability to control for potentially confounding factors and to examine factors that may interact with each other. The INHANCE consortium provides evidence of the scientific productivity and discoveries that can be obtained from data pooling projects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Toward a better understanding of the mechanisms of symbiosis: a comprehensive proteome map of a nascent insect symbiont.

    Science.gov (United States)

    Renoz, François; Champagne, Antoine; Degand, Hervé; Faber, Anne-Marie; Morsomme, Pierre; Foray, Vincent; Hance, Thierry

    2017-01-01

    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-2.3 T . 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-2.3 T 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.

  5. Understanding the growth mechanism of stabilizer-free Ag nanoparticles on reduced graphene oxide: the role of CO

    International Nuclear Information System (INIS)

    Gao Weiyin; Ran Chenxin; Wang Minqiang; Yao Xi; He Delong; Bai Jinbo

    2013-01-01

    In this study, one-step approach to prepare stabilizer-free Ag–graphene nanocomposites using DMAc-assisted thermal reduction method with uniform distribution of “near spherical” Ag nanoparticles (Ag NPs) in the range of 16–20 nm is reported. Interestingly, from the change of absorption spectrum as a function of reaction time, we observed that the characteristic absorption peak of Ag NPs shows no peak position shift in a quite long time without extra stabilizer while red-shift and broaden after continuous reaction. To explain this phenomenon, we further proposed a growth mechanism that CO, which is generated from reduction of functional groups on GO, adsorbed on the surface of Ag NPs and leaded to growth cease of Ag NPs into a narrow size distribution during the reduction of GO. Meanwhile, Ag NPs can catalyze the oxidation of adsorbed-CO to CO 2 in the presence of O 2 which can easily desorb from Ag surfaces. Hence, after fully removal of functional groups on GO, continuous supply of CO was cutoff while the desorption of adsorbed-CO was still happening continually, so Ag NPs start to gradually grow and resulting in aggregation. Moreover, the dosage of less DMAc or more AgNO 3 would cause the anisotropic growth and form multiply twinned structure of Ag NPs. Our study presents a useful understanding on the growth of Ag NPs on graphene.

  6. A molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice

    International Nuclear Information System (INIS)

    Meruelo, D.; Rossomando, A.

    1986-01-01

    The authors laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to fractionated x-irradiation-(FXI) induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. Not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. It is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help clone and characterize this locus. Currently chromosomal ''walking'' and ''hopping'' techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and substraction hybridization analysis is being used in the search for Ril-1. (author)

  7. 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.

  8. Human Pathophysiological Adaptations to the Space Environment

    Directory of Open Access Journals (Sweden)

    Gian C. Demontis

    2017-08-01

    Full Text Available Space is an extreme environment for the human body, where during long-term missions microgravity and high radiation levels represent major threats to crew health. Intriguingly, space flight (SF imposes on the body of highly selected, well-trained, and healthy individuals (astronauts and cosmonauts pathophysiological adaptive changes akin to an accelerated aging process and to some diseases. Such effects, becoming manifest over a time span of weeks (i.e., cardiovascular deconditioning to months (i.e., loss of bone density and muscle atrophy of exposure to weightlessness, can be reduced through proper countermeasures during SF and in due time are mostly reversible after landing. Based on these considerations, it is increasingly accepted that SF might provide a mechanistic insight into certain pathophysiological processes, a concept of interest to pre-nosological medicine. In this article, we will review the main stress factors encountered in space and their impact on the human body and will also discuss the possible lessons learned with space exploration in reference to human health on Earth. In fact, this is a productive, cross-fertilized, endeavor in which studies performed on Earth yield countermeasures for protection of space crew health, and space research is translated into health measures for Earth-bound population.

  9. Pathophysiology and management of pediatric ascites.

    Science.gov (United States)

    Sabri, Mahmoud; Saps, Miguel; Peters, John M

    2003-06-01

    Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

  10. Understanding the mechanical coupling between magma emplacement and the resulting deformation: the example of saucer-shaped sills

    Science.gov (United States)

    Galland, O.; Neumann, E. R.; Planke, S.

    2009-12-01

    The mechanical coupling between magma intrusions and the surrounding rocks plays a major role in the emplacement of volcanic plumbing systems. The deformation associated with magma emplacement has been widely studied, such as caldera inflation/deflation, volcano deformation during dike intrusion, and doming above laccoliths. However, the feedback processes, i.e. the effect of deformation resulting from intruding magma on the propagation of the intrusion itself, have rarely been studied. Saucer-shaped sills are adequate geological objects to understand such processes. Indeed, observation show that saucer-shaped sills are often associated with dome-like structures affecting the overlying sediments. In addition, there is a clear geometrical relation between the sills and the domes: the dome diameters are almost identical to those of saucers, and the tips of the inclined sheets of saucers are superimposed on the edges of the domes. In this presentation, we report on experimental investigations of the emplacement mechanisms of saucer-shaped sills and associated deformation. The model materials were (1) cohesive fine-grained silica flour, representing brittle crust, and (2) molten low-viscosity oil, representing magma. A weak layer located at the top of the injection inlet simulates strata. The main variable parameter is injection depth. During experiments, the surface of the model is digitalized through a structured light technique based on the moiré projection principle. Such a tool provides topographic maps of the surface of the model and allows a periodic (every 1.5 s) monitoring of the model topography. When the model magma starts intruding, a symmetrical dome rises above the inlet. Subsequently, the dome inflates and widens, and then evolves to a plateau-like feature, with nearly flat upper surface and steep sides. At the end of the experiments, the intruding liquid erupts at the edge of the plateau. The intrusions formed in the experiments are saucer-shaped sills

  11. 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

  12. Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine.

    Science.gov (United States)

    Jones, B A; Gores, G J

    1997-12-01

    Cell death of gastrointestinal epithelial cells occurs by a process referred to as apoptosis. In this review, we succinctly define apoptosis and summarize the role of apoptosis in the physiology and pathophysiology of epithelial cells in the liver, pancreas, and small and large intestine. The physiological mediators regulating apoptosis in gastrointestinal epithelial cells, when known, are discussed. Selected pathophysiological consequences of excessive apoptosis and inhibition of apoptosis are used to illustrate the significance of apoptosis in disease processes. These examples demonstrate that excessive apoptosis may result in epithelial cell atrophy, injury, and dysfunction, whereas inhibition of apoptosis results in hyperplasia and promotes malignant transformation. The specific cellular mechanisms responsible for dysregulation of epithelial cell apoptosis during pathophysiological disturbances are emphasized. Potential future areas of physiological research regarding apoptosis in gastrointestinal epithelia are highlighted when appropriate.

  13. Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.

    Science.gov (United States)

    Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M

    2016-11-01

    Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

    Science.gov (United States)

    Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

    2015-07-01

    Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

  16. 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...

  17. Understanding Coulomb Scattering Mechanism in Monolayer MoS2 Channel in the Presence of h-BN Buffer Layer.

    Science.gov (United States)

    Joo, Min-Kyu; Moon, Byoung Hee; Ji, Hyunjin; Han, Gang Hee; Kim, Hyun; Lee, Gwanmu; Lim, Seong Chu; Suh, Dongseok; Lee, Young Hee

    2017-02-08

    As the thickness becomes thinner, the importance of Coulomb scattering in two-dimensional layered materials increases because of the close proximity between channel and interfacial layer and the reduced screening effects. The Coulomb scattering in the channel is usually obscured mainly by the Schottky barrier at the contact in the noise measurements. Here, we report low-temperature (T) noise measurements to understand the Coulomb scattering mechanism in the MoS 2 channel in the presence of h-BN buffer layer on the silicon dioxide (SiO 2 ) insulating layer. One essential measure in the noise analysis is the Coulomb scattering parameter (α SC ) which is different for channel materials and electron excess doping concentrations. This was extracted exclusively from a 4-probe method by eliminating the Schottky contact effect. We found that the presence of h-BN on SiO 2 provides the suppression of α SC twice, the reduction of interfacial traps density by 100 times, and the lowered Schottky barrier noise by 50 times compared to those on SiO 2 at T = 25 K. These improvements enable us to successfully identify the main noise source in the channel, which is the trapping-detrapping process at gate dielectrics rather than the charged impurities localized at the channel, as confirmed by fitting the noise features to the carrier number and correlated mobility fluctuation model. Further, the reduction in contact noise at low temperature in our system is attributed to inhomogeneous distributed Schottky barrier height distribution in the metal-MoS 2 contact region.

  18. 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

  19. 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

  20. Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

    Directory of Open Access Journals (Sweden)

    A. Achiron

    2004-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4 and FCAR (Fc fragment of IgA, CD89 that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

  1. 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.

  2. Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.

    Science.gov (United States)

    Kim, Eunjung; Kim, Jae-Young; Smith, Matthew A; Haura, Eric B; Anderson, Alexander R A

    2018-03-01

    During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway. We measure how inhibition of the pathway modulates protein phosphorylation as well as cell viability under different microenvironmental conditions. Training the model on this data using Monte Carlo simulation results in a suite of in silico cells whose relative protein activities and cell viability match experimental observation. The calibrated model predicts distributional responses to kinase inhibitors and suggests drug resistance mechanisms that can be exploited in drug combination strategies. The suggested combination strategies are validated using in vitro experimental data. The validated in silico cells are further interrogated through an unsupervised clustering analysis and then integrated into a mathematical model of tumor growth in a homogeneous and resource-limited microenvironment. We assess posttreatment heterogeneity and predict vast differences across treatments with similar efficacy, further emphasizing that heterogeneity should modulate treatment strategies. The signaling model is also integrated into a hybrid cellular automata (HCA) model of tumor growth in a spatially heterogeneous microenvironment. As a proof of concept, we simulate tumor responses to targeted therapies in a spatially segregated tissue structure containing tumor

  3. Role of leukotrienes in asthma pathophysiology

    DEFF Research Database (Denmark)

    Bisgaard, H

    2000-01-01

    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......-inflammatory, steroid-sparing agents in asthma therapy. Several inflammatory mediators have been targeted in an attempt to thwart this inflammatory process, but so far with little success. The cysteinyl leukotrienes (CysLT), LTC(4), LTD(4), and LTE(4), have been shown to be essential mediators in asthma, making them...

  4. 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.

  5. Neurobehavioral aspects, pathophysiology, and management of Tourette syndrome.

    Science.gov (United States)

    Shprecher, David R; Schrock, Lauren; Himle, Michael

    2014-08-01

    This update summarizes progress in understanding Tourette syndrome clinical characteristics, etiology, and treatment over the past year. Premonitory sensory phenomena were found to have important impacts on Tourette syndrome quality of life. A rare genetic form of Tourette syndrome due to L-histidine-decarboxylase mutation, with similar features in human and rodent, has inspired new research on functional anatomy of Tourette syndrome. In response to new data, treatment guidelines have been revised to include behavioral therapy as first-line treatment. Novel dopamine receptor antagonists aripiprazole and ecopipam have shown potential efficacy - as well as tolerability concerns. Recent work has suggested efficacy and tolerability of topiramate and fluphenazine, but more rigorous studies are needed to further understand their role in Tourette syndrome management. Recent consensus guidelines explain when deep brain stimulation can be considered for severe refractory cases under a multidisciplinary team. More research is needed to identify better tolerated treatments for, to understand pathophysiology or functional anatomy of, and to predict or influence longitudinal outcome of Tourette syndrome.

  6. Tics and Tourette: a clinical, pathophysiological and etiological review.

    Science.gov (United States)

    Dale, Russell C

    2017-12-01

    Describe developments in the etiological understanding of Tourette syndrome. Tourette syndrome is a complex heterogenous clinical syndrome, which is not a unitary entity. Pathophysiological models describe gamma-aminobutyric acid-ergic-associated disinhibition of cortico-basal ganglia motor, sensory and limbic loops. MRI studies support basal ganglia volume loss, with additional white matter and cerebellar changes. Tourette syndrome cause likely involves multiple vulnerability genes and environmental factors. Only recently have some vulnerability gene findings been replicated, including histidine decarboxylase and neurexin 1, yet these rare variants only explain a small proportion of patients. Planned large genetic studies will improve genetic understanding. The role of inflammation as a contributor to disease expression is now supported by large epidemiological studies showing an association with maternal autoimmunity and childhood infection. Investigation of blood cytokines, blood mRNA and brain mRNA expression support the role of a persistent immune activation, and there are similarities with the immune literature of autistic spectrum disorder. Current treatment is symptomatic, although there is a better appreciation of factors that influence treatment response. At present, therapeutics is focused on symptom-based treatments, yet with improved etiological understanding, we will move toward disease-modifying therapies in the future.

  7. 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.

  8. Capillary leak syndrome: etiologies, pathophysiology, and management.

    Science.gov (United States)

    Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai

    2017-07-01

    In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  9. 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

  10. 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

  11. Transforming pathophysiology instruction through narrative pedagogy and Socratic questioning.

    Science.gov (United States)

    Rogge, M M

    2001-01-01

    Pathophysiology, heavily content driven, has typically been taught through the use of traditional behavioral pedagogy and a reliance on the formal lecture. The author describes the limitations of this approach to teaching pathophysiology and describes the use of narrative pedagogy and Socratic questioning as alternative methods of instruction to augment lecture methods. Specific strategies for transforming traditional classroom teaching by using Socratic questions in a pathophysiology course for nurse practitioners are described. Student and faculty reactions to the initial efforts to transform pathophysiology instruction are also described.

  12. 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...

  13. 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

  14. Pathophysiology and Nonsurgical Treatment of Chronic Subdural Hematoma: From Past to Present to Future.

    Science.gov (United States)

    Holl, Dana C; Volovici, Victor; Dirven, Clemens M F; Peul, Wilco C; van Kooten, Fop; Jellema, Korné; van der Gaag, Niels A; Miah, Ishita P; Kho, Kuan H; den Hertog, Heleen M; Lingsma, Hester F; Dammers, Ruben

    2018-05-14

    Chronic subdural hematoma (CSDH) is one of the more frequent pathologic entities in daily neurosurgical practice. Historically, CSDH was considered progressive recurrent bleeding with a traumatic cause. However, recent evidence has suggested a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds, and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH to direct further research questions aiming to optimize treatment for the individual patient. We performed a thorough literature search in PubMed, Ovid, EMBASE, CINAHL, and Google scholar, focusing on any aspect of the pathophysiology and nonsurgical treatment of CSDH. After a (minor) traumatic event, the dural border cell layer tears, which leads to the extravasation of cerebrospinal fluid and blood in the subdural space. A cascade of inflammation, impaired coagulation, fibrinolysis, and angiogenesis is set in motion. The most commonly used treatment is surgical drainage. However, because of the pathophysiologic mechanisms, the mortality and high morbidity associated with surgical drainage, drug therapy (dexamethasone, atorvastatin, tranexamic acid, or angiotensin-converting enzyme inhibitors) might be a beneficial alternative in many patients with CSDH. Based on pathophysiologic mechanisms, animal experiments, and small patient studies, medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the nonsurgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess which treatment is most effective in each individual patient. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  15. Prisms to Shift Pain Away: Pathophysiological and Therapeutic Exploration of CRPS with Prism Adaptation.

    Science.gov (United States)

    Christophe, Laure; Chabanat, Eric; Delporte, Ludovic; Revol, Patrice; Volckmann, Pierre; Jacquin-Courtois, Sophie; Rossetti, Yves

    Complex Regional Pain Syndrome (CRPS) is an invalidating chronic condition subsequent to peripheral lesions. There is growing consensus for a central contribution to CRPS. However, the nature of this central body representation disorder is increasingly debated. Although it has been repeatedly argued that CRPS results in motor neglect of the affected side, visual egocentric reference frame was found to be deviated toward the pain, that is, neglect of the healthy side. Accordingly, prism adaptation has been successfully used to normalize this deviation. This study aimed at clarifying whether 7 CRPS patients exhibited neglect as well as exploring the pathophysiological mechanisms of this manifestation and of the therapeutic effects of prism adaptation. Pain and quality of life, egocentric reference frames (visual and proprioceptive straight-ahead), and neglect tests (line bisection, kinematic analyses of motor neglect and motor extinction) were repeatedly assessed prior to, during, and following a one-week intense prism adaptation intervention. First, our results provide no support for visual and motor neglect in CRPS. Second, reference frames for body representations were not systematically deviated. Third, intensive prism adaptation intervention durably ameliorated pain and quality of life. As for spatial neglect, understanding the therapeutic effects of prism adaptation deserves further investigations.

  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. 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

  19. 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

  20. 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…

  1. The pathology and pathophysiology of vascular dementia.

    Science.gov (United States)

    Kalaria, Raj N

    2017-12-19

    Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. A Study of the Effect of Preschool Children's Participation in Sensorimotor Activities on Their Understanding of the Mechanical Equilibrium of a Balance Beam

    Science.gov (United States)

    Hadzigeorgiou, Yannis; Anastasiou, Leonidas; Konsolas, Manos; Prevezanou, Barbara

    2009-01-01

    The purpose of this study was to investigate whether participation in sensorimotor activities by preschool children involving their own bodily balance while walking on a beam over the floor has an effect on their understanding of the mechanical equilibrium of a balance beam. The balance beam consisted of a horizontal stick balancing around its…

  3. Tinnitus: Network pathophysiology-network pharmacology

    Directory of Open Access Journals (Sweden)

    Ana Belen eElgoyhen

    2012-01-01

    Full Text Available Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for 1 in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single FDA-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in central nervous system pathologies is changing from that of magic bullets that target individual chemoreceptors or disease-causing genes into that of magic shotguns, promiscuous or dirty drugs that target disease-causing networks, also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  4. Tinnitus: network pathophysiology-network pharmacology.

    Science.gov (United States)

    Elgoyhen, Ana B; Langguth, Berthold; Vanneste, Sven; De Ridder, Dirk

    2012-01-01

    Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for one in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single Food and Drug Administration (FDA)-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system (CNS) disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in CNS pathologies is changing from that of "magic bullets" that target individual chemoreceptors or "disease-causing genes" into that of "magic shotguns," "promiscuous" or "dirty drugs" that target "disease-causing networks," also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

  5. [Pathophysiology and new treatment of uveitis].

    Science.gov (United States)

    Yanai, Ryoji; Takeda, Atsunobu; Yoshimura, Takeru; Sonoda, Koh-Hei

    2014-01-01

    Uveitis is narrow-defined inflammation of the uvea, also clinically include all inflammatory conditions in the eye. Uveitis may occur as a consequence of various causes and background, such as autoimmune diseases, infections, and hematopoietic malignancy. We have to treat uveitis not only controlling the inflammation but also maintaining up the visual function of the eye because the most uveitis is chronic and relapsing inflammatory disorder. Behçét's disease is a systemic disease and results in loss of vision without adequate treatment. Behçét's disease was a representative of vision loss uveitis because Behçét's patient usually had treatment resistance of conventional treatment, such as colchicine and cyclosporine. However, biological therapy with TNF-α, which started from 2007, has revolutionized the treatment strategy of Behçét's disease. It is not too much to say that Behçét's patient is free from fear of vision loss by the dramatic decrease of ocular attach. Biological therapy is not approved as a treatment of uveitis except Behçét's disease. Some protracted cases of Sarcoidosis and Vogt-Koyanagi-Harada disease are resistant to corticosteroid therapy and require new treatment. In this review, we discuss the pathophysiology of uveitis and report new treatment of Behçét's disease by biological therapy.

  6. Orexinergic system and pathophysiology of epilepsy.

    Science.gov (United States)

    Doreulee, N; Alania, M; Vashalomidze, G; Skhirtladze, E; Kapanadze, Ts

    2010-11-01

    Neuropeptids orexins, also known as the hypocretins, are expressed in the lateral hypothalamus. Orexin-containing cells project widely throughout the brains, are crucial for the regulation of wakefulness and dysfunction of this system is associated with pathophysiology of narcolepsy-cataplexy. Orexin neurons play an important role in motivation, feeding and adaptive behaviors. Distribution of orexinergic receptors in the hippocampus tended to the ideas that orexins might be involved in the functions relating to the hippocampus. Effects of neuropeptide orexin-A on epileptiform activity in hippocampal slices were investigated. 500 µm thick hippocampal slices from 8-10 week-old rodents were used. Field excitatory postsynaptic potential (pop-fEPSP) and population spike in CA1 of hippocamopus were registered using standard protocol of in vitro electrophysiological experiments. Initial slope of the fEPSP and amplitude of II pop-spike were measured. Bursting neurons in CA3 were recorded in modified saline. We have found that orexin-A decreases duration/amplitude of multiple discharges of pop-spikes and inhibits spontaneous epileptiform afterdischarges induced by bicuculline methiodide in CA1. Orexin-A also modulates the frequency of discharges of bursting neurons in CA3. Our results suggest possible involvement of orexinergic system in antiepileptic action. Supported by ISTC Grant G-1318.

  7. Metabolic syndrome pathophysiology and clinical presentation.

    Science.gov (United States)

    Handelsman, Yehuda

    2009-01-01

    Metabolic syndrome is a relatively new definition, designed to help the health care practitioner to easily identify people at risk for the development of cardiovascular disease and diabetes. With the obesity epidemic, we are witnessing an epidemic of multiple-risk patients. Insulin resistance is the perceived pathophysiology of metabolic syndrome and defines its clinical presentation. Hypertension, dyslipedemia, polycystic ovarian syndrome, fatty liver disease, pre-diabetes, sleep and breathing disorder, certain cancers, and cognitive impairment are many of the presentations of the syndrome; patients with any of these conditions are at a high risk of developing cardiovascular disease and diabetes. The metabolic syndrome helps identify people at risk to allow early intervention for prevention. Lifestyle modification is the most important part of the management of people with the syndrome. Lately medications--though none approved by the U.S. Food and Drug Administration (FDA)--have been recommended by major medical societies when lifestyle modification is not enough or when it fails.

  8. Hemorrhoids: From basic pathophysiology to clinical management

    Science.gov (United States)

    Lohsiriwat, Varut

    2012-01-01

    This review discusses the pathophysiology, epidemiology, risk factors, classification, clinical evaluation, and current non-operative and operative treatment of hemorrhoids. Hemorrhoids are defined as the symptomatic enlargement and distal displacement of the normal anal cushions. The most common symptom of hemorrhoids is rectal bleeding associated with bowel movement. The abnormal dilatation and distortion of the vascular channel, together with destructive changes in the supporting connective tissue within the anal cushion, is a paramount finding of hemorrhoids. It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development, and could be a potential target for medical treatment. In most instances, hemorrhoids are treated conservatively, using many methods such as lifestyle modification, fiber supplement, suppository-delivered anti-inflammatory drugs, and administration of venotonic drugs. Non-operative approaches include sclerotherapy and, preferably, rubber band ligation. An operation is indicated when non-operative approaches have failed or complications have occurred. Several surgical approaches for treating hemorrhoids have been introduced including hemorrhoidectomy and stapled hemorrhoidopexy, but postoperative pain is invariable. Some of the surgical treatments potentially cause appreciable morbidity such as anal stricture and incontinence. The applications and outcomes of each treatment are thoroughly discussed. PMID:22563187

  9. Pathophysiology of AAA: heredity vs environment.

    Science.gov (United States)

    Björck, Martin; Wanhainen, Anders

    2013-01-01

    Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Clinical manifestations and pathophysiology of lissencephaly

    International Nuclear Information System (INIS)

    Oi, Shizuo; Sasaki, Koji; Yamada, Hiroshi; Ando, Shoko; Tamura, Yasunori; Fukuda, Kuniaki; Furukawa, Seikyo; Matsumoto, Satoshi.

    1985-01-01

    Four cases of lissencephaly were analyzed in light of clinical manifestations, CT findings and the state of hydrocephalus. Lissencephaly had been diagnosed mainly by autopsy until CT scan was introduced in the early 1970's. Since then, diagnosis of lissencephaly early in life is possible. Presently the major interest in this congenital CNS anomaly, which is caused by a neuronal migration disorder in the relatively late stages of fetal development, is to learn the dynamic pathophysiological state and management. The purpose of this paper is to analyze those points of lissencephaly in diagnosis during life and possible treatment in the hydrocephalic state. The common findings in CT in all four cases are as follows: No. 1. smooth cortical surface (agyria--pachygyria), No. 2. wide sylvian fissure (complete or incomplete lack of opercularization, No. 3. ventricular dilatation (remarkable bilateral enlargement of lateral ventricle and third ventricle--colpocephaly), No. 4. wide subdural or subarachnoid space in supratentorial region, No. 5. periventricular low density, No. 6. midline cavum, No. 7. normal CT findings in posterior fossa structure. Three out of four patients demonstrated full or bulged and tense anterior fontanella. Because of this suggestion of increased intracranial pressure and enlarged ventricles with periventricular lucency in CT findings, one patient underwent CT cisternography for dynamic analysis of the CSF circulation and continuous ICP monitoring for dynamic evaluation of the ICP pattern. The results revealed very much delayed CSF circulation and intermittently increased. ICP, with pressure waves appearing in 35.7 % of all recordings. (J.P.N.)

  11. A dynamical approach toward understanding mechanisms of team science: change, kinship, tension, and heritage in a transdisciplinary team.

    Science.gov (United States)

    Lotrecchiano, Gaetano R

    2013-08-01

    Since the concept of team science gained recognition among biomedical researchers, social scientists have been challenged with investigating evidence of team mechanisms and functional dynamics within transdisciplinary teams. Identification of these mechanisms has lacked substantial research using grounded theory models to adequately describe their dynamical qualities. Research trends continue to favor the measurement of teams by isolating occurrences of production over relational mechanistic team tendencies. This study uses a social constructionist-grounded multilevel mixed methods approach to identify social dynamics and mechanisms within a transdisciplinary team. A National Institutes of Health-funded research team served as a sample. Data from observations, interviews, and focus groups were qualitatively coded to generate micro/meso level analyses. Social mechanisms operative within this biomedical scientific team were identified. Dynamics that support such mechanisms were documented and explored. Through theoretical and emergent coding, four social mechanisms dominated in the analysis-change, kinship, tension, and heritage. Each contains relational social dynamics. This micro/meso level study suggests such mechanisms and dynamics are key features of team science and as such can inform problems of integration, praxis, and engagement in teams. © 2013 Wiley Periodicals, Inc.

  12. 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

  13. Toward an understanding of "Legacy P" - phosphorus sorption mechanisms in stream sediments as influenced by organic matter

    Science.gov (United States)

    Audette, Yuki; O'Halloran, Ivan P.; Nowell, Peter M.; Congreves, Katelyn; Voroney, R. Paul

    2017-04-01

    -P minerals, even under neutral to alkaline conditions. Thus, where OM-Fe-P forms predominate, we predict a high risk of SRP release from sediments when water chemistry changes. In addition, OM may inhibit the transformation of labile Ca-P forms to more stable Ca-P minerals. Loading of OM affects the development of hypoxia in aquatic systems, and the accumulation of OM can promote the release of both SRP and dissolved organic C to downstream environments. This study provides evidence that the presence of OM in stream sediments influences P sorption mechanisms and is critical in understanding P biogeochemistry in freshwater environments.

  14. New insights into the pathophysiology of dyslipidemia in type 2 diabetes.

    Science.gov (United States)

    Taskinen, Marja-Riitta; Borén, Jan

    2015-04-01

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for patients with type 2 diabetes, despite recent significant advances in management strategies to lessen CVD risk factors. A major cause is the atherogenic dyslipidemia, which consists of elevated plasma concentrations of both fasting and postprandial triglyceride-rich lipoproteins (TRLs), small dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) cholesterol. The different components of diabetic dyslipidemia are not isolated abnormalities but closely linked to each other metabolically. The underlying disturbances are hepatic overproduction and delayed clearance of TRLs. Recent results have unequivocally shown that triglyceride-rich lipoproteins and their remnants are atherogenic. To develop novel strategies for the prevention and treatment of dyslipidaemia, it is essential to understand the pathophysiology of dyslipoproteinaemia in humans. Here, we review recent advances in our understanding of the pathophysiology of diabetic dyslipidemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Epileptic Seizures Versus Syncope: Pathophysiology and Clinical Approach

    Directory of Open Access Journals (Sweden)

    Marios Charalambous

    2017-02-01

    Full Text Available Generalised epileptic seizures and syncope are two syndromes with similar clinical manifestation and their differentiation can be quite challenging. The aim of this review is to use an evidence-based approach in differentiating these two syndromes through the comprehension of the pathophysiological mechanisms involved and their clinical signs. Both syndromes affect regions of the forebrain and consciousness level, although, different mechanisms are involved. Syncope is a paroxysmal event secondary to a short-term decrease in cerebral perfusion, oxygenation or essential nutrients delivery. Generalised epileptic seizure activity is defined as the clinical manifestation of transient paroxysmal disturbances in brain function secondary to an imbalance between excitatory and inhibitory neurotransmitters. Clinical criteria, including precipitating events, clinical signs preceding, during and following the episodes and event duration, can be used to differentiate the two syndromes. Although these criteria might be useful for the practitioner, definite conclusions should be precluded due to the lack of original research articles and weak evidence on this specific field.Application: The review might be a useful tool for the general practitioner and clinical scientist as it will aid towards the differentiation of two syndromes, i.e. generalised epileptic seizures and syncope, with similar clinical presentation.

  16. Pathophysiologic insights into motor axonal function in Kennedy disease.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2007-11-06

    Kennedy disease (KD), or spinobulbomuscular atrophy, is a slowly progressive inherited neurodegenerative disorder, marked by prominent fasciculations that typically precede the development of other symptoms. Although the genetic basis of KD relates to triplet (CAG) repeat expansion in the androgen receptor (AR) gene on the X chromosome, the mechanisms underlying the clinical presentation in KD have yet to be established. Consequently, the present study applied axonal excitability techniques to investigate the pathophysiologic mechanisms associated with KD. Peripheral nerve excitability studies were undertaken in 7 patients with KD with compound muscle action potentials (CMAP) recorded from the right abductor pollicis brevis. Strength-duration time constant (KD 0.54 +/- 0.03 msec; controls, 0.41 +/- 0.02 msec, p TEd [90 to 100 msec], 50.75 +/- 1.98%; controls TEd [90 to 100 msec], 45.67 +/- 0.67%, p < 0.01) and hyperpolarizing (KD TEh [90 to 100 msec], 128.5 +/- 6.9%; controls TEh [90 to 100 msec], 120.5 +/- 2.4%) conditioning pulses. Measurements of refractoriness, superexcitability, and late subexcitability changed appropriately for axonal hyperpolarization, perhaps reflecting the effects of increased ectopic activity. In total, the increase in the strength-duration time constant may be the primary event, occurring early in course of the disease, contributing to the development of axonal hyperexcitability in Kennedy disease, and thereby to the generation of fasciculations, a characteristic hallmark of the disease.

  17. Depressive Disorder, Anxiety Disorder and Chronic Pain: Multiple Manifestations of a Common Clinical and Pathophysiological Core.

    Science.gov (United States)

    Arango-Dávila, Cesar A; Rincón-Hoyos, Hernán G

    A high proportion of depressive disorders are accompanied by anxious manifestations, just as depression and anxiety often present with many painful manifestations, or conversely, painful manifestations cause or worsen depressive and anxious expressions. There is increasingly more evidence of the pathophysiological, and neurophysiological and technical imaging similarity of pain and depression. Narrative review of the pathophysiological and clinical aspects of depression and chronic pain comorbidity. Research articles are included that emphasise the most relevant elements related to understanding the pathophysiology of both manifestations. The pathological origin, physiology and clinical approach to these disorders have been more clearly established with the latest advances in biochemical and cellular techniques, as well as the advent of imaging technologies. This information is systematised with comprehensive images and clinical pictures. The recognition that the polymorphism of inflammation-related genes generates susceptibility to depressive manifestations and may modify the response to antidepressant treatments establishes that the inflammatory response is not only an aetiopathogenic component of pain, but also of stress and depression. Likewise, the similarity in approach with images corroborates not only the structural, but the functional and pathophysiological analogy between depression and chronic pain. Knowledge of depression-anxiety-chronic pain comorbidity is essential in the search for effective therapeutic interventions. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  18. Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review.

    Science.gov (United States)

    Kolkka-Palomaa, M; Jääskeläinen, S K; Laine, M A; Teerijoki-Oksa, T; Sandell, M; Forssell, H

    2015-11-01

    Primary burning mouth syndrome (BMS) is a chronic oral condition characterized by burning pain often accompanied with taste dysfunction and xerostomia. The most compelling evidence concerning BMS pathophysiology comes from studies on the somatosensory system using neurophysiologic or psychophysical methods such as blink reflex, thermal quantitative sensory testing, as well as functional brain imaging. They have provided convincing evidence for neuropathic involvement at several levels of the somatosensory system in BMS pain pathophysiology. The number of taste function studies trying to substantiate the subjective taste disturbances or studies on salivary factors in BMS is much more limited, and most of them suffer from definitional and methodological problems. This review aims to critically evaluate the existing literature on the pathophysiology of BMS, paying special attention to the correctness of case selection and the methodology used in published studies, and to summarize the current state of knowledge. Based on the recognition of several gaps in the current understanding of the pathophysiology of BMS especially as regards taste and pain system interactions, the review ends with future scenarios for research in this area. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. 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

    materials to applications such as vibrating joints1,2, contacting and sliding surfaces in micro- and nanoelectromechanical systems for sensors and...Friction and Wear. R.W. Carpick, Midwest Mechanics 2014/2015 Invited Speaker , Iowa State University, Feb. 2015. 4. Invited. Atomic-Scale Processes...in Single Asperity Friction and Wear. R.W. Carpick, Midwest Mechanics 2014/2015 Invited Speaker , University of Minnesota, Feb. 2015. 5. Invited

  20. Recent Developments in the Classification, Evaluation, Pathophysiology, and Management of Scleroderma Renal Crisis.

    Science.gov (United States)

    Ghossein, Cybele; Varga, John; Fen