The Pathophysiology of Insomnia
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
Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro
2014-08-01
Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.
The Pathophysiology of Eosinophilic Esophagitis
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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.
Imaging Alzheimer's disease pathophysiology with PET
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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.
Pathophysiological relationships between heart failure and depression and anxiety.
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.
The features of HPOA on dynamic bone scintigraphy: A reflection of underlying pathophysiology
International Nuclear Information System (INIS)
Bernard, E.J.; Howman-Giles, R.; Macauley, D.I.; Uren, R.F.
1998-01-01
Full text: Hypertrophic pulmonary osteoarthropathy (HPOA) is the clinical syndrome of clubbing, arthritis and periostitis which may accompany a spectrum of underlying disease processes. Increased blood flow through involved extremities is an invariable accompaniment of the syndrome and it is hypothesised that the chronic increase in peripheral blood flow results in the known pathological changes of periosteal inflammation and proliferation, oedema, synovial congestion and exudation and hyperplasia of the finger pulp. The dynamic and blood pool phases of bone scintigraphy provide a unique tool for examining the vascular changes in bone and soft tissues and we describe the previously unreported features of the dynamic bone scan in HPOA. We performed three-phase bone scans on two adolescent patients with cystic fibrosis with knee discomfort. Both studies showed marked hyperaemia to the knees. On the blood pool phase, hyperaemia was seen to the tissues closely related to the periosteum of the long bones in upper and lower limbs, periarticular tissues and finger pulps. The delayed images showed the classic features of HPOA with linear uptake of tracer in the shafts and metaphyseal regions of the long bones and minor periarticular uptake of tracer. A WBC scan performed in one patient showed WBC accumulation in the periosteum of the metaphyseal regions, extending in the shafts, of the distal femurs and proximal tibias. Negligible WBC accumulation was seen in the synovium of the knees reflecting the non-inflammatory nature of the articular changes as is described in most patients with HPOA. In conclusion, the dynamic phases of the bone scan examination in HPOA reflect the pivotal underlying pathophysiological process of abnormally increased blood flow to the periosteal and periarticular tissues of involved long bones and finger pulps and further expands the known diagnostic features of this disease on bone scintigraphy
Pathophysiology of cervical myelopathy.
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.
Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?
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
An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).
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.
Obesity: Pathophysiology and Intervention
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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.
Pathophysiology, Evaluation, and Treatment of Bloating
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
Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.
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.
New insights into pathophysiology of vestibular migraine
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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
Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.
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.
An update on oxidative stress-mediated organ pathophysiology.
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.
A review on Alzheimer's disease pathophysiology and its management: an update.
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.
95th Anniversary of Pathophysiology in Croatia.
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
Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy
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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.
Directory of Open Access Journals (Sweden)
Erfanul Saker
2017-10-01
Full Text Available The purpose of this paper is to survey the literature on Gerbode defect and provide an overview of its history, anatomy, development, pathophysiology, diagnosis, and treatment options. The available literature on this topic, including case reports, was thoroughly reviewed. Gerbode defect is defined as abnormal shunting between the left ventricle and right atrium resulting from either a congenital defect or prior cardiac insults. The pathophysiology underlying the development of Gerbode defect is a disease process that injures the atrioventricular septum and leads to the abnormal shunting of blood. Although the most prevalent cause of Gerbode defect has historically been congenital, an increasing trend towards acquired cases has recently been reported owing to improved diagnostic capabilities and a greater number of invasive cardiac procedures. In conclusion, Gerbode defect is an increasingly recognized condition that warrants further study.
Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.
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.
Elucidation of pathophysiology and treatment of neuropathic pain
Vranken, Jan H.
2012-01-01
Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that
Diagnosing the pathophysiologic mechanisms of nocturnal polyuria.
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.
Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.
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.
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
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Susana Rovira-Llopis
2017-04-01
Full Text Available Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1, mitofusin-2 (MFN2 and optic atrophy (OPA-1, while fission is controlled by mitochondrial fission 1 (FIS1, dynamin-related protein 1 (DRP1 and mitochondrial fission factor (MFF. PARKIN and (PTEN-induced putative kinase 1 (PINK1 participate in the process of mitophagy, for which mitochondrial fission is necessary. In this review, we discuss the molecular pathways of mitochondrial dynamics, their impairment under type 2 diabetes, and pharmaceutical approaches for targeting mitochondrial dynamics, such as mitochondrial division inhibitor-1 (mdivi-1, dynasore, P110 and 15-oxospiramilactone. Furthermore, we discuss the pathophysiological implications of impaired mitochondrial dynamics, especially in type 2 diabetes.
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.
Transcranial magnetic stimulation and sleep disorders: pathophysiologic insights.
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.
Narcolepsy: Pathophysiology and Neuropsychological Changes
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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.
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.
Kataoka, Hajime
2017-07-01
Body fluid volume regulation is a complex process involving the interaction of various afferent (sensory) and neurohumoral efferent (effector) mechanisms. Historically, most studies focused on the body fluid dynamics in heart failure (HF) status through control of the balance of sodium, potassium, and water in the body, and maintaining arterial circulatory integrity is central to a unifying hypothesis of body fluid regulation in HF pathophysiology. The pathophysiologic background of the biochemical determinants of vascular volume in HF status, however, has not been known. I recently demonstrated that changes in vascular and red blood cell volumes are independently associated with the serum chloride concentration, but not the serum sodium concentration, during worsening HF and its recovery. Based on these observations and the established central role of chloride in the renin-angiotensin-aldosterone system, I propose a unifying hypothesis of the "chloride theory" for HF pathophysiology, which states that changes in the serum chloride concentration are the primary determinant of changes in plasma volume and the renin-angiotensin-aldosterone system under worsening HF and therapeutic resolution of worsening HF. Copyright © 2017 Elsevier Ltd. All rights reserved.
Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.
Maldonado, José R
2017-12-26
Delirium is the most common neuropsychiatric syndrome encountered by clinicians dealing with older adults and the medically ill and is best characterized by 5 core domains: cognitive deficits, attentional deficits, circadian rhythm dysregulation, emotional dysregulation, and alteration in psychomotor functioning. An extensive literature review and consolidation of published data into a novel interpretation of known pathophysiological causes of delirium. Available data suggest that numerous pathological factors may serve as precipitants for delirium, each having differential effects depending on patient-specific patient physiological characteristics (substrate). On the basis of an extensive literature search, a newly proposed theory, the systems integration failure hypothesis, was developed to bring together the most salient previously described theories, by describing the various contributions from each into a complex web of pathways-highlighting areas of intersection and commonalities and explaining how the variable contribution of these may lead to the development of various cognitive and behavioral dysfunctions characteristic of delirium. The specific cognitive and behavioral manifestations of the specific delirium picture result from a combination of neurotransmitter function and availability, variability in integration and processing of sensory information, motor responses to both external and internal cues, and the degree of breakdown in neuronal network connectivity, hence the term acute brain failure. The systems integration failure hypothesis attempts to explain how the various proposed delirium pathophysiologic theories interact with each other, causing various clinically observed delirium phenotypes. A better understanding of the underlying pathophysiology of delirium may eventually assist in designing better prevention and management approaches. Copyright © 2017 John Wiley & Sons, Ltd.
SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.
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.
Pathophysiology and management of pediatric ascites.
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.
Idiopathic Intracranial Hypertension – Pathophysiology Based on Case Series
Directory of Open Access Journals (Sweden)
Ljubisavljević Srdjan
2016-09-01
Full Text Available According to the definition, idiopathic intracranial hypertension (IIH is a pathological state characterized by an increase in intracranial pressure; however, there are no obvious intracranial pathological processes. The pathophysiology of this disorder is not clear, although there are many reports related to it.
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...
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
Pathophysiological understanding of HFpEF: microRNAs as part of the puzzle.
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.
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
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.
Tics and Tourette's: update on pathophysiology and tic control.
Ganos, Christos
2016-08-01
To describe recent advances in the pathophysiology of tics and Tourette syndrome, and novel insights on tic control. The cortico-basal ganglia-thalamo-cortical loops are implicated in generation of tics. Disruption of GABAergic inhibition lies at the core of tic pathophysiology, but novel animal models also implicate cholinergic and histaminergic neurotransmission. Tourette syndrome patients have altered awareness of volition and enhanced formation of habits. Premonitory urges are not the driving force behind all tics. The intensity of premonitory urges depends on patients' capacity to perceive interoceptive signals. The insular cortex is a key structure in this process. The trait intensity of premonitory urges is not a prerequisite of voluntary tic inhibition, a distinct form of motor control. Voluntary tic inhibition is most efficient in the body parts that tic the least. The prefrontal cortex is associated with the capacity to inhibit tics. The management of tics includes behavioral, pharmacological and surgical interventions. Treatment recommendations differ based on patients' age. The study of Tourette syndrome pathophysiology involves different neural disciplines and provides novel, exciting insights of brain function in health and disease. These in turn provide the basis for innovative treatment approaches of tics and their associations.
Central voice production and pathophysiology of spasmodic dysphonia.
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.
Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.
Thakur, Rupamoni; Mukherjee, Ashis K
2017-06-01
Protease inhibitors are important constituents of snake venom and play important roles in the pathophysiology of snakebite. Recently, research on snake venom protease inhibitors has provided valuable information to decipher the molecular details of various biological processes and offer insight for the development of some therapeutically important molecules from snake venom. The process of blood coagulation and fibrinolysis, in addition to affecting platelet function, are well known as the major targets of several snake venom protease inhibitors. This review summarizes the structure-functional aspects of snake venom protease inhibitors that have been described to date. Because diverse biological functions have been demonstrated by protease inhibitors, a comparative overview of their pharmacological and pathophysiological properties is also highlighted. In addition, since most snake venom protease inhibitors are non-toxic on their own, this review evaluates the different roles of individual protease inhibitors that could lead to the identification of drug candidates and diagnostic molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.
Klein, Oliver; Strohschein, Kristin; Nebrich, Grit; Oetjen, Janina; Trede, Dennis; Thiele, Herbert; Alexandrov, Theodore; Giavalisco, Patrick; Duda, Georg N; von Roth, Philipp; Geissler, Sven; Klose, Joachim; Winkler, Tobias
2014-10-01
Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological regions in injured skeletal muscle is inadequate, underlying mechanisms of the beneficial effects of mesenchymal stromal cell transplantation on primary trauma and trauma adjacent muscle area remain elusive. For discrimination of these pathophysiological regions, formalin-fixed injured skeletal muscle tissue was analyzed by MALDI imaging MS. By using two computational evaluation strategies, a supervised approach (ClinProTools) and unsupervised segmentation (SCiLS Lab), characteristic m/z species could be assigned to primary trauma and trauma adjacent muscle regions. Using "bottom-up" MS for protein identification and validation of results by immunohistochemistry, we could identify two proteins, skeletal muscle alpha actin and carbonic anhydrase III, which discriminate between the secondary damage on adjacent tissue and the primary traumatized muscle area. Our results underscore the high potential of MALDI imaging MS to describe the spatial characteristics of pathophysiological changes in muscle. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
Transforming pathophysiology instruction through narrative pedagogy and Socratic questioning.
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.
Migraine aura pathophysiology: the role of blood vessels and microembolisation
Dalkara, Turgay; Nozari, Ala; Moskowitz, Michael A
2010-01-01
Migraine attacks with auras are sometimes associated with underlying hereditary or acquired cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can cause neurovascular dysfunction and evoke cortical spreading depression, an event that is widely thought to underlie aura...
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.
Pathophysiology of MDS: genomic aberrations.
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.
Jaundice associated pruritis: a review of pathophysiology and treatment.
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.
Gender Differences in Epidemiology, Pathophysiology, and Treatment of Hypertension.
Di Giosia, Paolo; Giorgini, Paolo; Stamerra, Cosimo Andrea; Petrarca, Marco; Ferri, Claudio; Sahebkar, Amirhossein
2018-02-14
This review aims to examine gender differences in both the epidemiology and pathophysiology of hypertension and to explore gender peculiarities on the effects of antihypertensive agents in decreasing BP and CV events. Men and women differ in prevalence, awareness, and control rate of hypertension in an age-dependent manner. Studies suggest that sex hormones changes play a pivotal role in the pathophysiology of hypertension in postmenopausal women. Estrogens influence the vascular system inducing vasodilatation, inhibiting vascular remodeling processes, and modulating the renin-angiotensin aldosterone system and the sympathetic system. This leads to a protective effect on arterial stiffness during reproductive age that is dramatically reversed after menopause. Data on the efficacy of antihypertensive therapy between genders are conflicting, and the underrepresentation of aged women in large clinical trials could influence the results. Therefore, further clinical research is needed to uncover potential gender differences in hypertension to promote the development of a gender-oriented approach to antihypertensive treatment.
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.
The pathophysiology of Peyronie's disease.
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.
New insights into the pathophysiology of dyslipidemia in type 2 diabetes.
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.
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....
PATHO-PHYSIOLOGICAL MECHANISMS OF TOBACCO SMOKING EFFECT ON THE CARDIOVASCULAR SYSTEM
Directory of Open Access Journals (Sweden)
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.
Directory of Open Access Journals (Sweden)
Michael John Ellis
2016-08-01
Full Text Available Historically, patients with sports-related concussion (SRC have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS. Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually-tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further validate this evolving pathophysiological approach.
Ellis, Michael J; Leddy, John; Willer, Barry
2016-01-01
Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach.
The control of independent students’ work effectiveness during pathophysiology study
Directory of Open Access Journals (Sweden)
О. V. Melnikova
2013-06-01
can guarantee that student is prepared for practical class. Such method of control makes it possible for the teacher to define basic statements of the topic, common laws of pathological processes and peculiarities of these laws display in different organs and organs’ systems during the practical class. It can also help to devote more time during the practical classes for situational problems solutions. There can be no doubt that solution of situational problems on Pathophysiology develops the abilities for intellectual modeling of pathological processes in different organs and systems, allows to use the knowledge of basic sciences and forms the basis of clinical thinking in medical students. Such skills will be helpful for the students to make correct and quick decisions in their future practical activity. CONCLUSIONS: Individual work is an integral part of medical students’ education. It’s effectiveness determines the success of Pathophysiology study. The teacher’s control upon individual work of students will improve their skills in working with educational literature and scientific publications. These skills should make the basis for high professional qualification, which is reached by regular analysis of scientific publications on their medical specialty; for the ability to use scientific discoveries in practical medicine.
Fisiopatologia da enxaqueca Migraine pathophysiology
Directory of Open Access Journals (Sweden)
MAURICE B. VINCENT
1998-12-01
various imaging procedures during migraine also support the pathophysiological role of spreading depression. Three abnormal loci (chromosomes 1 and 19 have been recently found in familial hemiplegic migraine. This produces abnormalities in the voltage-dependent P/Q Ca channel, specific for the central nervous system, which regulates the release of various neurotransmitters, probably including serotonin. It is possible that a channelopathy underlies the pathophysiology of migraine, as in other paroxysmal neurological disorders secondary to membrane hyperexcitability.
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.
[Current concepts in pathophysiology of CRPS I].
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.
Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.
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.
Dry eye disease: pathophysiology, classification, and diagnosis.
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.
Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer.
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.
Zimna, Agnieszka; Kurpisz, Maciej
2015-01-01
The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia-inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy. PMID:26146622
Pathophysiology of gastroesophageal reflux disease
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
Pathophysiological mechanisms of insulin resistance
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
Assessing pathophysiology of cancer anorexia.
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.
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, ...
Gas embolism: pathophysiology and treatment
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
Review article: the pathophysiology, differential diagnosis and management of rumination syndrome.
Tack, J; Blondeau, K; Boecxstaens, V; Rommel, N
2011-04-01
Rumination syndrome, characterised by the effortless, often repetitive, regurgitation of recently ingested food into the mouth, was originally described in children and in the developmentally disabled. It is now well-recognised that rumination syndrome occurs in patients of all ages and cognitive abilities. To review a scholarly review on our current understanding of the rumination syndrome. The review was conducted on the basis of a medline search to identify relevant publications pertaining to the pathophysiology, clinical diagnosis and management of rumination syndrome. The Rome III consensus established diagnostic criteria for rumination syndrome in adults, children and infants. A typical history can be highly suggestive but oesophageal (high resolution) manometry/impedance with ingestion of a meal may help to distinguish rumination syndrome from other belching/regurgitation disorders. The pathophysiology is incompletely understood, but involves a rise in intra-gastric pressure, generated by a voluntary, but often unintentional, contraction of the abdominal wall musculature, at a time of low pressure in the lower oesophageal sphincter, causing retrograde movement of gastric contents into the oesophagus. To date, controlled trials in the treatment rumination syndrome are lacking. The mainstay of treatment for rumination syndrome is explanation and behavioural treatment which consists of habit reversal techniques that compete with the urge to regurgitate. Chewing gum, prokinetics, baclofen and even antireflux surgery have been proposed as adjunctive therapies, but high quality studies are generally lacking. Rumination is an under-recognised condition with incompletely understood pathophysiology. Behavioural therapy seems effective, but controlled treatment trials are lacking. © 2011 Blackwell Publishing Ltd.
LENUS (Irish Health Repository)
2012-02-01
Clathrin-mediated endocytosis (CME) is the best-characterized mechanism governing cellular membrane and protein trafficking. In this hypothesis review, we integrate recent evidence implicating CME and related cellular trafficking mechanisms in the pathophysiology of psychotic disorders such as schizophrenia and bipolar disorder. The evidence includes proteomic and genomic findings implicating proteins and genes of the clathrin interactome. Additionally, several important candidate genes for schizophrenia, such as dysbindin, are involved in processes closely linked to CME and membrane trafficking. We discuss that key aspects of psychosis neuropathology such as synaptic dysfunction, white matter changes and aberrant neurodevelopment are all influenced by clathrin-dependent processes, and that other cellular trafficking mechanisms previously linked to psychoses interact with the clathrin interactome in important ways. Furthermore, many antipsychotic drugs have been shown to affect clathrin-interacting proteins. We propose that the targeted pharmacological manipulation of the clathrin interactome may offer fruitful opportunities for novel treatments of schizophrenia.Molecular Psychiatry advance online publication, 11 October 2011; doi:10.1038\\/mp.2011.123.
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...
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
Physiological and pathophysiological bone turnover - role of the immune system.
Weitzmann, M Neale; Ofotokun, Ighovwerha
2016-09-01
Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration of bone structure and strength. Osteoporosis increases the risk of fragility fractures, a cause of substantial morbidity and mortality, especially in elderly patients. This imbalance between bone formation and bone resorption is brought about by natural ageing processes, but is frequently exacerbated by a number of pathological conditions. Of importance to the aetiology of osteoporosis are findings over the past two decades attesting to a deep integration of the skeletal system with the immune system (the immuno-skeletal interface (ISI)). Although protective of the skeleton under physiological conditions, the ISI might contribute to bone destruction in a growing number of pathophysiological states. Although numerous research groups have investigated how the immune system affects basal and pathological osteoclastic bone resorption, recent findings suggest that the reach of the adaptive immune response extends to the regulation of osteoblastic bone formation. This Review examines the evolution of the field of osteoimmunology and how advances in our understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures.
An, Gary; Faeder, James; Vodovotz, Yoram
2008-01-01
The pathophysiology of the burn patient manifests the full spectrum of the complexity of the inflammatory response. In the acute phase, inflammation may have negative effects via capillary leak, the propagation of inhalation injury, and development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care research. Conversely, inflammation is a necessary prologue and component in the later stage processes of wound healing. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens. Translational systems biology (TSB) is the application of dynamic mathematical modeling and certain engineering principles to biological systems to integrate mechanism with phenomenon and, importantly, to revise clinical practice. This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research.
A Unified Pathophysiological Construct of Diabetes and its Complications.
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.
Pathophysiological aspects of ureterorenoscopic management of upper urinary tract calculi
DEFF Research Database (Denmark)
Osther, Palle J S; Pedersen, Katja V; Lildal, Søren K
2016-01-01
PURPOSE OF REVIEW: Indications for ureterorenoscopy are expanding without hard scientific evidence to support its efficacy. Therefore, it is extremely important to focus on potential harmful effects of the procedure itself. This review explores how physiology of the upper urinary tract reacts...... of the β-receptor agonist isoproterenol in the irrigation fluid has shown a potential for reducing both intrarenal pressure and ureteral tone during ureterorenoscopy. SUMMARY: Upper urinary tract physiology has unique features that may be pushed into pathophysiological processes by the unique elements...
Langer, Arielle L; Ginzburg, Yelena Z
2017-06-01
Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.
Hypertension in women--pathophysiological and clinical aspects.
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.
Devanarayana, N.M.
2015-01-01
Abdominal pain-predominant functional gastrointestinal disorders (AP-FGIDs) are a worldwide pediatric problem with uncertain pathology. Main objectives of this thesis were to assess epidemiology, risk factors and underlying pathophysiological mechanisms of AP-FGIDs. A systematic review and
Chronic Pruritus in the Absence of Skin Disease: Pathophysiology, Diagnosis and Treatment.
Pereira, Manuel P; Kremer, Andreas E; Mettang, Thomas; Ständer, Sonja
2016-08-01
Chronic pruritus arises not only from dermatoses, but also, in up to half of cases, from extracutaneous origins. A multitude of systemic, neurological, psychiatric, and somatoform conditions are associated with pruritus in the absence of skin disease. Moreover, pruritus is a frequently observed side effect of many drugs. It is therefore difficult for physicians to make a correct diagnosis. Chronic pruritus patients frequently present to the dermatologist with skin lesions secondary to a long-lasting scratching behavior, such as lichenification and prurigo nodularis. A structured clinical history and physical examination are essential in order to evaluate the pruritus, along with systematic, medical history-adapted laboratory and radiological tests carried out according to the differential diagnosis. For therapeutic reasons, a symptomatic therapy should be promptly initiated parallel to the diagnostic procedures. Once the underlying factor(s) leading to the pruritus are identified, a targeted therapy should be implemented. Importantly, the treatment of accompanying disorders such as sleep disturbances or mental symptoms should be taken into consideration. Even after successful treatment of the underlying cause, pruritus may persist, likely due to chronicity processes including peripheral and central sensitization or impaired inhibition at spinal level. A vast arsenal of topical and systemic agents targeting these pathophysiological mechanisms has been used to deter further chronicity. The therapeutic options currently available are, however, still insufficient for many patients. Thus, future studies aiming to unveil the complex mechanisms underlying chronic pruritus and develop new therapeutic agents are urgently needed.
Pathophysiology of septic shock: From bench to bedside.
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.
Gkioka, Eleana; Korou, Laskarina Maria; Daskalopoulou, Afrodite; Misitzi, Angelica; Batsidis, Eleni; Bakoyiannis, Ioannis; Pergialiotis, Vasilios
2016-07-01
It is estimated that approximately 0.5%-3% of fetuses are prenatally exposed to cocaine (COC). The neurodevelopmental implications of this exposure are numerous and include motor skill impairments, alterations of social function, predisposition to anxiety, and memory function and attention deficits; these implications are commonly observed in experimental studies and ultimately affect both learning and IQ. According to previous studies, the clinical manifestations of prenatal COC exposure seem to persist at least until adolescence. The pathophysiological cellular processes that underlie these impairments include dysfunctional myelination, disrupted dendritic architecture, and synaptic alterations. On a molecular level, various neurotransmitters such as serotonin, dopamine, catecholamines, and γ-aminobutyric acid seem to participate in this process. Finally, prenatal COC abuse has been also associated with functional changes in the hormones of the hypothalamic-pituitary-adrenal axis that mediate neuroendocrine responses. The purpose of this review is to summarize the neurodevelopmental consequences of prenatal COC abuse, to describe the pathophysiological pathways that underlie these consequences, and to provide implications for future research in the field.
Pancreatitis in dogs and cats: definitions and pathophysiology.
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.
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.
Tinnitus: network pathophysiology-network pharmacology.
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.
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.
Pathophysiology of ADHD and associated problems – starting points for Neurofeedback interventions?
Directory of Open Access Journals (Sweden)
Björn eAlbrecht
2015-06-01
Full Text Available Attention deficit hyperactivity disorder (ADHD is characterized by severe and age-inappropriate levels of hyperactivity, impulsivity and inattention. ADHD is a heterogeneous disorder, and the majority of patients show comorbid or associated problems from other psychiatric disorders. Also, ADHD is associated with cognitive and motivational problems as well as resting-state abnormalities, associated with impaired brain activity in distinct neuronal networks. This needs to be considered in a multimodal treatment, of which neurofeedback may be a promising component. During neurofeedback, specific brain activity is fed-back using visual or auditory signals, allowing the participants to gain control over these otherwise unaware neuronal processes. Neurofeedback may be used to directly improve underlying neuronal deficits, and/or to establish more general self-regulatory skills that may be used to compensate behavioural difficulties.The current manuscript describes pathophysiological characteristics of ADHD, heterogeneity of ADHD subtypes and gender differences, as well as frequently associated behavioural problems such as oppositional defiant/conduct or tic disorder. It is discussed how neurofeedback may be helpful as a treatment approach within these contexts.
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.
Feng, Jian Q.; Clinkenbeard, Erica L.; Yuan, Baozhi; White, Kenneth E.; Drezner, Marc K.
2013-01-01
Although recent studies have established that osteocytes function as secretory cells that regulate phosphate metabolism, the biomolecular mechanism(s) underlying these effects remain incompletely defined. However, investigations focusing on the pathogenesis of X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and autosomal recessive hypophosphatemic rickets (ARHR), heritable disorders characterized by abnormal renal phosphate wasting and bone mineralization, have clearly implicated FGF23 as a central factor in osteocytes underlying renal phosphate wasting, documented new molecular pathways regulating FGF23 production, and revealed complementary abnormalities in osteocytes that regulate bone mineralization. The seminal observations leading to these discoveries were the following: 1) mutations in FGF23 cause ADHR by limiting cleavage of the bioactive intact molecule, at a subtilisin-like protein convertase (SPC) site, resulting in increased circulating FGF23 levels and hypophosphatemia; 2) mutations in DMP1 cause ARHR, not only by increasing serum FGF23, albeit by enhanced production and not limited cleavage, but also by limiting production of the active DMP1 component, the C-terminal fragment, resulting in dysregulated production of DKK1 and β-catenin, which contributes to impaired bone mineralization; and 3) mutations in PHEX cause XLH both by altering FGF23 proteolysis and production and causing dysregulated production of DKK1 and β-catenin, similar to abnormalities in ADHR and ARHR, but secondary to different central pathophysiological events. These discoveries indicate that ADHR, XLH, and ARHR represent three related heritable hypophosphatemic diseases that arise from mutations in, or dysregulation of, a single common gene product, FGF23 and, in ARHR and XLH, complimentary DMP1 and PHEX directed events that contribute to abnormal bone mineralization. PMID:23403405
The pathophysiology of trauma-induced coagulopathy.
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.
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.
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.
Studies on the Pathophysiology and Genetic Basis of Migraine
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
Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms.
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.
Gaber, Timo; Tran, Cam Loan; Schellmann, Saskia; Hahne, Martin; Strehl, Cindy; Hoff, Paula; Radbruch, Andreas; Burmester, Gerd-Rüdiger; Buttgereit, Frank
2013-06-01
Inflamed areas are characterized by infiltration of immune cells, local hypoxia and alterations of cellular redox states. We investigated the impact of hypoxia on survival, proliferation, cytokine secretion, intracellular energy and redox state of human CD4(+) T cells. We found that pathophysiological hypoxia (<2% O2 ) significantly decreased CD4(+) T-cell survival after mitogenic stimulation. This effect was not due to an increased caspase-3/7-mediated apoptosis or adenosine-5'-triphosphate (ATP) consumption/depletion. However, the ability of stimulated T cells to proliferate was reduced under hypoxic conditions, despite increased expression of CD25. Pathophysiological hypoxia was also found to modify intracellular ROS (iROS) levels in stimulated T cells over time as compared with levels found in normoxia. Physiological hypoxia (5% O2 ) did not decrease CD4(+) T-cell survival and proliferation or modify iROS levels as compared with normoxia. We conclude that pathophysiological hypoxia affects T-cell proliferation and viability via disturbed IL-2R signalling downstream of STAT5a phosphorylation, but not as a result of impaired cellular energy homeostasis. We suggest iROS links early events in T-cell stimulation to the inhibition of the lymphoproliferative response under pathophysiological hypoxic conditions. The level of iROS may therefore act as a mediator of immune functions leading to down-regulation of long-term T-cell activity in inflamed tissues. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Ozpinar, Alp; Mendez, Gustavo; Abla, Adib A
2017-01-01
Arteriovenous malformations (AVMs) are vascular deformities involving fistula formation of arterial to venous structures without an intervening capillary bed. Such anomalies can prove fatal as the high arterial flow can disrupt the integrity of venous walls, thus leading to dangerous sequelae such as hemorrhage. Diagnosis of these lesions in the central nervous system can often prove challenging as intracranial AVMs represent a heterogeneous vascular pathology with various presentations and symptomatology. The literature suggests that most brain AVMs (bAVMs) are identified following evaluation of the etiology of acute cerebral hemorrhage, or incidentally on imaging associated with seizure or headache workup. Given the low incidence of this disease, most of the data accrued on this pathology comes from single-center experiences. This chapter aims to distill the most important information from these studies as well as examine meta-analyses on bAVMs in order to provide a comprehensive introduction into the natural history, classification, genetic underpinnings of disease, and proposed pathophysiology. While there is yet much to be elucidated about AVMs of the central nervous system, we aim to provide an overview of bAVM etiology, classification, genetics, and pathophysiology inherent to the disease process. © 2017 Elsevier B.V. All rights reserved.
Lifescience Database Archive (English)
Full Text Available 10807517 Pathophysiological roles of interleukin-18 in inflammatory liver diseases....l) Show Pathophysiological roles of interleukin-18 in inflammatory liver diseases. PubmedID 10807517 Title P...athophysiological roles of interleukin-18 in inflammatory liver diseases. Authors
The role of the IGF-1 Ec in myoskeletal system and osteosarcoma pathophysiology.
Armakolas, Nikolaos; Armakolas, Athanasios; Antonopoulos, Athanasios; Dimakakos, Andreas; Stathaki, Martha; Koutsilieris, Michael
2016-12-01
Growth hormone (GH) regulated mainly liver-produced insulin-like growth factor 1 (IGF-1) is a key molecule in embryonic & post embryonic development that is also involved in cancer biology. Herein we review new insights of the role of igf-1 gene products and of the IGF-1Ec isoform in muscle and bone development/repair and its role in osteosarcoma pathophysiology, underlying the possible role of the Ec peptide as a future therapeutic target. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Mess, Christian; Zens, Katharina; Gorzelanny, Christian; Metze, Dieter; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.; Huck, Volker
2017-02-01
Application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of skin diseases. By means of multiphoton excitation, endogenous biomolecules like NADH, collagen or elastin show autofluorescence or second harmonic generation. Thus, these molecules provide information about the subcellular morphology, epidermal architecture and physiological condition of the skin. To gain a deeper understanding of the linkage between cellular structure and physiological processes, non-invasive multiphotonbased intravital tomography (MPT) and fluorescence lifetime imaging (FLIM) were combined within the scopes of inflammatory skin, chronic wounds and drug delivery in clinical application. The optical biopsies generated via MPT were morphologically analyzed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Independent morphometric algorithms reliably showed a perinuclear accumulation in lesional skin in contrast to an even distribution in healthy skin. Confirmatively, MPT-FLIM showed an obvious metabolic shift in lesions. Moreover, detection of the onset and progression of inflammatory processes could be achieved. The feasibility of primary in vivo tracking of applied therapeutic agents further broadened our scope: We examined the permeation and subsequent distribution of agents directly visualized in patientś skin in short-term repetitive measurements. Furthermore, we performed MPT-FLIM follow-up investigations in the long-term course of therapy. Therefore, clinical MPT-FLIM application offers new insights into the pathophysiology and the individual therapeutic course of skin diseases, facilitating a better understanding of the processes of inflammation and wound healing.
Directory of Open Access Journals (Sweden)
Chang Hyun Byon
2016-10-01
Full Text Available Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS, which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (H2O2 exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of H2O2 in regulating physiological and pathological signals in VSMC.
Pathogenesis and Pathophysiology of Pneumococcal Meningitis
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
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.
Ataman, Oleksandr V
2017-12-01
Pathophysiology in Ukraine has rich traditions and achievements in the scientific areas, as well as in teaching academic discipline. Its history, the main Ukrainian scientific schools and their famous representatives are briefly described. The content of existing study program, the main approaches to teaching, and some methodological and organizational problems needed to be solved are characterized. The necessity and usefulness of developing and implementing the three separate courses of discipline (Essential, Clinical and Advanced Pathophysiology) are substantiated. The place of Pathophysiology in the training of physicians with different kinds of their future activity is discussed. Relation of teaching Pathophysiology to Translational and Personalized Medicine is tried to be shown.
Ferreira, J?nio A.; Botelho, Ricardo V.
2015-01-01
Background: Craniometric studies have shown that both Chiari malformation (CM) and basilar invagination (BI) belong to a spectrum of malformations. A more precise method to differentiate between these types of CVJM is desirable. The Chamberlain′s line violation (CLV) is the most common method to identify BI. The authors sought to clarify the real importance of CLV in the spectrum of craniovertebral junction malformations (CVJM) and to identify possible pathophysiological relationships. Me...
Pathophysiology of diurnal drooling in Parkinson's disease
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
Secic, Damir; Husremovic, Dzenana; Kapur, Eldan; Jatic, Zaim; Hadziahmetovic, Nina; Vojnikovic, Benjamin; Fajkic, Almir; Meholjic, Amir; Bradic, Lejla; Hadzic, Amila
2017-01-01
Testing strategies can either have a very positive or negative effect on the learning process. The aim of this study was to examine the degree of consistency in evaluating the practicality and logic of questions from a medical school pathophysiology test, between students and family medicine doctors. The study engaged 77 family medicine doctors…
Capuani, Barbara; Della-Morte, David; Donadel, Giulia; Caratelli, Sara; Bova, Luca; Pastore, Donatella; De Canio, Michele; D'Aguanno, Simona; Coppola, Andrea; Pacifici, Francesca; Arriga, Roberto; Bellia, Alfonso; Ferrelli, Francesca; Tesauro, Manfredi; Federici, Massimo; Neri, Anna; Bernardini, Sergio; Sbraccia, Paolo; Di Daniele, Nicola; Sconocchia, Giuseppe; Orlandi, Augusto; Urbani, Andrea; Lauro, Davide
2015-05-01
Liver has a principal role in glucose regulation and lipids homeostasis. It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR(-/-)) and heterozygous (IR(+/-)) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications. Copyright © 2015 the American Physiological Society.
Component processes underlying future thinking.
D'Argembeau, Arnaud; Ortoleva, Claudia; Jumentier, Sabrina; Van der Linden, Martial
2010-09-01
This study sought to investigate the component processes underlying the ability to imagine future events, using an individual-differences approach. Participants completed several tasks assessing different aspects of future thinking (i.e., fluency, specificity, amount of episodic details, phenomenology) and were also assessed with tasks and questionnaires measuring various component processes that have been hypothesized to support future thinking (i.e., executive processes, visual-spatial processing, relational memory processing, self-consciousness, and time perspective). The main results showed that executive processes were correlated with various measures of future thinking, whereas visual-spatial processing abilities and time perspective were specifically related to the number of sensory descriptions reported when specific future events were imagined. Furthermore, individual differences in self-consciousness predicted the subjective feeling of experiencing the imagined future events. These results suggest that future thinking involves a collection of processes that are related to different facets of future-event representation.
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....
Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System
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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.
Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R
2016-01-01
Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.
Blended Learning Versus Traditional Lecture in Introductory Nursing Pathophysiology Courses.
Blissitt, Andrea Marie
2016-04-01
Currently, many undergraduate nursing courses use blended-learning course formats with success; however, little evidence exists that supports the use of blended formats in introductory pathophysiology courses. The purpose of this study was to compare the scores on pre- and posttests and course satisfaction between traditional and blended course formats in an introductory nursing pathophysiology course. This study used a quantitative, quasi-experimental, nonrandomized control group, pretest-posttest design. Analysis of covariance compared pre- and posttest scores, and a t test for independent samples compared students' reported course satisfaction of the traditional and blended course formats. Results indicated that the differences in posttest scores were not statistically significant between groups. Students in the traditional group reported statistically significantly higher satisfaction ratings than students in the blended group. The results of this study support the need for further research of using blended learning in introductory pathophysiology courses in undergraduate baccalaureate nursing programs. Further investigation into how satisfaction is affected by course formats is needed. Copyright 2016, SLACK Incorporated.
Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.
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.
Pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS
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Marco Venegas-Mariño
2017-08-01
Full Text Available Obstructive sleep apnea-hypopnea syndrome (OSAHS is a disease characterized by recurrent upper airway obstruction (UAO, with decreased airflow, intermittent hypoxemia, and awakening during sleep. Two essential factors are related to the pathophysiology of OSAHS: anatomical alterations and reduction or absence of neural control. While studying OSAHS, the site or sites of obstruction of the UA should be identified; they may extend from the nasal wings to the hypopharynx. Another important factor in this syndrome is the nervous influence on muscle tone of the hypopharynx, as well as the changes in blood pH, which are secondary to micro-arousals. Body position and sleep stage determine the severity. The pathophysiology of OSAHS should be understood to properly study a patient and provide the best treatment option.
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
Pathophysiology of spontaneous venous gas embolism
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.
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)
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.
The pathophysiology of lifelong premature ejaculation
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
Effects of biological sex on the pathophysiology of the heart.
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.
Directory of Open Access Journals (Sweden)
M. T. Vatutin
2015-01-01
Full Text Available Chronic obstructive pulmonary disease: definition, epidemiology, pathophysiology, clinical picture (GOLD 2013. Vatutin M.T., Smyrnova G.S., Taradin G.G. The represented translation of the new international guidelines (GOLD 2013 reflected the epidemiology, pathophysiology, clinical picture and treatment of chronic obstructive pulmonary disease.
Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome
DEFF Research Database (Denmark)
Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H
2005-01-01
Hepatorenal syndrome (HRS) is a functional and reversible impairment of renal function in patients with severe cirrhosis. Major pathophysiological elements include liver dysfunction, a circulatory derangement with central hypovolaemia and neurohumoral activation of potent vasoactive systems leading...
Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms
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
Unravelling narcolepsy : from pathophysiology to measuring treatment effects
Heide, van der A.
2017-01-01
Narcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. The first part of this thesis concernes an overview of the pathophysiology,
Retinal vein occlusion: pathophysiology and treatment options
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
Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.
Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc
2015-07-21
Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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
The role of beta-endorphin in the pathophysiology of major depression.
Hegadoren, K M; O'Donnell, T; Lanius, R; Coupland, N J; Lacaze-Masmonteil, N
2009-10-01
A role for beta-endorphin (beta-END) in the pathophysiology of major depressive disorder (MDD) is suggested by both animal research and studies examining clinical populations. The major etiological theories of depression include brain regions and neural systems that interact with opioid systems and beta-END. Recent preclinical data have demonstrated multiple roles for beta-END in the regulation of complex homeostatic and behavioural processes that are affected during a depressive episode. Additionally, beta-END inputs to regulatory pathways involving feeding behaviours, motivation, and specific types of motor activity have important implications in defining the biological foundations for specific depressive symptoms. Early research linking beta-END to MDD did so in the context of the hypothalamic-pituitary-adrenal (HPA) axis activity, where it was suggested that HPA axis dysregulation may account for depressive symptoms in some individuals. The primary aims of this paper are to use both preclinical and clinical research (a) to critically review data that explores potential roles for beta-END in the pathophysiology of MDD and (b) to highlight gaps in the literature that limit further development of etiological theories of depression and testable hypotheses. In addition to examining methodological and theoretical challenges of past clinical studies, we summarize studies that have investigated basal beta-END levels in MDD and that have used challenge tests to examine beta-END responses to a variety of experimental paradigms. A brief description of the synthesis, location in the CNS and behavioural pharmacology of this neuropeptide is also provided to frame this discussion. Given the lack of clinical improvement observed with currently available antidepressants in a significant proportion of depressed individuals, it is imperative that novel mechanisms be investigated for antidepressant potential. We conclude that the renewed interest in elucidating the role of beta
Reevaluation of the Thyroid Scan for the Assessment of Pathophysiologic Status of Thyroid Disease
International Nuclear Information System (INIS)
Woo, In Sook; Nah, Jung Il; Kim, Deog Yoon
1991-01-01
To diagnosis and understand the pathophysiologic status of thyroid disease, not only hormonal measurements but also thyroid scan is believed to have a unique role. Especially in the cases of the change of the thyroid function by thyroiditis, it is emphasized that thyroid scan can be helpful in differential diagnosis, Discordant results of thyroid hormone levels and thyroid scan are found in transient hyperthyroidism, or in transient hypothyroidism. We analysed and reevaluated thyroid scan to look at the importance of thyroid scan. The results are summarised as follows: 1) 80%. of hyperthyroid patients had hyperthyroidism increased RAIU with even density, they are compatible with Graves' disease. 2) 2.1% of hyperthyroid patients had normal or decreased RAIU, which are classified as high iodine turn over genuine hyperthyroidism. 3) 8.5% of hyperthyroid patients had markedly decreased RAIU at both 2 hour and 24 hour, whose pathologic processes are suggested to be heterogenous namely subacute thyroiditis, postpartum thyroiditis, Hashimoto's thyroiditis, and pamless thyroiditis. 4) 45% of hypothyroid patients had increased 24 hr RAIU, 30% of hypothyroid patients were normal, 25%, decreased. In conclusion, thyroid scan should be reevaluated its useful role to asses the pathophysiologic status of thyroid disease. Especially in cases of transient thyrotoxicosis, thyroid scan is essential to diagnose and follow up the disease process.
Reevaluation of the Thyroid Scan for the Assessment of Pathophysiologic Status of Thyroid Disease
Energy Technology Data Exchange (ETDEWEB)
Woo, In Sook; Nah, Jung Il; Kim, Deog Yoon [Kyunghee University College of Medicine, Seoul (Korea, Republic of)
1991-03-15
To diagnosis and understand the pathophysiologic status of thyroid disease, not only hormonal measurements but also thyroid scan is believed to have a unique role. Especially in the cases of the change of the thyroid function by thyroiditis, it is emphasized that thyroid scan can be helpful in differential diagnosis, Discordant results of thyroid hormone levels and thyroid scan are found in transient hyperthyroidism, or in transient hypothyroidism. We analysed and reevaluated thyroid scan to look at the importance of thyroid scan. The results are summarised as follows: 1) 80%. of hyperthyroid patients had hyperthyroidism increased RAIU with even density, they are compatible with Graves' disease. 2) 2.1% of hyperthyroid patients had normal or decreased RAIU, which are classified as high iodine turn over genuine hyperthyroidism. 3) 8.5% of hyperthyroid patients had markedly decreased RAIU at both 2 hour and 24 hour, whose pathologic processes are suggested to be heterogenous namely subacute thyroiditis, postpartum thyroiditis, Hashimoto's thyroiditis, and pamless thyroiditis. 4) 45% of hypothyroid patients had increased 24 hr RAIU, 30% of hypothyroid patients were normal, 25%, decreased. In conclusion, thyroid scan should be reevaluated its useful role to asses the pathophysiologic status of thyroid disease. Especially in cases of transient thyrotoxicosis, thyroid scan is essential to diagnose and follow up the disease process.
Pathophysiology of diurnal drooling in Parkinson’s disease
Lenie van den Engel-Hoek; Johanna Kalf; Bastiaan Bloem; George Borm; Machiel Zwarts; Bert de Swart; Marten Munneke
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
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.
Parkinson's disease : The syndrome, the pathogenesis and pathophysiology
Bartels, Anna L.; Leenders, Klaus L.
Parkinson's disease (PD) is characterised by a slowly expanding degeneration of neurons particularly in the mesencephalon. The causes are unknown although risk factors in the genetic and toxic domain are being discovered. An important pathophysiological feature in PD is the loss of part of the
Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology.
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.
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.
The levels of processing effect under nitrogen narcosis.
Kneller, Wendy; Hobbs, Malcolm
2013-01-01
Previous research has consistently demonstrated that inert gas (nitrogen) narcosis affects free recall but not recognition memory in the depth range of 30 to 50 meters of sea water (msw), possibly as a result of narcosis preventing processing when learned material is encoded. The aim of the current research was to test this hypothesis by applying a levels of processing approach to the measurement of free recall under narcosis. Experiment 1 investigated the effect of depth (0-2 msw vs. 37-39 msw) and level of processing (shallow vs. deep) on free recall memory performance in 67 divers. When age was included as a covariate, recall was significantly worse in deep water (i.e., under narcosis), compared to shallow water, and was significantly higher in the deep processing compared to shallow processing conditions in both depth conditions. Experiment 2 demonstrated that this effect was not simply due to the different underwater environments used for the depth conditions in Experiment 1. It was concluded memory performance can be altered by processing under narcosis and supports the contention that narcosis affects the encoding stage of memory as opposed to self-guided search (retrieval).
Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease*
Masters, Seth L.; Simon, Anna; Aksentijevich, Ivona; Kastner, Daniel L.
2010-01-01
The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system. Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us. We define six categories of autoinflammatory disease: IL-1β activation disorders (inflammasomopathies), NF-κB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes. A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside. PMID:19302049
Neurobehavioral aspects, pathophysiology, and management of Tourette syndrome.
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.
Chan, Yap-Hang; Hai, Jo Jo; Lau, Kui-Kai; Li, Sheung-Wai; Lau, Chu-Pak; Siu, Chung-Wah; Yiu, Kai-Hang; Tse, Hung-Fat
2017-08-24
Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P 200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.
Modern iron replacement therapy: clinical and pathophysiological insights.
Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa
2018-01-01
Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.
Pathophysiology of Manganese-Associated Neurotoxicity
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
Orthostatic intolerance: potential pathophysiology and therapy.
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.
Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.
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.
Processes underlying treatment success and failure in assertive community treatment.
Stull, Laura G; McGrew, John H; Salyers, Michelle P
2012-02-01
Processes underlying success and failure in assertive community treatment (ACT), a widely investigated treatment model for persons with severe mental illness, are poorly understood. The purpose of the current study was to examine processes in ACT by (1) understanding how consumers and staff describe the processes underlying treatment success and failure and (2) comparing processes identified by staff and consumers. Investigators conducted semi-structured interviews with 25 staff and 23 consumers from four ACT teams. Both staff and consumers identified aspects of the ACT team itself as the most critical in the process of consumer success. For failure, consumers identified consumer characteristics as most critical and staff identified lack of social relationships. Processes underlying failure were not viewed as merely the opposite of processes underlying success. In addition, there was notable disagreement between staff and consumers on important processes. Findings overlap with critical ingredients identified in previous studies, including aspects of the ACT team, social involvement and employment. In contrast to prior studies, there was little emphasis on hospitalizations and greater emphasis on not abusing substances, obtaining wants and desires, and consumer characteristics.
Stability of prebiotic, laminaran oligosaccharide under food processing conditions
Chamidah, A.
2018-04-01
Prebiotic stability tests on laminaran oligosaccharide under food processing conditions were urgently performed to determine the ability of prebiotics deal with processing. Laminaran, oligosaccharide is produced from enzymatic hydrolysis. To further apply this prebiotic, it is necessary to test its performance on food processing. Single prebiotic or in combination with probiotic can improve human digestive health. The effectiveness evaluation of prebiotic should be taken into account in regards its chemical and functional stabilities. This study aims to investigate the stability of laminaran, oligosaccharide under food processing condition.
Klein, O.; Strohschein, K.; Nebrich, G.; Oetjen, J.; Trede, D.; Thiele, H.; Alexandrov, T.; Giavalisco, P.; Duda, G.N.; Roth, P. von; Geissler, S.; Klose, J.; Winkler, T.
2014-01-01
Due to formation of fibrosis and the loss of contractile muscle tissue, severe muscle injuries often result in insufficient healing marked by a significant reduction of muscle force and motor activity. Our previous studies demonstrated that the local transplantation of mesenchymal stromal cells into an injured skeletal muscle of the rat improves the functional outcome of the healing process. Since, due to the lack of sufficient markers, the accurate discrimination of pathophysiological region...
Optimization of Wireless Transceivers under Processing Energy Constraints
Wang, Gaojian; Ascheid, Gerd; Wang, Yanlu; Hanay, Oner; Negra, Renato; Herrmann, Matthias; Wehn, Norbert
2017-09-01
Focus of the article is on achieving maximum data rates under a processing energy constraint. For a given amount of processing energy per information bit, the overall power consumption increases with the data rate. When targeting data rates beyond 100 Gb/s, the system's overall power consumption soon exceeds the power which can be dissipated without forced cooling. To achieve a maximum data rate under this power constraint, the processing energy per information bit must be minimized. Therefore, in this article, suitable processing efficient transmission schemes together with energy efficient architectures and their implementations are investigated in a true cross-layer approach. Target use cases are short range wireless transmitters working at carrier frequencies around 60 GHz and bandwidths between 1 GHz and 10 GHz.
Naveh-Benjamin, Moshe; Guez, Jonathan; Hara, Yoko; Brubaker, Matthew S; Lowenschuss-Erlich, Iris
2014-01-01
Divided attention (DA) at encoding has been shown to significantly disrupt later memory for the studied information. However, what type of processing gets disrupted during DA remains unresolved. In this study, we assessed the degree to which strategic effortful processes are affected under DA by comparing the effects of DA at encoding under intentional and pure incidental learning instructions. In three experiments, participants studied list of words or word pairs under either full or divided attention. Results of three experiments, which used different methodologies, converged to show that the effects of DA at encoding reduce memory performance to the same degree under incidental and intentional learning. Secondary task performance indicated that encoding under intentional learning instructions was more effortful than under incidental learning instructions. In addition, the results indicated enhanced attention to the initial appearance of the words under both types of learning instructions. Results are interpreted to imply that other processes, rather than only strategic effortful ones, might be affected by DA at encoding.
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...
Minimal Change Disease and IgA Deposition: Separate Entities or Common Pathophysiology?
Directory of Open Access Journals (Sweden)
Brandon S. Oberweis
2013-01-01
Full Text Available Introduction. Minimal Change Disease (MCD is the most common cause of nephrotic syndrome in children, while IgA nephropathy is the most common cause of glomerulonephritis worldwide. MCD is responsive to glucocorticoids, while the role of steroids in IgA nephropathy remains unclear. We describe a case of two distinct clinical and pathological findings, raising the question of whether MCD and IgA nephropathy are separate entities or if there is a common pathophysiology. Case Report. A 19-year old man with no medical history presented to the Emergency Department with a 20-day history of anasarca and frothy urine, BUN 68 mg/dL, Cr 2.3 mg/dL, urinalysis 3+ RBCs, 3+ protein, and urine protein : creatinine ratio 6.4. Renal biopsy revealed hypertrophic podocytes on light microscopy, podocyte foot process effacement on electron microscopy, and immunofluorescent mesangial staining for IgA. The patient was started on prednisone and exhibited dramatic improvement. Discussion. MCD typically has an overwhelming improvement with glucocorticoids, while the resolution of IgA nephropathy is rare. Our patient presented with MCD with the uncharacteristic finding of hematuria. Given the improvement with glucocorticoids, we raise the question of whether there is a shared pathophysiologic component of these two distinct clinical diseases that represents a clinical variant.
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.
Molecular pathophysiology of cerebral edema
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
Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A Review
Heesakkers, J.P.F.A.; Farag, F.; Bauer, R.M.M.J.; Sandhu, J.; Ridder, D. de; Stenzl, A.
2017-01-01
CONTEXT: The incidence and awareness of postprostatectomy incontinence (PPI) has increased during the past few years, probably because of an increase in prostate cancer surgery. Many theories have been postulated to explain the pathophysiology of PPI. OBJECTIVE: The current review scrutinizes
The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis
DEFF Research Database (Denmark)
Møller, Søren; Bendtsen, Flemming
2018-01-01
transplantation and point to the pathophysiological significance of portal hypertension. In this paper we aimed to review current knowledge on the pathophysiology of arterial vasodilatation and the hyperdynamic circulation in cirrhosis. This article is protected by copyright. All rights reserved.......Patients with cirrhosis and portal hypertension often develop complications from a variety of organ systems leading to a multiple organ failure. The combination of liver failure and portal hypertension result in a hyperdynamic circulatory state partly owing to simultaneous splanchnic and peripheral...... arterial vasodilatation. Increases in circulatory vasodilators are believed to be due to portosystemic shunting and bacterial translocation leading to redistribution of the blood volume with central hypovolemia. Portal hypertension per se and increased splanchnic blood flow are mainly responsible...
The rise of pathophysiologic research in the United States: the role of two Harvard hospitals.
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.
Pathophysiology of increased intestinal permeability in obstructive jaundice
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
New insights into the pathophysiology of postoperative cognitive dysfunction
DEFF Research Database (Denmark)
Krenk, Lene; Rasmussen, Lars Simon; Kehlet, H
2010-01-01
There is evidence that postoperative cognitive dysfunction (POCD) is a significant problem after major surgery, but the pathophysiology has not been fully elucidated. The interpretation of available studies is difficult due to differences in neuropsychological test batteries as well as the lack...
Pathophysiological and pharmacotherapeutic aspects of serotonin and serotonergic drugs
van Zwieten, P. A.; Blauw, G. J.; van Brummelen, P.
1990-01-01
A survey shall be given on the physiological, pathophysiological and pharmacotherapeutic backgrounds of the biogenic amine 5-hydroxytryptamine (serotonin; 5HT), to be preceded by a few historical remarks. 5HT is biosynthesized from L-tryptophan via hydroxylation and subsequent decarboxylation. 5HT
Convergence of macrostates under reproducible processes
International Nuclear Information System (INIS)
Rau, Jochen
2010-01-01
I show that whenever a system undergoes a reproducible macroscopic process the mutual distinguishability of macrostates, as measured by their relative entropy, diminishes. This extends the second law which regards only ordinary entropies, and hence only the distinguishability between macrostates and one specific reference state (equidistribution). The new result holds regardless of whether the process is linear or nonlinear. Its proof hinges on the monotonicity of quantum relative entropy under arbitrary coarse grainings, even those that cannot be represented by trace-preserving completely positive maps.
Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need
Corcoran, David
2018-01-01
The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424
Energy Technology Data Exchange (ETDEWEB)
Liang, Long; Zhang, Bin [Guangdong General Hospital/Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China); Southern Medical University, Graduate College, Guangzhou (China); Chen, Wen-bo; Liang, Chang-hong; Zhang, Shui-xing [Guangdong General Hospital/Guangdong Academy of Medical Sciences, Department of Radiology, Guangzhou, Guangdong Province (China); Chan, Kannie W.Y.; Li, Yu-guo; Liu, Guan-shu [The Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, Baltimore, MD (United States)
2016-06-15
To investigate the potential of intravoxel incoherent motion (IVIM) to assess the renal pathophysiological process in contrast-induced acute kidney injury (CIAKI). Twenty-seven rats were induced with CIAKI model, six rats were imaged longitudinally at 24 h prior to and 30 min, 12, 24, 48, 72 and 96 h after administration; three rats were randomly chosen from the rest for serum creatinine and histological studies. D, f, D* and ADC were calculated from IVIM, and renal blood flow (RBF) was obtained from arterial spin labelling (ASL). A progressive reduction in D and ADC was observed in cortex (CO) by 3.07 and 8.62 % at 30 min, and by 25.77 and 28.16 % at 48 h, respectively. A similar change in outer medulla (OM) and inner medulla (IM) was observed at a later time point (12-72 h). D values were strongly correlated with ADC (r = 0.885). As perfusion measurement, a significant decrease was shown for f in 12-48 h and an increase in 72-96 h. A slightly different trend was found for D*, which was decreased by 26.02, 21.78 and 10.19 % in CO, OM and IM, respectively, at 30 min. f and D* were strongly correlated with RBF in the cortex (r = 0.768, r = 0.67), but not in the medulla. IVIM is an effective imaging tool for monitoring progress in renal pathophysiology undergoing CIAKI. (orig.)
Pathophysiology of primary burning mouth syndrome with special focus on taste dysfunction: a review.
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.
Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.
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.
The pathophysiology of heart failure.
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.
Pathophysiology of Glucocorticoid Signaling.
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.
Ibáñez, Lourdes; Oberfield, Sharon E; Witchel, Selma; Auchus, Richard J; Chang, R Jeffrey; Codner, Ethel; Dabadghao, Preeti; Darendeliler, Feyza; Elbarbary, Nancy Samir; Gambineri, Alessandra; Garcia Rudaz, Cecilia; Hoeger, Kathleen M; López-Bermejo, Abel; Ong, Ken; Peña, Alexia S; Reinehr, Thomas; Santoro, Nicola; Tena-Sempere, Manuel; Tao, Rachel; Yildiz, Bulent O; Alkhayyat, Haya; Deeb, Asma; Joel, Dipesalema; Horikawa, Reiko; de Zegher, Francis; Lee, Peter A
2017-01-01
This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents. © 2017 S. Karger AG, Basel.
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.
Practical study on the integrated course of general pathology and pathophysiology
Institute of Scientific and Technical Information of China (English)
Qian ZHAO; Guo-hui FU; Ying HUANG; Wei LIU
2015-01-01
This paper aims at summarizing the experience of offering the integrated course of general pathology and pathophysiology for eight-year clinical medicine program, providing references for further improving the teaching quality,and laying a foundation for expanding the course to five-year clinical medicine program. Teaching contents of the integrated course of general pathology and pathophysiology focus on the crossing and integration of relevant discipline knowledge and properly integrating the traditional pathological knowledge,which emphasizes morphological changes of human body,with the pathophysiological knowledge,which emphasizes functional and metabolic changes of human body. It is helpful for breaking the boundaries of disciplines and enabling students to understand the laws of occurrence and development of diseases as a whole.The teaching model has been improved by introducing new teaching methods such as PBL,so as to avoid the shortcomings of traditional teaching method. The innovation consciousness,spirit of active learning,and critical thinking of students are trained via discussions of clinical cases,so as to lay a solid foundation for the learning of subsequent clinical courses and academic research in the future. In summary,integrated course benefits the overall optimization of the structure of medical courses,promotes the improvement of teaching quality,and can be expanded to five-year clinical medicine program in the future.
Diagnostic reasoning and underlying knowledge of students with preclinical patient contacts in PBL.
Diemers, Agnes D; van de Wiel, Margje W J; Scherpbier, Albert J J A; Baarveld, Frank; Dolmans, Diana H J M
2015-12-01
Medical experts have access to elaborate and integrated knowledge networks consisting of biomedical and clinical knowledge. These coherent knowledge networks enable them to generate more accurate diagnoses in a shorter time. However, students' knowledge networks are less organised and students have difficulties linking theory and practice and transferring acquired knowledge. Therefore we wanted to explore the development and transfer of knowledge of third-year preclinical students on a problem-based learning (PBL) course with real patient contacts. Before and after a 10-week PBL course with real patients, third-year medical students were asked to think out loud while diagnosing four types of paper patient problems (two course cases and two transfer cases), and explain the underlying pathophysiological mechanisms of the patient features. Diagnostic accuracy and time needed to think through the cases were measured. The think-aloud protocols were transcribed verbatim and different types of knowledge were coded and quantitatively analysed. The written pathophysiological explanations were translated into networks of concepts. Both the concepts and the links between concepts in students' networks were compared to model networks. Over the course diagnostic accuracy increased, case-processing time decreased, and students used less biomedical and clinical knowledge during diagnostic reasoning. The quality of the pathophysiological explanations increased: the students used more concepts, especially more model concepts, and they used fewer wrong concepts and links. The findings differed across course and transfer cases. The effects were generally less strong for transfer cases. Students' improved diagnostic accuracy and the improved quality of their knowledge networks suggest that integration of biomedical and clinical knowledge took place during a 10-week course. The differences between course and transfer cases demonstrate that transfer is complex and time-consuming. We
Formation process of Malaysian modern architecture under influence of nationalism
宇高, 雄志; 山崎, 大智
2001-01-01
This paper examines the Formation Process of Malaysian Modern Architecture under Influence of Nationalism,through the process of independence of Malaysia. The national style as "Malaysian national architecture" which hasengaged on background of political environment under the post colonial situation. Malaysian urban design is alsodetermined under the balance of both of ethnic culture and the national culture. In Malaysia, they decided to choosethe Malay ethnic culture as the national culture....
Pathophysiology of Barodontalgia: A Case Report and Review of the Literature
Directory of Open Access Journals (Sweden)
Marcus Stoetzer
2012-01-01
Full Text Available Changes in ambient pressure occur during flying, diving, or hyperbaric oxygen therapy and can cause different types of pathophysiological conditions and pain including toothache (barodontalgia. We report the case of a patient with severe pain in the region of his mandibular left first molar, which had been satisfactorily restored with a conservative restoration. Pain occurred during an airplane flight and persisted after landing. Radiology revealed a periapical radiolucency in the region of the distal root apex. Pain relief was achieved only after endodontic treatment. On the basis of this paper, we investigated the aetiology and management of barodontalgia. Dentists should advise patients to avoid exposure to pressure changes until all necessary surgical, conservative, and prosthetic procedures have been completed. The influence of pressure divergences should be noted at any time. Under changed environment pressures may be the changing perception of pathologies.
Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology
2018-01-01
Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits. PMID:29670770
Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy
International Nuclear Information System (INIS)
Mansberg, R.; Lewis, G.
1999-01-01
Full text: Skeletal scintigraphy is a sensitive procedure for evaluating disease and trauma involving the skeleton. Extra-skeletal pathophysiology is also often demonstrated. This may include uptake by tumours, soft tissue calcification and infection as well as renal pathology. Skeletal scintigraphy is often performed to evaluate hip and back pain and extra-osseous uterine pathophysiology can be demonstrated in both the early and late phases of the study as in the following cases. Three women underwent skeletal scintigraphy for the investigation of low back pain in two patients and post-partum hip pain in one. A large vascular uterus with deviation of the bladder was demonstrated in the post-partum patient. Increased pelvic vascularity and bladder deviation in the second patient was shown by ultrasound to correspond to a left-sided fibroid with associated adenomyosis. In the third case, right-sided pelvic vascularity and left bladder deviation were shown on ultrasound to be due to an anteverted, anteflexed uterus tilted to the right. These cases illustrate the importance of documenting extra-osseous findings on skeletal scintigraphy and the benefits of correlation with anatomical imaging
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
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...
Effects of Triphasic Exercise on Blood Rheology and Pathophysiology
African Journals Online (AJOL)
The aim of this work is to study the relevance of physiology and pathophysiology in blood rheology as effects of triphasic exercise. Regular exercise which has been established as life prolonging has led to decrease in both peripheral vascular and coronary morbidity that has been associated with certain improvements in ...
Davis, J; Desmond, M; Berk, M
2018-04-01
While lithium remains the most efficacious treatment for bipolar disorder, it can cause significant nephrotoxicity. The molecular mechanisms behind both this process and the development of nephrogenic diabetes insipidus still remain to be fully elucidated but appear to involve alterations in glycogen synthase kinase 3 signalling, G2 cell cycle progression arrest, alterations in inositol and prostaglandin signalling pathways, and dysregulated trafficking and transcription of aquaporin 2 water channels. The end result of this is a tubulointerstitial nephropathy with microcyst formation and relative glomerular sparing, both visible on pathology specimens and increasingly noted on non-invasive imaging. This paper will elucidate on the current evidence pertaining to the pathophysiology of lithium induced nephrotoxicity. This article is protected by copyright. All rights reserved.
Hepatocyte polyploidization and its association with pathophysiological processes
Wang, Min-Jun; Chen, Fei; Lau, Joseph T Y; Hu, Yi-Ping
2017-01-01
A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as ...
Asymmetric Spatial Processing Under Cognitive Load.
Naert, Lien; Bonato, Mario; Fias, Wim
2018-01-01
Spatial attention allows us to selectively process information within a certain location in space. Despite the vast literature on spatial attention, the effect of cognitive load on spatial processing is still not fully understood. In this study we added cognitive load to a spatial processing task, so as to see whether it would differentially impact upon the processing of visual information in the left versus the right hemispace. The main paradigm consisted of a detection task that was performed during the maintenance interval of a verbal working memory task. We found that increasing cognitive working memory load had a more negative impact on detecting targets presented on the left side compared to those on the right side. The strength of the load effect correlated with the strength of the interaction on an individual level. The implications of an asymmetric attentional bias with a relative disadvantage for the left (vs the right) hemispace under high verbal working memory (WM) load are discussed.
Asymmetric Spatial Processing Under Cognitive Load
Directory of Open Access Journals (Sweden)
Lien Naert
2018-04-01
Full Text Available Spatial attention allows us to selectively process information within a certain location in space. Despite the vast literature on spatial attention, the effect of cognitive load on spatial processing is still not fully understood. In this study we added cognitive load to a spatial processing task, so as to see whether it would differentially impact upon the processing of visual information in the left versus the right hemispace. The main paradigm consisted of a detection task that was performed during the maintenance interval of a verbal working memory task. We found that increasing cognitive working memory load had a more negative impact on detecting targets presented on the left side compared to those on the right side. The strength of the load effect correlated with the strength of the interaction on an individual level. The implications of an asymmetric attentional bias with a relative disadvantage for the left (vs the right hemispace under high verbal working memory (WM load are discussed.
The importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy.
Bosi, Marcello; De Vito, Andrea; Gobbi, Riccardo; Poletti, Venerino; Vicini, Claudio
2017-03-01
The objective of this study is to highlight the importance of anatomical and not-anatomical factors' identification for customized therapy in OSAHS patients. The data sources are: MEDLINE, The Cochrane Library and EMBASE. A systematic review was performed to identify studies that analyze the role of multiple interacting factors involved in the OSAHS pathophysiology. 85 out of 1242 abstracts were selected for full-text review. A variable combinations pathophysiological factors contribute to realize differentiated OSAHS phenotypes: a small pharyngeal airway with a low resistance to collapse (increased critical closing pressure), an inadequate responses of pharyngeal dilator muscles (wakefulness drive to breathe), an unstable ventilator responsiveness to hypercapnia (high loop gain), and an increased propensity to wake related to upper airway obstruction (low arousal threshold). Identifying if the anatomical or not-anatomical factors are predominant in each OSAHS patient represents the current challenge in clinical practice, moreover for the treatment decision-making. In the future, if a reliable and accurate pathophysiological pattern for each OSAHS patient can be identified, a customized therapy will be feasible, with a significant improvement of surgical success in sleep surgery and a better understanding of surgical failure.
van Ginkel, R; Büller, H A; Heymans, H S; Taminiau, J A; Boeckxstaens, G E; Benninga, M A
2003-06-28
The childhood prevalences of constipation and encopresis are 0.3-8% and 1-3% respectively. Following a recent stricter definition and classification, constipation and solitary encopresis are now recognised to be two separate entities. Constipation is characterised by infrequent defecation, often in combination with involuntary loss of faeces. Solitary encopresis most often occurs once a day after school hours. When there is no defecation, the frequency of encopresis increases, the abdominal pain becomes more severe and the appetite becomes less, until a large quantity of faeces is produced (often once per week). The physiology of the defecation and continence mechanism is complex and has only been unravelled in part. The multiple physiological mechanisms involved have a complementary and compensatory effect on each other. This makes it difficult to determine the underlying pathophysiological mechanisms of these functional disorders.
MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation.
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].
A Web-based e-learning course: integration of pathophysiology into pharmacology.
Tse, Mimi M Y; Lo, Lisa W L
2008-11-01
The Internet is becoming the preferred place to find information. Millions of people go online in search of health and medical information. Likewise, the demand for Web-based courses is growing. This paper presents the development, utilization, and evaluation of a Web-based e-learning course for nursing students, entitled Integration of Pathophysiology into Pharmacology. The pathophysiology component included cardiovascular, respiratory, central nervous and immune system diseases, while the pharmacology component was developed based on 150 commonly used drugs. One hundred and nineteen Year 1 nursing students took part in the course. The Web-based e-learning course materials were uploaded to a WebCT for students' self-directed learning and attempts to pass two scheduled online quizzes. At the end of the semester, students were given a questionnaire to measure the e-learning experience. Their experience in the e-learning course was a positive one. Students stated that they were able to understand rather than memorize the subject content, and develop their problem solving and critical thinking abilities. Online quizzes yielded satisfactory results. In the focus group interview, students indicated that they appreciated the time flexibility and convenience associated with Web-based learning, and also made good suggestions for enhancing Web-based learning. The Web-based approach is promising for teaching and learning pathophysiology and pharmacology for nurses and other healthcare professionals.
Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management
Directory of Open Access Journals (Sweden)
Shiyi Guo
2017-06-01
Full Text Available Restless legs syndrome (RLS, a common neurological sensorimotor disorder in western countries, has gained more and more attention in Asian countries. The prevalence of RLS is higher in older people and females. RLS is most commonly related to iron deficiency, pregnancy and uremia. The RLS symptoms show a significant circadian rhythm and a close relationship to periodic limb movements (PLMs in clinical observations, while the pathophysiological pathways are still unknown. The diagnostic criteria have been revised in 2012 to improve the validity of RLS diagnosis. Recent studies have suggested an important role of iron decrease of brain in RLS pathophysiology. Dopaminergic (DA system dysfunction in A11 cell groups has been recognized long ago from clinical treatment and autopsy. Nowadays, it is believed that iron dysfunction can affect DA system from different pathways and opioids have a protective effect on DA system. Several susceptible single nucleotide polymorphisms such as BTBD9 and MEIS1, which are thought to be involved in embryonic neuronal development, have been reported to be associated with RLS. Several pharmacological and non-pharmacological treatment are discussed in this review. First-line treatments of RLS include DA agents and α2δ agonists. Augmentation is very common in long-term treatment of RLS which makes prevention and management of augmentation very important for RLS patients. A combination of different types of medication is effective in preventing and treating augmentation. The knowledge on RLS is still limited, the pathophysiology and better management of RLS remain to be discovered.
Pathophysiology of the anorexia of aging.
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.
Pathophysiology of osteoporosis: new mechanistic insights.
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.
Pathophysiology of acute mountain sickness and high altitude pulmonary oedema
DEFF Research Database (Denmark)
Sutton, J R; Lassen, N
1979-01-01
We review the evidence that acute mountain sickness (AMS) and high altitude pulmonary oedema (HAPO) occur together more often than is realized. We hypothesize that AMS and HAPO have a common pathophysiological basis: both are due to increased pressure and flow in the microcirculation, causing...
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.
Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology
Directory of Open Access Journals (Sweden)
Roshan Dadachanji
2018-01-01
Full Text Available Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.
Elucidating the Role of Neurotensin in the Pathophysiology and Management of Major Mental Disorders
Directory of Open Access Journals (Sweden)
Mona M Boules
2014-06-01
Full Text Available Neurotensin (NT is a neuropeptide that is closely associated with, and is thought to modulate, dopaminergic and other neurotransmitter systems involved in the pathophysiology of various mental disorders. This review outlines data implicating NT in the pathophysiology and management of major mental disorders such as schizophrenia, drug addiction, and autism. The data suggest that NT receptor analogs have the potential to be used as novel therapeutic agents acting through modulation of neurotransmitter systems dys-regulated in these disorders.
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
Pathophysiology of muscle contractures in cerebral palsy.
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.
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
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.
Encapsulating Peritoneal Sclerosis: A study on pathophysiology, clinical aspects and management
S.M. Habib (Meelad)
2014-01-01
markdownabstract__Abstract__ This thesis describes the results of studies focusing on the pathophysiology, clinical aspects, and management of encapsulating peritoneal sclerosis (EPS). We have reported on the presence of inflammation in EPS, described several clinical aspects, and focused on
[Functional pathophysiology of consciousness].
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.
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.
Pathophysiology of heatstroke in dogs - revisited.
Bruchim, Yaron; Horowitz, Michal; Aroch, Itamar
2017-01-01
Heatstroke results from a failure to dissipate accumulated heat during exposure to hot environments, or during strenuous physical exercise under heat stress. It is characterized by core body temperatures > 41°C, with central nervous system dysfunction. Functional morphology and thermoregulatory effectors differences between dogs and humans may require special heatstroke protective adaptations in dogs, however, the risk factors for developing heatstroke are similar in both. In dogs, these include hot, especially highly humid environments, excessive physical activity, obesity, large (>15 kg) body weight, being of certain breed (e.g., Labrador retrievers and brachycephalic breeds), upper airway obstruction and prolonged seizures. Lack of acclimation to heat and physical fitness decreases the survival of heat stroked dogs. At the systemic level, blood pooling within the large internal organs (e.g., spleen, liver) is a major contributor to the development of shock and consequent intestinal ischemia, hypoxia and endothelial hyperpermeability, commonly occurring in heatstroke patients. Evoked serious complications include rhabdomyolysis, acute kidney injury, acute respiratory distress syndrome and ultimately, sepsis and disseminated intravascular coagulation. The most common clinical signs in dogs include acute collapse, tachypnea, spontaneous bleeding, shock signs and mental abnormalities, including depression, disorientation or delirium, seizures, stupor and coma. In such dogs, presence of peripheral blood nucleated red blood cells uniquely occurs, and is a highly sensitive diagnostic and prognostic biomarker. Despite early, appropriate body cooling, and intensive supportive treatment, with no available specific treatment to ameliorate the severe inflammatory and hemostatic derangements, the mortality rate is around 50%, similar to that of human heatstroke victims. This review discusses the pathophysiology of canine heatstroke from a veterinarian's point of view
Goubert, Dorien; Danneels, Lieven; Graven-Nielsen, Thomas; Descheemaeker, Filip; Coppieters, Iris; Meeus, Mira
2017-01-01
Background: The impairment in musculoskeletal structures in patients with low back pain (LBP) is often disproportionate to their complaint. Therefore, the need arises for exploration of alternative mechanisms contributing to the origin and maintenance of non-specific LBP. The recent focus has been on central nervous system phenomena in LBP and the pathophysiological mechanisms underlying the various symptoms and characteristics of chronic pain. Knowledge concerning changes in pain processing ...
Capillary leak syndrome: etiologies, pathophysiology, and management.
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.
Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub
2016-05-01
Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.
Postoperative ileus: Recent developments in pathophysiology and management.
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.
Retinovascular physiology and pathophysiology: new experimental approach/new insights
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
Altered Mitochondrial Dynamics and TBI Pathophysiology
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Tara Diane Fischer
2016-03-01
Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved
Pathophysiology of Headaches with a Prominent Vascular Component
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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.
Gait post-stroke: Pathophysiology and rehabilitation strategies.
Beyaert, C; Vasa, R; Frykberg, G E
2015-11-01
We reviewed neural control and biomechanical description of gait in both non-disabled and post-stroke subjects. In addition, we reviewed most of the gait rehabilitation strategies currently in use or in development and observed their principles in relation to recent pathophysiology of post-stroke gait. In both non-disabled and post-stroke subjects, motor control is organized on a task-oriented basis using a common set of a few muscle modules to simultaneously achieve body support, balance control, and forward progression during gait. Hemiparesis following stroke is due to disruption of descending neural pathways, usually with no direct lesion of the brainstem and cerebellar structures involved in motor automatic processes. Post-stroke, improvements of motor activities including standing and locomotion are variable but are typically characterized by a common postural behaviour which involves the unaffected side more for body support and balance control, likely in response to initial muscle weakness of the affected side. Various rehabilitation strategies are regularly used or in development, targeting muscle activity, postural and gait tasks, using more or less high-technology equipment. Reduced walking speed often improves with time and with various rehabilitation strategies, but asymmetric postural behaviour during standing and walking is often reinforced, maintained, or only transitorily decreased. This asymmetric compensatory postural behaviour appears to be robust, driven by support and balance tasks maintaining the predominant use of the unaffected side over the initially impaired affected side. Based on these elements, stroke rehabilitation including affected muscle strengthening and often stretching would first need to correct the postural asymmetric pattern by exploiting postural automatic processes in various particular motor tasks secondarily beneficial to gait. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Saleh, Suha M; Asi, Yara M; Hamed, Kastro M
2013-06-01
Due to growing demand from students and facilitated by innovations in educational technology, institutions of higher learning are increasingly offering online courses. Subjects in the hard sciences, such as pathophysiology, have traditionally been taught in the face-to-face format, but growing demand for preclinical science courses has compelled educators to incorporate online components into their classes to promote comprehension. Learning tools such as case studies are being integrated into such courses to aid in student interaction, engagement, and critical thinking skills. Careful assessment of pedagogical techniques is essential; hence, this study aimed to evaluate and compare student perceptions of the use of case studies in face-to-face and fully online pathophysiology classes. A series of case studies was incorporated into the curriculum of a pathophysiology class for both class modes (online and face to face). At the end of the semester, students filled out a survey assessing the effectiveness of the case studies. Both groups offered positive responses about the incorporation of case studies in the curriculum of the pathophysiology class. This study supports the argument that with proper use of innovative teaching tools, such as case studies, online pathophysiology classes can foster a sense of community and interaction that is typically only seen with face-to-face classes, based on student responses. Students also indicated that regardless of class teaching modality, use of case studies facilitates student learning and comprehension as well as prepares them for their future careers in health fields.
Targeting autophagy in obesity: from pathophysiology to management.
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.
Understanding changes in cardiovascular pathophysiology.
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.
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.
Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.
Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei
2017-03-01
The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.
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.
Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?
Basson, M D; Fielding, L P; Bilchik, A J; Zucker, K A; Ballantyne, G H; Sussman, J; Adrian, T E; Modlin, I M
1989-01-01
We hypothesized that bioactive peptides might be released into the portal circulation and mediate pathophysiologic alterations accompanying small bowel obstruction. We studied this question in a subacute canine small bowel obstruction model using 50 percent diameter occlusion. Control animals underwent sham laparotomy. Vasoactive intestinal peptide (VIP), peptide YY, and gastrin were measured in portal and systemic plasma by specific radioimmunoassays at 24-hour intervals as the obstruction progressed to completion over 5 days. All peptides in both groups demonstrated portal and peripheral gradients. In control dogs, peptide concentrations did not change postoperatively but VIP increased markedly in obstructed dogs, demonstrating a median portal level of 95 pmol/liter at 96 hours compared with 31.5 pmol/liter in control animals. These portal VIP levels are known to cause hypersecretion and splanchnic vasodilation in experimental models. The release of vasoactive compounds such as VIP may mediate local pathophysiology in human small bowel obstruction. A similar explanation of the systemic effects is consistent with the known cardiopulmonary bioactivity of VIP.
[Pathophysiology and treatment of orofacial pain.
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.
Dispute settlement process under GATT/WTO diplomatic or judicial ...
African Journals Online (AJOL)
This paper probes the mechanisms of the dispute resolution process under the World Trade Organisation (WTO) and the General Agreement on Tariff and Trade (GATT). It tries to analyse the evolution of the dispute process which was initially based on diplomatic procedures and gives an account of its evolution and ...
Directory of Open Access Journals (Sweden)
Małgorzata Nita
2014-01-01
Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.
Type 2 diabetes across generations: from pathophysiology to prevention and management
DEFF Research Database (Denmark)
Nolan, Christopher J; Damm, Peter; Prentki, Marc
2011-01-01
Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility ...
Directory of Open Access Journals (Sweden)
Vincenzo Salpietro
2014-01-01
Full Text Available Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency has been reported with neurological and magnetic resonance imaging (MRI abnormalities (e.g., delayed myelination and brain atrophy due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH, a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric CNS seems to be particularly vulnerable to alterations induced by
[Dysphagia in Parkinson's Disease: Pathophysiology, Diagnosis and Therapy].
Suttrup, I; Warnecke, T
2016-07-01
Oropharyngeal and esophageal dysphagia are a frequent, but seldom diagnosed symptom of Parkinson's disease (PD). More than 80 % of patients with PD develop dysphagia during the course of their disease leading to a reduced quality of life, complicated medication intake, malnutrition and aspiration pneumonia, which is a major cause of death in PD. The underlying pathophysiology is poorly understood. Impaired dopaminergic and non-dopaminergic mechanisms of the cortical swallowing network as well as peripheral neuromuscular involvement have been suggested to contribute to its multifactorial genesis. Diagnostic screening methods include PD-specific questionnaires and a modified water test. Fiber optic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS), which complement each other, are the gold standard for evaluation of PD-related dysphagia. For evaluation of esophageal dysphagia, the high-resolution manometry (HRM) may be a helpful tool. In addition to dysphagia-specific treatment by speech and language therapists (SLTs), optimized dopaminergic medication is a meaningful therapeutic option. A promising novel method is intensive training of expiratory muscle strength (EMST). Deep brain stimulation does not seem to have a clinically relevant effect on swallowing function in PD. © Georg Thieme Verlag KG Stuttgart · New York.
Pathophysiology of pelvic organ prolapse and stress urinary incontinence
Directory of Open Access Journals (Sweden)
Payal D Patel
2006-01-01
Full Text Available Although they may present with significant morbidity, pelvic organ prolapse and stress urinary incontinence are mainly afflicitions that affect quality of life. To appropiately treat these entities, comprehension of the various theories of pathophysiology is paramount. Utilizing a Medline search, this article reviews recent data concerning intrinsic (i.e., genetics, postmenopausal status and extrinsic factors (i.e., previous hysterectomy, childbirth leading to organ prolapse or stress incontinence
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.
Bruner-Tran, Kaylon L.; Herington, Jennifer L.; Duleba, Antoni J.; Taylor, Hugh S.; Osteen, Kevin G.
2013-01-01
Progesterone action normally mediates the balance between anti-inflammatory and pro-inflammatory processes throughout the female reproductive tract. However, in women with endometriosis, endometrial progesterone resistance, characterized by alterations in progesterone responsive gene and protein expression, is now considered a central element in disease pathophysiology. Recent studies additionally suggest that the peritoneal microenvironment of endometriosis patients exhibits altered physiological characteristics that may further promote inflammation-driven disease development and progression. Within this review, we summarize our current understanding of the pathogenesis of endometriosis with an emphasis on the role that inflammation plays in generating not only the progesterone-resistant eutopic endometrium but also a peritoneal microenvironment that may contribute significantly to disease establishment. Viewing endometriosis from the emerging perspective that a progesterone resistant endometrium and an immunologically compromised peritoneal microenvironment are biologically linked risk factors for disease development provides a novel mechanistic framework to identify new therapeutic targets for appropriate medical management. PMID:23598784
Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer
Directory of Open Access Journals (Sweden)
Luka Andrisic
2018-04-01
Full Text Available Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine. Keywords: Carcinogenesis, Cancer, Oxidative stress, Lipid peroxidation, 4-hydroxynonenal, Glutathione, Metabolomics, Immunochemistry, Biomarkers, Omics science
Concentration processes under tubesheet sludge piles in nuclear steam generators
International Nuclear Information System (INIS)
Gonzalez, F.; Spekkens, P.
1987-01-01
The process by which bulk water solutes are concentrated under tubesheet sludge piles in nuclear steam generators was investigated in the laboratory under simulated CANDU operating conditions. Concentration rates were found to depend on the tube heat flux and pile depth, although beyond a critical depth the concentration efficiency decreased. This efficiency could be expressed by a concentration coefficient, and was found to depend also on the sludge pile porosity. Solute concentration profiles in the sludge pile suggested that the concentration mechanism in a high-porosity/permeability pile is characterized by boiling mainly near or at the tube surface, while in low-porosity piles, the change of phase may also become important in the body of the sludge pile. In all cases, the full depth of the pile was active to some extent in the concentration process. As long as the heat transfer under the pile was continued, the solute remained under the pile and slowly migrated toward the bottom. When the heat transfer was stopped, the solute diffused back into the bulk solution at a rate slower than that of the concentration process
Insights into Pathophysiology from Medication-induced Tremor
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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.
From cell to bedside: some pathophysiologic considerations about the cardiac stimulation
International Nuclear Information System (INIS)
Gutierrez, O.
2013-01-01
Myocardial cell pathophysiology is presented as related to possible modification by electrical stimulation of the myocardium. The objective is a diagnostic and therapeutic clinical application such as is seen with bradyarrhythmias and tachyarrhythmias. In addition, the E C is an essential tool during catheter ablation procedures
Potential Role of Extracellular Vesicles in the Pathophysiology of Drug Addiction.
Rao, P S S; O'Connell, Kelly; Finnerty, Thomas Kyle
2018-01-23
Extracellular vesicles (EVs) are small vesicles secreted by cells and are known to carry sub-cellular components including microRNA, proteins, and lipids. Due to their ability to transport cargo between cells, EVs have been identified as important regulators of various pathophysiological conditions and can therefore influence treatment outcomes. In particular, the significance of microRNAs in EV-mediated cell-cell communication is well-documented. While the influence of EVs and the cargo delivered by EVs has been extensively reviewed in other neurological disorders, the available literature on the potential role of EVs in the pathophysiology of drug addiction has not been reviewed. Hence, in this article, the known effects of commonly abused drugs (ethanol, nicotine, opiates, cocaine, and cannabinoids) on EV secretion have been reviewed. In addition, the potential role of drugs of abuse in affecting the delivery of EV-packaged microRNAs, and the subsequent impact on neuronal health and continued drug dependence, has been discussed.
[Scientific connotation of processing Bombyx Batryticatus under high temperature].
Ma, Li; Wang, Xuan; Ma, Lin; Wang, Man-yuan; Qiu, Feng
2015-12-01
The aim of this study was to elucidate the scientific connotation of Bombyx Batryticatus processing with wheat bran under high temperature. The contents of soluble protein extracted from Bombyx Batryticatus and its processed products and the limited content of AFT in Bombyx Batryticatus and the processed one were compared. The concentration of protein was measured with the Bradford methods and the difference of protein between Bombyx Batryticatus and its processed products was compared by SDS-PAGE analysis. Aflatoxin B1, B2, G1, and G2 were determined by reversed-phase HPLC. The results showed that the soluble protein content of Bombyx Batryticatus and its processed products were (47.065 +/- 0.249), (29.756 +/- 1.961) mg x g(-1), correspondingly. Analysis of protein gel electrophoresis showed that there were no significant differences between the crude and processed one in protein varieties. 6 bands were detected: 31.90, 26.80, 18.71, 15.00, 10.18, 8.929 kDa. Below 10 kDa, the color of bands of the processed one was deeper than the crude one, which demonstrate that macromolecular protein was degradated into micromolecule. The content of AFG1, AFB1, AFG2, AFB2 were 0.382, 0.207, 0.223, 0.073 g x kg(-1), not exceeded 5 microg x kg(-1) while the processed one was not detected. Through processing with wheat bran under high temperature, the content of soluble protein in Bombyx Batryticatus decreased, the processing purpose for alleviating drug property was achieved. Meanwhile, the limited content of aflatoxins were reduced or cleared by processing procedure or absorbed by processing auxillary material, adding the safety of the traditional Chinese Medicine. In conclusion, as a traditional processing method, bran frying Bombyx Batryticatus was scientific and reasonable.
Fuel corrosion processes under waste disposal conditions
International Nuclear Information System (INIS)
Shoesmith, D.W.
2000-01-01
The release of the majority of radionuclides from spent nuclear fuel under permanent disposal conditions will be controlled by the rate of dissolution of the UO 2 fuel matrix. In this manuscript the mechanism of the coupled anodic (fuel dissolution) and cathodic (oxidant reduction) reactions which constitute the overall fuel corrosion process is reviewed, and the many published observations on fuel corrosion under disposal conditions discussed. The primary emphasis is on summarizing the overall mechanistic behaviour and establishing the primary factors likely to control fuel corrosion. Included are discussions on the influence of various oxidants including radiolytic ones, pH, temperature, groundwater composition, and the formation of corrosion product deposits. The relevance of the data recorded on unirradiated UO 2 to the interpretation of spent fuel behaviour is included. Based on the review, the data used to develop fuel corrosion models under the conditions anticipated in Yucca Mountain (NV, USA) are evaluated
Preeclampsia: from Pathophysiology to Treatment
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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
Pathophysiology of Portal Hypertension and Its Clinical Links
Seo, Yeon Seok; Shah, Vijay H
2011-01-01
Portal hypertension is a major cause of morbidity and mortality in patients with liver cirrhosis. Intrahepatic vascular resistance due to architectural distortion and intrahepatic vasoconstriction, increased portal blood flow due to splanchnic vasodilatation, and development of collateral circulation have been considered as major factors for the development of portal hypertension. Recently, sinusoidal remodeling and angiogenesis have been focused as potential etiologic factors and various researchers have tried to improve portal hypertension by modulating these new targets. This article reviews potential new treatments in the context of portal hypertension pathophysiology concepts. PMID:25755320
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
Probabilistic Design in a Sheet Metal Stamping Process under Failure Analysis
International Nuclear Information System (INIS)
Buranathiti, Thaweepat; Cao, Jian; Chen, Wei; Xia, Z. Cedric
2005-01-01
Sheet metal stamping processes have been widely implemented in many industries due to its repeatability and productivity. In general, the simulations for a sheet metal forming process involve nonlinearity, complex material behavior and tool-material interaction. Instabilities in terms of tearing and wrinkling are major concerns in many sheet metal stamping processes. In this work, a sheet metal stamping process of a mild steel for a wheelhouse used in automobile industry is studied by using an explicit nonlinear finite element code and incorporating failure analysis (tearing and wrinkling) and design under uncertainty. Margins of tearing and wrinkling are quantitatively defined via stress-based criteria for system-level design. The forming process utilizes drawbeads instead of using the blank holder force to restrain the blank. The main parameters of interest in this work are friction conditions, drawbead configurations, sheet metal properties, and numerical errors. A robust design model is created to conduct a probabilistic design, which is made possible for this complex engineering process via an efficient uncertainty propagation technique. The method called the weighted three-point-based method estimates the statistical characteristics (mean and variance) of the responses of interest (margins of failures), and provide a systematic approach in designing a sheet metal forming process under the framework of design under uncertainty
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...
The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas.
Hegyi, Péter; Rakonczay, Zoltán
2011-11-15
Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.
Bianchin, Marino Muxfeldt; Londero, Renata Gomes; Lima, José Eduardo; Bigal, Marcelo Eduardo
2010-08-01
The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.
Functional O-GlcNAc modifications: Implications in molecular regulation and pathophysiology
Wells, Lance
2016-01-01
O-linked β-N-acetylglucosamine (O-GlcNAc) is a regulatory post-translational modification of intracellular proteins. The dynamic and inducible cycling of the modification is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in response to UDP-GlcNAc levels in the hexosamine biosynthetic pathway (HBP). Due to its reliance on glucose flux and substrate availability, a major focus in the field has been on how O-GlcNAc contributes to metabolic disease. For years this post-translational modification has been known to modify thousands of proteins implicated in various disorders, but direct functional connections have until recently remained elusive. New research is beginning to reveal the specific mechanisms through which O-GlcNAc influences cell dynamics and disease pathology including clear examples of O-GlcNAc modification at a specific site on a given protein altering its biological functions. The following review intends to focus primarily on studies in the last half decade linking O-GlcNAc modification of proteins with chromatin-directed gene regulation, developmental processes, and several metabolically related disorders including Alzheimer’s, heart disease and cancer. These studies illustrate the emerging importance of this post-translational modification in biological processes and multiple pathophysiologies. PMID:24524620
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.
Signature and Pathophysiology of Non-canonical Pores in Voltage-Dependent Cation Channels.
Held, Katharina; Voets, Thomas; Vriens, Joris
2016-01-01
Opening and closing of voltage-gated cation channels allows the regulated flow of cations such as Na(+), K(+), and Ca(2+) across cell membranes, which steers essential physiological processes including shaping of action potentials and triggering Ca(2+)-dependent processes. Classical textbooks describe the voltage-gated cation channels as membrane proteins with a single, central aqueous pore. In recent years, however, evidence has accumulated for the existence of additional ion permeation pathways in this group of cation channels, distinct from the central pore, which here we collectively name non-canonical pores. Whereas the first non-canonical pores were unveiled only after making specific point mutations in the voltage-sensor region of voltage-gated Na(+) and K(+) channels, recent evidence indicates that they may also be functional in non-mutated channels. Moreover, several channelopathies have been linked to mutations that cause the appearance of a non-canonical ion permeation pathway as a new pathological mechanism. This review provides an integrated overview of the biophysical properties of non-canonical pores described in voltage-dependent cation channels (KV, NaV, Cav, Hv1, and TRPM3) and of the (patho)physiological impact of opening of such pores.
Maseroli, Elisa; Scavello, Irene; Vignozzi, Linda
2018-05-02
Erectile dysfunction is recognized as an opportunity for preventing cardiovascular (CV) events, and assessing the impairment of penile vascular flow by Doppler ultrasound is an important tool to ascertain CV risk. Conversely, the role of genital vascular impairment in the pathophysiology of female sexual dysfunction (FSD) remains contentious. To focus on the current scientific support for an association between CV risk factors and female sexual health in the 1st part of a 2-part review. A thorough literature search of peer-reviewed publications on the associations between CV risk factors and FSD and their underlying mechanisms was performed using the PubMed database. We present a summary of the evidence from clinical studies and discuss the possible mechanisms providing the pathophysiologic bases of vasculogenic FSD syndromes. The peripheral sexual response in women is a vascular-dependent event, and evidence suggests that cardiometabolic-related perturbations in endothelial function can determine vascular insufficiency in female genital tissues. Although epidemiologic and observational studies demonstrate that the prevalence of FSD is higher in women with diabetes mellitus, a cause-effect relation between these clinical conditions cannot be assumed. Evidence on the effect of obesity, metabolic syndrome, and polycystic ovary syndrome on sexual function in women is controversial. Data on the associations of dyslipidemia and hypertension with FSD are limited. Common cardiometabolic alterations could affect vascular function in the female genital tract. Based on limited data, there is an association between CV risk factors and female sexual health in women; however, this association appears milder than in men. Maseroli E, Scavello I, Vignozzi L. Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes. Sex Med Rev 2018;X:XXX-XXX. Copyright © 2018 International
Neuropsychiatric comorbidity in obesity: role of inflammatory processes
Directory of Open Access Journals (Sweden)
Nathalie eCastanon
2014-05-01
Full Text Available Neuropsychiatric symptoms are frequent in obesity. In addition to their substantial economic and health impact, these symptoms significantly interfere with the quality of life and social function of obese individuals. While the pathophysiological mechanisms underlying obesity-related neuropsychiatric symptoms are still under investigation and remain to be clearly identified, there is increasing evidence for a role of inflammatory processes. Obesity is characterized by a chronic low-grade inflammatory state that is likely to influence neuropsychiatric status given the well-known and highly documented effects of inflammation on brain activity/function and behavior. This hypothesis is supported by recent findings emanating from clinical investigations in obese subjects and from experimentations conducted in animal models of obesity. These studies converge to show that obesity-related inflammatory processes, originating either from the adipose tissue or gut microbiota environment, spread to the brain where they lead to substantial changes in neurocircuitry, neuroendocrine activity, neurotransmitter metabolism and activity, and neurogenesis. Together, these alterations contribute to shape the propitious bases for the development of obesity-related neuropsychiatric comorbidities.
Learning process mapping heuristics under stochastic sampling overheads
Ieumwananonthachai, Arthur; Wah, Benjamin W.
1991-01-01
A statistical method was developed previously for improving process mapping heuristics. The method systematically explores the space of possible heuristics under a specified time constraint. Its goal is to get the best possible heuristics while trading between the solution quality of the process mapping heuristics and their execution time. The statistical selection method is extended to take into consideration the variations in the amount of time used to evaluate heuristics on a problem instance. The improvement in performance is presented using the more realistic assumption along with some methods that alleviate the additional complexity.
Air leak after lung resection: pathophysiology and patients' implications.
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.
Recent developments in the pathophysiology of irritable bowel syndrome.
El-Salhy, Magdy
2015-07-07
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients.
Hepatocyte polyploidization and its association with pathophysiological processes.
Wang, Min-Jun; Chen, Fei; Lau, Joseph T Y; Hu, Yi-Ping
2017-05-18
A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans. Hepatocyte polyploidization is generally considered an indicator of terminal differentiation and cellular senescence, and related to the dysfunction of insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of hepatocyte polyploidization in the aged mouse liver can be reversed when the senescent hepatocytes are serially transplanted into young mouse livers. Here we review the current knowledge on the mechanism of hepatocytes polyploidization during postnatal growth, aging, and liver diseases. The biologic significance of polyploidization in senescent reversal, within the context of new ways to think of liver aging and liver diseases is considered.
Pathophysiological characterization of asthma transitions across adolescence.
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.
Pathophysiologic insights into motor axonal function in Kennedy disease.
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.
22 CFR 92.92 - Service of legal process under provisions of State law.
2010-04-01
... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Service of legal process under provisions of... AND RELATED SERVICES Quasi-Legal Services § 92.92 Service of legal process under provisions of State law. It may be found that a State statue purporting to regulate the service of process in foreign...
Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.
2012-01-01
This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962
Pancreatitis in dogs and cats – definitions and pathophysiology
Watson, Penelope Jayne
2014-01-01
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 c...
Pathophysiological Mechanisms of Laser Correction in Critical Conditions
Directory of Open Access Journals (Sweden)
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.
Yu, Huimin; Hasan, Nesrin M; In, Julie G; Estes, Mary K; Kovbasnjuk, Olga; Zachos, Nicholas C; Donowitz, Mark
2017-02-10
The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.
Genetics of liver disease: From pathophysiology to clinical practice.
Karlsen, Tom H; Lammert, Frank; Thompson, Richard J
2015-04-01
Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Physiology and pathophysiology of ClC-K/barttin channels.
Fahlke, Christoph; Fischer, Martin
2010-01-01
ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.
Left main coronary artery disease: pathophysiology, diagnosis, and treatment.
Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W
2018-06-01
The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.
Physiology and pathophysiology of ClC-K/barttin channels
Directory of Open Access Journals (Sweden)
Christoph eFahlke
2010-11-01
Full Text Available ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology and pathophysiology of ClC-K/barttin channels.
Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments
McQuade, Rachel M.; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C.; Nurgali, Kulmira
2016-01-01
Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers. PMID:27857691
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.
BURDEN OF PROOF IN CONSTITUTIONAL PROCESS UNDER CONSIDERATION OF DEMOCRATIC STATE
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Patrícia Mendanha Dias
2016-12-01
Full Text Available Under the aegis of the democratic rule of law, the contradictory it appears as a fundamental premise of constitutionalised process. In this view, the contradictory, more than just right party to exercise its right of defense, it should be seen as a form of compartipação in the process, allowing the parties to the probative production as an effective influence on acertamento right. Thus, it should be disproved the right mitigation attempts contradictory in the evidentiary phase and imposing aside the need to produce proofimpossible or difficult to perform, under penalty of offending the process understood in the modern normative framework.
Amiri, H.; Saeidi, K.; Borhani, P.; Manafirad, A.; Ghavami, M.; Zerbi, V.
2013-01-01
Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade
Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore
2014-01-01
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome. PMID:25763405
Directory of Open Access Journals (Sweden)
Joselyn Rojas
2014-01-01
Full Text Available Polycystic ovary syndrome (PCOS is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR, and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.
Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore
2014-01-01
Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.
Directory of Open Access Journals (Sweden)
Taysa Bervian Bassani
2015-07-01
Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.
Ultrasonic signal processing for sizing under-clad flaws
International Nuclear Information System (INIS)
Shankar, R.; Paradiso, T.J.; Lane, S.S.; Quinn, J.R.
1985-01-01
Ultrasonic digital data were collected from underclad cracks in sample pressure vessel specimen blocks. These blocks were weld cladded under different processes to simulate actual conditions in US Pressure Water Reactors. Each crack was represented by a flaw-echo dynamic curve which is a plot of the transducer motion on the surface as a function of the ultrasonic response into the material. Crack depth sizing was performed by identifying in the dynamic curve the crack tip diffraction signals from the upper and lower tips. This paper describes the experimental procedure, digital signal processing methods used and algorithms developed for crack depth sizing
Broeyer, Frederik Jan Ferdinand
2012-01-01
In this thesis the development of a pathophysiology-based method for the early evaluation of anthracycline-induced cardiotoxicity was described. We evaluated a comprehensive array of biomarkers, representing several aspects of anthracycline-induced cardiotoxicity, including cardiac injury and
Dynamic Processes in Nanostructured Crystals Under Ion Irradiation
Uglov, V. V.; Kvasov, N. T.; Shimanski, V. I.; Safronov, I. V.; Komarov, N. D.
2018-02-01
The paper presents detailed investigations of dynamic processes occurring in nanostructured Si(Fe) material under the radiation exposure, namely: heating, thermoelastic stress generation, elastic disturbances of the surrounding medium similar to weak shock waves, and dislocation generation. The performance calculations are proposed for elastic properties of the nanostructured material with a glance to size effects in nanoparticles.
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...
Pittenger, Christopher; Bloch, Michael H; Williams, Kyle
2011-12-01
Obsessive compulsive disorder is prevalent, disabling, incompletely understood, and often resistant to current therapies. Established treatments consist of specialized cognitive-behavioral psychotherapy and pharmacotherapy with medications targeting serotonergic and dopaminergic neurotransmission. However, remission is rare, and more than a quarter of OCD sufferers receive little or no benefit from these approaches, even when they are optimally delivered. New insights into the disorder, and new treatment strategies, are urgently needed. Recent evidence suggests that the ubiquitous excitatory neurotransmitter glutamate is dysregulated in OCD, and that this dysregulation may contribute to the pathophysiology of the disorder. Here we review the current state of this evidence, including neuroimaging studies, genetics, neurochemical investigations, and insights from animal models. Finally, we review recent findings from small clinical trials of glutamate-modulating medications in treatment-refractory OCD. The precise role of glutamate dysregulation in OCD remains unclear, and we lack blinded, well-controlled studies demonstrating therapeutic benefit from glutamate-modulating agents. Nevertheless, the evidence supporting some important perturbation of glutamate in the disorder is increasingly strong. This new perspective on the pathophysiology of OCD, which complements the older focus on monoaminergic neurotransmission, constitutes an important focus of current research and a promising area for the ongoing development of new therapeutics. Copyright © 2011 Elsevier Inc. All rights reserved.
Old and new aspects in the pathophysiology of pre-eclampsia
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Federico Prefumo
2007-12-01
Full Text Available Pre-eclampsia is a condition affecting the feto-placental unit and the mother. Three to five percent of pregnancies are complicated by pre-eclampsia, a multisystem disorder characterized by hypertension and proteinuria that occurs after 20 weeks of pregnancy. Pre-eclampsia is associated with substantial risks. For the fetus, these include intrauterine growth restriction, death, and prematurity with attendant complications, whereas the mother is at risk for complications of widespread alterations in endothelial function such as seizures (eclampsia, renal failure, pulmonary edema, stroke, and death. The establishment of pathological uterine perfusion raises the problem of stage two. The problem at stage three describes pre-eclampsia as a syndrome with the global maternal endothelial damage as the central pathophysiological feature.\tIt has been suggested that the pathophysiology of pre-eclampsia can be thought of as a ‘three-stage problem’, where each stage generates one, so far unsolved problem. An impaired trophoblast invasion is thought to be the central factor (first step regarding the etiology of pre-eclampsia. An increased uterine artery Doppler findings (PI, RI, lower maternal serum PAPP-A and free ßhCG levels, ischaemia modified albumin (IMA may be associated with pre-eclampsia.
Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review.
Lee, Mi Suk; Sohn, Kyungwoo; Kim, Yun Hee; Hwang, Min-Woo; Kwon, Young Kyu; Bae, Na Young; Chae, Han
2013-06-01
The purpose of this study was to review clinical studies on digestive system-related pathophysiological symptoms of each Sasang type to obtain the generalizable typespecific clinical features, which are important for the diagnosis of the Sasang type and subsequent disease treatment. Sasang typology and digestive system symptom-related keywords were used to search through eight domestic and foreign databases up to March 2012. The results were organized and analyzed based on four categories [digestive function, appetite, eating pattern, and body mass index (BMI)] to elucidate type-specific symptoms. Sasang type-specific digestive system-related symptoms were identified by reviewing 30 related articles that were gathered by searching through the databases. The Tae-Eum (TE) type had the highest digestive functions and the So-Eum (SE) type had the lowest. The TE type appeared to have larger volume with fast eating speed compared with the SE type and individuals in the TE category preferred fatty or salty food, which is responsible for the high occurrence rates of organic digestive diseases such as gastritis. Moreover, BMI was higher in the TE type and lower in the SE type. We systematically reviewed previously published clinical reports on digestive functions, which can be used to meet the objective of Sasang-type differentiation and pathophysiological pattern identification.
Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review
Directory of Open Access Journals (Sweden)
Mi Suk Lee
2013-06-01
Full Text Available The purpose of this study was to review clinical studies on digestive system-related pathophysiological symptoms of each Sasang type to obtain the generalizable typespecific clinical features, which are important for the diagnosis of the Sasang type and subsequent disease treatment. Sasang typology and digestive system symptom-related keywords were used to search through eight domestic and foreign databases up to March 2012. The results were organized and analyzed based on four categories [digestive function, appetite, eating pattern, and body mass index (BMI] to elucidate type-specific symptoms. Sasang type-specific digestive system-related symptoms were identified by reviewing 30 related articles that were gathered by searching through the databases. The Tae-Eum (TE type had the highest digestive functions and the So-Eum (SE type had the lowest. The TE type appeared to have larger volume with fast eating speed compared with the SE type and individuals in the TE category preferred fatty or salty food, which is responsible for the high occurrence rates of organic digestive diseases such as gastritis. Moreover, BMI was higher in the TE type and lower in the SE type. We systematically reviewed previously published clinical reports on digestive functions, which can be used to meet the objective of Sasang-type differentiation and pathophysiological pattern identification.
Minderhoud, I.M.
2007-01-01
Symptoms in Inflammatory Bowel Disease: pathophysiologic aspects and their relation with disease activity Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn's disease (CD). IBD patients frequently complain of fatigue, and a substantial proportion of the patients have
Physiological and pathophysiological insights of Nav1.4 and Nav1.5 comparison
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Gildas eLoussouarn
2016-01-01
Full Text Available Mutations in Nav1.4 and Nav1.5 α-subunits have been associated with muscular and cardiac channelopathies, respectively. Despite intense research on the structure and function of these channels, a lot of information is still missing to delineate the various physiological and pathophysiological processes underlying their activity at the molecular level. Nav1.4 and Nav1.5 sequences are similar, suggesting structural and functional homologies between the two orthologous channels. This also suggests that any characteristics described for one channel subunit may shed light on the properties of the counterpart channel subunit. In this review article, after a brief clinical description of the muscular and cardiac channelopathies related to Nav1.4 and Nav1.5 mutations, respectively, we compare the knowledge accumulated in different aspects of the expression and function of Nav1.4 and Nav1.5 α-subunits: the regulation of the two encoding genes (SCN4A and SCN5A, the associated/regulatory proteins and at last, the functional effect of the same missense mutations detected in Nav1.4 and Nav1.5. First, it appears that more is known on Nav1.5 expression and accessory proteins. Because of the high homologies of Nav1.5 binding sites and equivalent Nav1.4 sites, Nav1.5-related results may guide future investigations on Nav1.4. Second, the analysis of the same missense mutations in Nav1.4 and Nav1.5 revealed intriguing similarities regarding their effects on membrane excitability and alteration in channel biophysics. We believe that such comparison may bring new cues to the physiopathology of cardiac and muscular diseases.
Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms
Directory of Open Access Journals (Sweden)
Scott E. Friedman
2012-01-01
Full Text Available Pulmonary hypertension (PH is a potentially life-threatening condition arising from a wide variety of pathophysiologic mechanisms. Effective treatment requires a systematic diagnostic approach to identify all reversible mechanisms. Many of these mechanisms are relevant to those afflicted with obesity. The unique mechanisms of PH in the obese include obstructive sleep apnea, obesity hypoventilation syndrome, anorexigen use, cardiomyopathy of obesity, and pulmonary thromboembolic disease. Novel mechanisms of PH in the obese include endothelial dysfunction and hyperuricemia. A wide range of effective therapies exist to mitigate the disability of PH in the obese.
Pathophysiology of GPCR Homo- and Heterodimerization: Special Emphasis on Somatostatin Receptors
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Rishi K. Somvanshi
2012-04-01
Full Text Available G-protein coupled receptors (GPCRs are cell surface proteins responsible for translating >80% of extracellular reception to intracellular signals. The extracellular information in the form of neurotransmitters, peptides, ions, odorants etc is converted to intracellular signals via a wide variety of effector molecules activating distinct downstream signaling pathways. All GPCRs share common structural features including an extracellular N-terminal, seven-transmembrane domains (TMs linked by extracellular/intracellular loops and the C-terminal tail. Recent studies have shown that most GPCRs function as dimers (homo- and/or heterodimers or even higher order of oligomers. Protein-protein interaction among GPCRs and other receptor proteins play a critical role in the modulation of receptor pharmacology and functions. Although ~50% of the current drugs available in the market target GPCRs, still many GPCRs remain unexplored as potential therapeutic targets, opening immense possibility to discover the role of GPCRs in pathophysiological conditions. This review explores the existing information and future possibilities of GPCRs as tools in clinical pharmacology and is specifically focused for the role of somatostatin receptors (SSTRs in pathophysiology of diseases and as the potential candidate for drug discovery.
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
Pathophysiology and clinical characteristics of pain in most common locations in cancer patients.
Leppert, W; Zajaczkowska, R; Wordliczek, J; Dobrogowski, J; Woron, J; Krzakowski, M
2016-12-01
Pain is one of the most common symptoms in cancer patients, especially in advanced disease. However, pain also accompanies a significant percentage of patients during diagnostic and therapeutic procedures. In some patients pain may be the first symptom of the disease. The causes of pain in cancer patients are often multifactorial including direct and indirect cancer effects, anticancer therapy and co-morbidities. Moreover, pain in cancer patients often has mixed pathophysiology including both nociceptive and neuropathic components, especially in patients with bone metastases. In this article, basic knowledge regarding epidemiology, pathophysiology and clinical features of pain in cancer patients with a primary tumour localised in lung, gastrointestinal tract (stomach, colon and pancreas), breast in women and prostate in men are presented. Pain is a common symptom in cancer patients and its appropriate assessment and treatment may significantly improve in patients' and families' quality of life.
Strawbridge, Rona; Dupuis, Josée; Prokopenko, Inga; Barker, Adam; Ahlqvist, Emma; Rybin, Denis; Petrie, John; Bouatia-Naji, Nabila; Dimas, Antigone; Wheeler, Eleanor; Chen, Han; Voight, Benjamin; Taneera, Jalal; Kanoni, Stavroula; Peden, John
2011-01-01
textabstractOBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms...
Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats
Frintrop, Linda; Liesbrock, Johanna; Paulukat, Lisa; Johann, Sonja; Kas, Martien J; Tolba, Rene; Heussen, Nicole; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen
2017-01-01
OBJECTIVES: Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal
Roos, Cornelis J; Quax, Paul H A; Jukema, J Wouter
2012-02-01
Patients with obesity and diabetes mellitus are at increased risk for cardiovascular events and have a higher cardiovascular morbidity and mortality. This worse prognosis is partly explained by the late recognition of coronary heart disease in these patients, due to the absence of symptoms. Early identification of coronary heart disease is vital, to initiate preventive medical therapy and improve prognosis. At present, with the use of cardiovascular risk models, the identification of coronary heart disease in these patients remains inadequate. To this end, biomarkers should improve the early identification of patients at increased cardiovascular risk. The first part of this review describes the pathophysiologic pathway from obesity to coronary heart disease. The second part evaluates several mediators from this pathophysiologic pathway for their applicability as biomarkers for the identification of coronary heart disease.
Directory of Open Access Journals (Sweden)
Yoshihisa eYamano
2012-11-01
Full Text Available Human T-lymphotropic virus type 1 (HTLV-1, a human retrovirus, is the causative agent of a progressive neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. HAM/TSP is a chronic inflammatory disease of the central nervous system and is characterized by unremitting myelopathic symptoms such as spastic paraparesis, lower limb sensory disturbance, and bladder/bowel dysfunction. Approximately 0.25%–3.8% of HTLV-1-infected individuals develop HAM/TSP, which is more common in women than in men. Since the discovery of HAM/TSP, significant advances have been made with respect to elucidating the virological, molecular, and immunopathological mechanisms underlying this disease. These findings suggest that spinal cord invasion by HTLV-1-infected T cells triggers a strong virus-specific immune response and increases proinflammatory cytokine and chemokine production, leading to chronic lymphocytic inflammation and tissue damage in spinal cord lesions. However, little progress has been made in the development of an optimal treatment for HAM/TSP, more specifically in the identification of biomarkers for predicting disease progression and of molecular targets for novel therapeutic strategies targeting the underlying pathological mechanisms. This review summarizes current clinical and pathophysiological knowledge on HAM/TSP and discusses future focus areas for research on this disease.
Metabolic syndrome pathophysiology and clinical presentation.
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.
Pathophysiology and Immune Dysfunction in Endometriosis
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
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.
Advanced MR imaging in Lhermitte-Duclos disease: moving closer to pathology and pathophysiology
International Nuclear Information System (INIS)
Thomas, B.; Krishnamoorthy, T.; Kesavadas, C.; Radhakrishnan, V.V.
2007-01-01
Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) is an extremely rare cerebellar lesion of uncertain etiology. The debate as to whether it constitutes a neoplastic, malformative, or hamartomatous lesion is still continuing. In this report we explore the usefulness of susceptibility-weighted imaging (SWI), diffusion weighted imaging (DWI), perfusion imaging, and chemical shift imaging (CSI) in demonstrating the pathology and pathophysiology in two patients with LDD. MR imaging of the brain and the cervicodorsal spine was performed on a 1.5-T scanner in a 47-year-old woman presenting with numbness and paresthesia of both upper and lower limbs, and in a 17-year-old male with right frontal headache associated with neck pain. Routine imaging in the first patient showed a left-side cerebellar mass with characteristic 'tiger-striped' thick folia associated with Chiari I malformation, tonsillar herniation and cervicodorsal syringomyelia and in the second patient a right cerebellar mass with similar findings. The SWI demonstrated the characteristic deep running veins between the folia, which is thought to be the cause for vascular contrast enhancement. Diffusion showed a T2 shine-through effect with mild increased diffusivity, and perfusion showed increase in relative cerebral blood volume, relative cerebral blood flow, and mean transit time in the lesion. MR spectroscopy demonstrated reduction in metabolites and a prominent lactate peak in both the patients. The pathological and pathophysiological significance of these findings is discussed. MRI with the newer imaging capabilities can demonstrate the pathology and pathophysiology in Lhermitte-Duclos disease better. SWI helps in detecting the veins around the thickened folia. (orig.)
Advanced MR imaging in Lhermitte-Duclos disease: moving closer to pathology and pathophysiology
Energy Technology Data Exchange (ETDEWEB)
Thomas, B.; Krishnamoorthy, T.; Kesavadas, C. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Imaging Sciences and Interventional Radiology, Kerala (India); Radhakrishnan, V.V. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Department of Pathology, Kerala (India)
2007-09-15
Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) is an extremely rare cerebellar lesion of uncertain etiology. The debate as to whether it constitutes a neoplastic, malformative, or hamartomatous lesion is still continuing. In this report we explore the usefulness of susceptibility-weighted imaging (SWI), diffusion weighted imaging (DWI), perfusion imaging, and chemical shift imaging (CSI) in demonstrating the pathology and pathophysiology in two patients with LDD. MR imaging of the brain and the cervicodorsal spine was performed on a 1.5-T scanner in a 47-year-old woman presenting with numbness and paresthesia of both upper and lower limbs, and in a 17-year-old male with right frontal headache associated with neck pain. Routine imaging in the first patient showed a left-side cerebellar mass with characteristic 'tiger-striped' thick folia associated with Chiari I malformation, tonsillar herniation and cervicodorsal syringomyelia and in the second patient a right cerebellar mass with similar findings. The SWI demonstrated the characteristic deep running veins between the folia, which is thought to be the cause for vascular contrast enhancement. Diffusion showed a T2 shine-through effect with mild increased diffusivity, and perfusion showed increase in relative cerebral blood volume, relative cerebral blood flow, and mean transit time in the lesion. MR spectroscopy demonstrated reduction in metabolites and a prominent lactate peak in both the patients. The pathological and pathophysiological significance of these findings is discussed. MRI with the newer imaging capabilities can demonstrate the pathology and pathophysiology in Lhermitte-Duclos disease better. SWI helps in detecting the veins around the thickened folia. (orig.)
Urinary collagen fragments are significantly altered in diabetes: a link to pathophysiology.
Directory of Open Access Journals (Sweden)
David M Maahs
2010-09-01
Full Text Available The pathogenesis of diabetes mellitus (DM is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D or type 2 diabetes (T2D.Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299 or T2D (n = 288, was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382 from control subjects (n = 315 with 94% (95% CI: 92-95 accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68 and T2D (n = 42 was employed, enabling identification of 131 biomarker candidates (40 were sequenced differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108 with 88% (95% CI: 81-94% accuracy, and in patients with impaired renal function (n = 369 with 85% (95% CI: 81-88% accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed.These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary
Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.
Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan
2016-03-14
To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and
Alwan, Wisam; Nestle, Frank O
2015-01-01
Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.
Experience with an Independent Study Program in Pathophysiology for Doctor of Pharmacy Students.
Nahata, Milap C.
1986-01-01
A pharmacy doctoral program's independent-study component in pathophysiology, supported by computer-assisted instruction and self-evaluation, has the advantages of self-pacing, reduced faculty time commitment, and increased ability to work effectively with physicians. Disadvantages include student feeling of isolation, imbalanced content, and…
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
Pathophysiologic mechanisms of biomedical nanomaterials
Energy Technology Data Exchange (ETDEWEB)
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.
Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome.
Khan, Farhan H; Ahlberg, Caitlyn D; Chow, Christopher A; Shah, Divya R; Koo, Brian B
2017-08-01
Restless legs syndrome (RLS) is a common, chronic neurologic condition, which causes a persistent urge to move the legs in the evening that interferes with sleep. Human and animal studies have been used to study the pathophysiologic state of RLS and much has been learned about the iron and dopamine systems in relation to RLS. Human neuropathologic and imaging studies have consistently shown decreased iron in different brain regions including substantia nigra and thalamus. These same areas also demonstrate a state of relative dopamine excess. While it is not known how these changes in dopamine or iron produce the symptoms of RLS, genetic and hormone studies of RLS have identified other biologic systems or genes, such as the endogenous opioid and melanocortin systems and BTBD9 and MEIS1, that may explain some of the iron or dopamine changes in relation to RLS. This manuscript will review what is known about the pathophysiology of RLS, especially as it relates to changes in iron, dopamine, genetics, and hormonal systems.
Cognitive Processes Underlying the Artistic Experience
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Alejandra Wah
2017-08-01
Full Text Available Based on the field of aesthetics, for centuries philosophers and more recently scientists have been concerned with understanding the artistic experience focusing on emotional responses to the perception of artworks. By contrast, in the last decades, evolutionary biology has been concerned with explaining the artistic experience by focusing on the cognitive processes underlying this experience. Up until now, the cognitive mechanisms that allow humans to experience objects and events as art remain largely unexplored and there is still no conventional use of terms for referring to the processes which may explain why the artistic experience is characteristically human and universal to human beings (Dissanayake, 1992, p. 24; Donald, 2006, p. 4. In this paper, I will first question whether it is productive to understand the artistic experience in terms of perception and emotion, and I will subsequently propose a possible alternative explanation to understand this experience. Drawing upon the work of Ellen Dissanayake (1992, 2000, 2015, Merlin Donald (2001, 2006, 2013, Antonio Damasio (1994, 2000, 2003, 2010, Barend van Heusden (2004, 2009, 2010, and Alejandra Wah (2014, I will argue that this experience is characterized by particular degrees of imagination and consciousness.
Insights into pathophysiology of punding reveal possible treatment strategies.
Fasano, A; Petrovic, I
2010-06-01
Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, nongoal oriented, repetitive activity. Men tend to repetitively tinker with technical equipment such as radio sets, clocks, watches and car engines, the parts of which may be analyzed, arranged, sorted and cataloged but rarely put back together. Women, in contrast, incessantly sort through their handbags, tidy continuously, brush their hair or polish their nails. Punders are normally aware of the inapposite and obtuse nature of the behavior; however, despite the consequent self-injury, they do not stop such behavior. The most common causes of punding are dopaminergic replacement therapy in patients affected by Parkinson's disease (PD) and cocaine and amphetamine use in addicts. The vast majority of information about punding comes from PD cases. A critical review of these cases shows that almost all afflicted patients (90%) were on treatment with drugs acting mainly on dopamine receptors D1 and D2, whereas only three cases were reported in association with selective D2 and D3 agonists. Epidemiological considerations and available data from animal models suggest that punding, drug-induced stereotypies, addiction and dyskinesias all share a common pathophysiological process. Punding may be related to plastic changes in the ventral and dorsal striatal structures, including the nucleus accumbens, and linked to psychomotor stimulation and reward mechanisms. Possible management guidelines are proposed.
Systematic review of type-specific pathophysiological symptoms of Sasang typology
Directory of Open Access Journals (Sweden)
Yoo Ri Han
2016-06-01
Full Text Available Previous studies on the Sasang typology have focused on the differential diagnosis of each Sasang type with type-specific pathophysiological symptoms (TSPS. The purpose of this study was to elucidate the latent physiological mechanism related to these clinical indicators. We searched six electronic databases for articles published from 1990 to 2015 using the Sasang typology-related keywords, and found and analyzed 35 such articles. The results were summarized into six TSPS categories: perspiration, temperature preference, sleep, defecation, urination, and susceptibility to stress. The Tae-Eum and So-Eum types showed contrasting features with TSPS, and the So-Yang type was in the middle. The Tae-Eum type has good digestive function, regular bowel movement and defecation, high sleep quality, and low susceptibility to stress and cold. The Tae-Eum type has relatively large volumes of sweat and feels fresh after sweating; however, the urine is highly concentrated. These clinical features might be related to the biopsychological traits of the Tae-Eum type, including a low trait anxiety level and high ponderal and body mass indices. This study used the autonomic reactivity hypothesis for explaining the pathophysiological predispositions in the Sasang typology. The Tae-Eum and So-Eum Sasang types have a low threshold in parasympathetic and sympathetic activation, respectively. This study provides a foundation for integrating traditional Korean personalized medicine and Western biomedicine.
The role of the lacrimal functional unit in the pathophysiology of dry eye.
Stern, Michael E; Gao, Jianping; Siemasko, Karyn F; Beuerman, Roger W; Pflugfelder, Stephen C
2004-03-01
The majority of dry eye symptoms are due to a chronic inflammation of the lacrimal functional unit resulting in a loss of tear film integrity and normal function. This leads to a reduction in the ability of the ocular surface to respond to environmental challenges. The underlying cause of tear film dysfunction is the alteration of tear aqueous, mucin, and lipid components. This may result from a systemic autoimmune disease or a local autoimmune event. A lack of systemic androgen support to the lacrimal gland has been shown to be a facilitative factor in the initiation of this type of pathophysiology. Tear secretion is controlled by the lacrimal functional unit consisting of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland and the interconnecting innervation. If any portion of this functional unit is compromised, lacrimal gland support to the ocular surface is impeded. Factors such as neurogenic inflammation and T cell involvement in the disease pathogenesis as well as newly developed animal models of ocular surface inflammation are discussed.
X-ray microtomography study of the compaction process of rods under tapping.
Fu, Yang; Xi, Yan; Cao, Yixin; Wang, Yujie
2012-05-01
We present an x-ray microtomography study of the compaction process of cylindrical rods under tapping. The process is monitored by measuring the evolution of the orientational order parameter, local, and overall packing densities as a function of the tapping number for different tapping intensities. The slow relaxation dynamics of the orientational order parameter can be well fitted with a stretched-exponential law with stretching exponents ranging from 0.9 to 1.6. The corresponding relaxation time versus tapping intensity follows an Arrhenius behavior which is reminiscent of the slow dynamics in thermal glassy systems. We also investigated the boundary effect on the ordering process and found that boundary rods order faster than interior ones. In searching for the underlying mechanism of the slow dynamics, we estimated the initial random velocities of the rods under tapping and found that the ordering process is compatible with a diffusion mechanism. The average coordination number as a function of the tapping number at different tapping intensities has also been measured, which spans a range from 6 to 8.
Dysmotility in Esophageal Atresia: Pathophysiology, Characterization, and Treatment
Faure, Christophe; Righini Grunder, Franziska
2017-01-01
Esophageal dysmotility is almost universal after esophageal atresia (EA) repair and is mainly related to the developmental anomaly of the esophagus. Esophageal dysmotility is involved in the pathophysiology of numerous symptoms and comorbidities associated with EA such as gastroesophageal reflux disease, aspiration and respiratory complications, and symptoms of dysphagia and feeding disorders. High-resolution esophageal manometry (HREM) has facilitated the characterization of the dysmotility, but there is an incomplete correlation between symptoms and manometrical patterns. Impedance coupled to HREM should help to predict the clinical outcome and therefore personalize patient management. Nowadays, the management of esophageal dysmotility in patients with EA is essentially based on treatment of associated inflammation related to peptic or eosinophilic esophagitis. PMID:28620599
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...
International Nuclear Information System (INIS)
Buell, U.; Schicha, H.
1990-01-01
Nuclear procedures have long been successful in displaying parameters related to physiological and/or pathophysiological mechanisms inherent in organs or systems. Since a major advantage of PET is its ability to measure actual concentration, we now expect to gain such data in absolute terms. The use of stimuli, however, makes it possible to determine parameters in the form of ratios (stimulus-to-rest). Moreover, these ratios are correlated closely with the capacity of reserve mechanisms experienced from applied pathophysiology, in addition to which some are accessible by means of SPET. The clinical validity of findings related to coronary and cerebrovascular perfusion reserves have already been confirmed by SPET and/or PET. These results, if complemented by parameters of metabolic reserve, would constitute a most powerful tool in functional clinical diagnostics, allowing determination of differences between actual values and critical thresholds. This is one of the most promising approaches exclusively available from PET. (orig.)
Divided Attention and Processes Underlying Sense of Agency
Directory of Open Access Journals (Sweden)
Wen eWen
2016-01-01
Full Text Available Sense of agency refers to the subjective feeling of controlling events through one’s behavior or will. Sense of agency results from matching predictions of one’s own actions with actual feedback regarding the action. Furthermore, when an action involves a cued goal, performance-based inference contributes to sense of agency. That is, if people achieve their goal, they would believe themselves to be in control. Previous studies have shown that both action-effect comparison and performance-based inference contribute to sense of agency; however, the dominance of one process over the other may shift based on task conditions such as the presence or absence of specific goals. In this study, we examined the influence of divided attention on these two processes underlying sense of agency in two conditions. In the experimental task, participants continuously controlled a moving dot for 10 s while maintaining a string of three or seven digits in working memory. We found that when there was no cued goal (no-cued-goal condition, sense of agency was impaired by high cognitive load. Contrastingly, when participants controlled the dot based on a cued goal (cued-goal-directed condition, their sense of agency was lower than in the no-cued-goal condition and was not affected by cognitive load. The results suggest that the action-effect comparison process underlying sense of agency requires attention. On the other hand, the weaker influence of divided attention in the cued-goal-directed condition could be attributed to the dominance of performance-based inference, which is probably automatic.
Sharma, Alok; Couture, Justin
2014-02-01
To review the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). A literature search was conducted in PubMed and EMBASE using the terms attention deficit hyperactive disorder, ADHD, pathophysiology, etiology, and neurobiology. Limits applied were the following: published in the past 10 years (January 2003 to August 2013), humans, review, meta-analysis, and English language. These yielded 63 articles in PubMed and 74 in EMBASE. After removing duplicate/irrelevant articles, 86 articles and their relevant reference citations were reviewed. ADHD is a neurological disorder that affects children, but symptoms may persist into adulthood. Individuals suffering from this disorder exhibit hyperactivity, inattention, impulsivity, and problems in social interaction and academic performance. Medications used to treat ADHD such as methylphenidate, amphetamine, and atomoxetine indicate a dopamine/norepinephrine deficit as the neurochemical basis of ADHD, but the etiology is more complex. Moreover, these agents have poor adverse effect profiles and a multitude of drug interactions. Because these drugs are also dispensed to adults who may have concomitant conditions or medications, a pharmacist needs to be aware of these adverse events and drug interactions. This review, therefore, focuses on the pathophysiology, etiology, and treatment of ADHD and details the adverse effects and drug interaction profiles of the drugs used to treat it. Published research shows the benefit of drug therapy for ADHD in children, but given the poor adverse effect and drug interaction profiles, these must be dispensed with caution.
The Role of the Autonomic Nervous System in the Pathophysiology of Obesity
Directory of Open Access Journals (Sweden)
Daniela Guarino
2017-09-01
Full Text Available Obesity is reaching epidemic proportions globally and represents a major cause of comorbidities, mostly related to cardiovascular disease. The autonomic nervous system (ANS dysfunction has a two-way relationship with obesity. Indeed, alterations of the ANS might be involved in the pathogenesis of obesity, acting on different pathways. On the other hand, the excess weight induces ANS dysfunction, which may be involved in the haemodynamic and metabolic alterations that increase the cardiovascular risk of obese individuals, i.e., hypertension, insulin resistance and dyslipidemia. This article will review current evidence about the role of the ANS in short-term and long-term regulation of energy homeostasis. Furthermore, an increased sympathetic activity has been demonstrated in obese patients, particularly in the muscle vasculature and in the kidneys, possibily contributing to increased cardiovascular risk. Selective leptin resistance, obstructive sleep apnea syndrome, hyperinsulinemia and low ghrelin levels are possible mechanisms underlying sympathetic activation in obesity. Weight loss is able to reverse metabolic and autonomic alterations associated with obesity. Given the crucial role of autonomic dysfunction in the pathophysiology of obesity and its cardiovascular complications, vagal nerve modulation and sympathetic inhibition may serve as therapeutic targets in this condition.
Bone pain induced by metastatic cancer: pathophysiology and treatment
International Nuclear Information System (INIS)
Salas-Herrera, Isaias; Huertas-Gabert, Luis Carlos
2004-01-01
Cancer patients who develop bone metastases are an estimated 60 to 84% . Of these 79% experienced pain syndromes are difficult to manage, of which 50% die without adequate pain relief and with a poor quality of life. Therefore, it is necessary to have accessible and effective medications for the management of this condition. The pathophysiology of pain in bone is reviewed and the drugs used most frequently in the management of this type of cancer pain are described. Furthermore an algorithm of 6 steps is presented and can guide the physician when making a therapeutic decision. (author) [es
Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing
Frässle, Stefan; Krach, Sören; Paulus, Frieder Michel; Jansen, Andreas
2016-06-01
While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right-handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left-handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization.
Redox processes at a nanostructured interface under strong electric fields.
Steurer, Wolfram; Surnev, Svetlozar; Netzer, Falko P; Sementa, Luca; Negreiros, Fabio R; Barcaro, Giovanni; Durante, Nicola; Fortunelli, Alessandro
2014-09-21
Manipulation of chemistry and film growth via external electric fields is a longstanding goal in surface science. Numerous systems have been predicted to show such effects but experimental evidence is sparse. Here we demonstrate in a custom-designed UHV apparatus that the application of spatially extended, homogeneous, very high (>1 V nm(-1)) DC-fields not only changes the system energetics but triggers dynamic processes which become important much before static contributions appreciably modify the potential energy landscape. We take a well characterized ultrathin NiO film on a Ag(100) support as a proof-of-principle test case, and show how it gets reduced to supported Ni clusters under fields exceeding the threshold of +0.9 V nm(-1). Using an effective model, we trace the observed interfacial redox process down to a dissociative electron attachment resonant mechanism. The proposed approach can be easily implemented and generally applied to a wide range of interfacial systems, thus opening new opportunities for the manipulation of film growth and reaction processes at solid surfaces under strong external fields.
Gemne, G
1982-12-01
The article reviews available pathophysiological evidence for a multifactorial etiology of the Raynaud type of peripheral circulation disorder in persons exposed to vibration from handheld tools and discusses the consequences this viewpoint may have for diagnostics, preventive work, and research.
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.
Cognitive Processes in Decisions Under Risk Are Not the Same As in Decisions Under Uncertainty
Directory of Open Access Journals (Sweden)
Kirsten G Volz
2012-07-01
Full Text Available We deal with risk versus uncertainty, a distinction that is of fundamental importance for cognitive neuroscience yet largely neglected. In a world of risk (small world, all alternatives, consequences, and probabilities are known. In uncertain (large worlds, some of this information is unknown or unknowable. Most of cognitive neuroscience studies exclusively study the neural correlates for decisions under risk (e.g., lotteries, with the tacit implication that understanding these would lead to an understanding of decision making in general. First, we show that normative strategies for decisions under risk do not generalize to uncertain worlds, where simple heuristics are often the more accurate strategies. Second, we argue that the cognitive processes for making decisions in a world of risk are not the same as those for dealing with uncertainty. Because situations with known risks are the exception rather than the rule in human evolution, it is unlikely that our brains are adapted to them. We therefore suggest a paradigm shift towards studying decision processes in uncertain worlds and provide first examples.
Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics
Pakbaz, Zahra; Wun, Ted
2014-01-01
Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the pot...
Pathophysiology of Cushing's disease.
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
Pittenger, Christopher
2017-01-01
While the normal functions of histamine (HA) in the central nervous system have gradually come into focus over the past 30 years, the relationship of abnormalities in neurotransmitter HA to human disease has been slower to emerge. New insight came with the 2010 description of a rare nonsense mutation in the biosynthetic enzyme histidine decarboxylase (Hdc) that was associated with Tourette syndrome (TS) and related conditions in a single family pedigree. Subsequent genetic work has provided further support for abnormalities of HA signaling in sporadic TS. As a result of this genetic work, Hdc knockout mice, which were generated more than 15 years ago, have been reexamined as a model of the pathophysiology of TS and related conditions. Parallel work in these KO mice and in human carriers of the Hdc mutation has revealed abnormalities in the basal ganglia system and its modulation by dopamine (DA) and has confirmed the etiologic, face, and predictive validity of the model. The Hdc-KO model thus serves as a unique platform to probe the pathophysiology of TS and related conditions, and to generate specific hypotheses for subsequent testing in humans. This chapter summarizes the development and validation of this model and recent and ongoing work using it to further investigate pathophysiological changes that may contribute to these disorders.
Concussion: the history of clinical and pathophysiological concepts and misconceptions.
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.
[Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment].
Wirth, R; Diekmann, R; Janssen, G; Fleiter, O; Fricke, L; Kreilkamp, A; Modreker, M K; Marburger, C; Nels, S; Pourhassan, M; Schaefer, R; Willschrei, H-P; Volkert, D
2018-04-01
Refeeding syndrome is a life-threatening complication that may occur after initiation of nutritional therapy in malnourished patients, as well as after periods of fasting and hunger. Refeeding syndrome can be effectively prevented and treated if its risk factors and pathophysiology are known. The initial measurement of thiamine level and serum electrolytes, including phosphate and magnesium, their supplementation if necessary, and a slow increase in nutritional intake along with close monitoring of serum electrolytes play an important role. Since refeeding syndrome is not well known and the symptoms can be extremely heterogeneous, this complication is poorly recognized, especially against the background of severe disease and multimorbidity. This overview aims to summarize the current knowledge and increase awareness about refeeding syndrome.
Pathophysiology of AAA: heredity vs environment.
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.
Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy.
Behl, Tapan; Velpandian, Thirumurthy; Kotwani, Anita
2017-05-01
The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
The Sphenopalatine Ganglion: Anatomy, Pathophysiology, and Therapeutic Targeting in Headache.
Robbins, Matthew S; Robertson, Carrie E; Kaplan, Eugene; Ailani, Jessica; Charleston, Larry; Kuruvilla, Deena; Blumenfeld, Andrew; Berliner, Randall; Rosen, Noah L; Duarte, Robert; Vidwan, Jaskiran; Halker, Rashmi B; Gill, Nicole; Ashkenazi, Avi
2016-02-01
The sphenopalatine ganglion (SPG) has attracted the interest of practitioners treating head and face pain for over a century because of its anatomical connections and role in the trigemino-autonomic reflex. In this review, we discuss the anatomy of the SPG, as well as what is known about its role in the pathophysiology of headache disorders, including cluster headache and migraine. We then address various therapies that target the SPG, including intranasal medication delivery, new SPG blocking catheter devices, neurostimulation, chemical neurolysis, and ablation procedures. © 2015 American Headache Society.
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.
Pathophysiology of the nodular and micronodular small bowel fold
International Nuclear Information System (INIS)
Olmstead, W.W.; Ros, P.R.; Moser, R.P.; Shekitka, K.M.; Lichtenstein, J.E.; Buck, J.L.
1987-01-01
The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is just at the resolution of current roentgenographic technique. When the villi are enlarged, they can be seen radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor, inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold
Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options.
Bunevicius, Robertas; Prange, Arthur J
2006-01-01
Graves' disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves' hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves' disease, it is not always clear from the literature whether patients had Graves' disease: in some studies, the patients were thought to have Graves' disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves' hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with beta-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves' autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with beta-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.
Process antecedents of challenging, under-cover and readily-adopted innovations.
Adams, Richard; Tranfield, David; Denyer, David
2013-01-01
The purpose of the study is to test the utility of a taxonomy of innovation based on perceived characteristics in the context of healthcare by exploring the extent to which discrete innovation types could be distinguished from each other in terms of process antecedents. A qualitative approach was adopted to explore the process antecedents of nine exemplar cases of "challenging", "under-cover" and "readily-adopted" healthcare innovations. Data were collected by semi-structured interview and from secondary sources, and content analysed according to a theoretically informed framework of innovation process. Cluster analysis was applied to determine whether innovation types could be distinguished on the basis of process characteristics. The findings provide moderate support for the proposition that innovations differentiated on the basis of the way they are perceived by potential users exhibit different process characteristics. Innovations exhibiting characteristics previously believed negatively to impact adoption may be successfully adopted but by a different configuration of processes than by innovations exhibiting a different set of characteristics. The findings must be treated with caution because the sample consists of self-selected cases of successful innovation and is limited by sample size. Nevertheless, the study sheds new light on important process differences in healthcare innovation. The paper offers a heuristic device to aid clinicians and managers to better understand the relatively novel task of promoting and managing innovation in healthcare. The paper advances the argument that there is under-exploited opportunity for cross-disciplinary organisational learning for innovation management in the NHS. If efficiency and quality improvement targets are to be met through a strategy of encouraging innovation, it may be advantageous for clinicians and managers to reflect on what this study found mostly to be absent from the processes of the innovations studied
Enzymatic AND logic gates operated under conditions characteristic of biomedical applications.
Melnikov, Dmitriy; Strack, Guinevere; Zhou, Jian; Windmiller, Joshua Ray; Halámek, Jan; Bocharova, Vera; Chuang, Min-Chieh; Santhosh, Padmanabhan; Privman, Vladimir; Wang, Joseph; Katz, Evgeny
2010-09-23
Experimental and theoretical analyses of the lactate dehydrogenase and glutathione reductase based enzymatic AND logic gates in which the enzymes and their substrates serve as logic inputs are performed. These two systems are examples of the novel, previously unexplored class of biochemical logic gates that illustrate potential biomedical applications of biochemical logic. They are characterized by input concentrations at logic 0 and 1 states corresponding to normal and pathophysiological conditions. Our analysis shows that the logic gates under investigation have similar noise characteristics. Both significantly amplify random noise present in inputs; however, we establish that for realistic widths of the input noise distributions, it is still possible to differentiate between the logic 0 and 1 states of the output. This indicates that reliable detection of pathophysiological conditions is indeed possible with such enzyme logic systems.
Directory of Open Access Journals (Sweden)
Muñiz P
2014-05-01
Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.
Levin, Roy J; Both, Stephanie; Georgiadis, Janniko; Kukkonen, Tuuli; Park, Kwangsung; Yang, Claire C
2016-05-01
The article consists of six sections written by separate authors that review female genital anatomy, the physiology of female sexual function, and the pathophysiology of female sexual dysfunction but excluding hormonal aspects. To review the physiology of female sexual function and the pathophysiology of female sexual dysfunction especially since 2010 and to make specific recommendations according to the Oxford Centre for evidence based medicine (2009) "levels of evidence" wherever relevant. Recommendations were made for particular studies to be undertaken especially in controversial aspects in all six sections of the reviewed topics. Despite numerous laboratory assessments of female sexual function, genital assessments alone appear insufficient to characterise fully the complete sexual response. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
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.
Pathophysiological changes that affect drug disposition in protein-energy malnourished children
Directory of Open Access Journals (Sweden)
Oshikoya Kazeem A
2009-12-01
Full Text Available Abstract Protein-energy malnutrition (PEM is a major public health problem affecting a high proportion of infants and older children world-wide and accounts for a high childhood morbidity and mortality in the developing countries. The epidemiology of PEM has been extensively studied globally and management guidelines formulated by the World Health Organization (WHO. A wide spectrum of infections such as measles, malaria, acute respiratory tract infection, intestinal parasitosis, tuberculosis and HIV/AIDS may complicate PEM with two or more infections co-existing. Thus, numerous drugs may be required to treat the patients. In-spite of abundant literature on the epidemiology and management of PEM, focus on metabolism and therapeutic drug monitoring is lacking. A sound knowledge of pathophysiology of PEM and pharmacology of the drugs frequently used for their treatment is required for safe and rational treatment. In this review, we discuss the pathophysiological changes in children with PEM that may affect the disposition of drugs frequently used for their treatment. This review has established abnormal disposition of drugs in children with PEM that may require dosage modification. However, the relevance of these abnormalities to the clinical management of PEM remains inconclusive. At present, there are no good indications for drug dosage modification in PEM; but for drug safety purposes, further studies are required to accurately determine dosages of drugs frequently used for children with PEM.
Pathophysiology of gastro-esophageal reflux disease: a role for mucosa integrity?
Farré, R
2013-10-01
Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed. © 2013 John Wiley & Sons Ltd.
2010-10-26
... consideration and processing of applications for financial assistance under the RRIF Program. FOR FURTHER...) regarding FRA's consideration and processing of applications for financial assistance under the RRIF Program... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Notice Regarding Consideration and...
Synthesis of Optimal Processing Pathway for Microalgae-based Biorefinery under Uncertainty
DEFF Research Database (Denmark)
Rizwan, Muhammad; Lee, Jay H.; Gani, Rafiqul
2015-01-01
decision making, we propose a systematic framework for the synthesis and optimal design of microalgae-based processing network under uncertainty. By incorporating major uncertainties into the biorefinery superstructure model we developed previously, a stochastic mixed integer nonlinear programming (s......The research in the field of microalgae-based biofuels and chemicals is in early phase of the development, and therefore a wide range of uncertainties exist due to inconsistencies among and shortage of technical information. In order to handle and address these uncertainties to ensure robust......MINLP) problem is formulated for determining the optimal biorefinery structure under given parameter uncertainties modelled as sampled scenarios. The solution to the sMINLP problem determines the optimal decisions with respect to processing technologies, material flows, and product portfolio in the presence...
An optimization methodology for identifying robust process integration investments under uncertainty
Energy Technology Data Exchange (ETDEWEB)
Svensson, Elin; Berntsson, Thore [Department of Energy and Environment, Division of Heat and Power Technology, Chalmers University of Technology, SE-412 96 Goeteborg (Sweden); Stroemberg, Ann-Brith [Fraunhofer-Chalmers Research Centre for Industrial Mathematics, Chalmers Science Park, SE-412 88 Gothenburg (Sweden); Patriksson, Michael [Department of Mathematical Sciences, Chalmers University of Technology and Department of Mathematical Sciences, University of Gothenburg, SE-412 96 Goeteborg (Sweden)
2009-02-15
Uncertainties in future energy prices and policies strongly affect decisions on investments in process integration measures in industry. In this paper, we present a five-step methodology for the identification of robust investment alternatives incorporating explicitly such uncertainties in the optimization model. Methods for optimization under uncertainty (or, stochastic programming) are thus combined with a deep understanding of process integration and process technology in order to achieve a framework for decision-making concerning the investment planning of process integration measures under uncertainty. The proposed methodology enables the optimization of investments in energy efficiency with respect to their net present value or an environmental objective. In particular, as a result of the optimization approach, complex investment alternatives, allowing for combinations of energy efficiency measures, can be analyzed. Uncertainties as well as time-dependent parameters, such as energy prices and policies, are modelled using a scenario-based approach, enabling the identification of robust investment solutions. The methodology is primarily an aid for decision-makers in industry, but it will also provide insight for policy-makers into how uncertainties regarding future price levels and policy instruments affect the decisions on investments in energy efficiency measures. (author)
An optimization methodology for identifying robust process integration investments under uncertainty
International Nuclear Information System (INIS)
Svensson, Elin; Berntsson, Thore; Stroemberg, Ann-Brith; Patriksson, Michael
2009-01-01
Uncertainties in future energy prices and policies strongly affect decisions on investments in process integration measures in industry. In this paper, we present a five-step methodology for the identification of robust investment alternatives incorporating explicitly such uncertainties in the optimization model. Methods for optimization under uncertainty (or, stochastic programming) are thus combined with a deep understanding of process integration and process technology in order to achieve a framework for decision-making concerning the investment planning of process integration measures under uncertainty. The proposed methodology enables the optimization of investments in energy efficiency with respect to their net present value or an environmental objective. In particular, as a result of the optimization approach, complex investment alternatives, allowing for combinations of energy efficiency measures, can be analyzed. Uncertainties as well as time-dependent parameters, such as energy prices and policies, are modelled using a scenario-based approach, enabling the identification of robust investment solutions. The methodology is primarily an aid for decision-makers in industry, but it will also provide insight for policy-makers into how uncertainties regarding future price levels and policy instruments affect the decisions on investments in energy efficiency measures. (author)
Investigation of hydrogen isotopes interaction processes with lithium under neutron irradiation
Energy Technology Data Exchange (ETDEWEB)
Zaurbekova, Zhanna, E-mail: zaurbekova@nnc.kz [Institute of Atomic Energy, National Nuclear Center of RK, Kurchatov (Kazakhstan); Skakov, Mazhyn; Ponkratov, Yuriy; Kulsartov, Timur; Gordienko, Yuriy; Tazhibayeva, Irina; Baklanov, Viktor; Barsukov, Nikolay [Institute of Atomic Energy, National Nuclear Center of RK, Kurchatov (Kazakhstan); Chikhray, Yevgen [Institute of Experimental and Theoretical Physics of Kazakh National University, Almaty (Kazakhstan)
2016-11-01
Highlights: • The experiments on study of helium and tritium generation and release processes under neutron irradiation from lithium saturated with deuterium are described in paper. • The values of relative tritium and helium yield from lithium sample at different levels of neutron irradiation is calculated. • It was concluded that the main affecting process on tritium release from lithium is its interaction with lithium atoms with formation of lithium tritide. - Abstract: The paper describes the experiments on study of helium and tritium generation and release processes from lithium saturated with deuterium under neutron irradiation (in temperature range from 473 to 773 K). The diagrams of two reactor experiments show the time dependences of helium, DT, T{sub 2}, and tritium water partial pressures changes in experimental chamber with investigated lithium sample. According to experimental results, the values of relative tritium and helium yield from lithium sample at different levels of neutron irradiation were calculated. The time dependences of relative tritium and helium yield from lithium sample were plotted. It was concluded that the main affecting process on tritium release from lithium is its interaction with lithium atoms with formation of lithium tritide.
Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea
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
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.
Eye Movement Analysis of Information Processing under Different Testing Conditions.
Dillon, Ronna F.
1985-01-01
Undergraduates were given complex figural analogies items, and eye movements were observed under three types of feedback: (1) elaborate feedback; (2) subjects verbalized their thinking and application of rules; and (3) no feedback. Both feedback conditions enhanced the rule-governed information processing during inductive reasoning. (Author/GDC)
Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke
DEFF Research Database (Denmark)
Lassen, N A
1990-01-01
Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also...
Bhaskar, S.; Saeidi, K.; Borhani, P.; Amiri, H.
2013-01-01
Migraine is characterised by debilitating pain, which affects the quality of life in affected patients in both the western and the eastern worlds. The purpose of this article is to give a detailed outline of the pathophysiology of migraine pain, which is one of the most confounding pathologies among
Methodology for optimization of process integration schemes in a biorefinery under uncertainty
International Nuclear Information System (INIS)
Marta Abreu de las Villas (Cuba))" data-affiliation=" (Departamento de Ingeniería Química. Facultad de Química y Farmacia. Universidad Central Marta Abreu de las Villas (Cuba))" >González-Cortés, Meilyn; Marta Abreu de las Villas (Cuba))" data-affiliation=" (Departamento de Ingeniería Química. Facultad de Química y Farmacia. Universidad Central Marta Abreu de las Villas (Cuba))" >Martínez-Martínez, Yenisleidys; Marta Abreu de las Villas (Cuba))" data-affiliation=" (Departamento de Ingeniería Química. Facultad de Química y Farmacia. Universidad Central Marta Abreu de las Villas (Cuba))" >Albernas-Carvajal, Yailet; Marta Abreu de las Villas (Cuba))" data-affiliation=" (Departamento de Ingeniería Química. Facultad de Química y Farmacia. Universidad Central Marta Abreu de las Villas (Cuba))" >Pedraza-Garciga, Julio; Marta Abreu de las Villas (Cuba))" data-affiliation=" (Departamento de Ingeniería Química. Facultad de Química y Farmacia. Universidad Central Marta Abreu de las Villas (Cuba))" >Morales-Zamora, Marlen
2017-01-01
The uncertainty has a great impact in the investment decisions, operability of the plants and in the feasibility of integration opportunities in the chemical processes. This paper, presents the steps to consider the optimization of process investment in the processes integration under conditions of uncertainty. It is shown the potentialities of the biomass cane of sugar for the integration with several plants in a biorefinery scheme for the obtaining chemical products, thermal and electric energy. Among the factories with potentialities for this integration are the pulp and paper and sugar factories and other derivative processes. Theses factories have common resources and also have a variety of products that can be exchange between them so certain products generated in a one of them can be raw matter in another plant. The methodology developed guide to obtaining of feasible investment projects under uncertainty. As objective function was considered the maximization of net profitable value in different scenarios that are generated from the integration scheme. (author)
Under-Nutrition in Older People: A Serious and Growing Global Problem!
Directory of Open Access Journals (Sweden)
Visvanathan R
2003-01-01
Full Text Available Everyone agrees that adequate nutrient intake is important to all living things. Without food or water, life on earth would cease to exist. In the field of medical health, some gains have been made in meeting maternal and child nutritional needs. There is great community awareness regarding the importance of meeting the nutritional needs of the developing foetus and child. Malnutrition secondary to decreased intake in older people and weight loss is also a serious problem with unfortunately, very little notice from the community at large. As one ages, several physiological processes may contribute towards the development of protein energy malnutrition. Under-nutrition in older people is sadly far too common, even in developed countries. It is very likely that the same concerted effort used to address child malnutrition is required to combat under-nutrition in our elders. Protein energy malnutrition in older people comes at a significant cost to the individual, families, communities and the healthcare system. Failure to address this syndrome is not only unethical and unhealthy, but also costly. Vigilance and community awareness is important in ensuring that this important syndrome is detected and managed appropriately. This review mainly attempts to describe the pathophysiology, prevalence and consequences of under-nutrition and aims to highlight the importance of this clinical syndrome and the recent growth in our understanding of the processes behind its development. Some management strategies are also briefly described.
BACE inhibition-dependent repair of Alzheimer's pathophysiology.
Keskin, Aylin D; Kekuš, Maja; Adelsberger, Helmuth; Neumann, Ulf; Shimshek, Derya R; Song, Beomjong; Zott, Benedikt; Peng, Tingying; Förstl, Hans; Staufenbiel, Matthias; Nelken, Israel; Sakmann, Bert; Konnerth, Arthur; Busche, Marc Aurel
2017-08-08
Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear. Using histochemistry, in vivo Ca 2+ imaging, and behavioral analyses in a mouse model of AD, we demonstrate that along with reducing prefibrillary Aβ surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaired long-range circuit function, and memory defects. The functional neuronal impairments reappeared after infusion of soluble Aβ, mechanistically linking Aβ pathology to neuronal and cognitive dysfunction. These data highlight the potential benefits of BACE inhibition for the effective treatment of a wide range of AD-like pathophysiological and cognitive impairments.
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
Missing cells: pathophysiology, diagnosis and management of (pancytopenia in childhood
Directory of Open Access Journals (Sweden)
Miriam eErlacher
2015-07-01
Full Text Available Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia whereas antibody mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. In contrast, pancytopenia is frequently associated with a hypocellular bone marrow and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC can reliably be differentiated on a morphological level the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pancytopenia, their pathophysiology, characteristic bone marrow findings and therapeutic approaches.
Female Pattern Hair Loss: a clinical and pathophysiological review.
Ramos, Paulo Müller; Miot, Hélio Amante
2015-01-01
Female Pattern Hair Loss or female androgenetic alopecia is the main cause of hair loss in adult women and has a major impact on patients' quality of life. It evolves from the progressive miniaturization of follicles that lead to a subsequent decrease of the hair density, leading to a non-scarring diffuse alopecia, with characteristic clinical, dermoscopic and histological patterns. In spite of the high frequency of the disease and the relevance of its psychological impact, its pathogenesis is not yet fully understood, being influenced by genetic, hormonal and environmental factors. In addition, response to treatment is variable. In this article, authors discuss the main clinical, epidemiological and pathophysiological aspects of female pattern hair loss.
Kenzie, Erin S; Parks, Elle L; Bigler, Erin D; Wright, David W; Lim, Miranda M; Chesnutt, James C; Hawryluk, Gregory W J; Gordon, Wayne; Wakeland, Wayne
2018-01-01
Despite increasing public awareness and a growing body of literature on the subject of concussion, or mild traumatic brain injury, an urgent need still exists for reliable diagnostic measures, clinical care guidelines, and effective treatments for the condition. Complexity and heterogeneity complicate research efforts and indicate the need for innovative approaches to synthesize current knowledge in order to improve clinical outcomes. Methods from the interdisciplinary field of systems science, including models of complex systems, have been increasingly applied to biomedical applications and show promise for generating insight for traumatic brain injury. The current study uses causal-loop diagramming to visualize relationships between factors influencing the pathophysiology and recovery trajectories of concussive injury, including persistence of symptoms and deficits. The primary output is a series of preliminary systems maps detailing feedback loops, intrinsic dynamics, exogenous drivers, and hubs across several scales, from micro-level cellular processes to social influences. Key system features, such as the role of specific restorative feedback processes and cross-scale connections, are examined and discussed in the context of recovery trajectories. This systems approach integrates research findings across disciplines and allows components to be considered in relation to larger system influences, which enables the identification of research gaps, supports classification efforts, and provides a framework for interdisciplinary collaboration and communication-all strides that would benefit diagnosis, prognosis, and treatment in the clinic.
Directory of Open Access Journals (Sweden)
Erin S. Kenzie
2018-04-01
Full Text Available Despite increasing public awareness and a growing body of literature on the subject of concussion, or mild traumatic brain injury, an urgent need still exists for reliable diagnostic measures, clinical care guidelines, and effective treatments for the condition. Complexity and heterogeneity complicate research efforts and indicate the need for innovative approaches to synthesize current knowledge in order to improve clinical outcomes. Methods from the interdisciplinary field of systems science, including models of complex systems, have been increasingly applied to biomedical applications and show promise for generating insight for traumatic brain injury. The current study uses causal-loop diagramming to visualize relationships between factors influencing the pathophysiology and recovery trajectories of concussive injury, including persistence of symptoms and deficits. The primary output is a series of preliminary systems maps detailing feedback loops, intrinsic dynamics, exogenous drivers, and hubs across several scales, from micro-level cellular processes to social influences. Key system features, such as the role of specific restorative feedback processes and cross-scale connections, are examined and discussed in the context of recovery trajectories. This systems approach integrates research findings across disciplines and allows components to be considered in relation to larger system influences, which enables the identification of research gaps, supports classification efforts, and provides a framework for interdisciplinary collaboration and communication—all strides that would benefit diagnosis, prognosis, and treatment in the clinic.
Oral submucous fibrosis: An update on pathophysiology of malignant transformation.
Arakeri, Gururaj; Patil, Shekar Gowda; Aljabab, Abdulsalam S; Lin, Kuan-Chou; Merkx, M A W; Gao, Shan; Brennan, Peter A
2017-07-01
Oral submucous fibrosis (OSMF) is a potentially malignant condition associated with areca nut chewing. Formerly confined to the Indian subcontinent, it is now often seen in Asian populations of the United Kingdom, USA and other developed countries, and is therefore a serious problem for global health. What makes it more sinister is the malignant transformation rate, which has been reported to be around 7.6% over a 17-year period. In this concise article, we review the current trends in the pathophysiology of malignant transformation of OSMF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Role of renal vascular potassium channels in physiology and pathophysiology
DEFF Research Database (Denmark)
Salomonsson, Max; Brasen, Jens Christian; Sorensen, Charlotte Mehlin
2017-01-01
The control of renal vascular tone is important for the regulation of salt and water balance, blood pressure and the protection against damaging elevated glomerular pressure. The K+ conductance is a major factor in the regulation of the membrane potential (Vm ) in vascular smooth muscle (VSMC...... the ambiguous in vitro and in vivo results. We discuss the role of single types of K+ channels and the integrated function of several classes. We also deal with the possible role of renal vascular K+ channels in the pathophysiology of hypertension, diabetes mellitus and sepsis. This article is protected...
The pathophysiology of the trigeminal autonomic cephalalgias, with clinical implications
DEFF Research Database (Denmark)
Barloese, Mads C J
2018-01-01
, it is obvious that this brainstem reflex is regulated by higher centers that seemingly play a pivotal role in the attacks and the wide range of other symptoms indicating a homeostatic disturbance. These symptoms, as well as a number of well-validated findings, implicate the hypothalamus in the pathophysiology....... over the course of the past 2-3 decades, novel therapies and technological advances have helped increase our knowledge of these clinical syndromes, and will likely continue to do so in the coming years as we witness the arrival of new drugs and neurostimulation options. In this review, the clinical...
Branney, Jonathan; Priego-Hernández, Jacqueline
2018-02-01
It is important for nurses to have a thorough understanding of the biosciences such as pathophysiology that underpin nursing care. These courses include content that can be difficult to learn. Team-based learning is emerging as a strategy for enhancing learning in nurse education due to the promotion of individual learning as well as learning in teams. In this study we sought to evaluate the use of team-based learning in the teaching of applied pathophysiology to undergraduate student nurses. A mixed methods observational study. In a year two, undergraduate nursing applied pathophysiology module circulatory shock was taught using Team-based Learning while all remaining topics were taught using traditional lectures. After the Team-based Learning intervention the students were invited to complete the Team-based Learning Student Assessment Instrument, which measures accountability, preference and satisfaction with Team-based Learning. Students were also invited to focus group discussions to gain a more thorough understanding of their experience with Team-based Learning. Exam scores for answers to questions based on Team-based Learning-taught material were compared with those from lecture-taught material. Of the 197 students enrolled on the module, 167 (85% response rate) returned the instrument, the results from which indicated a favourable experience with Team-based Learning. Most students reported higher accountability (93%) and satisfaction (92%) with Team-based Learning. Lectures that promoted active learning were viewed as an important feature of the university experience which may explain the 76% exhibiting a preference for Team-based Learning. Most students wanted to make a meaningful contribution so as not to let down their team and they saw a clear relevance between the Team-based Learning activities and their own experiences of teamwork in clinical practice. Exam scores on the question related to Team-based Learning-taught material were comparable to those
Shorakae, Soulmaz; Teede, Helena; de Courten, Barbora; Lambert, Gavin; Boyle, Jacqueline; Moran, Lisa J
2015-07-01
Polycystic ovary syndrome (PCOS) has become increasingly common over recent years and is associated with reproductive features as well as cardiometabolic risk factors, including visceral obesity, dyslipidemia and impaired glucose homeostasis, and potentially cardiovascular disease. Emerging evidence suggests that these long-term metabolic effects are linked to a low-grade chronic inflammatory state with the triad of hyperinsulinemia, hyperandrogenism, and low-grade inflammation acting together in a vicious cycle in the pathophysiology of PCOS. Dysregulation of the sympathetic nervous system may also act as an important component, potentially creating a tetrad in the pathophysiology of PCOS. The aim of this review is to examine the role of chronic inflammation and the sympathetic nervous system in the development of obesity and PCOS and review potential therapeutic options to alleviate low-grade inflammation in this setting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Markov decision processes: a tool for sequential decision making under uncertainty.
Alagoz, Oguzhan; Hsu, Heather; Schaefer, Andrew J; Roberts, Mark S
2010-01-01
We provide a tutorial on the construction and evaluation of Markov decision processes (MDPs), which are powerful analytical tools used for sequential decision making under uncertainty that have been widely used in many industrial and manufacturing applications but are underutilized in medical decision making (MDM). We demonstrate the use of an MDP to solve a sequential clinical treatment problem under uncertainty. Markov decision processes generalize standard Markov models in that a decision process is embedded in the model and multiple decisions are made over time. Furthermore, they have significant advantages over standard decision analysis. We compare MDPs to standard Markov-based simulation models by solving the problem of the optimal timing of living-donor liver transplantation using both methods. Both models result in the same optimal transplantation policy and the same total life expectancies for the same patient and living donor. The computation time for solving the MDP model is significantly smaller than that for solving the Markov model. We briefly describe the growing literature of MDPs applied to medical decisions.
Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics
Pakbaz, Zahra; Wun, Ted
2014-01-01
Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271
Current Pathophysiological Aspects and Therapeutic Modalities for Pemphigus Vulgaris : A Review
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J Raviraj
2007-01-01
Full Text Available Pemphigus vulgaris (PV is an autoimmune disorder manifesting primarily as blisters involving the mucocutaneous systems. The current medical literature indicates many breakthroughs in the research of pathophysiology and treatment aspects of PV. This article tries to describe some of the novel aspects briefing the role of nondesmoglein antibodies and the role of TNF-alpha in the etiopathogenesis of pemphigus vulgaris and the role of newer therapeutic modalities like Rituximab, Etanercept, intravenous Immunoglobulins, cholinergic drugs, arid the like in the treatment of PV.
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
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.
The pathophysiology of migraine: implications for clinical management.
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.
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
Pathophysiological Characteristics Underlying Different Glucose Response Curves
DEFF Research Database (Denmark)
Hulman, Adam; Witte, Daniel R; Vistisen, Dorte
2018-01-01
different glucose curve patterns and studied their stability and reproducibility over 3 years of follow-up. RESEARCH DESIGN AND METHODS: We analyzed data from participants without diabetes from the observational cohort from the European Group for the Study of Insulin Resistance: Relationship between Insulin...... and secretion. The glucose patterns identified at follow-up were similar to those at baseline, suggesting that the latent class method is robust. We integrated our classification model into an easy-to-use online application that facilitates the assessment of glucose curve patterns for other studies. CONCLUSIONS...... Sensitivity and Cardiovascular Disease study; participants had a five-time point OGTT at baseline (n = 1,443) and after 3 years (n = 1,045). Measures of insulin sensitivity and secretion were assessed at baseline with a euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance test. Heterogeneous...
Bakanauskienė Irena; Baronienė Laura
2017-01-01
This article is intended to theoretically justify the decision-making process model for the cases, when active participation of investing entities in controlling the activities of an organisation and their results is noticeable. Based on scientific literature analysis, a concept of controlled conditions is formulated, and using a rational approach to the decision-making process, a model of the 11-steps decision-making process under controlled intervention is presented. Also, there have been u...
Group-buying inventory policy with demand under Poisson process
Directory of Open Access Journals (Sweden)
Tammarat Kleebmek
2016-02-01
Full Text Available The group-buying is the modern business of selling in the uncertain market. With an objective to minimize costs for sellers arising from ordering and reordering, we present in this paper the group buying inventory model, with the demand governed by a Poisson process and the product sale distributed as Binomial distribution. The inventory level is under continuous review, while the lead time is fixed. A numerical example is illustrated.
Chaves Filho, Adriano José Maia; Lima, Camila Nayane Carvalho; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Maes, Michael; Macedo, Danielle
2018-01-03
Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, inflammation, mitochondrial dysfunction, cytotoxicity, excitotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant inflammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the detection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity. This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pathophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
Perspectives on aetiology, pathophysiology and management of shock in African children
Directory of Open Access Journals (Sweden)
Julius Nteziyaremye
Full Text Available Paediatric shock is still a common emergency of public health importance with an estimated 400,000â500,000 reported cases annually. Mortality due to paediatric shock has varied over the years. Data in 1980s show that mortality rates due to septic shock in children were over 50%; but by the end of the year 2000 data indicated that though a marked decline in mortality rates had been achieved, it had stagnated at about 20%. Descriptions of paediatric shock reveal the lack of a common definition and there are important gaps in evidence-based management in different settings. In well-resourced healthcare systems with well-functioning intensive care facilities, the widespread implementation of shock management guidelines based on the Paediatric Advanced Life Support and European Paediatric Advanced Life Support courses have reduced mortality. In resource limited settings with diverse infectious causative agents, the Emergency Triage Assessment and Treatment (ETAT approach is more pragmatic, but its impact remains circumscribed to centres where ETAT has been implemented and sustained. Advocacy for common management pathways irrespective of underlying cause have been suggested. However, in sub Saharan Africa, the diversity of underlying causative organisms and patient phenotypes may limit a single approach to shock management.Data from a large fluid trial (the FEAST trial in East Africa have provided vital insight to shock management. In this trial febrile children with clinical features of impaired perfusion were studied. Rapid infusion of fluid boluses, irrespective of whether the fluid was colloid or crystalloid, when compared to maintenance fluids alone had an increased risk of mortality at 48â¯h. All study participants were promptly managed for underlying conditions and comorbidity such as malaria, bacteraemia, severe anaemia, meningitis, pneumonia, convulsions, hypoglycaemia and others. The overall low mortality in the trial suggests the
Ferreira, Jânio A; Botelho, Ricardo V
2015-01-01
Craniometric studies have shown that both Chiari malformation (CM) and basilar invagination (BI) belong to a spectrum of malformations. A more precise method to differentiate between these types of CVJM is desirable. The Chamberlain's line violation (CLV) is the most common method to identify BI. The authors sought to clarify the real importance of CLV in the spectrum of craniovertebral junction malformations (CVJM) and to identify possible pathophysiological relationships. We evaluated the CLV in a sample of CVJM, BI, CM patients and a control group of normal subjects and correlated their data with craniocervical angular craniometry. A total of 97 subjects were studied: 32 normal subjects, 41 CM patients, 9 basilar invagination type 1 (BI1) patients, and 15 basilar invagination type 2 (BI2) patients. The mean CLV violation in the groups were: The control group, 0.16 ± 0.45 cm; the CM group, 0.32 ± 0.48 cm; the BI1 group, 1.35 ± 0.5 cm; and the BI2 group, 1.98 ± 0.18 cm. There was strong correlation between CLV and Boogard's angle (R = 0.82, P = 0.000) and the clivus canal angle (R = 0.7, P = 0.000). CM's CLV is discrete and similar to the normal subjects. BI1 and BI2 presented with at least of 0.95 cm CLV and these violations were strongly correlated with a primary cranial angulation (clivus horizontalization) and an acute clivus canal angle (a secondary craniocervical angle).
The pathophysiology of the nodular and micronodular small bowel fold
International Nuclear Information System (INIS)
Olmsted, W.W.; Ros, P.R.; Moser, R.P.; Shekita, K.M.; Lichtenstein, J.E.
1986-01-01
The normal small bowel fold is easily seen on conventional studies of the small intestine, but visualization of the small bowel villus is at the limit of resolution of current roentgenographic technique. When the villi are enlarged, they appear radiographically as an irregularity or micronodularity of the small bowel fold. The anatomy of the fold and the pathophysiology of diseases producing fold nodularity (tumor,inflammatory disease, NLH, mastocytosis) and micronodularity (lymphangiectasia, Waldenstrom macroglobulinemia, Whipple disease) are presented, with an emphasis on radiologic-pathologic correlation. The radiologist should suggest certain diseases or conditions based on the roentgenographic characteristics of the closely analyzed small bowel fold
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.
Marquet, P.; Rothenfusser, K.; Rappaz, B.; Depeursinge, Christian; Jourdain, P.; Magistretti, Pierre J.
2016-01-01
parallelization and automation processes, represents an appealing imaging modality to both identify original cellular biomarkers of diseases as well to explore the underlying pathophysiological processes.
Seidel, Kathrin; Kahl, Johannes; Paoletti, Flavio; Birlouez, Ines; Busscher, Nicolaas; Kretzschmar, Ursula; Särkkä-Tirkkonen, Marjo; Seljåsen, Randi; Sinesio, Fiorella; Torp, Torfinn; Baiamonte, Irene
2015-02-01
The market for processed food is rapidly growing. The industry needs methods for "processing with care" leading to high quality products in order to meet consumers' expectations. Processing influences the quality of the finished product through various factors. In carrot baby food, these are the raw material, the pre-processing and storage treatments as well as the processing conditions. In this study, a quality assessment was performed on baby food made from different pre-processed raw materials. The experiments were carried out under industrial conditions using fresh, frozen and stored organic carrots as raw material. Statistically significant differences were found for sensory attributes among the three autoclaved puree samples (e.g. overall odour F = 90.72, p processed from frozen carrots show increased moisture content and decrease of several chemical constituents. Biocrystallization identified changes between replications of the cooking. Pre-treatment of raw material has a significant influence on the final quality of the baby food.
77 FR 43492 - Expedited Vocational Assessment Under the Sequential Evaluation Process
2012-07-25
..., or visit our Internet site, Social Security Online, at http://www.socialsecurity.gov . SUPPLEMENTARY... SOCIAL SECURITY ADMINISTRATION 20 CFR Parts 404 and 416 [Docket No. SSA-2010-0060] RIN 0960-AH26 Expedited Vocational Assessment Under the Sequential Evaluation Process AGENCY: Social Security...
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...
Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.
2012-01-01
This is the first installment of 2 articles that discuss the biology and pathophysiology of wound healing, review the role that growth factors play in this process, and describe current ways of growth factor delivery into the wound bed. Part 1 discusses the latest advances in clinicians’ understanding of the control points that regulate wound healing. Importantly, biological similarities and differences between acute and chronic wounds are considered, including the signaling pathways that initiate cellular and tissue responses after injury, which may be impeded during chronic wound healing. PMID:22713781
Neuroimaging of affect processing in schizophrenia
International Nuclear Information System (INIS)
Habel, U.; Kircher, T.; Schneider, F.
2005-01-01
Functional imaging of normal and dysfunctional emotional processes is an important tool for a better understanding of the pathophysiology of affective symptoms in schizophrenia patients. These symptoms are still poorly characterized with respect to their neural correlates. Comparisons of cerebral activation during emotional paradigms offered the possibility for a better characterization of cerebral dysfunctions during emotional processing in schizophrenia. Abnormal activation patterns reveal a complex dysfunctional subcortical-cortical network. This is modulated by respective genotypes as well as psycho- and pharmacotherapy. (orig.) [de
Amblyaudia: Review of Pathophysiology, Clinical Presentation, and Treatment of a New Diagnosis.
Kaplan, Alyson B; Kozin, Elliott D; Remenschneider, Aaron; Eftekhari, Kian; Jung, David H; Polley, Daniel B; Lee, Daniel J
2016-02-01
Similar to amblyopia in the visual system, "amblyaudia" is a term used to describe persistent hearing difficulty experienced by individuals with a history of asymmetric hearing loss (AHL) during a critical window of brain development. Few clinical reports have described this phenomenon and its consequent effects on central auditory processing. We aim to (1) define the concept of amblyaudia and (2) review contemporary research on its pathophysiology and emerging clinical relevance. PubMed, Embase, and Cochrane databases. A systematic literature search was performed with combinations of search terms: "amblyaudia," "conductive hearing loss," "sensorineural hearing loss," "asymmetric," "pediatric," "auditory deprivation," and "auditory development." Relevant articles were considered for inclusion, including basic and clinical studies, case series, and major reviews. During critical periods of infant brain development, imbalanced auditory input associated with AHL may lead to abnormalities in binaural processing. Patients with amblyaudia can demonstrate long-term deficits in auditory perception even with correction or resolution of AHL. The greatest impact is in sound localization and hearing in noisy environments, both of which rely on bilateral auditory cues. Diagnosis and quantification of amblyaudia remain controversial and poorly defined. Prevention of amblyaudia may be possible through early identification and timely management of reversible causes of AHL. Otolaryngologists, audiologists, and pediatricians should be aware of emerging data supporting amblyaudia as a diagnostic entity and be cognizant of the potential for lasting consequences of AHL. Prevention of long-term auditory deficits may be possible through rapid identification and correction. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.
DEFF Research Database (Denmark)
Capaci, Francesca; Kulahci, Murat; Vanhatalo, Erik
2017-01-01
Industrial manufacturing processes often operate under closed-loop control, where automation aims to keep important process variables at their set-points. In process industries such as pulp, paper, chemical and steel plants, it is often hard to find production processes operating in open loop....... Instead, closed-loop control systems will actively attempt to minimize the impact of process disturbances. However, we argue that an implicit assumption in most experimental investigations is that the studied system is open loop, allowing the experimental factors to freely affect the important system...... responses. This scenario is typically not found in process industries. The purpose of this article is therefore to explore issues of experimental design and analysis in processes operating under closed-loop control and to illustrate how Design of Experiments can help in improving and optimizing...
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.
Machado-Vieira, Rodrigo; Mallinger, Alan G
2012-11-01
The association between major depressive disorder (MDD) and cardiovascular disease (CVD) is among the best described medical comorbidities. The presence of MDD increases the risk of cardiac admissions and mortality and increases healthcare costs in patients with CVD, and similarly, CVD affects the course and outcome of MDD. The potential shared biological mechanisms involved in these comorbid conditions are not well known. However, the enzyme monoamine oxidase-A (MAO-A), which has a key role in the degradation of catecholamines, has been associated with the pathophysiology and therapeutics of both MDD and CVD. Increased MAO-A activity results in the dysregulation of downstream targets of this enzyme and thus affects the pathophysiology of the two diseases. These deleterious effects include altered noradrenaline turnover, with a direct elevation in oxidative stress parameters, as well as increased platelet activity and cytokine levels. These effects were shown to be reversed by MAO inhibitors. Here, a model describing a key role for the MAO-A in comorbid MDD and CVD is proposed, with focus on the shared pathophysiological mechanisms and the potential therapeutic relevance of agents targeting this enzyme.
Orexinergic system and pathophysiology of epilepsy.
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.
Directory of Open Access Journals (Sweden)
Bakanauskienė Irena
2017-12-01
Full Text Available This article is intended to theoretically justify the decision-making process model for the cases, when active participation of investing entities in controlling the activities of an organisation and their results is noticeable. Based on scientific literature analysis, a concept of controlled conditions is formulated, and using a rational approach to the decision-making process, a model of the 11-steps decision-making process under controlled intervention is presented. Also, there have been unified conditions, describing the case of controlled interventions thus providing preconditions to ensure the adequacy of the proposed decision-making process model.
The redox biology network in cancer pathophysiology and therapeutics
Directory of Open Access Journals (Sweden)
Gina Manda
2015-08-01
Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular
Mapping Common Aphasia Assessments to Underlying Cognitive Processes and Their Neural Substrates.
Lacey, Elizabeth H; Skipper-Kallal, Laura M; Xing, Shihui; Fama, Mackenzie E; Turkeltaub, Peter E
2017-05-01
Understanding the relationships between clinical tests, the processes they measure, and the brain networks underlying them, is critical in order for clinicians to move beyond aphasia syndrome classification toward specification of individual language process impairments. To understand the cognitive, language, and neuroanatomical factors underlying scores of commonly used aphasia tests. Twenty-five behavioral tests were administered to a group of 38 chronic left hemisphere stroke survivors and a high-resolution magnetic resonance image was obtained. Test scores were entered into a principal components analysis to extract the latent variables (factors) measured by the tests. Multivariate lesion-symptom mapping was used to localize lesions associated with the factor scores. The principal components analysis yielded 4 dissociable factors, which we labeled Word Finding/Fluency, Comprehension, Phonology/Working Memory Capacity, and Executive Function. While many tests loaded onto the factors in predictable ways, some relied heavily on factors not commonly associated with the tests. Lesion symptom mapping demonstrated discrete brain structures associated with each factor, including frontal, temporal, and parietal areas extending beyond the classical language network. Specific functions mapped onto brain anatomy largely in correspondence with modern neural models of language processing. An extensive clinical aphasia assessment identifies 4 independent language functions, relying on discrete parts of the left middle cerebral artery territory. A better understanding of the processes underlying cognitive tests and the link between lesion and behavior may lead to improved aphasia diagnosis, and may yield treatments better targeted to an individual's specific pattern of deficits and preserved abilities.
Metting, Zwany; Cerliani, Leonardo; Rodiger, Lars A.; van der Naalt, Joukje
2013-01-01
Background: A subgroup of patients with mild traumatic brain injury (TBI) experiences residual symptoms interfering with their return to work. The pathophysiological substrate of the suboptimal outcome in these patients is a source of debate. Objective: To provide greater insight into the
Levin, Roy J.; Both, Stephanie; Georgiadis, Janniko; Kukkonen, Tuuli; Park, Kwangsung; Yang, Claire C.
Introduction: The article consists of six sections written by separate authors that review female genital anatomy, the physiology of female sexual function, and the pathophysiology of female sexual dysfunction but excluding hormonal aspects. Aim: To review the physiology of female sexual function
Wostyn, Peter; Killer, Hanspeter Esriel; De Deyn, Peter Paul
The underlying pathophysiology of primary open-angle glaucoma remains unclear, but the lamina cribrosa seems to be the primary site of injury, and raised intraocular pressure is a major risk factor. In recent years, a decreased intracranial pressure, leading to an abnormally high trans-lamina
Stochastic stability of mechanical systems under renewal jump process parametric excitation
DEFF Research Database (Denmark)
Iwankiewicz, R.; Nielsen, Søren R.K.; Larsen, Jesper Winther
2005-01-01
A dynamic system under parametric excitation in the form of a non-Erlang renewal jump process is considered. The excitation is a random train of nonoverlapping rectangular pulses with equal, deterministic heights. The time intervals between two consecutive jumps up (or down), are the sum of two...
Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy
Energy Technology Data Exchange (ETDEWEB)
Fujii, Tadashige; Tanaka, Masao; Takeda, Tadashi; Kawashima, Akira; Kubo, Keiji; Kobayashi, Toshio; Handa, Kenjiro; Yoshimura, Kazuhiko (Shinshu Univ., Matsumoto, Nagano (Japan). Faculty of Medicine)
1993-09-01
In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc-MAA were performed in 19 cases of polycythemia including polycythemia rubra vera and in 11 cases of secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV 1.0%, V25 and PaO[sub 2] and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases. It seems to be important to evaluate the pathophysiology of pulmonary circulation in polycythemia rubra vera as well as secondary polycythemia due to cardio-pulmonary diseases, because pulmonary perfusion impairment and moderate right ventricular visualization are observed frequently in polycythemia rubra vera. (author).
Study of pathophysiology of pulmonary circulation in polycythemia using scintigraphy
International Nuclear Information System (INIS)
Fujii, Tadashige; Tanaka, Masao; Takeda, Tadashi; Kawashima, Akira; Kubo, Keiji; Kobayashi, Toshio; Handa, Kenjiro; Yoshimura, Kazuhiko
1993-01-01
In order to evaluate the pathophysiology of pulmonary circulation in polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with 99m-Tc-MAA were performed in 19 cases of polycythemia including polycythemia rubra vera and in 11 cases of secondary polycythemia due to pulmonary diseases. Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all cases and 54.5% of them showed moderate lung uptake. The grade of right ventricular visualization was moderate in one case and slight in 16 cases; right ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy, only one of which showed right ventricular hypertrophy on electrocardiography. Abnormalities of lung perfusion consisted of scattered small areas of hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related to decrease in FEV 1.0%, V25 and PaO 2 and increase in circulating blood volume and peripheral red blood cell counts. Abnormalities of pulmonary function consisted of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in 36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of secondary polycythemia due to pulmonary diseases showed more marked right ventricular visualization, pulmonary perfusion impairment and abnormalities of various kinds of pulmonary function than polycythemia rubra vera cases. It seems to be important to evaluate the pathophysiology of pulmonary circulation in polycythemia rubra vera as well as secondary polycythemia due to cardio-pulmonary diseases, because pulmonary perfusion impairment and moderate right ventricular visualization are observed frequently in polycythemia rubra vera. (author)
Application of computer picture processing to dynamic strain measurement under electromagnetic field
International Nuclear Information System (INIS)
Yagawa, G.; Soneda, N.
1987-01-01
For the structural design of fusion reactors, it is very important to ensure the structural integrity of components under various dynamic loading conditions due to a solid-electromagnetic field interaction, an earthquake, MHD effects and so on. As one of the experimental approaches to assess the dynamic fracture, we consider the strain measurement near a crack tip under a transient electromagnetic field, which in general involves several experimental difficulties. The authors have developed a strain measurement method using a picture processing technique. In this method, locations of marks printed on a surface of specimen are determined by the picture processing. The displacement field is interpolated using the mark displacements and finite elements. Finally the strain distribution is calculated by differentiating the displacement field. In the present study, the method is improved and automated apply to the measurement of dynamic strain distribution under an electromagnetic field. Then the effects of dynamic loading on the strain distribution are investigated by comparing the dynamic results with the static ones. (orig./GL)
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
Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale.
Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix
2017-01-01
The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.
Evidence of different underlying processes in pattern recall and decision-making.
Gorman, Adam D; Abernethy, Bruce; Farrow, Damian
2015-01-01
The visual search characteristics of expert and novice basketball players were recorded during pattern recall and decision-making tasks to determine whether the two tasks shared common visual-perceptual processing strategies. The order in which participants entered the pattern elements in the recall task was also analysed to further examine the nature of the visual-perceptual strategies and the relative emphasis placed upon particular pattern features. The experts demonstrated superior performance across the recall and decision-making tasks [see also Gorman, A. D., Abernethy, B., & Farrow, D. (2012). Classical pattern recall tests and the prospective nature of expert performance. The Quarterly Journal of Experimental Psychology, 65, 1151-1160; Gorman, A. D., Abernethy, B., & Farrow, D. (2013a). Is the relationship between pattern recall and decision-making influenced by anticipatory recall? The Quarterly Journal of Experimental Psychology, 66, 2219-2236)] but a number of significant differences in the visual search data highlighted disparities in the processing strategies, suggesting that recall skill may utilize different underlying visual-perceptual processes than those required for accurate decision-making performance in the natural setting. Performance on the recall task was characterized by a proximal-to-distal order of entry of the pattern elements with participants tending to enter the players located closest to the ball carrier earlier than those located more distal to the ball carrier. The results provide further evidence of the underlying perceptual processes employed by experts when extracting visual information from complex and dynamic patterns.
International Nuclear Information System (INIS)
Kim, Jong Hyun; Seong, Poong Hyun
2002-01-01
This paper proposes a quantitative approach to modeling the information processing of NPP operators. The aim of this work is to derive the amount of the information processed during a certain control task under input information overload. We primarily develop the information processing model having multiple stages, which contains information flow. Then the uncertainty of the information is quantified using the Conant's model, a kind of information theory. We also investigate the applicability of this approach to quantifying the information reduction of operators under the input information overload
Directory of Open Access Journals (Sweden)
Moschos MM
2016-10-01
Full Text Available Marilita M Moschos, Eirini Nitoda 1st Department of Ophthalmology, Medical School, National & Kapodistrian University of Athens, Athens, Greece Aim: The aim of this review was to summarize the ocular action of the most common phosphodiesterase (PDE inhibitors used for the treatment of erectile dysfunction and the subsequent visual disorders.Method: This is a literature review of several important articles focusing on the pathophysiology of visual disorders induced by PDE inhibitors.Results: PDE inhibitors have been associated with ocular side effects, including changes in color vision and light perception, blurred vision, transient alterations in electroretinogram (ERG, conjunctival hyperemia, ocular pain, and photophobia. Sildenafil and tadalafil may induce reversible increase in intraocular pressure and be involved in the development of nonarteritic ischemic optic neuropathy. Reversible idiopathic serous macular detachment, central serous chorioretinopathy, and ERG disturbances have been related to the significant impact of sildenafil and tadalafil on retinal perfusion.Discussion: So far, PDE inhibitors do not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors. However, physicians should write down any visual symptom observed during PDE treatment and refer the patients to ophthalmologists. Keywords: erectile dysfunction, pathophysiological mechanisms, phosphodiesterase inhibitors, PDE5, visual disorders
TFOS DEWS II pathophysiology report.
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.
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
High paraffin Kumkol petroleum processing under fuel and lubricant petroleum scheme
International Nuclear Information System (INIS)
Nadirov, N.K.; Konaev, Eh.N.
1997-01-01
Technological opportunity of high paraffin Kumkol petroleum processing under the fuel and lubricant scheme with production of lubricant materials in short supply, combustible materials and technical paraffin is shown. Mini petroleum block putting into operation on Kumkol deposit is reasonable economically and raises profitableness of hydrocarbon raw material production. (author)
Seino, Susumu
2003-01-01
K(ATP) channels are present in pancreatic and extrapancreatic tissues such as heart and smooth muscle, and display diverse molecular composition. They contain two different structural subunits: an inwardly rectifying potassium channel subunit (Kir6.x) and a sulfonylurea receptor (SURX). Recent studies on genetically engineered Kir6.2 knockout mice have provided a better understanding of the physiological and pathophysiological roles of Kir6.2-containing K(ATP) channels. Kir6.2/SUR1 has a pivotal role in pancreatic insulin secretion. Kir6.2/SUR2A mediates the effects of K(ATP) channels openers on cardiac excitability and contractility and contributes to ischemic preconditioning. However, controversy remains on the physiological properties of the K(ATP) channels in vascular smooth muscle cells. Kir6.1 knockout mice exhibit sudden cardiac death due to cardiac ischemia, indicating that Kir6.1 rather than Kir6.2 is critical in the regulation of vascular tone. This article summarizes current understanding of the physiology and pathophysiology of Kir6.1- and Kir6.2-containing K(ATP) channels.
2014-01-01
Introduction Evaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A noninvasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research for staging of autoimmune disease severity or efficacy of therapeutical intervention. Sodium 18 F-fluoride (18 F-NaF) is a bone-seeking tracer well-suited for molecular imaging. Therefore, we systematically examined the use of 18 F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)–induced arthritis for quantification of pathological bone metabolism. Methods F-fluoride was injected into mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints in the fore- and hindpaws was analyzed by PET measurements. For validation of bone metabolism quantified by 18 F-fluoride PET, bone surface parameters of high-resolution μCT measurements were used. Results Before clinical arthritis onset, no distinct accumulation of 18 F-fluoride was detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course of experimental autoimmune disease, 18 F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, 18 F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT enabled identification of exact localization of 18 F-fluoride signaling in bone and soft tissue. Conclusions The results of this study suggest that small-animal PET/CT using 18 F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the
Research on Collapse Process of Cable-Stayed Bridges under Strong Seismic Excitations
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Xuewei Wang
2017-01-01
Full Text Available In order to present the collapse process and failure mechanism of long-span cable-stayed bridges under strong seismic excitations, a rail-cum-road steel truss cable-stayed bridge was selected as engineering background, the collapse failure numerical model of the cable-stayed bridge was established based on the explicit dynamic finite element method (FEM, and the whole collapse process of the cable-stayed bridge was analyzed and studied with three different seismic waves acted in the horizontal longitudinal direction, respectively. It can be found from the numerical simulation analysis that the whole collapse failure process and failure modes of the cable-stayed bridge under three different seismic waves are similar. Furthermore, the piers and the main pylons are critical components contributing to the collapse of the cable-stayed bridge structure. However, the cables and the main girder are damaged owing to the failure of piers and main pylons during the whole structure collapse process, so the failure of cable and main girder components is not the main reason for the collapse of cable-stayed bridge. The analysis results can provide theoretical basis for collapse resistance design and the determination of critical damage components of long-span highway and railway cable-stayed bridges in the research of seismic vulnerability analysis.
An Intelligent Complex Event Processing with D Numbers under Fuzzy Environment
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Fuyuan Xiao
2016-01-01
Full Text Available Efficient matching of incoming mass events to persistent queries is fundamental to complex event processing systems. Event matching based on pattern rule is an important feature of complex event processing engine. However, the intrinsic uncertainty in pattern rules which are predecided by experts increases the difficulties of effective complex event processing. It inevitably involves various types of the intrinsic uncertainty, such as imprecision, fuzziness, and incompleteness, due to the inability of human beings subjective judgment. Nevertheless, D numbers is a new mathematic tool to model uncertainty, since it ignores the condition that elements on the frame must be mutually exclusive. To address the above issues, an intelligent complex event processing method with D numbers under fuzzy environment is proposed based on the Technique for Order Preferences by Similarity to an Ideal Solution (TOPSIS method. The novel method can fully support decision making in complex event processing systems. Finally, a numerical example is provided to evaluate the efficiency of the proposed method.
Location-Dependent Query Processing Under Soft Real-Time Constraints
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Zoubir Mammeri
2009-01-01
Full Text Available In recent years, mobile devices and applications achieved an increasing development. In database field, this development required methods to consider new query types like location-dependent queries (i.e. the query results depend on the query issuer location. Although several researches addressed problems related to location-dependent query processing, a few works considered timing requirements that may be associated with queries (i.e., the query results must be delivered to mobile clients on time. The main objective of this paper is to propose a solution for location-dependent query processing under soft real-time constraints. Hence, we propose methods to take into account client location-dependency and to maximize the percentage of queries respecting their deadlines. We validate our proposal by implementing a prototype based on Oracle DBMS. Performance evaluation results show that the proposed solution optimizes the percentage of queries meeting their deadlines and the communication cost.
Directory of Open Access Journals (Sweden)
Cosimo Marcello Bruno
2012-01-01
Full Text Available The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate. Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis. Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided.
Ghossein, Cybele; Varga, John; Fenves, Andrew Z
2016-01-01
Scleroderma renal crisis (SRC) is an uncommon complication of systemic sclerosis. Despite the advent of angiotensin-converting inhibitor therapy, SRC remains a life-threatening complication. Recent studies have contributed to a better understanding of SRC, but much remains unknown regarding its pathophysiology, risk factors, and optimal management. Genetic studies provide evidence that immune dysregulation might be a contributing factor, providing hope that further research in this direction might illuminate pathogenesis and provide novel predictors for this complication.
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.
[Pathophysiology and new treatment of uveitis].
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.
Epidural haematoma: pathophysiological significance of extravasation and arteriovenous shunting
International Nuclear Information System (INIS)
Habash, A.H.; Sortland, O.; Zwetnow, N.N.
1982-01-01
35 patients with epidural bleeding operated on at Rikshospitalet, Oslo, during the period 1965 - 1980 had preoperative angiography with visualization of the external carotid artery. Twenty-one patients had extravasation of contrast medium from meningeal arteries. Seventeen of the 21 had also shunting of contrast medium from meningeal arteries to meningeal or diploic veins, while 20 of the 21 also had bled from a ruptured meningeal artery at operation. It was further found that of 20 patients who deteriorated after trauma 18 had an epidural arteriovenous shunt or extravasation. Conversely, of 15 patients who improved after trauma 12 had no evidence of a shunt. The strong correlation between the clinical course and the occurrence of extravasation supports previous experimental and clinical data, indicating the epidural arteriovenous shunt to be a major factor in the pathophysiology and the outcome of epidural bleeding. (author)
Association of tinnitus and electromagnetic hypersensitivity: hints for a shared pathophysiology?
Directory of Open Access Journals (Sweden)
Michael Landgrebe
Full Text Available BACKGROUND: Tinnitus is a frequent condition with high morbidity and impairment in quality of life. The pathophysiology is still incompletely understood. Electromagnetic fields are discussed to be involved in the multi-factorial pathogenesis of tinnitus, but data proofing this relationship are very limited. Potential health hazards of electromagnetic fields (EMF have been under discussion for long. Especially, individuals claiming themselves to be electromagnetic hypersensitive suffer from a variety of unspecific symptoms, which they attribute to EMF-exposure. The aim of the study was to elucidate the relationship between EMF-exposure, electromagnetic hypersensitivity and tinnitus using a case-control design. METHODOLOGY: Tinnitus occurrence and tinnitus severity were assessed by questionnaires in 89 electromagnetic hypersensitive patients and 107 controls matched for age-, gender, living surroundings and workplace. Using a logistic regression approach, potential risk factors for the development of tinnitus were evaluated. FINDINGS: Tinnitus was significantly more frequent in the electromagnetic hypersensitive group (50.72% vs. 17.5% whereas tinnitus duration and severity did not differ between groups. Electromagnetic hypersensitivity and tinnitus were independent risk factors for sleep disturbances. However, measures of individual EMF-exposure like e.g. cell phone use did not show any association with tinnitus. CONCLUSIONS: Our data indicate that tinnitus is associated with subjective electromagnetic hypersensitivity. An individual vulnerability probably due to an over activated cortical distress network seems to be responsible for, both, electromagnetic hypersensitivity and tinnitus. Hence, therapeutic efforts should focus on treatment strategies (e.g. cognitive behavioral therapy aiming at normalizing this dysfunctional distress network.
Role of brain orexin in the pathophysiology of functional gastrointestinal disorders.
Okumura, Toshikatsu; Nozu, Tsukasa
2011-04-01
Orexins are neuropeptides that are localized in neurons within the lateral hypothalamic area and regulate feeding behavior. The lateral hypothalamic area plays an important role in not only feeding but the central regulation of other functions including gut physiology. Accumulating evidence have shown that orexins acts in the brain to regulate a wide variety of body functions including gastrointestinal functions. The purpose of this review is to summarize relevant findings on brain orexins and a digestive system, and discuss the pathophysiological roles of the peptides with special reference to functional gastrointestinal disorders. Exogenously administered orexin or endogenously released orexin in the brain potently stimulates gastric acid secretion in pylorus-ligated conscious rats. The vagal cholinergic pathway is involved in the orexin-induced stimulation of acid secretion, suggesting that orexin-containing neurons in lateral hypothalamic area activates neurons in the dorsal motor nucleus in medulla oblongata, followed by increasing vagal outflow, thereby stimulating gastric acid secretion. In addition, brain orexin stimulates gastric motility, pancreatic secretion and induce gastroprotective action. On the other hand, brain orexin is involved in a number of physiological functions other than gut physiology, such as control of sleep/awake cycle and anti-depressive action in addition to increase in appetite. From these evidence, we would like to make a hypothesis that decreased orexin signaling in the brain may play a role in the pathophysiology in a part of patients with functional gastrointestinal disorders who are frequently accompanied with appetite loss, sleep disturbance, depressive state and the inhibition of gut function. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Spitzer, A Robert
2014-09-01
Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the ventrolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over
Enhanced performance of denitrifying sulfide removal process under micro-aerobic condition
International Nuclear Information System (INIS)
Chen Chuan; Ren Nanqi; Wang Aijie; Liu Lihong; Lee, Duu-Jong
2010-01-01
The denitrifying sulfide removal (DSR) process with bio-granules comprising both heterotrophic and autotrophic denitrifiers can simultaneously convert nitrate, sulfide and acetate into di-nitrogen gas, elementary sulfur and carbon dioxide, respectively, at high loading rates. This study determines the reaction rate of sulfide oxidized into sulfur, as well as the reduction of nitrate to nitrite, would be enhanced under a micro-aerobic condition. The presence of limited oxygen mitigated the inhibition effects of sulfide on denitrifier activities, and enhanced the performance of DSR granules. The advantages and disadvantages of applying the micro-aerobic condition to the DSR process are discussed.
An update on equine post-operative ileus: Definitions, pathophysiology and management.
Lisowski, Z M; Pirie, R S; Blikslager, A T; Lefebvre, D; Hume, D A; Hudson, N P H
2018-05-01
Post-operative ileus (POI) is a serious condition which any horse undergoing abdominal surgery is at risk of developing, leading to increased hospitalisation time and resulting costs. Advances in the understanding of the development of equine POI are mainly based on human and rodent literature, where manipulation-induced inflammation has been identified as a trigger, with activation of resident muscularis externa macrophages playing a crucial role in the pathophysiology. Despite many pharmacological trials in all species, there is no single completely successful treatment for POI, highlighting that the condition is multifactorial in cause and requires a multimodal approach to minimise its incidence. © 2017 EVJ Ltd.
Negative pressure pulmonary edema revisited: Pathophysiology and review of management
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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.
Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale
Ewen, Sebastian; Mahfoud, Felix
2017-01-01
The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome. PMID:28154583
Pasquali, Renato
2012-01-01
Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409
Directory of Open Access Journals (Sweden)
Lars Wojtecki
2016-08-01
Full Text Available Huntington’s disease (HD is one of the most disabling degenerative movement disorders, as it not only affects the motor system but also leads to cognitive disabilities and psychiatric symptoms. Deep brain stimulation (DBS of the pallidum is a promising symptomatic treatment targeting the core motor symptom: chorea. This article gives an overview of preliminary evidence on pathophysiology, safety and efficacy of DBS in HD.
New insights into the pathophysiology of achalasia and implications for future treatment.
Furuzawa-Carballeda, Janette; Torres-Landa, Samuel; Valdovinos, Miguel Ángel; Coss-Adame, Enrique; Martín Del Campo, Luis A; Torres-Villalobos, Gonzalo
2016-09-21
Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.
Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?
Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J
2015-06-01
Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Fuel corrosion processes under waste disposal conditions
International Nuclear Information System (INIS)
Shoesmith, D.W.
1999-09-01
Under the oxidizing conditions likely to be encountered in the Yucca Mountain Repository, fuel dissolution is a corrosion process involving the coupling of the anodic dissolution of the fuel with the cathodic reduction of oxidants available within the repository. The oxidants potentially available to drive fuel corrosion are environmental oxygen, supplied by the transport through the permeable rock of the mountain and molecular and radical species produced by the radiolysis of available aerated water. The mechanism of these coupled anodic and cathodic reactions is reviewed in detail. While gaps in understanding remain, many kinetic features of these reactions have been studied in considerable detail, and a reasonably justified mechanism for fuel corrosion is available. The corrosion rate is determined primarily by environmental factors rather than the properties of the fuel. Thus, with the exception of increase in rate due to an increase in surface area, pre-oxidation of the fuel has little effect on the corrosion rate
Fuel corrosion processes under waste disposal conditions
Energy Technology Data Exchange (ETDEWEB)
Shoesmith, D.W. [Univ. of Western Ontario, Dept. of Chemistry, London, Ontario (Canada)
1999-09-01
Under the oxidizing conditions likely to be encountered in the Yucca Mountain Repository, fuel dissolution is a corrosion process involving the coupling of the anodic dissolution of the fuel with the cathodic reduction of oxidants available within the repository. The oxidants potentially available to drive fuel corrosion are environmental oxygen, supplied by the transport through the permeable rock of the mountain and molecular and radical species produced by the radiolysis of available aerated water. The mechanism of these coupled anodic and cathodic reactions is reviewed in detail. While gaps in understanding remain, many kinetic features of these reactions have been studied in considerable detail, and a reasonably justified mechanism for fuel corrosion is available. The corrosion rate is determined primarily by environmental factors rather than the properties of the fuel. Thus, with the exception of increase in rate due to an increase in surface area, pre-oxidation of the fuel has little effect on the corrosion rate.
Face processing pattern under top-down perception: a functional MRI study
Li, Jun; Liang, Jimin; Tian, Jie; Liu, Jiangang; Zhao, Jizheng; Zhang, Hui; Shi, Guangming
2009-02-01
Although top-down perceptual process plays an important role in face processing, its neural substrate is still puzzling because the top-down stream is extracted difficultly from the activation pattern associated with contamination caused by bottom-up face perception input. In the present study, a novel paradigm of instructing participants to detect faces from pure noise images is employed, which could efficiently eliminate the interference of bottom-up face perception in topdown face processing. Analyzing the map of functional connectivity with right FFA analyzed by conventional Pearson's correlation, a possible face processing pattern induced by top-down perception can be obtained. Apart from the brain areas of bilateral fusiform gyrus (FG), left inferior occipital gyrus (IOG) and left superior temporal sulcus (STS), which are consistent with a core system in the distributed cortical network for face perception, activation induced by top-down face processing is also found in these regions that include the anterior cingulate gyrus (ACC), right oribitofrontal cortex (OFC), left precuneus, right parahippocampal cortex, left dorsolateral prefrontal cortex (DLPFC), right frontal pole, bilateral premotor cortex, left inferior parietal cortex and bilateral thalamus. The results indicate that making-decision, attention, episodic memory retrieving and contextual associative processing network cooperate with general face processing regions to process face information under top-down perception.
Brand, Matthias; Schiebener, Johannes; Pertl, Marie-Theres; Delazer, Margarete
2014-01-01
Recent models on decision making under risk conditions have suggested that numerical abilities are important ingredients of advantageous decision-making performance, but empirical evidence is still limited. The results of our first study show that logical reasoning and basic mental calculation capacities predict ratio processing and that ratio processing predicts decision making under risk. In the second study, logical reasoning together with executive functions predicted probability processing (numeracy and probability knowledge), and probability processing predicted decision making under risk. These findings suggest that increasing an individual's understanding of ratios and probabilities should lead to more advantageous decisions under risk conditions.
The neural bases of cognitive processes in gambling disorder
Potenza, Marc N.
2014-01-01
Functional imaging is offering powerful new tools to investigate the neurobiology of cognitive functioning in people with and without psychiatric conditions like gambling disorder. Based on similarities between gambling and substance-use disorders in neurocognitive and other domains, gambling disorder has recently been classified in DSM-5 as a behavioral addiction. Despite the advances in understanding, there exist multiple unanswered questions about the pathophysiology underlying gambling di...
MicroRNAs take part in pathophysiology and pathogenesis of Male Pattern Baldness.
Goodarzi, Hamed R; Abbasi, Ali; Saffari, Mojtaba; Tabei, Mohammad B; Noori Daloii, Mohammad R
2010-07-01
Male Pattern Baldness (MPB) or androgenetic alopecia is a common form of hair loss with androgens and genetics having etiological significance. Androgens are thought to pathophysiologically power on cascades of chronically dramatic alterations in genetically susceptible scalp dermal papillas, specialized cells in hair follicles in which androgens react, and finally resulting in a patterned alopecia. However, the exact mechanisms through which androgens, positive regulators of growth and anabolism in most body sites, paradoxically exert their effects on balding hair follicles, are not yet known. The role of microRNAs, a recently discovered class of non-coding RNAs, with a wide range of regulatory functions, has been documented in hair follicle formation and their deregulation in cancer of prostate, a target organ of androgens has also been delineated. Yet, there is a lack of knowledge in agreement with microRNAs' contribution in pathophysiology of MPB. To investigate the role of microRNAs in pathogenesis of MPB, we selected seven microRNAs, predicted bioinformatically on a reverse engineering basis, from previously published microarray gene expression data and analyzed their expression in balding relative to non-balding dermal papillas. We found for the first time upregulation of four microRNAs (miR-221, miR-125b, miR-106b and miR-410) that could participate in pathogenesis of MPB. Regarding microRNAs' therapeutic potential and accessibility of hair follicles for gene therapy, these microRNAs can be considered as good candidates for a new revolutionized generation of treatments.
Understanding Nutrient Processing Under Similar Hydrologic Conditions Along a River Continuum
Garayburu-Caruso, V. A.; Mortensen, J.; Van Horn, D. J.; Gonzalez-Pinzon, R.
2015-12-01
Eutrophication is one of the main causes of water impairment across the US. The fate of nutrients in streams is typically described by the dynamic coupling of physical processes and biochemical processes. However, isolating each of these processes and determining its contribution to the whole system is challenging due to the complexity of the physical, chemical and biological domains. We conducted column experiments seeking to understand nutrient processing in shallow sediment-water interactions along representative sites of the Jemez River-Rio Grande continuum (eight stream orders), in New Mexico (USA). For each stream order, we used a set of 6 columns packed with 3 different sediments, i.e., Silica Cone Density Sand ASTM D 1556 (0.075-2.00 mm), gravel (> 2mm) and native sediments from each site. We incubated the sediments for three months and performed tracer experiments in the laboratory under identical flow conditions, seeking to normalize the physical processes along the river continuum. We added a short-term pulse injection of NO3, resazurin and NaCl to each column and determined metabolism and NO3 processing using the Tracer Additions for Spiraling Curve Characterization method (TASCC). Our methods allowed us to study how changes in bacterial communities and sediment composition along the river continuum define nutrient processing.
Wild-Wall, Nele; Falkenstein, Michael
2010-01-01
By using event-related potentials (ERPs) the present study examines if age-related differences in preparation and processing especially emerge during divided attention. Binaurally presented auditory cues called for focused (valid and invalid) or divided attention to one or both ears. Responses were required to subsequent monaurally presented valid targets (vowels), but had to be suppressed to non-target vowels or invalidly cued vowels. Middle-aged participants were more impaired under divided attention than young ones, likely due to an age-related decline in preparatory attention following cues as was reflected in a decreased CNV. Under divided attention, target processing was increased in the middle-aged, likely reflecting compensatory effort to fulfill task requirements in the difficult condition. Additionally, middle-aged participants processed invalidly cued stimuli more intensely as was reflected by stimulus ERPs. The results suggest an age-related impairment in attentional preparation after auditory cues especially under divided attention and latent difficulties to suppress irrelevant information.
Enhanced performance of denitrifying sulfide removal process under micro-aerobic condition.
Chen, Chuan; Ren, Nanqi; Wang, Aijie; Liu, Lihong; Lee, Duu-Jong
2010-07-15
The denitrifying sulfide removal (DSR) process with bio-granules comprising both heterotrophic and autotrophic denitrifiers can simultaneously convert nitrate, sulfide and acetate into di-nitrogen gas, elementary sulfur and carbon dioxide, respectively, at high loading rates. This study determines the reaction rate of sulfide oxidized into sulfur, as well as the reduction of nitrate to nitrite, would be enhanced under a micro-aerobic condition. The presence of limited oxygen mitigated the inhibition effects of sulfide on denitrifier activities, and enhanced the performance of DSR granules. The advantages and disadvantages of applying the micro-aerobic condition to the DSR process are discussed. 2010 Elsevier B.V. All rights reserved.
Nuclear structure and weak rates of heavy waiting point nuclei under rp-process conditions
Nabi, Jameel-Un; Böyükata, Mahmut
2017-01-01
The structure and the weak interaction mediated rates of the heavy waiting point (WP) nuclei 80Zr, 84Mo, 88Ru, 92Pd and 96Cd along N = Z line were studied within the interacting boson model-1 (IBM-1) and the proton-neutron quasi-particle random phase approximation (pn-QRPA). The energy levels of the N = Z WP nuclei were calculated by fitting the essential parameters of IBM-1 Hamiltonian and their geometric shapes were predicted by plotting potential energy surfaces (PESs). Half-lives, continuum electron capture rates, positron decay rates, electron capture cross sections of WP nuclei, energy rates of β-delayed protons and their emission probabilities were later calculated using the pn-QRPA. The calculated Gamow-Teller strength distributions were compared with previous calculation. We present positron decay and continuum electron capture rates on these WP nuclei under rp-process conditions using the same model. For the rp-process conditions, the calculated total weak rates are twice the Skyrme HF+BCS+QRPA rates for 80Zr. For remaining nuclei the two calculations compare well. The electron capture rates are significant and compete well with the corresponding positron decay rates under rp-process conditions. The finding of the present study supports that electron capture rates form an integral part of the weak rates under rp-process conditions and has an important role for the nuclear model calculations.
New advances in cell physiology and pathophysiology of the exocrine pancreas.
Mössner, Joachim
2010-01-01
This review provides some aspects on the physiology of stimulation and inhibition of pancreatic digestive enzyme secretion and the pathophysiology of pancreatic acinar cell function leading to pancreatitis. Cholecystokinin (CCK) stimulates both directly via CCK-A receptors on acinar cells and indirectly via CCK-B receptors on nerves, followed by acetylcholine release, pancreatic enzyme secretion. It is still not known whether CCK-A receptors exist in human acinar cells, in contrast to acinar cells of rodents where CCK-A receptors have been well described. CCK has numerous actions both in the periphery and in the central nervous systems. CCK inhibits gastric motility and regulates satiety. Another major function of CCK is stimulation of gallbladder contraction. This function enables that bile acids act simultaneously with pancreatic lipolytic enzymes. Secretin is a major stimulator of bicarbonate secretion. Trypsinogen is activated by the gut mucosal enzyme enterokinase. The other pancreatic proenzymes are activated by trypsin. Termination of enzyme secretion may be regulated by negative feedback mechanisms via destruction of CCK-releasing peptides by trypsin. Furthermore, the ileum may act as a brake by release of inhibitory hormones such as PYY and somatostatin. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen is regarded as an initiation step. This activation of trypsinogen may be caused by the lysosomal enzyme cathepsin B. However, autoactivation of trypsinogen itself may be a possibility in pathogenesis. Autoactivation is enhanced in certain mutations of trypsinogen. Furthermore, an imbalance of protease inhibitors and active proteases may be involved. The role of pancreatic lipolytic enzymes, the role of bicarbonate secretion, and toxic Ca(2+) signals by excessive liberation from the endoplasmic reticulum have to be discussed in the pathogenesis of acute pancreatitis
Efficient Option Pricing under Levy Processes, with CVA and FVA
Directory of Open Access Journals (Sweden)
Jimmy eLaw
2015-07-01
Full Text Available We generalize the Piterbarg (2010 model to include 1 bilateral default risk as in Burgard and Kjaer (2012, and 2 jumps in the dynamics of the underlying asset using general classes of L'evy processes of exponential type. We develop an efficient explicit-implicit scheme for European options and barrier options taking CVA-FVA into account. We highlight the importance of this work in the context of trading, pricing and management a derivative portfolio given the trajectory of regulations.
Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective.
Zaccardi, Francesco; Webb, David R; Yates, Thomas; Davies, Melanie J
2016-02-01
role for insulin resistance in the development of a cluster of cardiometabolic alterations (dyslipidaemia, inflammation, high blood pressure) was suggested. Possibly as a consequence of the secular changes in diabetes risk factors, in the last 10 years the limitation of a simple distinction between 'type I' and 'type II' diabetes has been increasingly recognised, with subjects showing the coexistence of insulin resistance and immune activation against β-cells. With the advancement of our cellular and molecular understanding of diabetes, a more pathophysiological classification that overcomes the historical and simple 'glucocentric' view could result in a better patient phenotyping and therapeutic approach. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Metabolism of very long-chain Fatty acids: genes and pathophysiology.
Sassa, Takayuki; Kihara, Akio
2014-02-01
Fatty acids (FAs) are highly diverse in terms of carbon (C) chain-length and number of double bonds. FAs with C>20 are called very long-chain fatty acids (VLCFAs). VLCFAs are found not only as constituents of cellular lipids such as sphingolipids and glycerophospholipids but also as precursors of lipid mediators. Our understanding on the function of VLCFAs is growing in parallel with the identification of enzymes involved in VLCFA synthesis or degradation. A variety of inherited diseases, such as ichthyosis, macular degeneration, myopathy, mental retardation, and demyelination, are caused by mutations in the genes encoding VLCFA metabolizing enzymes. In this review, we describe mammalian VLCFAs by highlighting their tissue distribution and metabolic pathways, and we discuss responsible genes and enzymes with reference to their roles in pathophysiology.
Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.
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.
Geographical, environmental and pathophysiological influences on the human blood transcriptome.
Tabassum, Rubina; Nath, Artika; Preininger, Marcela; Gibson, Greg
2013-12-01
Gene expression variation provides a read-out of both genetic and environmental influences on gene activity. Geographical, genomic and sociogenomic studies have highlighted how life circumstances of an individual modify the expression of hundreds and in some cases thousands of genes in a co-ordinated manner. This review places such results in the context of a conserved set of 90 transcripts known as Blood Informative Transcripts (BIT) that capture the major conserved components of variation in the peripheral blood transcriptome. Pathophysiological states are also shown to associate with the perturbation of transcript abundance along the major axes. Discussion of false negative rates leads us to argue that simple significance thresholds provide a biased perspective on assessment of differential expression that may cloud the interpretation of studies with small sample sizes.
Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.
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.
Weber
1998-12-01
For the past 33 years, Organizational Behavior and Human Decision Processes has thrived under a single editor. That editor, James C. Naylor, is retiring from his long stewardship. This article chronicles the course of the journal under Jim's direction and marks some of the accomplishments and changes over the past three decades that go to his credit. Copyright 1998 Academic Press.
Directory of Open Access Journals (Sweden)
Syed Omar Kazmi
2018-01-01
Full Text Available Extracorporeal membrane oxygenation (ECMO is a life-saving technique that is widely being used in centers throughout the world. However, there is a paucity of literature surrounding the mechanisms affecting cerebral physiology while on ECMO. Studies have shown alterations in cerebral blood flow characteristics and subsequently autoregulation. Furthermore, the mechanical aspects of the ECMO circuit itself may affect cerebral circulation. The nature of these physiological/pathophysiological changes can lead to profound neurological complications. This review aims at describing the changes to normal cerebral autoregulation during ECMO, illustrating the various neuromonitoring tools available to assess markers of cerebral autoregulation, and finally discussing potential neurological complications that are associated with ECMO.
Directory of Open Access Journals (Sweden)
Alberto J. Espay
2018-01-01
Conclusions: In response to emotional stimuli, functional tremor is associated with alterations in activation and functional connectivity in networks involved in emotion processing and theory of mind. These findings may be relevant to the pathophysiology of functional movement disorders.
Hemorrhoids: From basic pathophysiology to clinical management
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
The pathophysiology of amenorrhea in the adolescent.
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.
20 CFR 10.7 - What forms are needed to process claims under the FECA?
2010-04-01
... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false What forms are needed to process claims under the FECA? 10.7 Section 10.7 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT...' COMPENSATION ACT, AS AMENDED General Provisions Definitions and Forms § 10.7 What forms are needed to process...
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Jarred W Younger
Full Text Available The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.
Li, Xiaoqing; Zhang, Yuping; Xia, Jinyan; Swaab, Tamara Y
2017-07-28
Although numerous studies have demonstrated that the language processing system can predict upcoming content during comprehension, there is still no clear picture of the anticipatory stage of predictive processing. This electroencephalograph study examined the cognitive and neural oscillatory mechanisms underlying anticipatory processing during language comprehension, and the consequences of this prediction for bottom-up processing of predicted/unpredicted content. Participants read Mandarin Chinese sentences that were either strongly or weakly constraining and that contained critical nouns that were congruent or incongruent with the sentence contexts. We examined the effects of semantic predictability on anticipatory processing prior to the onset of the critical nouns and on integration of the critical nouns. The results revealed that, at the integration stage, the strong-constraint condition (compared to the weak-constraint condition) elicited a reduced N400 and reduced theta activity (4-7Hz) for the congruent nouns, but induced beta (13-18Hz) and theta (4-7Hz) power decreases for the incongruent nouns, indicating benefits of confirmed predictions and potential costs of disconfirmed predictions. More importantly, at the anticipatory stage, the strongly constraining context elicited an enhanced sustained anterior negativity and beta power decrease (19-25Hz), which indicates that strong prediction places a higher processing load on the anticipatory stage of processing. The differences (in the ease of processing and the underlying neural oscillatory activities) between anticipatory and integration stages of lexical processing were discussed with regard to predictive processing models. Copyright © 2017 Elsevier Ltd. All rights reserved.
The Investigations of Friction under Die Surface Vibration in Cold Forging Process
DEFF Research Database (Denmark)
Jinming, Sha
investigation, and the second stage is to design and manufacture a more practical tool system which can be used to forging some industrial components with larger capacity. The high performance and power piezoelectric actuator stack as the vibration source will be used for designing the vibration system in order...... to 50% with vibration being applied in forming process. Furthermore, by using finite element method, a series of the simulations of the cold forging process under die surface excitation have been implemented in order to further understand the influence of vibration on friction, especially the influence...
Oldehinkel, Marianne; Beckmann, Christian F.; Franke, Barbara; Hartman, Catharina A.; Hoekstra, Pieter J.; Oosterlaan, Jaap; Heslenfeld, Dirk; Buitelaar, Jan K.; Mennes, Maarten
2016-01-01
Background: Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal
Directory of Open Access Journals (Sweden)
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.
Etiology, pathophysiology and classifications of the diabetic Charcot foot
Papanas, Nikolaos; Maltezos, Efstratios
2013-01-01
In people with diabetes mellitus, the Charcot foot is a specific manifestation of peripheral neuropathy that may involve autonomic neuropathy with high blood flow to the foot, leading to increased bone resorption. It may also involve peripheral somatic polyneuropathy with loss of protective sensation and high risk of unrecognized acute or chronic minor trauma. In both cases, there is excess local inflammatory response to foot injury, resulting in local osteoporosis. In the Charcot foot, the acute and chronic phases have been described. The former is characterized by local erythema, edema, and marked temperature elevation, while pain is not a prominent symptom. In the latter, signs of inflammation gradually recede and deformities may develop, increasing the risk of foot ulceration. The most common anatomical classification describes five patterns, according to the localization of bone and joint pathology. This review article aims to provide a brief overview of the diabetic Charcot foot in terms of etiology, pathophysiology, and classification. PMID:23705058
[Irritable bowel syndrome: New pathophysiological hypotheses and practical issues].
Duboc, H; Dior, M; Coffin, B
2016-08-01
In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.
The rumination syndrome in adults: A review of the pathophysiology, diagnosis and treatment
Directory of Open Access Journals (Sweden)
Papadopoulos V
2007-01-01
Full Text Available Rumination in adults is considered to be the effortless regurgitation of recently ingested food into the mouth, followed by either rechewing and reswallowing or expulsion of the regurgitate. On the basis of the definition of rumination as a unique category of functional gastroduodenal disorders, according to the newly established Rome III classification, a review of the pathophysiology, diagnosis and treatment of the rumination syndrome in adults is presented after systematic and critical approach of all articles that could be retrieved through PubMed using the term "rumination".
Expected Power-Utility Maximization Under Incomplete Information and with Cox-Process Observations
International Nuclear Information System (INIS)
Fujimoto, Kazufumi; Nagai, Hideo; Runggaldier, Wolfgang J.
2013-01-01
We consider the problem of maximization of expected terminal power utility (risk sensitive criterion). The underlying market model is a regime-switching diffusion model where the regime is determined by an unobservable factor process forming a finite state Markov process. The main novelty is due to the fact that prices are observed and the portfolio is rebalanced only at random times corresponding to a Cox process where the intensity is driven by the unobserved Markovian factor process as well. This leads to a more realistic modeling for many practical situations, like in markets with liquidity restrictions; on the other hand it considerably complicates the problem to the point that traditional methodologies cannot be directly applied. The approach presented here is specific to the power-utility. For log-utilities a different approach is presented in Fujimoto et al. (Preprint, 2012).
Expected Power-Utility Maximization Under Incomplete Information and with Cox-Process Observations
Energy Technology Data Exchange (ETDEWEB)
Fujimoto, Kazufumi, E-mail: m_fuji@kvj.biglobe.ne.jp [Bank of Tokyo-Mitsubishi UFJ, Ltd., Corporate Risk Management Division (Japan); Nagai, Hideo, E-mail: nagai@sigmath.es.osaka-u.ac.jp [Osaka University, Division of Mathematical Science for Social Systems, Graduate School of Engineering Science (Japan); Runggaldier, Wolfgang J., E-mail: runggal@math.unipd.it [Universita di Padova, Dipartimento di Matematica Pura ed Applicata (Italy)
2013-02-15
We consider the problem of maximization of expected terminal power utility (risk sensitive criterion). The underlying market model is a regime-switching diffusion model where the regime is determined by an unobservable factor process forming a finite state Markov process. The main novelty is due to the fact that prices are observed and the portfolio is rebalanced only at random times corresponding to a Cox process where the intensity is driven by the unobserved Markovian factor process as well. This leads to a more realistic modeling for many practical situations, like in markets with liquidity restrictions; on the other hand it considerably complicates the problem to the point that traditional methodologies cannot be directly applied. The approach presented here is specific to the power-utility. For log-utilities a different approach is presented in Fujimoto et al. (Preprint, 2012).
Independent component processes underlying emotions during natural music listening.
Rogenmoser, Lars; Zollinger, Nina; Elmer, Stefan; Jäncke, Lutz
2016-09-01
The aim of this study was to investigate the brain processes underlying emotions during natural music listening. To address this, we recorded high-density electroencephalography (EEG) from 22 subjects while presenting a set of individually matched whole musical excerpts varying in valence and arousal. Independent component analysis was applied to decompose the EEG data into functionally distinct brain processes. A k-means cluster analysis calculated on the basis of a combination of spatial (scalp topography and dipole location mapped onto the Montreal Neurological Institute brain template) and functional (spectra) characteristics revealed 10 clusters referring to brain areas typically involved in music and emotion processing, namely in the proximity of thalamic-limbic and orbitofrontal regions as well as at frontal, fronto-parietal, parietal, parieto-occipital, temporo-occipital and occipital areas. This analysis revealed that arousal was associated with a suppression of power in the alpha frequency range. On the other hand, valence was associated with an increase in theta frequency power in response to excerpts inducing happiness compared to sadness. These findings are partly compatible with the model proposed by Heller, arguing that the frontal lobe is involved in modulating valenced experiences (the left frontal hemisphere for positive emotions) whereas the right parieto-temporal region contributes to the emotional arousal. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
DEFF Research Database (Denmark)
Møller, Jonas B; Pedersen, Maria; Tanaka, Haruhiko
2014-01-01
OBJECTIVE This cross-sectional clinical study compared the pathophysiology of type 2 diabetes in Japanese and Caucasians and investigated the role of demographic, genetic, and lifestyle-related risk factors for insulin resistance and β-cell response. RESEARCH DESIGN AND METHODS A total of 120 Jap...
Martinucci, I; de Bortoli, N; Savarino, E; Piaggi, P; Bellini, M; Antonelli, A; Savarino, V; Frazzoni, M; Marchi, S
2014-04-01
Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs). Patients with heartburn and negative endoscopy were treated with esomeprazole or pantoprazole 40 mg daily for 8 weeks. According to MII-pH (off therapy) analysis, patients with normal acid exposure time (AET), normal reflux number, and lack of association between symptoms and refluxes were selected; of whom 30 patients with a symptom relief higher than 50% after PPIs composed Group A, and 30 patients, matched for sex and age, without symptom relief composed Group B. A group of 20 healthy volunteers (HVs) was enrolled. For each patient and HV, we evaluated the baseline impedance levels at channel 3, during the overnight rest, at three different times. Group A (vs Group B) showed an increase in the following parameters: mean AET (1.4 ± 0.8% vs 0.5 ± 0.6%), mean reflux number (30.4 ± 8.7 vs 24 ± 6.9), proximal reflux number (11.1 ± 5.2 vs 8.2 ± 3.6), acid reflux number (17.9 ± 6.1 vs 10.7 ± 6.9). Baseline impedance levels were lower in Group A than in Group B and in HVs (p heartburn and normal AET could achieve a better understanding of pathophysiology in reflux disease patients, and could improve the distinction between FH and hypersensitive esophagus. © 2014 John Wiley & Sons Ltd.
Yanagawa, Masato; Uchida, Kazushige; Ando, Yugo; Tomiyama, Takashi; Yamaguchi, Takashi; Ikeura, Tsukasa; Fukui, Toshiro; Nishio, Akiyoshi; Uemura, Yoshiko; Miyara, Takayuki; Okamoto, Hiroyuki; Satoi, Souhei; Okazaki, Kazuichi
2018-03-01
Pathophysiology of type 1 autoimmune pancreatitis (AIP) is still unclear. We previously reported that M2 macrophages might play an important role in type 1 AIP. Recently, it has been reported that basophils regulate differentiation to M2 macrophages. In this study, we investigated basophils from the pancreatic tissue and peripheral blood of individuals with type 1 AIP. By using immunohistochemistry, we investigated basophils in pancreatic tissue from 13 patients with type 1 AIP and examined expression of toll-like receptors (TLRs) by these cells. Additionally, we obtained peripheral blood samples from 27 healthy subjects, 40 patients with type 1 AIP, 8 patients with alcoholic chronic pancreatitis, 10 patients with bronchial asthma, and 10 patients with atopic dermatitis, and analyzed activation of basophils by stimulating them with ligands of TLR1-9. We also compared TLR expression in basophils from the tissue and blood samples. Basophils were detected in pancreatic tissues from 10 of 13 patients with type 1 AIP. Flow cytometric analysis revealed that the ratios of basophils activated by TLR4 stimulation in type 1 AIP (9.875 ± 1.148%) and atopic dermatitis (11.768 ± 1.899%) were significantly higher than those in healthy subjects (5.051 ± 0.730%; P pathophysiology of type 1 AIP.
Sfyri, Peggy; Matsakas, Antonios
2017-07-08
Atherosclerosis is a chronic inflammatory process that, in the presence of hyperlipidaemia, promotes the formation of atheromatous plaques in large vessels of the cardiovascular system. It also affects peripheral arteries with major implications for a number of other non-vascular tissues such as the skeletal muscle, the liver and the kidney. The aim of this review is to critically discuss and assimilate current knowledge on the impact of peripheral atherosclerosis and its implications on skeletal muscle homeostasis. Accumulating data suggests that manifestations of peripheral atherosclerosis in skeletal muscle originates in a combination of increased i)-oxidative stress, ii)-inflammation, iii)-mitochondrial deficits, iv)-altered myofibre morphology and fibrosis, v)-chronic ischemia followed by impaired oxygen supply, vi)-reduced capillary density, vii)- proteolysis and viii)-apoptosis. These structural, biochemical and pathophysiological alterations impact on skeletal muscle metabolic and physiologic homeostasis and its capacity to generate force, which further affects the individual's quality of life. Particular emphasis is given on two major areas representing basic and applied science respectively: a)-the abundant evidence from a well-recognised atherogenic model; the Apolipoprotein E deficient mouse and the role of a western-type diet and b)-on skeletal myopathy and oxidative stress-induced myofibre damage from human studies on peripheral arterial disease. A significant source of reactive oxygen species production and oxidative stress in cardiovascular disease is the family of NADPH oxidases that contribute to several pathologies. Finally, strategies targeting NADPH oxidases in skeletal muscle in an attempt to attenuate cellular oxidative stress are highlighted, providing a better understanding of the crossroads between peripheral atherosclerosis and skeletal muscle pathophysiology.
B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?
International Nuclear Information System (INIS)
Hengeveld, P J; Kersten, M J
2015-01-01
Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC's capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC's BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916)
Gaucher Disease: The Metabolic Defect, Pathophysiology, Phenotypes And Natural History
Baris, Hagit N.; Cohen, Ian J.; Mistry, Pramod K.
2015-01-01
Gaucher disease (GD), a prototype lysosomal storage disorder, results from inherited deficiency of lysosomal glucocerebrosidase due to biallelic mutations in GBA. The result is widespread accumulation of macrophages engorged with predominantly lysosomal glucocerebroside. A complex multisystem phenotype arises involving the liver, spleen, bone marrow and occasionally the lungs in type 1 Gaucher disease; in neuronopathic fulminant type 2 and chronic type 3 disease there is in addition progressive neurodegenerative disease. Manifestations of Gaucher disease type 1 (GD1) include hepatosplenomegaly, cytopenia, a complex pattern of bone involvement with avascular osteonecrosis (AVN), osteoporosis, fractures and lytic lesions. Enzyme replacement therapy became the standard of care in 1991, and this has transformed the natural history of GD1. This article reviews the clinical phenotypes of GD, diagnosis, pathophysiology and its natural history. A subsequent chapter discusses the treatment options. PMID:25345088
Awad, Amer; Stüve, Olaf
2011-01-01
Transverse myelitis is a focal inflammatory disorder of the spinal cord which may arise due to different etiologies. Transverse myelitis may be idiopathic or related/secondary to other diseases including infections, connective tissue disorders and other autoimmune diseases. It may be also associated with optic neuritis (neuromyelitis optica), which may precede transverse myelitis. In this manuscript we review the pathophysiology of different types of transverse myelitis and neuromyelitis optica and discuss diagnostic criteria for idiopathic transverse myelitis and risk of development of multiple sclerosis after an episode of transverse myelitis. We also discuss treatment options including corticosteroids, immunosuppressives and monoclonal antibodies, plasma exchange and intravenous immunoglobulins. PMID:22379456
Directory of Open Access Journals (Sweden)
Chinami Matsumoto
2008-01-01
Full Text Available ‘Oketsu’ is a pathophysiologic concept in Japanese traditional (Kampo medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for ‘Oketsu’. Sixteen rheumatoid arthritis (RA patients were treated with keishibukuryogan (KBG, a representative Kampo medicine for improving ‘Oketsu’. Plasma samples were diagnosed as either having an ‘Oketsu’ (n = 19 or ‘non-Oketsu’ (n = 29 state according to Terasawa's ‘Oketsu’ scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the ‘Oketsu’ scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the ‘Oketsu’ and ‘non-Oketsu’ states. Hierarchical clustering gave three major clusters (I, II, III. The majority (68.4% of ‘Oketsu’ samples were clustered into one cluster as the principal component of cluster I. The remaining ‘Oketsu’ profiles constituted a minor component of cluster II and were all derived from patients cured of the ‘Oketsu’ state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for ‘Oketsu’. A reduction in measurement/pre-processing conditions (from 55 to 16 gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine ‘Oketsu’ has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing ‘Oketsu’ using a combination of proteomic and bioinformatics-based classification methods.
Faecal soiling: pathophysiology of postdefaecatory incontinence.
Pucciani, F
2013-08-01
Passive postdefaecatory incontinence is poorly understood and yet is an important clinical problem. The aim of this study was to characterize the pathophysiology of postdefaecatory incontinence in patients affected by faecal soiling. Seventy-two patients (30 women, age range 49-79 years; 42 men, age range, 53-75 years) affected by faecal passive incontinence with faecal soiling were included in the study. Two patient groups were identified: Group 1 comprised 42 patients with postdefaecatory incontinence and Group 2 had 30 patients without incontinence after bowel movements. After a preliminary clinical evaluation, including the Faecal Incontinence Severity Index (FISI) score and the obstructed defaecation syndrome (ODS) score, all patients of Groups 1 and 2 were studied by means of endoanal ultrasound and anorectal manometry. The results were compared with those from 20 healthy control subjects. A significantly higher ODS score was found in Group 1 (P IAS) in Group 2 (P IAS atrophy and the FISI score (ρs 0.78; P < 0.03). Anal resting pressure (Pmax and Pm ) was significantly lower in Group 2 (P < 0.04). The straining test was considered positive in 30 (71.4%) patients in Group 1, significantly greater than in Group 2 (P < 0.01). A significantly higher conscious rectal sensitivity threshold (CRST) was found in Group 1 patients (P < 0.01). The ODS score, a positive straining test and high CRST values suggest that postdefaecatory incontinence is secondary to impaired defaecation. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
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.)
Pathophysiology and clinical implications of peroperative fluid management in elective surgery
DEFF Research Database (Denmark)
Holte, Kathrine
2010-01-01
The purpose of this thesis was to describe pathophysiological aspects of perioperative fluid administration and create a rational background for future, clinical outcome studies. In laparoscopic cholecystectomy, we have found "liberal" crystalloid administration ( approximately 3 liters) to improve....... Based on the current evidence, administration of liters intravenous fluid without specific indication in major surgical procedures should be avoided, while administration of liters in patients with anastomoses may not be recommended, an issue needing clarification in large-scale clinical studies...... perioperative physiology and clinical outcome, which has implication for fluid management in other laparoscopic procedures such as laparoscopic fundoplication, laparoscopic repair of ventral hernia, hysterectomy etc., where 2-3 liters crystalloid should be administered based on the present evidence. That equal...
Sanchez, Christopher A
2011-02-01
It has been suggested that pain perception and attention are closely linked at both a neural and a behavioural level. If pain and attention are so linked, it is reasonable to speculate that those who vary in working memory capacity (WMC) should be affected by pain differently. This study compares the performance of individuals who differ in WMC as they perform processing and memory span tasks while under mild pain and not. While processing performance under mild pain does not interact with WMC, the ability to store information for later recall does. This suggests that pain operates much like an additional processing burden, and that the ability to overcome this physical sensation is related to differences in WMC. © 2011 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business
Guidelines regarding the Review Process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2011-01-01
These guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views [fr
Guidelines regarding the review process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2002-01-01
These guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views
Guidelines regarding the review process under the convention on nuclear safety
International Nuclear Information System (INIS)
1998-01-01
These guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing national reports submitted in accordance with Article 5 and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of national reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views
Guidelines regarding the Review Process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2011-01-01
These guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views
Guidelines regarding the review process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
1999-01-01
These guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing national reports submitted in accordance with Article 5 and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of national reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views
Guidelines regarding the Review Process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2011-01-01
These guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views [es
Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues.
Classen, Joseph; Koschel, Jiri; Oehlwein, Christian; Seppi, Klaus; Urban, Peter; Winkler, Christian; Wüllner, Ullrich; Storch, Alexander
2017-08-01
Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.
Pathophysiology and pathological findings of heatstroke in dogs
Directory of Open Access Journals (Sweden)
Romanucci M
2013-01-01
Full Text Available Mariarita Romanucci, Leonardo Della SaldaDepartment of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, Teramo, ItalyAbstract: Canine heatstroke is a life-threatening condition resulting from an imbalance between heat dissipation and production, and characterized by a nonpyrogenic elevation in core body temperature above 41°C (105.8°F. Several exogenous and endogenous factors may predispose dogs to the development of heatstroke; on the other hand, adaptive mechanisms also exists which allow organisms to combat the deleterious effects of heat stress, which are represented by the cellular heat-shock response and heat acclimatization. The pathophysiology and consequences of heatstroke share many similarities to those observable in sepsis and are related to the interaction between the direct cytotoxicity of heat, the acute physiological alterations associated with hyperthermia, such as increased metabolic demand, hypoxia, and circulatory failure, and the inflammatory and coagulation responses of the host to the widespread endothelial and tissue injuries, which may culminate in disseminated intravascular coagulation, systemic inflammatory response syndrome, and multiple organ dysfunction.Keywords: thermoregulation, acclimatization, heat shock proteins, hyperthermia, systemic inflammatory response, multiple organ dysfunction
Vitiligo: An Update on Pathophysiology and Treatment Options.
Speeckaert, Reinhart; van Geel, Nanja
2017-12-01
The pathophysiology of vitiligo is becoming increasingly clarified. In non-segmental vitiligo, early factors include activation of innate immunity, inflammasome activation, oxidative stress, and loss of melanocyte adhesion. Nonetheless, the main mechanism leading to non-segmental vitiligo involves an immune-mediated destruction of melanocytes. Anti-melanocyte-specific cytotoxic T cells exert a central role in the final effector stage. Genetic research revealed a multi-genetic inheritance displaying an overlap with other autoimmune disorders. However, some melanocyte-specific genes were also affected. Segmental vitiligo carries a different pathogenesis with most evidence indicating a mosaic skin disorder. Current management includes topical corticosteroids and immunomodulators. Narrow-band ultraviolet B can be used in patients not responding to topical treatment or in patients with extensive disease. Pigment cell transplantation offers an alternative for the treatment of segmental vitiligo or stable non-segmental lesions. Recent findings have revealed new targets for treatment that could lead to more efficient therapies. Targeted immunotherapy may halt the active immune pathways, although combination therapy may still be required to induce satisfying repigmentation. A recently established core set of outcome measures, new measurement instruments, and biomarker research pave the way for future standardized clinical trials.
Vaccarino, Viola; Badimon, Lina; Corti, Roberto; de Wit, Cor; Dorobantu, Maria; Hall, Alistair; Koller, Akos; Marzilli, Mario; Pries, Axel; Bugiardini, Raffaele
2011-04-01
Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women.
Energy Technology Data Exchange (ETDEWEB)
Daghrir, Rimeh, E-mail: rimeh.daghrir@ete.inrs.ca [Institut National de la Recherche Scientifique, Centre Eau, Terre et Environnement, 490 rue de la Couronne, Québec, Qc G1K 9A9 (Canada); Drogui, Patrick, E-mail: patrick.drogui@ete.inrs.ca [Institut National de la Recherche Scientifique, Centre Eau, Terre et Environnement, 490 rue de la Couronne, Québec, Qc G1K 9A9 (Canada); Delegan, Nazar, E-mail: delegan@emt.inrs.ca [Institut National de la Recherche Scientifique, INRS-Énergie, Matériaux et Télécommunications, 1650 Blvd. Lionel-Boulet, Varennes, Qc J3X 1S2 (Canada); El Khakani, My Ali, E-mail: elkhakani@emt.inrs.ca [Institut National de la Recherche Scientifique, INRS-Énergie, Matériaux et Télécommunications, 1650 Blvd. Lionel-Boulet, Varennes, Qc J3X 1S2 (Canada)
2014-01-01
The degradation of chlortetracycline in synthetic solution and in municipal effluent was investigated using a photoelectrocatalytic oxidation process under visible irradiation. The N-doped TiO{sub 2} used as photoanode with 3.4 at.% of nitrogen content was prepared by means of a radiofrequency magnetron sputtering (RF-MS) process. Under visible irradiation, higher photoelectrocatalytic removal efficiency of CTC was recorded using N-doped TiO{sub 2} compared to the conventional electrochemical oxidation, direct photolysis and photocatalysis processes. The photoelectrocatalytic process operated at 0.6 A of current intensity during 180 min of treatment time promotes the degradation of 99.1 ± 0.1% of CTC. Under these conditions, removal rates of 85.4 ± 3.6%, 87.4 ± 3.1% and 55.7 ± 2.9% of TOC, TN and NH{sub 4}{sup +} have been recorded. During the treatment, CTC was mainly transformed into CO{sub 2} and H{sub 2}O. The process was also found to be effective in removing indicator of pathogens such as fecal coliform (log-inactivation was higher than 1.2 units). - Highlights: •PECO process is a feasible technology for the treatment of MWW contaminated by CTC. •99.1% ± 0.1% of CTC was degraded by PECO using N-doped TiO{sub 2}. •85.4% ± 3.6% of TOC removal and 97.5% ± 1.2% of COD removal were achieved. •87.4% ± 3.1% of TN removal and 55.7% ± 2.9% of NH{sub 4}{sup +} removal were recorded. •More than 94% of fecal coliform was removed (abatement > 1.2-log units)
The paper proposes a pathophysiologic framework to explain the well-established epidemiological association between exposure to ambient air particle pollution and premature cardiovascular mortality, and offers insights into public health solutions that extend beyond regularory en...
Evidence-Based Revised View of the Pathophysiology of Preeclampsia.
Ahmed, Asif; Rezai, Homira; Broadway-Stringer, Sophie
2017-01-01
Preeclampsia is a life-threatening vascular disorder of pregnancy due to a failing stressed placenta. Millions of women risk death to give birth each year and globally each year, almost 300,000 lose their life in this process and over 500,000 babies die as a consequence of preeclampsia. Despite decades of research, we lack pharmacological agents to treat it. Maternal endothelial oxidative stress is a central phenomenon responsible for the preeclampsia phenotype of high maternal blood pressure and proteinuria. In 1997, it was proposed that preeclampsia arises due to the loss of VEGF activity, possibly due to elevation in anti-angiogenic factor, soluble Flt-1 (sFlt-1). Researchers showed that high sFlt-1 and soluble endoglin (sEng) elicit the severe preeclampsia phenotype in pregnant rodents. We demonstrated that heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway prevents placental stress and suppresses sFlt-1 and sEng release. Likewise, hydrogen sulphide (H 2 S)/cystathionine-γ-lyase (Cth) systems limit sFlt-1 and sEng and protect against the preeclampsia phenotype in mice. Importantly, H 2 S restores placental vasculature, and in doing so improves lagging fetal growth. These molecules act as the inhibitor systems in pregnancy and when they fail, preeclampsia is triggered. In this review, we discuss what are the hypotheses and models for the pathophysiology of preeclampsia on the basis of Bradford Hill causation criteria for disease causation and how further in vivo experimentation is needed to establish 'proof of principle'. Hypotheses that fail to meet the Bradford Hill causation criteria include abnormal spiral artery remodelling and inflammation and should be considered associated or consequential to the disorder. In contrast, the protection against cellular stress hypothesis that states that the protective pathways mitigate cellular stress by limiting elevation of anti-angiogenic factors or oxidative stress and the subsequent clinical signs of preeclampsia
Obsolescence : The underlying processes
Thomsen, A.F.; Nieboer, N.E.T.; Van der Flier, C.L.
2015-01-01
Obsolescence, defined as the process of declining performance of buildings, is a serious threat for the value, the usefulness and the life span of housing properties. Thomsen and van der Flier (2011) developed a model in which obsolescence is categorised on the basis of two distinctions, namely
Optimal processing pathway selection for microalgae-based biorefinery under uncertainty
DEFF Research Database (Denmark)
Rizwan, Muhammad; Zaman, Muhammad; Lee, Jay H.
2015-01-01
We propose a systematic framework for the selection of optimal processing pathways for a microalgaebased biorefinery under techno-economic uncertainty. The proposed framework promotes robust decision making by taking into account the uncertainties that arise due to inconsistencies among...... and shortage in the available technical information. A stochastic mixed integer nonlinear programming (sMINLP) problem is formulated for determining the optimal biorefinery configurations based on a superstructure model where parameter uncertainties are modeled and included as sampled scenarios. The solution...... the accounting of uncertainty are compared with respect to different objectives. (C) 2015 Elsevier Ltd. All rights reserved....
Study of drain-extended NMOS under electrostatic discharge stress in 28 nm and 40 nm CMOS process
Wang, Weihuai; Jin, Hao; Dong, Shurong; Zhong, Lei; Han, Yan
2016-02-01
Researches on the electrostatic discharge (ESD) performance of drain-extended NMOS (DeNMOS) under the state-of-the-art 28 nm and 40 nm bulk CMOS process are performed in this paper. Three distinguishing phases of avalanche breakdown stage, depletion region push-out stage and parasitic NPN turn on stage of the gate-grounded DeNMOS (GG-DeNMOS) fabricated under 28 nm CMOS process measured with transmission line pulsing (TLP) test are analyzed through TCAD simulations and tape-out silicon verification detailedly. Damage mechanisms and failure spots of GG-DeNMOS under both CMOS processes are thermal breakdown of drain junction. Improvements based on the basic structure adjustments can increase the GG-DeNMOS robustness from original 2.87 mA/μm to the highest 5.41 mA/μm. Under 40 nm process, parameter adjustments based on the basic structure have no significant benefits on the robustness improvements. By inserting P+ segments in the N+ implantation of drain or an entire P+ strip between the N+ implantation of drain and polysilicon gate to form the typical DeMOS-SCR (silicon-controlled rectifier) structure, the ESD robustness can be enhanced from 1.83 mA/μm to 8.79 mA/μm and 29.78 mA/μm, respectively.
Guidelines regarding the Review Process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2013-01-01
These Guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 of the Convention and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views. [fr
Guidelines regarding the Review Process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2013-01-01
These Guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 of the Convention and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views.
Guidelines regarding the Review Process under the Convention on Nuclear Safety
International Nuclear Information System (INIS)
2013-01-01
These Guidelines, established by the Contracting Parties pursuant to Article 22 of the Convention, are intended to be read in conjunction with the text of the Convention. Their purpose is to provide guidance to the Contracting Parties on the process for reviewing National Reports submitted in accordance with Article 5 of the Convention and thereby to facilitate the efficient review of implementation by the Contracting Parties of their obligations under the Convention. The aim of the review process should be to achieve a thorough examination of National Reports submitted in accordance with Article 5 of the Convention, so that Contracting Parties can learn from each other's solutions to common and individual nuclear safety problems and, above all, contribute to improving nuclear safety worldwide through a constructive exchange of views. [es
Yang, Xin; Zeng, Zhenxiang; Wang, Ruidong; Sun, Xueshan
2016-01-01
This paper presents a novel method on the optimization of bi-objective Flexible Job-shop Scheduling Problem (FJSP) under stochastic processing times. The robust counterpart model and the Non-dominated Sorting Genetic Algorithm II (NSGA-II) are used to solve the bi-objective FJSP with consideration of the completion time and the total energy consumption under stochastic processing times. The case study on GM Corporation verifies that the NSGA-II used in this paper is effective and has advantages to solve the proposed model comparing with HPSO and PSO+SA. The idea and method of the paper can be generalized widely in the manufacturing industry, because it can reduce the energy consumption of the energy-intensive manufacturing enterprise with less investment when the new approach is applied in existing systems.
Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido
2015-01-01
Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.
Isidori, Andrea M.; Graziadio, Chiara; Paragliola, Rosa Maria; Cozzolino, Alessia; Ambrogio, Alberto G.; Colao, Annamaria; Corsello, Salvatore M.; Pivonello, Rosario
2015-01-01
Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment. The mechanisms involved in the development of hypertension differ, whether glucocorticoid excess is acute or chronic, and the source endogenous or exogenous, introducing inconsistencies among published studies. The pleiotropic effects of glucocorticoids and the overlap of the several regulatory mechanisms controlling blood pressure suggest that a rigorous comparison of in-vivo and in-vitro studies is necessary to draw reliable conclusions. This review, developed during the first ‘Altogether to Beat Cushing's syndrome’ workshop held in Capri in 2012, evaluates the most important peculiarities of hypertension associated with CS, with a particular focus on its pathophysiology. A critical appraisal of most significant animal and human studies is compared with a systematic review of the few available clinical trials. A special attention is dedicated to the description of the clinical features and cardiovascular damage secondary to glucocorticoid excess. On the basis of the consensus reached during the workshop, a pathophysiology-oriented therapeutic algorithm has been developed and it could serve as a first attempt to rationalize the treatment of hypertension in Cushing's syndrome. PMID:25415766
Attention Modulates the Neural Processes Underlying Multisensory Integration of Emotion
Directory of Open Access Journals (Sweden)
Hao Tam Ho
2011-10-01
Full Text Available Integrating emotional information from multiple sensory modalities is generally assumed to be a pre-attentive process (de Gelder et al., 1999. This assumption, however, presupposes that the integrative process occurs independent of attention. Using event-potentials (ERP the present study investigated whether the neural processes underlying the integration of dynamic facial expression and emotional prosody is indeed unaffected by attentional manipulations. To this end, participants were presented with congruent and incongruent face-voice combinations (eg, an angry face combined with a neutral voice and performed different two-choice tasks in four consecutive blocks. Three of the tasks directed the participants' attention to emotion expressions in the face, the voice or both. The fourth task required participants to attend to the synchronicity between voice and lip movements. The results show divergent modulations of early ERP components by the different attentional manipulations. For example, when attention was directed to the face (or the voice, incongruent stimuli elicited a reduced N1 as compared to congruent stimuli. This effect was absent, when attention was diverted away from the emotionality in both face and voice suggesting that the detection of emotional incongruence already requires attention. Based on these findings, we question whether multisensory integration of emotion occurs indeed pre-attentively.
Sinclair, D.; Oranje, B.; Razak, K.A.; Siegel, S.J.; Schmid, S.
2017-01-01
Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and in relevant rodent models. This includes electroencephalographic measurement of event related potentials, neural oscillations and mismatch negativity, as well as habituation and pre-pulse inhibition of startle. We outline robust evidence of disrupted sensory processing in individuals with ASD and FXS, and in respective animal models, focusing on the auditory sensory domain. Animal models provide an excellent opportunity to examine common mechanisms of sensory pathophysiology in order to develop therapeutics. PMID:27235081
The pathophysiology of chronic thromboembolic pulmonary hypertension
Directory of Open Access Journals (Sweden)
Gérald Simonneau
2017-03-01
Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres.
Directory of Open Access Journals (Sweden)
Eitan Fibach
2017-12-01
Full Text Available Thalassemia (thal is an autosomal recessive, hereditary, chronic hemolytic anemia due to a partial or complete deficiency in the synthesis of α-globin chains (α-thal or β-globin chains (β-thal that compose the major adult hemoglobin (α2β2. It is caused by one or more mutations in the corresponding genes. The unpaired globin chains are unstable; they precipitate intracellularly, resulting in hemolysis, premature destruction of red blood cell [RBC] precursors in the bone marrow, and a short life-span of mature RBCs in the circulation. The state of anemia is treated by frequent RBC transfusions. This therapy results in the accumulation of iron (iron overload, a condition that is exacerbated by the breakdown products of hemoglobin (heme and iron and the increased iron uptake for the chronic accelerated, but ineffective, RBC production. Iron catalyzes the generation of reactive oxygen species, which in excess are toxic, causing damage to vital organs such as the heart and liver and the endocrine system. Herein, we review recent findings regarding the pathophysiology underlying the major symptoms of β-thal and potential therapeutic modalities for the amelioration of its complications, as well as new modalities that may provide a cure for the disease.
Graf, Heiko; Wiegers, Maike; Metzger, Coraline D; Walter, Martin; Grön, Georg; Abler, Birgit
2014-10-31
Impaired sexual function is increasingly recognized as a side effect of psychopharmacological treatment. However, underlying mechanisms of action of the different drugs on sexual processing are still to be explored. Using functional magnetic resonance imaging, we previously investigated effects of serotonergic (paroxetine) and dopaminergic (bupropion) antidepressants on sexual functioning (Abler et al., 2011). Here, we studied the impact of noradrenergic and antidopaminergic medication on neural correlates of visual sexual stimulation in a new sample of subjects. Nineteen healthy heterosexual males (mean age 24 years, SD 3.1) under subchronic intake (7 days) of the noradrenergic agent reboxetine (4 mg/d), the antidopaminergic agent amisulpride (200mg/d), and placebo were included and studied with functional magnetic resonance imaging within a randomized, double-blind, placebo-controlled, within-subjects design during an established erotic video-clip task. Subjective sexual functioning was assessed using the Massachusetts General Hospital-Sexual Functioning Questionnaire. Relative to placebo, subjective sexual functioning was attenuated under reboxetine along with diminished neural activations within the caudate nucleus. Altered neural activations correlated with decreased sexual interest. Under amisulpride, neural activations and subjective sexual functioning remained unchanged. In line with previous interpretations of the role of the caudate nucleus in the context of primary reward processing, attenuated caudate activation may reflect detrimental effects on motivational aspects of erotic stimulus processing under noradrenergic agents. © The Author 2015. Published by Oxford University Press on behalf of CINP.
Pathophysiology of esophageal impairment due to button battery ingestion.
Völker, Johannes; Völker, Christine; Schendzielorz, Philipp; Schraven, Sebastian P; Radeloff, Andreas; Mlynski, Robert; Hagen, Rudolf; Rak, Kristen
2017-09-01
The increased use of button batteries with high energy densities in devices of daily life presents a high risk of injury, especially for toddlers and young children. If an accidental ingestion of a button battery occurs, this foreign body can become caught in the constrictions of the esophagus and cause serious damage to the adjacent tissue layers. The consequences can be ulcerations, perforations with fistula formation and damage to the surrounding anatomical structures. In order to gain a better understanding of the pathophysiology after ingestion, we carried out systematic studies on fresh preparations of porcine esophagi. The lithium button battery type CR2032, used most frequently in daily life, was exposed in preparations of porcine esophagi and incubated under the addition of artificial saliva at 37 °C. A total of eight esophagi were analysed by different methods. Measurements of the pH value around the battery electrodes and histological studies of the tissue damage were carried out after 0.5-24 h exposure time. In addition, macroscopic time-lapse images were recorded. Measurements of the battery voltage and the course of the electric current supplemented the experiments. The investigations showed that the batteries caused an electrolysis reaction in the moist environment. The positive electrode formed an acidic and the negative electrode a basic medium. Consequently, a coagulation necrosis at the positive pole, and a deep colliquation necrosis at the minus pole occurred. After an exposure time of 12 h, tissue damage caused by the lye corrosion was observed on the side of the negative electrode up to the lamina muscularis. The corrosion progressed up to the final exposure time of 24 h, but the batteries still had sufficient residual voltage, such that further advancing damage would be expected. Button battery ingestion in humans poses an acute life-threatening danger and immediate endoscopic removal of the foreign body is essential. After only 2
Pathophysiology and treatment of psychosis in Parkinson's disease: a review.
Zahodne, Laura B; Fernandez, Hubert H
2008-01-01
Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past 15 years, from an initial interpretation of symptoms as dopaminergic drug adverse effects to the current view of a complex interplay of extrinsic and disease-related factors.PD psychosis has unique clinical features, namely that it arises within a context of a clear sensorium and retained insight, there is relative prominence of visual hallucinations and progression occurs over time. PD psychosis tends to emerge later in the disease course, and disease duration represents one risk factor for its development. The use of anti-PD medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for PD psychosis. Other risk factors discussed in the literature include older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression.Recent efforts have aimed to explore the complex pathophysiology of PD psychosis, which is now known to involve an interaction between extrinsic, drug-related and intrinsic, disease-related components. The most important extrinsic factor is use of dopaminergic medication, which plays a prominent role in PD psychosis. Intrinsic factors include visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); neurochemical (dopamine, serotonin, acetylcholine, etc.) and structural abnormalities involving site-specific Lewy body deposition; and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype). Preliminary reports have also shown a potential relationship
Park, Il Ho; Lee, Boung Chul; Kim, Jae-Jin; Kim, Joong Il; Koo, Min-Seung
2017-04-19
Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry. SIGNIFICANCE STATEMENT Amotivation is present in both depression and schizophrenia
Using Pupil Diameter Changes for Measuring Mental Workload under Mental Processing
Batmaz, Ihsan; Ozturk, Mustafa
In this study, it is aimed to evaluate the mental workload by using a practical way which based on measuring pupil diameter changes that occurs under mental processing. To determine the mental effort required for each task, the video record of subjects` eyes are taken while they are performed different tasks and pupils were measured from the records. A group of university student, one female 9 males participated to the experiment. Additionally, NASA-TLX questionnaire is applied for the related mental tasks. For verification of results obtained from both indices, the correlation coefficient is calculated task base. The results show that there is weak and negative correlation between the indices on task base except 3rd task. By investigating pupil diameter measurements data too, it is founded that pupil dilates under mental workload during performing related tasks. For all tasks, pupil diameters of response periods increased according to reference baseline period.
Abel Merino Orozco; Ana Arraiz Pérez; Fernando Sabirón Sierra
2016-01-01
Under 6s football competition is a school sport that has inherent educational implications. Moreover, it is a booming non-formal socio-educational framework where families and children lay training expectations and dreams. The aim is to comprehend the emerging learning processes promoted in this environment for 6 years-old children, when the child starts the institutionalization process in the ruled sport. The research uses a case study design, the ethnographic mode, through participant obser...
The underlying processes of a soil mite metacommunity on a small scale
Guo, Chuanwei; Lin, Lin; Wu, Donghui; Zhang, Limin
2017-01-01
Metacommunity theory provides an understanding of how ecological processes regulate local community assemblies. However, few field studies have evaluated the underlying mechanisms of a metacommunity on a small scale through revealing the relative roles of spatial and environmental filtering in structuring local community composition. Based on a spatially explicit sampling design in 2012 and 2013, this study aims to evaluate the underlying processes of a soil mite metacommunity on a small spatial scale (50 m) in a temperate deciduous forest located at the Maoershan Ecosystem Research Station, Northeast China. Moran’s eigenvector maps (MEMs) were used to model independent spatial variables. The relative importance of spatial (including trend variables, i.e., geographical coordinates, and broad- and fine-scale spatial variables) and environmental factors in driving the soil mite metacommunity was determined by variation partitioning. Mantel and partial Mantel tests and a redundancy analysis (RDA) were also used to identify the relative contributions of spatial and environmental variables. The results of variation partitioning suggested that the relatively large and significant variance was a result of spatial variables (including broad- and fine-scale spatial variables and trend), indicating the importance of dispersal limitation and autocorrelation processes. The significant contribution of environmental variables was detected in 2012 based on a partial Mantel test, and soil moisture and soil organic matter were especially important for the soil mite metacommunity composition in both years. The study suggested that the soil mite metacommunity was primarily regulated by dispersal limitation due to broad-scale and neutral biotic processes at a fine-scale and that environmental filtering might be of subordinate importance. In conclusion, a combination of metacommunity perspectives between neutral and species sorting theories was suggested to be important in the