Pathophysiological relationships between heart failure and depression and anxiety.

Science.gov (United States)

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

2014-04-01

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

Pathophysiology of increased intestinal permeability in obstructive jaundice

Science.gov (United States)

Assimakopoulos, Stelios F; Scopa, Chrisoula D; Vagianos, Constantine E

2007-01-01

Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome. PMID:18161914

Traumatic brain injury alters methionine metabolism: implications for pathophysiology

Directory of Open Access Journals (Sweden)

Pramod K Dash

2016-04-01

Full Text Available Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM that serves as the principal methyl (-CH3 donor for DNA and histone methyltransferases to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling.. Under conditions of oxidative stress, homocysteine (which is derived from SAM enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (n = 20 and patients with mild TBI (GCS > 12; n = 20 or severe TBI (GCS < 8; n = 20 within the first 24 hours of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS. Severe TBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to healthy volunteers, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline. Mild TBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser

Prenatal cocaine exposure and its impact on cognitive functions of offspring: a pathophysiological insight.

Science.gov (United States)

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.

Connective tissue alteration in abdominal wall hernia

DEFF Research Database (Denmark)

Henriksen, N A; Yadete, D H; Sørensen, Lars Tue

2011-01-01

The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations in abdom...

Does vasoactive intestinal polypeptide mediate the pathophysiology of bowel obstruction?

Science.gov (United States)

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.

Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal.

Science.gov (United States)

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.

[Current concepts in pathophysiology of CRPS I].

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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.

Contribution of Circulatory Disturbances in Subchondral Bone to the Pathophysiology of Osteoarthritis.

Science.gov (United States)

Aaron, Roy K; Racine, Jennifer; Dyke, Jonathan P

2017-08-01

This review describes the contributions of abnormal bone circulation to the pathophysiology of osteoarthritis. Combining dynamic imaging with MRI and PET with previous observations reveals that venous stasis and a venous outlet syndrome is most likely the key circulatory pathology associated with the initiation or progression of osteoarthritis. MRI and PET have revealed that venous outflow obstruction results in physicochemical changes in subchondral bone to which osteoblasts are responsive. The osteoblasts express an altered pattern of cytokines, many of which can serve as structural or signaling molecules contributing to both bone remodeling and cartilage degeneration. The patterns of circulatory changes are associated with alterations in the physicochemical environment of subchondral bone, including hypoxia. Osteoblast cytokines can transit the subchondral bone plate and calcified cartilage and communicate with chondrocytes.

Phenotype- and genotype-specific structural alterations in spasmodic dysphonia.

Science.gov (United States)

Bianchi, Serena; Battistella, Giovanni; Huddleston, Hailey; Scharf, Rebecca; Fleysher, Lazar; Rumbach, Anna F; Frucht, Steven J; Blitzer, Andrew; Ozelius, Laurie J; Simonyan, Kristina

2017-04-01

Spasmodic dysphonia is a focal dystonia characterized by involuntary spasms in the laryngeal muscles that occur selectively during speaking. Although hereditary trends have been reported in up to 16% of patients, the causative etiology of spasmodic dysphonia is unclear, and the influences of various phenotypes and genotypes on disorder pathophysiology are poorly understood. In this study, we examined structural alterations in cortical gray matter and white matter integrity in relationship to different phenotypes and putative genotypes of spasmodic dysphonia to elucidate the structural component of its complex pathophysiology. Eighty-nine patients with spasmodic dysphonia underwent high-resolution magnetic resonance imaging and diffusion-weighted imaging to examine cortical thickness and white matter fractional anisotropy in adductor versus abductor forms (distinct phenotypes) and in sporadic versus familial cases (distinct genotypes). Phenotype-specific abnormalities were localized in the left sensorimotor cortex and angular gyrus and the white matter bundle of the right superior corona radiata. Genotype-specific alterations were found in the left superior temporal gyrus, supplementary motor area, and the arcuate portion of the left superior longitudinal fasciculus. Our findings suggest that phenotypic differences in spasmodic dysphonia arise at the level of the primary and associative areas of motor control, whereas genotype-related pathophysiological mechanisms may be associated with dysfunction of regions regulating phonological and sensory processing. Identification of structural alterations specific to disorder phenotype and putative genotype provides an important step toward future delineation of imaging markers and potential targets for novel therapeutic interventions for spasmodic dysphonia. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

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

[Irritable bowel syndrome: New pathophysiological hypotheses and practical issues].

Science.gov (United States)

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 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.

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

Science.gov (United States)

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

2014-01-01

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

Medical Management of Endometriosis: Emerging Evidence Linking Inflammation to Disease Pathophysiology

Science.gov (United States)

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

Old and new aspects in the pathophysiology of pre-eclampsia

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

2015-09-01

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

Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

Science.gov (United States)

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.

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

Targeting autophagy in obesity: from pathophysiology to management.

Science.gov (United States)

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

2018-04-23

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

Imaging Alzheimer's disease pathophysiology with PET

Directory of Open Access Journals (Sweden)

Lucas Porcello Schilling

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

Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.

Science.gov (United States)

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

2016-06-01

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

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.

Pathophysiology of cervical myelopathy.

Science.gov (United States)

Baptiste, Darryl C; Fehlings, Michael G

2006-01-01

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

Transforming pathophysiology instruction through narrative pedagogy and Socratic questioning.

Science.gov (United States)

Rogge, M M

2001-01-01

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

Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.

Science.gov (United States)

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.

Reliability versus reproducibility

International Nuclear Information System (INIS)

Lautzenheiser, C.E.

1976-01-01

Defect detection and reproducibility of results are two separate but closely related subjects. It is axiomatic that a defect must be detected from examination to examination or reproducibility of results is very poor. On the other hand, a defect can be detected on each of subsequent examinations for higher reliability and still have poor reproducibility of results

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.

Cerebral Pathophysiology in Extracorporeal Membrane Oxygenation: Pitfalls in Daily Clinical Management

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.

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

Science.gov (United States)

Hammer, Heinz F

2014-02-01

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

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

Science.gov (United States)

Lee, Kang Nyeong; Lee, Oh Young

2014-01-01

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 1014 cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS. PMID:25083061

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome.

Science.gov (United States)

Lee, Kang Nyeong; Lee, Oh Young

2014-07-21

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.

The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects

Science.gov (United States)

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

The Need for Reproducibility

Energy Technology Data Exchange (ETDEWEB)

Robey, Robert W. [Los Alamos National Laboratory

2016-06-27

The purpose of this presentation is to consider issues of reproducibility, specifically it determines whether bitwise reproducible computation is possible, if computational research in DOE improves its publication process, and if reproducible results can be achieved apart from the peer review process?

Astroglial role in the pathophysiology of status epilepticus: an overview.

Science.gov (United States)

Vargas-Sánchez, Karina; Mogilevskaya, Maria; Rodríguez-Pérez, John; Rubiano, María G; Javela, José J; González-Reyes, Rodrigo E

2018-06-01

Status epilepticus is a medical emergency with elevated morbidity and mortality rates, and represents a leading cause of epilepsy-related deaths. Though status epilepticus can occur at any age, it manifests more likely in children and elderly people. Despite the common prevalence of epileptic disorders, a complete explanation for the mechanisms leading to development of self-limited or long lasting seizures (as in status epilepticus) are still lacking. Apart from neurons, research evidence suggests the involvement of immune and glial cells in epileptogenesis. Among glial cells, astrocytes represent an ideal target for the study of the pathophysiology of status epilepticus, due to their key role in homeostatic balance of the central nervous system. During status epilepticus, astroglial cells are activated by the presence of cytokines, damage associated molecular patterns and reactive oxygen species. The persistent activation of astrocytes leads to a decrease in glutamate clearance with a corresponding accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Moreover, major alterations in astrocytic gap junction coupling, inflammation and receptor expression, facilitate the generation of seizures. Astrocytes are also involved in dysregulation of inhibitory transmission in the central nervous system and directly participate in ionic homeostatic alterations during status epilepticus. In the present review, we focus on the functional and structural changes in astrocytic activity that participate in the development and maintenance of status epilepticus, with special attention on concurrent inflammatory alterations. We also include potential astrocytic treatment targets for status epilepticus.

Pathophysiology of gastro-esophageal reflux disease: a role for mucosa integrity?

Science.gov (United States)

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.

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.

Science.gov (United States)

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

2013-09-01

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

Abnormal function of monoamine oxidase-A in comorbid major depressive disorder and cardiovascular disease: pathophysiological and therapeutic implications (review).

Science.gov (United States)

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.

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....

Pathological and Pathophysiological Alterations in Temporal Lobe Structures After Mild Traumatic Brain Injury

Science.gov (United States)

2014-01-31

Acetylcholinesterase inhibition in the basolateral amygdala plays a key role in the induction of status epilepticus after soman exposure...alterations in the rat basolateral amygdala after soman-induced status epilepticus : Relation to anxiety-like behavior...INHIBITION IN THE BASOLA TERAL AMYGDALA PLAYS A KEY ROLE IN THE INDUCTION OF STATUS EPILEPTICUS AFTER SOMAN EXPOSURE. Prager EM, Aroniadou

Obesity: Pathophysiology and Intervention

Directory of Open Access Journals (Sweden)

Yi Zhang

2014-11-01

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

Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction

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

Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer’s Disease

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Peter J. Fried

2017-08-01

Full Text Available Background: Transcranial magnetic stimulation (TMS can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD increases, it is critical to understand their reproducibility (i.e., test–retest reliability in the populations of interest.Objective: Reproducibility of TMS measures was evaluated in older adults, including healthy, AD, and Type-2 diabetes mellitus (T2DM groups.Methods: Participants received two identical neurophysiological assessments within a year including motor thresholds, baseline motor evoked potentials (MEPs, short- and long-interval intracortical inhibition (SICI, LICI and intracortical facilitation (ICF, and MEP changes following intermittent theta-burst stimulation (iTBS. Cronbach’s α coefficients were calculated to assess reproducibility. Multiple linear regression analyses were used to investigate factors related to intraindividual variability.Results: Reproducibility was highest for motor thresholds, followed by baseline MEPs, SICI and LICI, and was lowest for ICF and iTBS aftereffects. The AD group tended to show higher reproducibility than T2DM or controls. Intraindividual variability of baseline MEPs was related to age and variability of RMT, while the intraindividual variability in post-iTBS measures was related to baseline MEP variability, intervisit duration, and Brain-derived neurotrophic factor (BDNF polymorphism.Conclusion: Increased reproducibility in AD may reflect pathophysiological declines in the efficacy of neuroplastic mechanisms. Reproducibility of iTBS aftereffects can be improved by keeping baseline MEPs consistent, controlling for BDNF genotype, and waiting at least a week between visits.Significance: These findings provide the first direct assessment of reproducibility of TMS measures in older clinical populations. Reproducibility coefficients may be used to adjust

Pathophysiology, Evaluation, and Treatment of Bloating

Science.gov (United States)

Gabbard, Scott L.; Crowell, Michael D.

2011-01-01

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

Highly Efficient and Reproducible Nonfullerene Solar Cells from Hydrocarbon Solvents

KAUST Repository

Wadsworth, Andrew; Ashraf, Raja; Abdelsamie, Maged; Pont, Sebastian; Little, Mark; Moser, Maximilian; Hamid, Zeinab; Neophytou, Marios; Zhang, Weimin; Amassian, Aram; Durrant, James R.; Baran, Derya; McCulloch, Iain

2017-01-01

With chlorinated solvents unlikely to be permitted for use in solution-processed organic solar cells in industry, there must be a focus on developing nonchlorinated solvent systems. Here we report high-efficiency devices utilizing a low-bandgap donor polymer (PffBT4T-2DT) and a nonfullerene acceptor (EH-IDTBR) from hydrocarbon solvents and without using additives. When mesitylene was used as the solvent, rather than chlorobenzene, an improved power conversion efficiency (11.1%) was achieved without the need for pre- or post-treatments. Despite altering the processing conditions to environmentally friendly solvents and room-temperature coating, grazing incident X-ray measurements confirmed that active layers processed from hydrocarbon solvents retained the robust nanomorphology obtained with hot-processed chlorinated solvents. The main advantages of hydrocarbon solvent-processed devices, besides the improved efficiencies, were the reproducibility and storage lifetime of devices. Mesitylene devices showed better reproducibility and shelf life up to 4000 h with PCE dropping by only 8% of its initial value.

Highly Efficient and Reproducible Nonfullerene Solar Cells from Hydrocarbon Solvents

KAUST Repository

Wadsworth, Andrew

2017-06-01

With chlorinated solvents unlikely to be permitted for use in solution-processed organic solar cells in industry, there must be a focus on developing nonchlorinated solvent systems. Here we report high-efficiency devices utilizing a low-bandgap donor polymer (PffBT4T-2DT) and a nonfullerene acceptor (EH-IDTBR) from hydrocarbon solvents and without using additives. When mesitylene was used as the solvent, rather than chlorobenzene, an improved power conversion efficiency (11.1%) was achieved without the need for pre- or post-treatments. Despite altering the processing conditions to environmentally friendly solvents and room-temperature coating, grazing incident X-ray measurements confirmed that active layers processed from hydrocarbon solvents retained the robust nanomorphology obtained with hot-processed chlorinated solvents. The main advantages of hydrocarbon solvent-processed devices, besides the improved efficiencies, were the reproducibility and storage lifetime of devices. Mesitylene devices showed better reproducibility and shelf life up to 4000 h with PCE dropping by only 8% of its initial value.

Alterations in cardiac autonomic control in spinal cord injury.

Science.gov (United States)

Biering-Sørensen, Fin; Biering-Sørensen, Tor; Liu, Nan; Malmqvist, Lasse; Wecht, Jill Maria; Krassioukov, Andrei

2018-01-01

A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury. Copyright © 2017 Elsevier B.V. All rights reserved.

The antiphospholipid syndrome and its pathophysiological rol in the normal pressure hydrocephalus

International Nuclear Information System (INIS)

Quintana, Gerardo; Restrepo, Jose Felix; Iglesias, Antonio

2008-01-01

The antiphospholipid syndrome (APS) is an autoimmune disease with diverse manifestations, mainly thrombotic, in any part of the body, where the central system nervous is frequently involved and course with prominent clinical manifestations. In addition to presenting thrombus, the disease can present psychiatric alterations and a variety of non thrombotic neurological syndromes. Our report describes the clinical characteristics of presentation, laboratory finding and treatment in two cases: the first one of normal pressure hydrocephalus (NPH) associated to neurosyphilis and the other one and APS secondary to systemic lupus erythematosus (SLE). We emphasize the potential pathogenic role of the antiphospholipid antibodies in the generation of such a neurological entity. We commented and discussed the possible pathophysiological mechanisms in which the presence of such auto-antibody

Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.

Directory of Open Access Journals (Sweden)

Mojgan Masoodi

Full Text Available Ulcerative colitis (UC is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.

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

Directory of Open Access Journals (Sweden)

Caroline L Smith

2005-10-01

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

Magni Reproducibility Example

DEFF Research Database (Denmark)

2016-01-01

An example of how to use the magni.reproducibility package for storing metadata along with results from a computational experiment. The example is based on simulating the Mandelbrot set.......An example of how to use the magni.reproducibility package for storing metadata along with results from a computational experiment. The example is based on simulating the Mandelbrot set....

Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

Science.gov (United States)

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

2016-04-01

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

An update on oxidative stress-mediated organ pathophysiology.

Science.gov (United States)

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

2013-12-01

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

Dry eye disease: pathophysiology, classification, and diagnosis.

Science.gov (United States)

Perry, Henry D

2008-04-01

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

Reproducibility of Computer-Aided Detection Marks in Digital Mammography

International Nuclear Information System (INIS)

Kim, Seung Ja; Moon, Woo Kyung; Cho, Nariya; Kim, Sun Mi; Im, Jung Gi; Cha, Joo Hee

2007-01-01

To evaluate the performance and reproducibility of a computeraided detection (CAD) system in mediolateral oblique (MLO) digital mammograms taken serially, without release of breast compression. A CAD system was applied preoperatively to the fulfilled digital mammograms of two MLO views taken without release of breast compression in 82 patients (age range: 33 83 years; mean age: 49 years) with previously diagnosed breast cancers. The total number of visible lesion components in 82 patients was 101: 66 masses and 35 microcalcifications. We analyzed the sensitivity and reproducibility of the CAD marks. The sensitivity of the CAD system for first MLO views was 71% (47/66) for masses and 80% (28/35) for microcalcifications. The sensitivity of the CAD system for second MLO views was 68% (45/66) for masses and 17% (6/35) for microcalcifications. In 84 ipsilateral serial MLO image sets (two patients had bilateral cancers), identical images, regardless of the existence of CAD marks, were obtained for 35% (29/84) and identical images with CAD marks were obtained for 29% (23/78). Identical images, regardless of the existence of CAD marks, for contralateral MLO images were 65% (52/80) and identical images with CAD marks were obtained for 28% (11/39). The reproducibility of CAD marks for the true positive masses in serial MLO views was 84% (42/50) and that for the true positive microcalcifications was 0% (0/34). The CAD system in digital mammograms showed a high sensitivity for detecting masses and microcalcifications. However, reproducibility of microcalcification marks was very low in MLO views taken serially without release of breast compression. Minute positional change and patient movement can alter the images and result in a significant effect on the algorithm utilized by the CAD for detecting microcalcifications

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

Science.gov (United States)

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

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

DEFF Research Database (Denmark)

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

2009-01-01

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

95th Anniversary of Pathophysiology in Croatia.

Science.gov (United States)

Kovač, Zdenko

2017-12-01

University level of Pathophysiology research and teaching in Croatia had started with the third year of Medical School of Zagreb in academic year 1919./20. Ever since, despite historical changes of the main university stake holder, the state of Croatia, Department of Pathophysiology development progressed and has made visible academic achievements, with a broader effect in medical community. The first 95 years of academic tradition and major achievements are shortly described in this paper. Professor Miroslav Mikuličić envisioned Pathophysiology in close relations with Pharmacology and made the pioneering steps of establishing the "double" department at Šalata. His group was academically very pro-active, with strong international scientific participation and recruitment of professionals. The group published the first voluminous textbook of Pharmacology and Pathophysiology, in Croatian. In fifties, professor Pavao Sokolić established clinical pathophysiology within the Hospital Centre at Rebro. Out of "double" department two new departments were founded, the Pathophysiology one was completed with the clinical ward. That institutional move from Šalata hill to the Rebro hill was a necessary gigantic step and a prerequisite for the proper further development. It was in accordance with the concept of the Mikuličić's program of Pathophysiology from 1917. Pavao Sokolić has been remembered for his visions, deep insights into etiopathogenesis, ability to transfer knowledge and friendly relations to students. Sharp intellectual power, emanating charisma, academic erudition and unique clinical competencies made the legendary image of the "Teacher" - as students used to refer to him with admiration. He was second to no one when complex patient issues were to be resolved. Clinical Hospital Centre Zagreb and his Department at Rebro have become a referral point to whom to go to despair. Students recognized in their Teacher the landmark of Croatian medicine, which made a

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

Science.gov (United States)

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

2015-01-01

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

Pathophysiology of gastroesophageal reflux disease

NARCIS (Netherlands)

Boeckxstaens, Guy E.; Rohof, Wout O.

2014-01-01

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

Pathophysiological mechanisms of insulin resistance

NARCIS (Netherlands)

Brands, M.

2013-01-01

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

Reproducibility of a 3-dimensional gyroscope in measuring shoulder anteflexion and abduction

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Penning Ludo I F

2012-07-01

Full Text Available Abstract Background Few studies have investigated the use of a 3-dimensional gyroscope for measuring the range of motion (ROM in the impaired shoulder. Reproducibility of digital inclinometer and visual estimation is poor. This study aims to investigate the reproducibility of a tri axial gyroscope in measurement of anteflexion, abduction and related rotations in the impaired shoulder. Methods Fifty-eight patients with either subacromial impingement (27 or osteoarthritis of the shoulder (31 participated. Active anteflexion, abduction and related rotations were measured with a tri axial gyroscope according to a test retest protocol. Severity of shoulder impairment and patient perceived pain were assessed by the Disability of Arm Shoulder and Hand score (DASH and the Visual Analogue Scale (VAS. VAS scores were recorded before and after testing. Results In two out of three hospitals patients with osteoarthritis (n = 31 were measured, in the third hospital patients with subacromial impingement (n = 27. There were significant differences among hospitals for the VAS and DASH scores measured before and after testing. The mean differences between the test and retest means for anteflexion were −6 degrees (affected side, 9 (contralateral side and for abduction 15 degrees (affected side and 10 degrees (contralateral side. Bland & Altman plots showed that the confidence intervals for the mean differences fall within −6 up to 15 degrees, individual test - retest differences could exceed these limits. A simulation according to ‘Generalizability Theory’ produces very good coefficients for anteflexion and related rotation as a comprehensive measure of reproducibility. Optimal reproducibility is achieved with 2 repetitions for anteflexion. Conclusions Measurements were influenced by patient perceived pain. Differences in VAS and DASH might be explained by different underlying pathology. These differences in shoulder pathology however did not alter

Assessing pathophysiology of cancer anorexia.

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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.

Convergence of neuro-endocrine-immune pathways in the pathophysiology of irritable bowel syndrome.

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Buckley, Maria M; O'Mahony, Siobhain M; O'Malley, Dervla

2014-07-21

Disordered signalling between the brain and the gut are generally accepted to underlie the functional bowel disorder, irritable bowel syndrome (IBS). However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. This common gastrointestinal disorder is characterised by alterations in bowel habit such as diarrhoea and/or constipation, bloating and abdominal pain, and symptom exacerbation has been linked with periods of stress, both psychosocial and infection-related. Indeed, a high level of comorbidity exists between IBS and stress-related mood disorders such as anxiety and depression. Moreover, studies have observed alterations in autonomic output and neuro-endocrine signalling in IBS patients. Accumulating evidence indicates that a maladaptive stress response, probably mediated by the stress hormone, corticotropin-releasing factor contributes to the initiation, persistence and severity of symptom flares. Other risk factors for developing IBS include a positive family history, childhood trauma, dietary factors and prior gastrointestinal infection. An emerging role has been attributed to the importance of immune factors in the pathophysiology of IBS with evidence of altered cytokine profiles and increased levels of mucosal immune cells. These factors have also been shown to have direct effects on neural signalling. This review discusses how pathological changes in neural, immune and endocrine pathways, and communication between these systems, contribute to symptom flares in IBS.

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

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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

Pathophysiology and pathological findings of heatstroke in dogs

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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

Pathophysiological hypoxia affects the redox state and IL-2 signalling of human CD4+ T cells and concomitantly impairs survival and proliferation.

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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.

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

Pathophysiology of Glucocorticoid Signaling.

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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.

Reproducibility in a multiprocessor system

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Bellofatto, Ralph A; Chen, Dong; Coteus, Paul W; Eisley, Noel A; Gara, Alan; Gooding, Thomas M; Haring, Rudolf A; Heidelberger, Philip; Kopcsay, Gerard V; Liebsch, Thomas A; Ohmacht, Martin; Reed, Don D; Senger, Robert M; Steinmacher-Burow, Burkhard; Sugawara, Yutaka

2013-11-26

Fixing a problem is usually greatly aided if the problem is reproducible. To ensure reproducibility of a multiprocessor system, the following aspects are proposed; a deterministic system start state, a single system clock, phase alignment of clocks in the system, system-wide synchronization events, reproducible execution of system components, deterministic chip interfaces, zero-impact communication with the system, precise stop of the system and a scan of the system state.

A Unified Pathophysiological Construct of Diabetes and its Complications.

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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.

Standing Together for Reproducibility in Large-Scale Computing: Report on reproducibility@XSEDE

OpenAIRE

James, Doug; Wilkins-Diehr, Nancy; Stodden, Victoria; Colbry, Dirk; Rosales, Carlos; Fahey, Mark; Shi, Justin; Silva, Rafael F.; Lee, Kyo; Roskies, Ralph; Loewe, Laurence; Lindsey, Susan; Kooper, Rob; Barba, Lorena; Bailey, David

2014-01-01

This is the final report on reproducibility@xsede, a one-day workshop held in conjunction with XSEDE14, the annual conference of the Extreme Science and Engineering Discovery Environment (XSEDE). The workshop's discussion-oriented agenda focused on reproducibility in large-scale computational research. Two important themes capture the spirit of the workshop submissions and discussions: (1) organizational stakeholders, especially supercomputer centers, are in a unique position to promote, enab...

Theory of reproducing kernels and applications

CERN Document Server

Saitoh, Saburou

2016-01-01

This book provides a large extension of the general theory of reproducing kernels published by N. Aronszajn in 1950, with many concrete applications. In Chapter 1, many concrete reproducing kernels are first introduced with detailed information. Chapter 2 presents a general and global theory of reproducing kernels with basic applications in a self-contained way. Many fundamental operations among reproducing kernel Hilbert spaces are dealt with. Chapter 2 is the heart of this book. Chapter 3 is devoted to the Tikhonov regularization using the theory of reproducing kernels with applications to numerical and practical solutions of bounded linear operator equations. In Chapter 4, the numerical real inversion formulas of the Laplace transform are presented by applying the Tikhonov regularization, where the reproducing kernels play a key role in the results. Chapter 5 deals with ordinary differential equations; Chapter 6 includes many concrete results for various fundamental partial differential equations. In Chapt...

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.

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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.

Hypertension in women--pathophysiological and clinical aspects.

Science.gov (United States)

Erdine, Serap; Arslan, Eren; Olszanecka, Agnieszka

2012-01-01

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

From morphology to clinical pathophysiology: multiphoton fluorescence lifetime imaging at patients' bedside

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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.

MicroRNAs take part in pathophysiology and pathogenesis of Male Pattern Baldness.

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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.

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

Science.gov (United States)

Makris, Konstantinos; Spanou, Loukia

2016-05-01

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

Pancreatitis in dogs and cats: definitions and pathophysiology.

Science.gov (United States)

Watson, P

2015-01-01

Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. © 2015 British Small Animal Veterinary Association.

Knee joint pain potentially due to bone alterations in a knee osteoarthritis patient.

Science.gov (United States)

Komatsu, Masatoshi; Nakamura, Yukio; Kamimura, Mikio; Uchiyama, Shigeharu; Mukaiyama, Keijiro; Ikegami, Shota; Kato, Hiroyuki

2014-12-01

Osteoarthritis (OA) is the leading cause of musculoskeletal pain and functional disability worldwide. However, the etiology of this condition is still largely unknown. We report the clinical course of an elderly man with knee OA. Plain radiographs and MRI examinations performed during follow-up suggested that the pathophysiology of the patient's knee OA and joint pain may have been primarily due to bone alterations.

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.

Frequency-Dependent Altered Functional Connections of Default Mode Network in Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Youjun Li

2017-08-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder associated with the progressive dysfunction of cognitive ability. Previous research has indicated that the default mode network (DMN is closely related to cognition and is impaired in Alzheimer’s disease. Because recent studies have shown that different frequency bands represent specific physiological functions, DMN functional connectivity studies of the different frequency bands based on resting state fMRI (RS-fMRI data may provide new insight into AD pathophysiology. In this study, we explored the functional connectivity based on well-defined DMN regions of interest (ROIs from the five frequency bands: slow-5 (0.01–0.027 Hz, slow-4 (0.027–0.073 Hz, slow-3 (0.073–0.198 Hz, slow-2 (0.198–0.25 Hzs and standard low-frequency oscillations (LFO (0.01–0.08 Hz. We found that the altered functional connectivity patterns are mainly in the frequency band of slow-5 and slow-4 and that the decreased connections are long distance, but some relatively short connections are increased. In addition, the altered functional connections of the DMN in AD are frequency dependent and differ between the slow-5 and slow-4 bands. Mini-Mental State Examination scores were significantly correlated with the altered functional connectivity patterns in the slow-5 and slow-4 bands. These results indicate that frequency-dependent functional connectivity changes might provide potential biomarkers for AD pathophysiology.

[Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

Science.gov (United States)

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.

Reproducibility principles, problems, practices, and prospects

CERN Document Server

Maasen, Sabine

2016-01-01

Featuring peer-reviewed contributions from noted experts in their fields of research, Reproducibility: Principles, Problems, Practices, and Prospects presents state-of-the-art approaches to reproducibility, the gold standard sound science, from multi- and interdisciplinary perspectives. Including comprehensive coverage for implementing and reflecting the norm of reproducibility in various pertinent fields of research, the book focuses on how the reproducibility of results is applied, how it may be limited, and how such limitations can be understood or even controlled in the natural sciences, computational sciences, life sciences, social sciences, and studies of science and technology. The book presents many chapters devoted to a variety of methods and techniques, as well as their epistemic and ontological underpinnings, which have been developed to safeguard reproducible research and curtail deficits and failures. The book also investigates the political, historical, and social practices that underlie repro...

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.

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.

DMPD: Pathophysiological roles of interleukin-18 in inflammatory liver diseases. [Dynamic Macrophage Pathway CSML Database

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

Epigenetic Alterations in Fanconi Anaemia: Role in Pathophysiology and Therapeutic Potential.

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Hélio Belo

Full Text Available Fanconi anaemia (FA is an inherited disorder characterized by chromosomal instability. The phenotype is variable, which raises the possibility that it may be affected by other factors, such as epigenetic modifications. These play an important role in oncogenesis and may be pharmacologically manipulated. Our aim was to explore whether the epigenetic profiles in FA differ from non-FA individuals and whether these could be manipulated to alter the disease phenotype. We compared expression of epigenetic genes and DNA methylation profile of tumour suppressor genes between FA and normal samples. FA samples exhibited decreased expression levels of genes involved in epigenetic regulation and hypomethylation in the promoter regions of tumour suppressor genes. Treatment of FA cells with histone deacetylase inhibitor Vorinostat increased the expression of DNM3Tβ and reduced the levels of CIITA and HDAC9, PAK1, USP16, all involved in different aspects of epigenetic and immune regulation. Given the ability of Vorinostat to modulate epigenetic genes in FA patients, we investigated its functional effects on the FA phenotype. This was assessed by incubating FA cells with Vorinostat and quantifying chromosomal breaks induced by DNA cross-linking agents. Treatment of FA cells with Vorinostat resulted in a significant reduction of aberrant cells (81% on average. Our results suggest that epigenetic mechanisms may play a role in oncogenesis in FA. Epigenetic agents may be helpful in improving the phenotype of FA patients, potentially reducing tumour incidence in this population.

The pathophysiology of bronchiectasis

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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

GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

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Guillermo Gonzalez-Burgos

2011-01-01

Full Text Available Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

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Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

Testing Reproducibility in Earth Sciences

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Church, M. A.; Dudill, A. R.; Frey, P.; Venditti, J. G.

2017-12-01

Reproducibility represents how closely the results of independent tests agree when undertaken using the same materials but different conditions of measurement, such as operator, equipment or laboratory. The concept of reproducibility is fundamental to the scientific method as it prevents the persistence of incorrect or biased results. Yet currently the production of scientific knowledge emphasizes rapid publication of previously unreported findings, a culture that has emerged from pressures related to hiring, publication criteria and funding requirements. Awareness and critique of the disconnect between how scientific research should be undertaken, and how it actually is conducted, has been prominent in biomedicine for over a decade, with the fields of economics and psychology more recently joining the conversation. The purpose of this presentation is to stimulate the conversation in earth sciences where, despite implicit evidence in widely accepted classifications, formal testing of reproducibility is rare.As a formal test of reproducibility, two sets of experiments were undertaken with the same experimental procedure, at the same scale, but in different laboratories. Using narrow, steep flumes and spherical glass beads, grain size sorting was examined by introducing fine sediment of varying size and quantity into a mobile coarse bed. The general setup was identical, including flume width and slope; however, there were some variations in the materials, construction and lab environment. Comparison of the results includes examination of the infiltration profiles, sediment mobility and transport characteristics. The physical phenomena were qualitatively reproduced but not quantitatively replicated. Reproduction of results encourages more robust research and reporting, and facilitates exploration of possible variations in data in various specific contexts. Following the lead of other fields, testing of reproducibility can be incentivized through changes to journal

Alterations in membrane trafficking and pathophysiological implications in lysosomal storage disorders.

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Kuech, Eva-Maria; Brogden, Graham; Naim, Hassan Y

2016-11-01

Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes. The progressive accumulation of uncleaved substrates occurs in multiple organs and finally causes a broad spectrum of different pathologies including visceral, neurological, skeletal and hematologic manifestations. Besides deficient lysosomal enzymes and transporters other defects may lead to lysosomal storage disorders, including activator defects, membrane defects or defects in modifier proteins. In this review we concentrate on four different lysosomal storage disorders: Niemann-Pick type C, Fabry disease, Gaucher disease and Pompe disease. While the last three are caused by defective lysosomal hydrolases, Niemann-Pick type C is caused by the inability to export LDL-derived cholesterol out of the lysosome. We want to emphasise potential implications of membrane trafficking defects on the pathology of these diseases, as many mutations interfere with correct lysosomal protein trafficking and alter cellular lipid homeostasis. Current therapeutic strategies are summarised, including substrate reduction therapy as well as pharmacological chaperone therapy which directly aim to improve folding and lysosomal transport of misfolded mutant proteins. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Pathophysiology and management of pediatric ascites.

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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.

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

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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

Current challenges and problems in teaching pathophysiology in Ukraine - another reaction to Churilov's paper.

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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.

Osteocyte Alterations Induce Osteoclastogenesis in an In Vitro Model of Gaucher Disease

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Constanza Bondar

2017-01-01

Full Text Available Gaucher disease (GD is caused by mutations in the glucosylceramidase β (GBA 1 gene that confer a deficient level of activity of glucocerebrosidase (GCase. This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood. The bone tissue homeostasis is maintained by a balance between resorption of old bone by osteoclasts and new bone formation by osteoblasts. A central player in this balance is the osteocyte as it controls both processes. We studied the involvement of osteocytes in an in vitro chemical model of Gaucher disease. The osteocyte cell line MLO-Y4 was exposed to conduritol-β-epoxide (CBE, an inhibitor of GCase, for a period of 7, 14 and 21 days. Conditioned media from CBE-treated osteocytes was found to induce osteoclast differentiation. GCase inhibition caused alterations in Cx43 expression and distribution pattern and an increase in osteocyte apoptosis. Osteoclast differentiation involved osteocyte apoptotic bodies, receptor activator of nuclear factor κ-B ligand (RANKL and soluble factors. Thus, our results indicate that osteocytes may have a role to play in the bone pathophysiology of GD.

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

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Ellis, Demetrius

2015-01-01

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

Evaluation of the color stability of two techniquesfor reproducing artificial irides after microwave polymerization

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Marcelo Coelho Goiato

2011-06-01

Full Text Available The use of ocular prostheses for ophthalmic patients aims to rebuild facial aesthetics and provide an artificial substitute to the visual organ. Natural intemperate conditions promote discoloration of artificial irides and many studies have attempted to produce irides with greater chromatic paint durability using different paint materials. OBJECTIVES: The present study evaluated the color stability of artificial irides obtained with two techniques (oil painting and digital image and submitted to microwave polymerization. MATERIAL AND METHODS: Forty samples were fabricated simulating ocular prostheses. each sample was constituted by one disc of acrylic resin N1 and one disc of colorless acrylic resin with the iris interposed between the discs. The irides in brown and blue color were obtained by oil painting or digital image. The color stability was determined by a reflection spectrophotometer and measurements were taken before and after microwave polymerization. Statistical analysis of the techniques for reproducing artificial irides was performed by applying the normal data distribution test followed by 2-way ANOVA and Tukey HSD test (α=.05. RESULTS: Chromatic alterations occurred in all specimens and statistically significant differences were observed between the oil-painted samples and those obtained by digital imaging. There was no statistical difference between the brown and blue colors. Independently of technique, all samples suffered color alterations after microwave polymerization. CONCLUSION: The digital imaging technique for reproducing irides presented better color stability after microwave polymerization.

Pathophysiology of diurnal drooling in Parkinson's disease

NARCIS (Netherlands)

Kalf, J.G.; Munneke, M.; Engel-Hoek, L. van den; Swart, B.J.M. de; Borm, G.F.; Bloem, B.R.; Zwarts, M.J.

2011-01-01

Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

Repeatability, Reproducibility and Standardisation of a Laser Doppler Imaging Technique for the Evaluation of Normal Mouse Hindlimb Perfusion

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Arturo Brunetti

2012-12-01

Full Text Available Background. Preclinical perfusion studies are useful for the improvement of diagnosis and therapy in dermatologic, cardiovascular and rheumatic human diseases. The Laser Doppler Perfusion Imaging (LDPI technique has been used to evaluate superficial alterations of the skin microcirculation in surgically induced murine hindlimb ischemia. We assessed the reproducibility and the accuracy of LDPI acquisitions and identified several critical factors that could affect LDPI measurements in mice. Methods. Twenty mice were analysed. Statistical standardisation and a repeatability and reproducibility analysis were performed on mouse perfusion signals with respect to differences in body temperature, the presence or absence of hair, the type of anaesthesia used for LDPI measurements and the position of the mouse body. Results. We found excellent correlations among measurements made by the same operator (i.e., repeatability under the same experimental conditions and by two different operators (i.e., reproducibility. A Bland-Altman analysis showed the absence of bias in repeatability (p = 0.29 or reproducibility (p = 0.89. The limits of agreement for repeatability were –0.357 and –0.033, and for reproducibility, they were –0.270 and 0.238. Significant differences in perfusion values were observed in different experimental groups. Conclusions. Different experimental conditions must be considered as a starting point for the evaluation of new drugs and strategic therapies.

Reproducing Epidemiologic Research and Ensuring Transparency.

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Coughlin, Steven S

2017-08-15

Measures for ensuring that epidemiologic studies are reproducible include making data sets and software available to other researchers so they can verify published findings, conduct alternative analyses of the data, and check for statistical errors or programming errors. Recent developments related to the reproducibility and transparency of epidemiologic studies include the creation of a global platform for sharing data from clinical trials and the anticipated future extension of the global platform to non-clinical trial data. Government agencies and departments such as the US Department of Veterans Affairs Cooperative Studies Program have also enhanced their data repositories and data sharing resources. The Institute of Medicine and the International Committee of Medical Journal Editors released guidance on sharing clinical trial data. The US National Institutes of Health has updated their data-sharing policies. In this issue of the Journal, Shepherd et al. (Am J Epidemiol. 2017;186:387-392) outline a pragmatic approach for reproducible research with sensitive data for studies for which data cannot be shared because of legal or ethical restrictions. Their proposed quasi-reproducible approach facilitates the dissemination of statistical methods and codes to independent researchers. Both reproducibility and quasi-reproducibility can increase transparency for critical evaluation, further dissemination of study methods, and expedite the exchange of ideas among researchers. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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....

A Simple and Reproducible Method to Prepare Membrane Samples from Freshly Isolated Rat Brain Microvessels.

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Brzica, Hrvoje; Abdullahi, Wazir; Reilly, Bianca G; Ronaldson, Patrick T

2018-05-07

The blood-brain barrier (BBB) is a dynamic barrier tissue that responds to various pathophysiological and pharmacological stimuli. Such changes resulting from these stimuli can greatly modulate drug delivery to the brain and, by extension, cause considerable challenges in the treatment of central nervous system (CNS) diseases. Many BBB changes that affect pharmacotherapy, involve proteins that are localized and expressed at the level of endothelial cells. Indeed, such knowledge on BBB physiology in health and disease has sparked considerable interest in the study of these membrane proteins. From a basic science research standpoint, this implies a requirement for a simple but robust and reproducible method for isolation of microvessels from brain tissue harvested from experimental animals. In order to prepare membrane samples from freshly isolated microvessels, it is essential that sample preparations be enriched in endothelial cells but limited in the presence of other cell types of the neurovascular unit (i.e., astrocytes, microglia, neurons, pericytes). An added benefit is the ability to prepare samples from individual animals in order to capture the true variability of protein expression in an experimental population. In this manuscript, details regarding a method that is utilized for isolation of rat brain microvessels and preparation of membrane samples are provided. Microvessel enrichment, from samples derived, is achieved by using four centrifugation steps where dextran is included in the sample buffer. This protocol can easily be adapted by other laboratories for their own specific applications. Samples generated from this protocol have been shown to yield robust experimental data from protein analysis experiments that can greatly aid the understanding of BBB responses to physiological, pathophysiological, and pharmacological stimuli.

Blended Learning Versus Traditional Lecture in Introductory Nursing Pathophysiology Courses.

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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.

Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease

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Jian-Jun Liu

2017-05-01

Discussion: DKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.

Enacting the International/Reproducing Eurocentrism

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Zeynep Gülşah Çapan

Full Text Available Abstract This article focuses on the way in which Eurocentric conceptualisations of the ‘international’ are reproduced in different geopolitical contexts. Even though the Eurocentrism of International Relations has received growing attention, it has predominantly been concerned with unearthing the Eurocentrism of the ‘centre’, overlooking its varied manifestations in other geopolitical contexts. The article seeks to contribute to discussions about Eurocentrism by examining how different conceptualisations of the international are at work at a particular moment, and how these conceptualisations continue to reproduce Eurocentrism. It will focus on the way in which Eurocentric designations of spatial and temporal hierarchies were reproduced in the context of Turkey through a reading of how the ‘Gezi Park protests’ of 2013 and ‘Turkey’ itself were written into the story of the international.

Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

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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.

Altered pharyngeal muscles in Parkinson disease.

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Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

2012-06-01

Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

Plants altering hormonal milieu: A review

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Prashant Tiwari

2017-02-01

Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

Plants altering hormonal milieu: A review

Directory of Open Access Journals (Sweden)

Prashant Tiwari

2017-01-01

Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

Reproducibility of somatosensory spatial perceptual maps.

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Steenbergen, Peter; Buitenweg, Jan R; Trojan, Jörg; Veltink, Peter H

2013-02-01

Various studies have shown subjects to mislocalize cutaneous stimuli in an idiosyncratic manner. Spatial properties of individual localization behavior can be represented in the form of perceptual maps. Individual differences in these maps may reflect properties of internal body representations, and perceptual maps may therefore be a useful method for studying these representations. For this to be the case, individual perceptual maps need to be reproducible, which has not yet been demonstrated. We assessed the reproducibility of localizations measured twice on subsequent days. Ten subjects participated in the experiments. Non-painful electrocutaneous stimuli were applied at seven sites on the lower arm. Subjects localized the stimuli on a photograph of their own arm, which was presented on a tablet screen overlaying the real arm. Reproducibility was assessed by calculating intraclass correlation coefficients (ICC) for the mean localizations of each electrode site and the slope and offset of regression models of the localizations, which represent scaling and displacement of perceptual maps relative to the stimulated sites. The ICCs of the mean localizations ranged from 0.68 to 0.93; the ICCs of the regression parameters were 0.88 for the intercept and 0.92 for the slope. These results indicate a high degree of reproducibility. We conclude that localization patterns of non-painful electrocutaneous stimuli on the arm are reproducible on subsequent days. Reproducibility is a necessary property of perceptual maps for these to reflect properties of a subject's internal body representations. Perceptual maps are therefore a promising method for studying body representations.

Crossroads between peripheral atherosclerosis, western-type diet and skeletal muscle pathophysiology: emphasis on apolipoprotein E deficiency and peripheral arterial disease.

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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.

Reproducibility of surface roughness in reaming

DEFF Research Database (Denmark)

Müller, Pavel; De Chiffre, Leonardo

An investigation on the reproducibility of surface roughness in reaming was performed to document the applicability of this approach for testing cutting fluids. Austenitic stainless steel was used as a workpiece material and HSS reamers as cutting tools. Reproducibility of the results was evaluat...

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

Science.gov (United States)

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

2015-01-01

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

Pathophysiology of spontaneous venous gas embolism

Science.gov (United States)

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

1991-01-01

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

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)

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

Directory of Open Access Journals (Sweden)

Hyunjoo Park

2013-03-01

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

The pathophysiology of lifelong premature ejaculation

Science.gov (United States)

2016-01-01

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

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: DEFINITION, EPIDEMIOLOGY, PATHOPHYSIOLOGY, CLINICAL PICTURE AND TREATMENT (GOLD 2013

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...

Central voice production and pathophysiology of spasmodic dysphonia.

Science.gov (United States)

Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

2018-01-01

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

Reproducibility of central lumbar vertebral BMD

International Nuclear Information System (INIS)

Chan, F.; Pocock, N.; Griffiths, M.; Majerovic, Y.; Freund, J.

1997-01-01

Full text: Lumbar vertebral bone mineral density (BMD) using dual X-ray absorptiometry (DXA) has generally been calculated from a region of interest which includes the entire vertebral body. Although this region excludes part of the transverse processes, it does include the outer cortical shell of the vertebra. Recent software has been devised to calculate BMD in a central vertebral region of interest which excludes the outer cortical envelope. Theoretically this area may be more sensitive to detecting osteoporosis which affects trabecular bone to a greater extent than cortical bone. Apart from the sensitivity of BMD estimation, the reproducibility of any measurement is important owing to the slow rate of change of bone mass. We have evaluated the reproducibility of this new vertebral region of interest in 23 women who had duplicate lumbar spine DXA scans performed on the same day. The patients were repositioned between each measurement. Central vertebral analysis was performed for L2-L4 and the reproducibility of area, bone mineral content (BMC) and BMD calculated as the coefficient of variation; these values were compared with those from conventional analysis. Thus we have shown that the reproducibility of the central BMD is comparable to the conventional analysis which is essential if this technique is to provide any additional clinical data. The reasons for the decrease in reproducibility of the area and hence BMC requires further investigation

Reproducibility of brain ADC histograms

International Nuclear Information System (INIS)

Steens, S.C.A.; Buchem, M.A. van; Admiraal-Behloul, F.; Schaap, J.A.; Hoogenraad, F.G.C.; Wheeler-Kingshott, C.A.M.; Tofts, P.S.; Cessie, S. le

2004-01-01

The aim of this study was to assess the effect of differences in acquisition technique on whole-brain apparent diffusion coefficient (ADC) histogram parameters, as well as to assess scan-rescan reproducibility. Diffusion-weighted imaging (DWI) was performed in 7 healthy subjects with b-values 0-800, 0-1000, and 0-1500 s/mm 2 and fluid-attenuated inversion recovery (FLAIR) DWI with b-values 0-1000 s/mm 2 . All sequences were repeated with and without repositioning. The peak location, peak height, and mean ADC of the ADC histograms and mean ADC of a region of interest (ROI) in the white matter were compared using paired-sample t tests. Scan-rescan reproducibility was assessed using paired-sample t tests, and repeatability coefficients were reported. With increasing maximum b-values, ADC histograms shifted to lower values, with an increase in peak height (p<0.01). With FLAIR DWI, the ADC histogram shifted to lower values with a significantly higher, narrower peak (p<0.01), although the ROI mean ADC showed no significant differences. For scan-rescan reproducibility, no significant differences were observed. Different DWI pulse sequences give rise to different ADC histograms. With a given pulse sequence, however, ADC histogram analysis is a robust and reproducible technique. Using FLAIR DWI, the partial-voluming effect of cerebrospinal fluid, and thus its confounding effect on histogram analyses, can be reduced

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

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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

An update on the pathophysiology and management of polycystic liver disease.

Science.gov (United States)

Wong, May Yw; McCaughan, Geoffrey W; Strasser, Simone I

2017-06-01

Polycystic liver disease (PLD) is characterized by the presence of multiple cholangiocyte-derived hepatic cysts that progressively replace liver tissue. They are classified as an inherited ciliopathy /cholangiopathy as pathology exists at the level of the primary cilia of cholangiocytes. Aberrant expression of the proteins in primary cilia can impair their structures and functions, thereby promoting cystogenesis. Areas covered: This review begins by looking at the epidemiology of PLD and its natural history. It then describes the pathophysiology and corresponding potential treatment strategies for PLD. Expert commentary: Traditionally, therapies for symptomatic PLD have been limited to symptomatic management and surgical interventions. Such techniques are not completely effective, do not alter the natural history of the disease, and are linked with high rate of re-accumulation of cysts. As a result, there has been a push for drugs targeted at abnormal cellular signaling cascades to address deregulated proliferation, cell dedifferentiation, apoptosis and fluid secretion. Currently, the only available drug treatments that halt disease progression and improve quality of life in PLD patients are somatostatin analogues. Numerous preclinical studies suggest that targeting components of the signaling pathways that influence cyst development can ameliorate growth of hepatic cysts.

The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome.

Science.gov (United States)

El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

2017-02-01

The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

Unravelling narcolepsy : from pathophysiology to measuring treatment effects

NARCIS (Netherlands)

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,

Optical coherence tomography in retinitis pigmentosa: reproducibility and capacity to detect macular and retinal nerve fiber layer thickness alterations.

Science.gov (United States)

Garcia-Martin, Elena; Pinilla, Isabel; Sancho, Eva; Almarcegui, Carmen; Dolz, Isabel; Rodriguez-Mena, Diego; Fuertes, Isabel; Cuenca, Nicolas

2012-09-01

To evaluate the ability of time-domain and Fourier-domain optical coherence tomographies (OCTs) to detect macular and retinal nerve fiber layer atrophies in retinitis pigmentosa (RP). To test the intrasession reproducibility using three OCT instruments (Stratus, Cirrus, and Spectralis). Eighty eyes of 80 subjects (40 RP patients and 40 healthy subjects) underwent a visual field examination, together with 3 macular scans and 3 optic disk evaluations by the same experienced examiner using 3 OCT instruments. Differences between healthy and RP eyes were compared. The relationship between measurements with each OCT instrument was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. Macular and retinal nerve fiber layer atrophies were detected in RP patients for all OCT parameters. Macular and retinal nerve fiber layer thicknesses, as determined by the different OCTs, were correlated but significantly different (P < 0.05). Reproducibility was moderately high using Stratus, good using Cirrus and Spectralis, and excellent using the Tru-track technology of Spectralis. In RP eyes, measurements showed higher variability compared with healthy eyes. Differences in thickness measurements existed between OCT instruments, despite there being a high degree of correlation. Fourier-domain OCT can be considered a valid and repeatability technique to detect retinal nerve fiber layer atrophy in RP patients.

Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms.

Science.gov (United States)

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.

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

Science.gov (United States)

Ellis, Demetrius

2016-01-01

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

Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

Science.gov (United States)

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

Narcolepsy: Pathophysiology and Neuropsychological Changes

Directory of Open Access Journals (Sweden)

Angela Naumann

2003-01-01

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

Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

Directory of Open Access Journals (Sweden)

Emilio L. Streck

2014-05-01

Full Text Available Introduction: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. Methodology: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. Results: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. Conclusions: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects.

Diagnosing the pathophysiologic mechanisms of nocturnal polyuria.

Science.gov (United States)

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.

Retinal vein occlusion: pathophysiology and treatment options

OpenAIRE

Karia, Niral

2010-01-01

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

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

Examination of reproducibility in microbiological degredation experiments

DEFF Research Database (Denmark)

Sommer, Helle Mølgaard; Spliid, Henrik; Holst, Helle

1998-01-01

Experimental data indicate that certain microbiological degradation experiments have a limited reproducibility. Nine identical batch experiments were carried out on 3 different days to examine reproducibility. A pure culture, isolated from soil, grew with toluene as the only carbon and energy...... source. Toluene was degraded under aerobic conditions at a constant temperature of 28 degreesC. The experiments were modelled by a Monod model - extended to meet the air/liquid system, and the parameter values were estimated using a statistical nonlinear estimation procedure. Model reduction analysis...... resulted in a simpler model without the biomass decay term. In order to test for model reduction and reproducibility of parameter estimates, a likelihood ratio test was employed. The limited reproducibility for these experiments implied that all 9 batch experiments could not be described by the same set...

Pathophysiology of diurnal drooling in Parkinson’s disease

NARCIS (Netherlands)

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

Cardiometabolic Risk and Female Sexuality-Part I. Risk Factors and Potential Pathophysiological Underpinnings for Female Vasculogenic Sexual Dysfunction Syndromes.

Science.gov (United States)

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

Altered cortical causality after remifentanil administration in healthy volunteers

DEFF Research Database (Denmark)

Khodayari-Rostamabad, Ahmad; Graversen, Carina; Olesen, Soren S

2014-01-01

and after infusion of remifentanil and placebo. Additionally, to assess cognitive function and analgesic effect, continuous reaction time (CRT) and bone pressure and heat pain were assessed, respectively. The causality information was extracted from the EEG by phase slope index (PSI). Among the features...... being reproducible between the two baseline recordings, several PSI features were altered by remifentanil administration in comparison to placebo. Furthermore, several of the PSI features altered by remifentanil were correlated to changes in both CRT and pain scores. The results indicate...... that remifentanil administration influence the information flow between several brain areas. Hence, the EEG causality approach offers the potential to assist in deciphering the cortical effects of remifentanil administration....

Metabolic and vascular pattern in medial pterygoid muscle is altered by chronic stress in an animal model of hypodontia.

Science.gov (United States)

Fernández, Rodrigo Alberto Restrepo; Pereira, Yamba Carla Lara; Iyomasa, Daniela Mizusaki; Calzzani, Ricardo Alexandre; Leite-Panissi, Christie Ramos Andrade; Iyomasa, Mamie Mizusaki; Nascimento, Glauce Crivelaro

2018-03-01

Psychological stress is an important perpetuating, worsening and risk factor for temporomandibular disorders of muscular or articular origin. Occlusion instability, by the way, is considered a risk factor of this pathology and can be reproduced in some experimental animal models. The exact physiologic mechanism underlying these relations however, remains unclear. Our purpose was to test the hypothesis that chronic stress and unilateral exodontia induce metabolic and vascular changes in the medial pterygoid muscle of rats. Adult Wistar rats were submitted to chronic unpredictable stress and/or unilateral exodontia and their plasma and medial pterygoid muscle were removed for analysis. The parameters evaluated included plasma levels of corticosterone, metabolic activity by succinate dehydrogenase, oxidative capacity by nicotinamide adenine dinucleotide diaphorase, capillary density by laminin and alfa-CD staining and reactive oxidative species production. Chronic unpredictable stress as an isolated factor, increased oxidative metabolism, capillary density and reactive oxygen species production at medial pterygoid muscle. Conversely, exodontia has a main effect in metabolism, promoting glycolytic transformation of muscle fibers. Association of both factors induced a major glycolytic pattern in muscle and vascular changes. Our findings provide insights into the mechanisms, possibly inducing metabolic and vascular alterations on medial pterygoid muscle of rats, by which chronic stress and occlusal instabilities might be involved as risk factors in the pathophysiology of temporomandibular disorders with muscular components. Copyright © 2017 Elsevier Inc. All rights reserved.

Guidelines for Reproducibly Building and Simulating Systems Biology Models.

Science.gov (United States)

Medley, J Kyle; Goldberg, Arthur P; Karr, Jonathan R

2016-10-01

Reproducibility is the cornerstone of the scientific method. However, currently, many systems biology models cannot easily be reproduced. This paper presents methods that address this problem. We analyzed the recent Mycoplasma genitalium whole-cell (WC) model to determine the requirements for reproducible modeling. We determined that reproducible modeling requires both repeatable model building and repeatable simulation. New standards and simulation software tools are needed to enhance and verify the reproducibility of modeling. New standards are needed to explicitly document every data source and assumption, and new deterministic parallel simulation tools are needed to quickly simulate large, complex models. We anticipate that these new standards and software will enable researchers to reproducibly build and simulate more complex models, including WC models.

Brain grey matter volume alterations in late-life depression.

Science.gov (United States)

Du, Mingying; Liu, Jia; Chen, Ziqi; Huang, Xiaoqi; Li, Jing; Kuang, Weihong; Yang, Yanchun; Zhang, Wei; Zhou, Dong; Bi, Feng; Kendrick, Keith M; Gong, Qiyong

2014-11-01

Voxel-based morphometry (VBM) studies have demonstrated that grey matter abnormalities are involved in the pathophysiology of late-life depression (LLD), but the findings are inconsistent and have not been quantitatively reviewed. The aim of the present study was to conduct a meta-analysis that integrated the reported VBM studies, to determine consistent grey matter alterations in individuals with LLD. A systematic search was conducted to identify VBM studies that compared patients with LLD and healthy controls. We performed a meta-analysis using the effect size signed differential mapping method to quantitatively estimate regional grey matter abnormalities in patients with LLD. We included 9 studies with 11 data sets comprising 292 patients with LLD and 278 healthy controls in our meta-analysis. The pooled and subgroup meta-analyses showed robust grey matter reductions in the right lentiform nucleus extending into the parahippocampus, the hippocampus and the amygdala, the bilateral medial frontal gyrus and the right subcallosal gyrus as well as a grey matter increase in the right lingual gyrus. Meta-regression analyses showed that mean age and the percentage of female patients with LLD were not significantly related to grey matter changes. The analysis techniques, patient characteristics and clinical variables of the studies included were heterogeneous, and most participants were medicated. The present meta-analysis is, to our knowledge, the first to overcome previous inconsistencies in the VBM studies of LLD and provide robust evidence for grey matter alterations within fronto-striatal-limbic networks, thereby implicating them in the pathophysiology of LLD. The mean age and the percentage of female patients with LLD did not appear to have a measurable impact on grey matter changes, although we cannot rule out the contributory effects of medication.

Parkinson's disease : The syndrome, the pathogenesis and pathophysiology

NARCIS (Netherlands)

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

Elucidation of pathophysiology and treatment of neuropathic pain

NARCIS (Netherlands)

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

Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology.

Science.gov (United States)

Hintze, Justin M; Ludlow, Christy L; Bansberg, Stephen F; Adler, Charles H; Lott, David G

2017-10-01

Objective The purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task-specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia) and ( etiology, aetiology, diagnosis, pathogenesis, or pathophysiology). Conclusion The diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high-speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia. Implications for Practice A 3-tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

Reproducibility of duplex ultrasonography and air plethysmography used for the evaluation of chronic venous insufficiency.

Science.gov (United States)

Asbeutah, Akram Mahmoud; Riha, Andrea Zdena; Cameron, James Donald; McGrath, Barry Patrick

2005-04-01

The purpose of this study was to determine the reproducibility of measurements on duplex ultrasonography (DU) and air plethysmography (APG) in subjects with post-thrombotic syndrome. Duplex ultrasonography and APG were used to measure indices of lower limb venous reflux in 15 limbs with a history of deep vein thrombosis and evidence of venous insufficiency as diagnosed by ultrasonography. Three limbs were in class 0; 4 were in classes 1 to 3; and 8 were in classes 4 to 6, according to clinical, etiologic, anatomic, and pathophysiologic clinical classification. Duplex ultrasonography was performed 3 times on the same day, and venous diameter, area, peak reflux velocity, reflux flow volume, and reflux duration measurements were obtained. Air plethysmography was performed on 2 days, 7 to 10 days apart, with 1 measurement on the first day and 2 measurements on the second day. Values obtained from APG included outflow fraction, venous filling index, ejection fraction, and residual volume fraction. The measurements were performed by a vascular technologist blinded to the previous test results. One-way analysis of variance, the Student paired t test, and Bland-Altman plots were used to examine the statistical differences of the DU and APG parameters for all measurements. The mean coefficient of variation for within-subject measurements of all DU and APG parameters measured was less than 10%. Bland-Altman plots showed that there were no apparent trends with increasing values over a wide range for any of the DU parameters, nor were there any for the APG parameters. Under ideal conditions, when measured by a highly trained technologist, both DU and APG showed satisfactory reproducibility.

Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations.

Science.gov (United States)

Miura, Yuri; Endo, Tamao

2016-08-01

Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of the lacrimal functional unit in the pathophysiology of dry eye.

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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.

Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.

Science.gov (United States)

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

2018-03-15

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

Modern iron replacement therapy: clinical and pathophysiological insights.

Science.gov (United States)

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.

Fisiopatologia da enxaqueca Migraine pathophysiology

Directory of Open Access Journals (Sweden)

MAURICE B. VINCENT

1998-12-01

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

Pathophysiology of Manganese-Associated Neurotoxicity

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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

Genotypic variability enhances the reproducibility of an ecological study.

Science.gov (United States)

Milcu, Alexandru; Puga-Freitas, Ruben; Ellison, Aaron M; Blouin, Manuel; Scheu, Stefan; Freschet, Grégoire T; Rose, Laura; Barot, Sebastien; Cesarz, Simone; Eisenhauer, Nico; Girin, Thomas; Assandri, Davide; Bonkowski, Michael; Buchmann, Nina; Butenschoen, Olaf; Devidal, Sebastien; Gleixner, Gerd; Gessler, Arthur; Gigon, Agnès; Greiner, Anna; Grignani, Carlo; Hansart, Amandine; Kayler, Zachary; Lange, Markus; Lata, Jean-Christophe; Le Galliard, Jean-François; Lukac, Martin; Mannerheim, Neringa; Müller, Marina E H; Pando, Anne; Rotter, Paula; Scherer-Lorenzen, Michael; Seyhun, Rahme; Urban-Mead, Katherine; Weigelt, Alexandra; Zavattaro, Laura; Roy, Jacques

2018-02-01

Many scientific disciplines are currently experiencing a 'reproducibility crisis' because numerous scientific findings cannot be repeated consistently. A novel but controversial hypothesis postulates that stringent levels of environmental and biotic standardization in experimental studies reduce reproducibility by amplifying the impacts of laboratory-specific environmental factors not accounted for in study designs. A corollary to this hypothesis is that a deliberate introduction of controlled systematic variability (CSV) in experimental designs may lead to increased reproducibility. To test this hypothesis, we had 14 European laboratories run a simple microcosm experiment using grass (Brachypodium distachyon L.) monocultures and grass and legume (Medicago truncatula Gaertn.) mixtures. Each laboratory introduced environmental and genotypic CSV within and among replicated microcosms established in either growth chambers (with stringent control of environmental conditions) or glasshouses (with more variable environmental conditions). The introduction of genotypic CSV led to 18% lower among-laboratory variability in growth chambers, indicating increased reproducibility, but had no significant effect in glasshouses where reproducibility was generally lower. Environmental CSV had little effect on reproducibility. Although there are multiple causes for the 'reproducibility crisis', deliberately including genetic variability may be a simple solution for increasing the reproducibility of ecological studies performed under stringently controlled environmental conditions.

The Economics of Reproducibility in Preclinical Research.

Directory of Open Access Journals (Sweden)

Leonard P Freedman

2015-06-01

Full Text Available Low reproducibility rates within life science research undermine cumulative knowledge production and contribute to both delays and costs of therapeutic drug development. An analysis of past studies indicates that the cumulative (total prevalence of irreproducible preclinical research exceeds 50%, resulting in approximately US$28,000,000,000 (US$28B/year spent on preclinical research that is not reproducible-in the United States alone. We outline a framework for solutions and a plan for long-term improvements in reproducibility rates that will help to accelerate the discovery of life-saving therapies and cures.

Does systematic variation improve the reproducibility of animal experiments?

NARCIS (Netherlands)

Jonker, R.M.; Guenther, A.; Engqvist, L.; Schmoll, T.

2013-01-01

Reproducibility of results is a fundamental tenet of science. In this journal, Richter et al.1 tested whether systematic variation in experimental conditions (heterogenization) affects the reproducibility of results. Comparing this approach with the current standard of ensuring reproducibility

Estrogens and Androgens in Skeletal Physiology and Pathophysiology.

Science.gov (United States)

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

2017-01-01

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

Science.gov (United States)

Dumesic, Daniel A.; Oberfield, Sharon E.; Stener-Victorin, Elisabet; Marshall, John C.; Laven, Joop S.

2015-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown. PMID:26426951

Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects. Acetazolamid in der zerebrovaskulaeren Diagnostik: Physiologische und pathophysiologische Aspekte

Energy Technology Data Exchange (ETDEWEB)

Lerch, H.; Franke, W.G.; Templin, A. (Medizinische Akademie ' Carl Gustav Carus' , Klinik fuer Nuklearmedizin, Dresden (Germany) Medizinische Akademie ' Carl Gustav Carus' , Klinik fuer Psychiatrie und Neurologie, Abt. Neurologie, Dresden (Germany))

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{sub 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.).

Psychiatric manifestations of Graves' hyperthyroidism: pathophysiology and treatment options.

Science.gov (United States)

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.

Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies.

Science.gov (United States)

Stan, Ana D; Lewis, David A

2012-06-01

Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain's own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

Functional O-GlcNAc modifications: Implications in molecular regulation and pathophysiology

Science.gov (United States)

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

Learning Reproducibility with a Yearly Networking Contest

KAUST Repository

Canini, Marco

2017-08-10

Better reproducibility of networking research results is currently a major goal that the academic community is striving towards. This position paper makes the case that improving the extent and pervasiveness of reproducible research can be greatly fostered by organizing a yearly international contest. We argue that holding a contest undertaken by a plurality of students will have benefits that are two-fold. First, it will promote hands-on learning of skills that are helpful in producing artifacts at the replicable-research level. Second, it will advance the best practices regarding environments, testbeds, and tools that will aid the tasks of reproducibility evaluation committees by and large.

Thou Shalt Be Reproducible! A Technology Perspective

Directory of Open Access Journals (Sweden)

Patrick Mair

2016-07-01

Full Text Available This article elaborates on reproducibility in psychology from a technological viewpoint. Modernopen source computational environments are shown and explained that foster reproducibilitythroughout the whole research life cycle, and to which emerging psychology researchers shouldbe sensitized, are shown and explained. First, data archiving platforms that make datasets publiclyavailable are presented. Second, R is advocated as the data-analytic lingua franca in psychologyfor achieving reproducible statistical analysis. Third, dynamic report generation environments forwriting reproducible manuscripts that integrate text, data analysis, and statistical outputs such asfigures and tables in a single document are described. Supplementary materials are provided inorder to get the reader started with these technologies.

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...

Molecular pathophysiology of cerebral edema

Science.gov (United States)

Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

Reproducible research in palaeomagnetism

Science.gov (United States)

Lurcock, Pontus; Florindo, Fabio

2015-04-01

The reproducibility of research findings is attracting increasing attention across all scientific disciplines. In palaeomagnetism as elsewhere, computer-based analysis techniques are becoming more commonplace, complex, and diverse. Analyses can often be difficult to reproduce from scratch, both for the original researchers and for others seeking to build on the work. We present a palaeomagnetic plotting and analysis program designed to make reproducibility easier. Part of the problem is the divide between interactive and scripted (batch) analysis programs. An interactive desktop program with a graphical interface is a powerful tool for exploring data and iteratively refining analyses, but usually cannot operate without human interaction. This makes it impossible to re-run an analysis automatically, or to integrate it into a larger automated scientific workflow - for example, a script to generate figures and tables for a paper. In some cases the parameters of the analysis process itself are not saved explicitly, making it hard to repeat or improve the analysis even with human interaction. Conversely, non-interactive batch tools can be controlled by pre-written scripts and configuration files, allowing an analysis to be 'replayed' automatically from the raw data. However, this advantage comes at the expense of exploratory capability: iteratively improving an analysis entails a time-consuming cycle of editing scripts, running them, and viewing the output. Batch tools also tend to require more computer expertise from their users. PuffinPlot is a palaeomagnetic plotting and analysis program which aims to bridge this gap. First released in 2012, it offers both an interactive, user-friendly desktop interface and a batch scripting interface, both making use of the same core library of palaeomagnetic functions. We present new improvements to the program that help to integrate the interactive and batch approaches, allowing an analysis to be interactively explored and refined

Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A Review

NARCIS (Netherlands)

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

Reproducibility of ultrasonic testing

International Nuclear Information System (INIS)

Lecomte, J.-C.; Thomas, Andre; Launay, J.-P.; Martin, Pierre

The reproducibility of amplitude quotations for both artificial and natural reflectors was studied for several combinations of instrument/search unit, all being of the same type. This study shows that in industrial inspection if a range of standardized equipment is used, a margin of error of about 6 decibels has to be taken into account (confidence interval of 95%). This margin is about 4 to 5 dB for natural or artificial defects located in the central area and about 6 to 7 dB for artificial defects located on the back surface. This lack of reproducibility seems to be attributable first to the search unit and then to the instrument and operator. These results were confirmed by analysis of calibration data obtained from 250 tests performed by 25 operators under shop conditions. The margin of error was higher than the 6 dB obtained in the study [fr

Development of a Consistent and Reproducible Porcine Scald Burn Model

Science.gov (United States)

Kempf, Margit; Kimble, Roy; Cuttle, Leila

2016-01-01

There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined. PMID:27612153

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...

Transcriptomics Profiling of Alzheimer’s Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs

Science.gov (United States)

Magistri, Marco; Velmeshev, Dmitry; Makhmutova, Madina; Faghihi, Mohammad Ali

2015-01-01

Abstract The underlying genetic variations of late-onset Alzheimer’s disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD pathological process. Transcriptome profiling using deep sequencing technology offers insight into common altered pathways regardless of underpinning genetic or epigenetic factors and thus represents an ideal tool to investigate molecular mechanisms related to the pathophysiology of LOAD. We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of LOAD and age-matched controls. We further validated our data using qRT-PCR on a larger set of postmortem brain tissues, confirming downregulation of the gene encoding substance P (TAC1) and upregulation of the gene encoding the plasminogen activator inhibitor-1 (SERPINE1). Pathway analysis indicates dysregulation in neural communication, cerebral vasculature, and amyloid-β clearance. Beside protein coding genes, we identified several annotated and non-annotated long noncoding RNAs that are differentially expressed in LOAD brain tissues, three of them are activity-dependent regulated and one is induced by Aβ1 - 42 exposure of human neural cells. Our data provide a comprehensive list of transcriptomics alterations in LOAD hippocampi and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD. PMID:26402107

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

Science.gov (United States)

Tishler, Peter V

2013-01-01

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

Preserve specimens for reproducibility

Czech Academy of Sciences Publication Activity Database

Krell, F.-T.; Klimeš, Petr; Rocha, L. A.; Fikáček, M.; Miller, S. E.

2016-01-01

Roč. 539, č. 7628 (2016), s. 168 ISSN 0028-0836 Institutional support: RVO:60077344 Keywords : reproducibility * specimen * biodiversity Subject RIV: EH - Ecology, Behaviour Impact factor: 40.137, year: 2016 http://www.nature.com/nature/journal/v539/n7628/full/539168b.html

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

Science.gov (United States)

Shimano, Hitoshi; Sato, Ryuichiro

2017-12-01

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

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

NARCIS (Netherlands)

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

Reproducibility of 201Tl myocardial imaging

International Nuclear Information System (INIS)

McLaughlin, P.R.; Martin, R.P.; Doherty, P.; Daspit, S.; Goris, M.; Haskell, W.; Lewis, S.; Kriss, J.P.; Harrison, D.C.

1977-01-01

Seventy-six thallium-201 myocardial perfusion studies were performed on twenty-five patients to assess their reproducibility and the effect of varying the level of exercise on the results of imaging. Each patient had a thallium-201 study at rest. Fourteen patients had studies on two occasions at maximum exercise, and twelve patients had studies both at light and at maximum exercise. Of 70 segments in the 14 patients assessed on each of two maximum exercise tests, 64 (91 percent) were reproducible. Only 53 percent (16/30) of the ischemic defects present at maximum exercise were seen in the light exercise study in the 12 patients assessed at two levels of exercise. Correlation of perfusion defects with arteriographically proven significant coronary stenosis was good for the left anterior descending and right coronary arteries, but not as good for circumflex artery disease. Thallium-201 myocardial imaging at maximum exercise is reproducible within acceptable limits, but careful attention to exercise technique is essential for valid comparative studies

Undefined cellulase formulations hinder scientific reproducibility.

Science.gov (United States)

Himmel, Michael E; Abbas, Charles A; Baker, John O; Bayer, Edward A; Bomble, Yannick J; Brunecky, Roman; Chen, Xiaowen; Felby, Claus; Jeoh, Tina; Kumar, Rajeev; McCleary, Barry V; Pletschke, Brett I; Tucker, Melvin P; Wyman, Charles E; Decker, Stephen R

2017-01-01

In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparations may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations.

A PHYSICAL ACTIVITY QUESTIONNAIRE: REPRODUCIBILITY AND VALIDITY

Directory of Open Access Journals (Sweden)

Nicolas Barbosa

2007-12-01

Full Text Available This study evaluates the Quantification de L'Activite Physique en Altitude chez les Enfants (QAPACE supervised self-administered questionnaire reproducibility and validity on the estimation of the mean daily energy expenditure (DEE on Bogotá's schoolchildren. The comprehension was assessed on 324 students, whereas the reproducibility was studied on a different random sample of 162 who were exposed twice to it. Reproducibility was assessed using both the Bland-Altman plot and the intra-class correlation coefficient (ICC. The validity was studied in a sample of 18 girls and 18 boys randomly selected, which completed the test - re-test study. The DEE derived from the questionnaire was compared with the laboratory measurement results of the peak oxygen uptake (Peak VO2 from ergo-spirometry and Leger Test. The reproducibility ICC was 0.96 (95% C.I. 0.95-0.97; by age categories 8-10, 0.94 (0.89-0. 97; 11-13, 0.98 (0.96- 0.99; 14-16, 0.95 (0.91-0.98. The ICC between mean TEE as estimated by the questionnaire and the direct and indirect Peak VO2 was 0.76 (0.66 (p<0.01; by age categories, 8-10, 11-13, and 14-16 were 0.89 (0.87, 0.76 (0.78 and 0.88 (0.80 respectively. The QAPACE questionnaire is reproducible and valid for estimating PA and showed a high correlation with the Peak VO2 uptake

Human Pathophysiological Adaptations to the Space Environment

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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.

Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

Science.gov (United States)

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

Reproducible statistical analysis with multiple languages

DEFF Research Database (Denmark)

Lenth, Russell; Højsgaard, Søren

2011-01-01

This paper describes the system for making reproducible statistical analyses. differs from other systems for reproducible analysis in several ways. The two main differences are: (1) Several statistics programs can be in used in the same document. (2) Documents can be prepared using OpenOffice or ......Office or \\LaTeX. The main part of this paper is an example showing how to use and together in an OpenOffice text document. The paper also contains some practical considerations on the use of literate programming in statistics....

Towards Reproducibility in Computational Hydrology

Science.gov (United States)

Hutton, Christopher; Wagener, Thorsten; Freer, Jim; Han, Dawei; Duffy, Chris; Arheimer, Berit

2017-04-01

Reproducibility is a foundational principle in scientific research. The ability to independently re-run an experiment helps to verify the legitimacy of individual findings, and evolve (or reject) hypotheses and models of how environmental systems function, and move them from specific circumstances to more general theory. Yet in computational hydrology (and in environmental science more widely) the code and data that produces published results are not regularly made available, and even if they are made available, there remains a multitude of generally unreported choices that an individual scientist may have made that impact the study result. This situation strongly inhibits the ability of our community to reproduce and verify previous findings, as all the information and boundary conditions required to set up a computational experiment simply cannot be reported in an article's text alone. In Hutton et al 2016 [1], we argue that a cultural change is required in the computational hydrological community, in order to advance and make more robust the process of knowledge creation and hypothesis testing. We need to adopt common standards and infrastructures to: (1) make code readable and re-useable; (2) create well-documented workflows that combine re-useable code together with data to enable published scientific findings to be reproduced; (3) make code and workflows available, easy to find, and easy to interpret, using code and code metadata repositories. To create change we argue for improved graduate training in these areas. In this talk we reflect on our progress in achieving reproducible, open science in computational hydrology, which are relevant to the broader computational geoscience community. In particular, we draw on our experience in the Switch-On (EU funded) virtual water science laboratory (http://www.switch-on-vwsl.eu/participate/), which is an open platform for collaboration in hydrological experiments (e.g. [2]). While we use computational hydrology as

Participant Nonnaiveté and the reproducibility of cognitive psychology.

Science.gov (United States)

Zwaan, Rolf A; Pecher, Diane; Paolacci, Gabriele; Bouwmeester, Samantha; Verkoeijen, Peter; Dijkstra, Katinka; Zeelenberg, René

2017-07-25

Many argue that there is a reproducibility crisis in psychology. We investigated nine well-known effects from the cognitive psychology literature-three each from the domains of perception/action, memory, and language, respectively-and found that they are highly reproducible. Not only can they be reproduced in online environments, but they also can be reproduced with nonnaïve participants with no reduction of effect size. Apparently, some cognitive tasks are so constraining that they encapsulate behavior from external influences, such as testing situation and prior recent experience with the experiment to yield highly robust effects.

Systematic heterogenization for better reproducibility in animal experimentation.

Science.gov (United States)

Richter, S Helene

2017-08-31

The scientific literature is full of articles discussing poor reproducibility of findings from animal experiments as well as failures to translate results from preclinical animal studies to clinical trials in humans. Critics even go so far as to talk about a "reproducibility crisis" in the life sciences, a novel headword that increasingly finds its way into numerous high-impact journals. Viewed from a cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. So far, poor reproducibility and translational failures in animal experimentation have mostly been attributed to biased animal data, methodological pitfalls, current publication ethics and animal welfare constraints. More recently, the concept of standardization has also been identified as a potential source of these problems. By reducing within-experiment variation, rigorous standardization regimes limit the inference to the specific experimental conditions. In this way, however, individual phenotypic plasticity is largely neglected, resulting in statistically significant but possibly irrelevant findings that are not reproducible under slightly different conditions. By contrast, systematic heterogenization has been proposed as a concept to improve representativeness of study populations, contributing to improved external validity and hence improved reproducibility. While some first heterogenization studies are indeed very promising, it is still not clear how this approach can be transferred into practice in a logistically feasible and effective way. Thus, further research is needed to explore different heterogenization strategies as well as alternative routes toward better reproducibility in animal experimentation.

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

Science.gov (United States)

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

2015-11-01

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

Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies.

Science.gov (United States)

Kaye, Walter H; Frank, Guido K; Bailer, Ursula F; Henry, Shannan E; Meltzer, Carolyn C; Price, Julie C; Mathis, Chester A; Wagner, Angela

2005-05-19

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect, raises the possibility that these symptoms reflect disturbed brain function that contributes to the pathophysiology of this illness. Recent brain imaging studies have identified altered activity in frontal, cingulate, temporal, and parietal cortical regions in AN and BN. Importantly, such disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Emerging data point to a dysregulation of serotonin pathways in cortical and limbic structures that may be related to anxiety, behavioral inhibition, and body image distortions. In specific, recent studies using PET with serotonin specific radioligands implicate alterations of 5-HT1A and 5-HT2A receptors and the 5-HT transporter. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.

Alteration in ocular blood flow and its effect on the progression of glaucoma

Directory of Open Access Journals (Sweden)

Sher Zaman Safi

2017-04-01

Full Text Available Glaucoma is a multifactorial neurodegenerative disease that can result in permanent vision loss by damaging optic nerves due to higher pressure in the eye. Although most of the fundamental pathophysiological mechanisms involved in glaucoma are undetermined but alteration in ocular blood flow(OBFin tissues such as optic nerve, retina, choroid and iris is an important risk factor for glaucoma. Various factors such as limited knowledge of the factors causing optic nerve damage, confusion in the measurement assays and lack of therapies, make hindrances in the understanding of glaucoma. Researchers are continuously accumulating evidence to suggest that alterations in OBF play important role in the pathogenesis of glaucoma but most of the times they have diverse and contradictory conclusions regarding changes in the OBF and risk of glaucoma. In this article we have reviewed different aspects of glaucoma and the effect of OBF in the disease progression

The control of independent students’ work effectiveness during pathophysiology study

Directory of Open Access Journals (Sweden)

О. V. Melnikova

2013-06-01

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

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.

Reproducibility of a reaming test

DEFF Research Database (Denmark)

Pilny, Lukas; Müller, Pavel; De Chiffre, Leonardo

2012-01-01

The reproducibility of a reaming test was analysed to document its applicability as a performance test for cutting fluids. Reaming tests were carried out on a drilling machine using HSS reamers. Workpiece material was an austenitic stainless steel, machined using 4.75 m∙min-1 cutting speed and 0......). Process reproducibility was assessed as the ability of different operators to ensure a consistent rating of individual lubricants. Absolute average values as well as experimental standard deviations of the evaluation parameters were calculated, and uncertainty budgeting was performed. Results document...... a built-up edge occurrence hindering a robust evaluation of cutting fluid performance, if the data evaluation is based on surface finish only. Measurements of hole geometry provide documentation to recognize systematic error distorting the performance test....

Reproducibility of a reaming test

DEFF Research Database (Denmark)

Pilny, Lukas; Müller, Pavel; De Chiffre, Leonardo

2014-01-01

The reproducibility of a reaming test was analysed to document its applicability as a performance test for cutting fluids. Reaming tests were carried out on a drilling machine using HSS reamers. Workpiece material was an austenitic stainless steel, machined using 4.75 m•min−1 cutting speed and 0......). Process reproducibility was assessed as the ability of different operators to ensure a consistent rating of individual lubricants. Absolute average values as well as experimental standard deviations of the evaluation parameters were calculated, and uncertainty budgeting was performed. Results document...... a built–up edge occurrence hindering a robust evaluation of cutting fluid performance, if the data evaluation is based on surface finish only. Measurements of hole geometry provide documentation to recognise systematic error distorting the performance test....

Gender Differences in Epidemiology, Pathophysiology, and Treatment of Hypertension.

Science.gov (United States)

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.

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

Science.gov (United States)

Jones, B A; Gores, G J

1997-12-01

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

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI) in adolescent rats.

Science.gov (United States)

Yamakawa, Glenn R; Lengkeek, Connor; Salberg, Sabrina; Spanswick, Simon C; Mychasiuk, Richelle

2017-01-01

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours). In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau), in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored.

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI in adolescent rats.

Directory of Open Access Journals (Sweden)

Glenn R Yamakawa

Full Text Available Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI, we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours. In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau, in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored.

Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

Science.gov (United States)

Leake, A; Ferrier, I N

1993-01-01

Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

Effect of Initial Conditions on Reproducibility of Scientific Research

Science.gov (United States)

Djulbegovic, Benjamin; Hozo, Iztok

2014-01-01

Background: It is estimated that about half of currently published research cannot be reproduced. Many reasons have been offered as explanations for failure to reproduce scientific research findings- from fraud to the issues related to design, conduct, analysis, or publishing scientific research. We also postulate a sensitive dependency on initial conditions by which small changes can result in the large differences in the research findings when attempted to be reproduced at later times. Methods: We employed a simple logistic regression equation to model the effect of covariates on the initial study findings. We then fed the input from the logistic equation into a logistic map function to model stability of the results in repeated experiments over time. We illustrate the approach by modeling effects of different factors on the choice of correct treatment. Results: We found that reproducibility of the study findings depended both on the initial values of all independent variables and the rate of change in the baseline conditions, the latter being more important. When the changes in the baseline conditions vary by about 3.5 to about 4 in between experiments, no research findings could be reproduced. However, when the rate of change between the experiments is ≤2.5 the results become highly predictable between the experiments. Conclusions: Many results cannot be reproduced because of the changes in the initial conditions between the experiments. Better control of the baseline conditions in-between the experiments may help improve reproducibility of scientific findings. PMID:25132705

Reproducibility of graph metrics in fMRI networks

Directory of Open Access Journals (Sweden)

Qawi K Telesford

2010-12-01

Full Text Available The reliability of graph metrics calculated in network analysis is essential to the interpretation of complex network organization. These graph metrics are used to deduce the small-world properties in networks. In this study, we investigated the test-retest reliability of graph metrics from functional magnetic resonance imaging (fMRI data collected for two runs in 45 healthy older adults. Graph metrics were calculated on data for both runs and compared using intraclass correlation coefficient (ICC statistics and Bland-Altman (BA plots. ICC scores describe the level of absolute agreement between two measurements and provide a measure of reproducibility. For mean graph metrics, ICC scores were high for clustering coefficient (ICC=0.86, global efficiency (ICC=0.83, path length (ICC=0.79, and local efficiency (ICC=0.75; the ICC score for degree was found to be low (ICC=0.29. ICC scores were also used to generate reproducibility maps in brain space to test voxel-wise reproducibility for unsmoothed and smoothed data. Reproducibility was uniform across the brain for global efficiency and path length, but was only high in network hubs for clustering coefficient, local efficiency and degree. BA plots were used to test the measurement repeatability of all graph metrics. All graph metrics fell within the limits for repeatability. Together, these results suggest that with exception of degree, mean graph metrics are reproducible and suitable for clinical studies. Further exploration is warranted to better understand reproducibility across the brain on a voxel-wise basis.

Language-Agnostic Reproducible Data Analysis Using Literate Programming.

Science.gov (United States)

Vassilev, Boris; Louhimo, Riku; Ikonen, Elina; Hautaniemi, Sampsa

2016-01-01

A modern biomedical research project can easily contain hundreds of analysis steps and lack of reproducibility of the analyses has been recognized as a severe issue. While thorough documentation enables reproducibility, the number of analysis programs used can be so large that in reality reproducibility cannot be easily achieved. Literate programming is an approach to present computer programs to human readers. The code is rearranged to follow the logic of the program, and to explain that logic in a natural language. The code executed by the computer is extracted from the literate source code. As such, literate programming is an ideal formalism for systematizing analysis steps in biomedical research. We have developed the reproducible computing tool Lir (literate, reproducible computing) that allows a tool-agnostic approach to biomedical data analysis. We demonstrate the utility of Lir by applying it to a case study. Our aim was to investigate the role of endosomal trafficking regulators to the progression of breast cancer. In this analysis, a variety of tools were combined to interpret the available data: a relational database, standard command-line tools, and a statistical computing environment. The analysis revealed that the lipid transport related genes LAPTM4B and NDRG1 are coamplified in breast cancer patients, and identified genes potentially cooperating with LAPTM4B in breast cancer progression. Our case study demonstrates that with Lir, an array of tools can be combined in the same data analysis to improve efficiency, reproducibility, and ease of understanding. Lir is an open-source software available at github.com/borisvassilev/lir.

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.

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

Transcranial magnetic stimulation and sleep disorders: pathophysiologic insights.

Science.gov (United States)

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

2013-11-01

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

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

Alteration of intestinal barrier function during activity-based anorexia in mice.

Science.gov (United States)

Jésus, Pierre; Ouelaa, Wassila; François, Marie; Riachy, Lina; Guérin, Charlène; Aziz, Moutaz; Do Rego, Jean-Claude; Déchelotte, Pierre; Fetissov, Sergueï O; Coëffier, Moïse

2014-12-01

Anorexia nervosa is a severe eating disorder often leading to malnutrition and cachexia, but its pathophysiology is still poorly defined. Chronic food restriction during anorexia nervosa may induce gut barrier dysfunction, which may contribute to disease development and its complications. Here we have characterized intestinal barrier function in mice with activity-based anorexia (ABA), an animal model of anorexia nervosa. Male C57Bl/6 ABA or limited food access (LFA) mice were placed respectively in cages with or without activity wheel. After 5 days of acclimatization, both ABA and LFA mice had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9 and until the end of experiment at day 17. A group of pair-fed mice (PF) was also compared to ABA. On day 17, food intake was lower in ABA than LFA mice (2.0 ± 0.18 g vs. 3.0 ± 0.14 g, p anorexia nervosa. The role of these alterations in the pathophysiology of anorexia nervosa should be further evaluated. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Beyond Bundles - Reproducible Software Environments with GNU Guix

CERN Multimedia

CERN. Geneva; Wurmus, Ricardo

2018-01-01

Building reproducible data analysis pipelines and numerical experiments is a key challenge for reproducible science, in which tools to reproduce software environments play a critical role. The advent of “container-based” deployment tools such as Docker and Singularity has made it easier to replicate software environments. These tools are very much about bundling the bits of software binaries in a convenient way, not so much about describing how software is composed. Science is not just about replicating, though—it demands the ability to inspect and to experiment. In this talk we will present GNU Guix, a software management toolkit. Guix departs from container-based solutions in that it enables declarative composition of software environments. It is comparable to “package managers” like apt or yum, but with a significant difference: Guix provides accurate provenance tracking of build artifacts, and bit-reproducible software. We will illustrate the many ways in which Guix can improve how software en...

Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

Directory of Open Access Journals (Sweden)

Alma Y. Galvez-Contreras

2017-07-01

Full Text Available Growth factors (GFs are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD and autism spectrum disorders (ASD. In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF, glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders.

Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

Science.gov (United States)

Galvez-Contreras, Alma Y.; Campos-Ordonez, Tania; Gonzalez-Castaneda, Rocio E.; Gonzalez-Perez, Oscar

2017-01-01

Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders. PMID:28751869

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...

Alterations of N-3 polyunsaturated fatty acid-activated K2P channels in hypoxia-induced pulmonary hypertension

DEFF Research Database (Denmark)

Nielsen, Gorm; Wandall-Frostholm, Christine; Sadda, Veeranjaneyulu

2013-01-01

Polyunsaturated fatty acid (PUFA)-activated two-pore domain potassium channels (K2P ) have been proposed to be expressed in the pulmonary vasculature. However, their physiological or pathophysiological roles are poorly defined. Here, we tested the hypothesis that PUFA-activated K2P are involved...... in pulmonary vasorelaxation and that alterations of channel expression are pathophysiologically linked to pulmonary hypertension. Expression of PUFA-activated K2P in the murine lung was investigated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), by patch...... clamp (PC) and myography. K2P -gene expression was examined in chronic hypoxic mice. qRT-PCR showed that the K2P 2.1 and K2P 6.1 were the predominantly expressed K2P in the murine lung. IHC revealed protein expression of K2P 2.1 and K2P 6.1 in the endothelium of pulmonary arteries and of K2P 6...

[Natural head position's reproducibility on photographs].

Science.gov (United States)

Eddo, Marie-Line; El Hayeck, Émilie; Hoyeck, Maha; Khoury, Élie; Ghoubril, Joseph

2017-12-01

The purpose of this study is to evaluate the reproducibility of natural head position with time on profile photographs. Our sample is composed of 96 students (20-30 years old) at the department of dentistry of Saint Joseph University in Beirut. Two profile photographs were taken in natural head position about a week apart. No significant differences were found between T0 and T1 (E = 1.065°). Many studies confirmed this reproducibility with time. Natural head position can be adopted as an orientation for profile photographs in orthodontics. © EDP Sciences, SFODF, 2017.

Audiovisual biofeedback improves diaphragm motion reproducibility in MRI

Science.gov (United States)

Kim, Taeho; Pollock, Sean; Lee, Danny; O’Brien, Ricky; Keall, Paul

2012-01-01

Purpose: In lung radiotherapy, variations in cycle-to-cycle breathing results in four-dimensional computed tomography imaging artifacts, leading to inaccurate beam coverage and tumor targeting. In previous studies, the effect of audiovisual (AV) biofeedback on the external respiratory signal reproducibility has been investigated but the internal anatomy motion has not been fully studied. The aim of this study is to test the hypothesis that AV biofeedback improves diaphragm motion reproducibility of internal anatomy using magnetic resonance imaging (MRI). Methods: To test the hypothesis 15 healthy human subjects were enrolled in an ethics-approved AV biofeedback study consisting of two imaging sessions spaced ∼1 week apart. Within each session MR images were acquired under free breathing and AV biofeedback conditions. The respiratory signal to the AV biofeedback system utilized optical monitoring of an external marker placed on the abdomen. Synchronously, serial thoracic 2D MR images were obtained to measure the diaphragm motion using a fast gradient-recalled-echo MR pulse sequence in both coronal and sagittal planes. The improvement in the diaphragm motion reproducibility using the AV biofeedback system was quantified by comparing cycle-to-cycle variability in displacement, respiratory period, and baseline drift. Additionally, the variation in improvement between the two sessions was also quantified. Results: The average root mean square error (RMSE) of diaphragm cycle-to-cycle displacement was reduced from 2.6 mm with free breathing to 1.6 mm (38% reduction) with the implementation of AV biofeedback (p-value biofeedback (p-value biofeedback (p-value = 0.012). The diaphragm motion reproducibility improvements with AV biofeedback were consistent with the abdominal motion reproducibility that was observed from the external marker motion variation. Conclusions: This study was the first to investigate the potential of AV biofeedback to improve the motion

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 ...

Short- and long-term reproducibility of radioisotopic examination of gastric emptying

Energy Technology Data Exchange (ETDEWEB)

Jonderko, K. (Silesian School of Medicine, Katowice (Poland). Dept. of Gastroenterology)

1990-01-01

Reproducibility of gastric emptying (GE) of a radiolabelled solid meal was assessed. The short-term reproducibility was evaluated on the basis of 12 paired GE examinations performed 1-3 days apart. Twelve paired GE examinations taken 3-8 months apart enabled long-term reproducibility assessment. Reproducibility of GE parameters was expressed in terms of the coefficient of variation, CV. No significant between-day variation of solid GE was found either regarding the short-term or the long-term reproducibility. Although slightly higher CV values characterized the long-term reproducibility of the GE parameters considered, the variations of the differences between repeated GE examinations did not differ significantly between short- and long-term GE reproducibility. The results obtained justify the use of radioisotopic GE measurement for the assessment of early and late results of pharmacologic or surgical management. (author).

ReproPhylo: An Environment for Reproducible Phylogenomics.

Directory of Open Access Journals (Sweden)

Amir Szitenberg

2015-09-01

Full Text Available The reproducibility of experiments is key to the scientific process, and particularly necessary for accurate reporting of analyses in data-rich fields such as phylogenomics. We present ReproPhylo, a phylogenomic analysis environment developed to ensure experimental reproducibility, to facilitate the handling of large-scale data, and to assist methodological experimentation. Reproducibility, and instantaneous repeatability, is built in to the ReproPhylo system and does not require user intervention or configuration because it stores the experimental workflow as a single, serialized Python object containing explicit provenance and environment information. This 'single file' approach ensures the persistence of provenance across iterations of the analysis, with changes automatically managed by the version control program Git. This file, along with a Git repository, are the primary reproducibility outputs of the program. In addition, ReproPhylo produces an extensive human-readable report and generates a comprehensive experimental archive file, both of which are suitable for submission with publications. The system facilitates thorough experimental exploration of both parameters and data. ReproPhylo is a platform independent CC0 Python module and is easily installed as a Docker image or a WinPython self-sufficient package, with a Jupyter Notebook GUI, or as a slimmer version in a Galaxy distribution.

Reproducibility in Computational Neuroscience Models and Simulations

Science.gov (United States)

McDougal, Robert A.; Bulanova, Anna S.; Lytton, William W.

2016-01-01

Objective Like all scientific research, computational neuroscience research must be reproducible. Big data science, including simulation research, cannot depend exclusively on journal articles as the method to provide the sharing and transparency required for reproducibility. Methods Ensuring model reproducibility requires the use of multiple standard software practices and tools, including version control, strong commenting and documentation, and code modularity. Results Building on these standard practices, model sharing sites and tools have been developed that fit into several categories: 1. standardized neural simulators, 2. shared computational resources, 3. declarative model descriptors, ontologies and standardized annotations; 4. model sharing repositories and sharing standards. Conclusion A number of complementary innovations have been proposed to enhance sharing, transparency and reproducibility. The individual user can be encouraged to make use of version control, commenting, documentation and modularity in development of models. The community can help by requiring model sharing as a condition of publication and funding. Significance Model management will become increasingly important as multiscale models become larger, more detailed and correspondingly more difficult to manage by any single investigator or single laboratory. Additional big data management complexity will come as the models become more useful in interpreting experiments, thus increasing the need to ensure clear alignment between modeling data, both parameters and results, and experiment. PMID:27046845

Reproducibility of computer-aided detection system in digital mammograms

International Nuclear Information System (INIS)

Kim, Seung Ja; Cho, Nariya; Cha, Joo Hee; Chung, Hye Kyung; Lee, Sin Ho; Cho, Kyung Soo; Kim, Sun Mi; Moon, Woo Kyung

2005-01-01

To evaluate the reproducibility of the computer-aided detection (CAD) system for digital mammograms. We applied the CAD system (ImageChecker M1000-DM, version 3.1; R2 Technology) to full field digital mammograms. These mammograms were taken twice at an interval of 10-45 days (mean:25 days) for 34 preoperative patients (breast cancer n=27, benign disease n=7, age range:20-66 years, mean age:47.9 years). On the mammograms, lesions were visible in 19 patients and these were depicted as 15 masses and 12 calcification clusters. We analyzed the sensitivity, the false positive rate (FPR) and the reproducibility of the CAD marks. The broader sensitivities of the CAD system were 80% (12 of 15), 67%(10 of 15) for masses and those for calcification clusters were 100% (12 of 12). The strict sensitivities were 50% (15 of 30) and 50% (15 of 30) for masses and 92% (22 of 24) and 79% (19 of 24) for the clusters. The FPR for the masses was 0.21-0.22/image, the FPR for the clusters was 0.03-0.04/image and the total FPR was 0.24-0.26/image. Among 132 mammography images, the identical images regardless of the existence of CAD marks were 59% (78 of 132), and the identical images with CAD marks were 22% (15 of 69). The reproducibility of the CAD marks for the true positive mass was 67% (12 of 18) and 71% (17 of 24) for the true positive cluster. The reproducibility of CAD marks for the false positive mass was 8% (4 of 53), and the reproducibility of CAD marks for the false positive clusters was 14% (1 of 7). The reproducibility of the total mass marks was 23% (16 of 71), and the reproducibility of the total cluster marks was 58% (18 of 31). CAD system showed higher sensitivity and reproducibility of CAD marks for the calcification clusters which are related to breast cancer. Yet the overall reproducibility of CAD marks was low; therefore, the CAD system must be applied considering this limitation

The importance of obstructive sleep apnoea and hypopnea pathophysiology for customized therapy.

Science.gov (United States)

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.

Regional blood flows by the microsphere method: reproducibility in portal hypertensive rats and influence of a portal vein catheter

International Nuclear Information System (INIS)

Hadengue, A.; Lee, S.S.; Koshy, A.; Girod, C.; Lebrec, D.

1988-01-01

To determine the reproducibility of splanchnic blood flow measurements by the microsphere method in rats with portal hypertension and the effects of laparotomy with portal vein cannulation, eight groups of 10 rats were studied. Microspheres were labelled with 113 Sn or 141 Ce. Laparotomy with portal cannulation had no significant effect in sham-operated rats. In awake portal hypertensive rats, cardiac output and splanchnic blood flow were lower in portal vein cannulated rats compared with those of non-cannulated animals. In anesthetized portal hypertensive rats blood flows were unaffected by portal cannulation, but arterial pressure and heart rate were elevated. Anesthesia also decreased portal pressure in portal hypertensive rats. We conclude that the microsphere method remains reproducible in portal hypertensive rat models. Laparotomy with portal cannulation can alter systemic and splanchnic hemodynamics in portal hypertensive rats; these effects can also be changed during pentobarbital anesthesia. Regional blood flow measurements in portal hypertensive rats should be performed in animals without portal cannulation and preferably in the awake state

Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

Directory of Open Access Journals (Sweden)

Anne J Blood

Full Text Available There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

Histopathologic reproducibility of thyroid disease in an epidemiologic study

International Nuclear Information System (INIS)

Ron, E.; Griffel, B.; Liban, E.; Modan, B.

1986-01-01

An investigation of the long-term effects of childhood scalp irradiation demonstrated a significantly increased risk of thyroid tumors in the irradiated population. Because of the complexity of thyroid cancer diagnosis, a histopathologic slide review of 59 of the 68 patients (irradiated and nonirradiated) with thyroid disease was undertaken. The review revealed 90% agreement (kappa = +0.85, P less than 0.01) between the original and review diagnosis. Four of 27 cases previously diagnosed as malignant were reclassified as benign, yielding a cancer misdiagnosis rate of 14.8%. All four of the misdiagnosed cancers were of follicular or mixed papillary-follicular type. As a result of the histologic review, the ratio of malignant to benign tumors decreased from 2.55 to 1.75. Since disagreement in diagnosis was similar in the irradiated and nonirradiated groups, the relative risk of radiation-associated neoplasms did not change substantially. The histopathologic review shows that although there were some problems in diagnostic reproducibility, they were not statistically significant and did not alter our previous conclusions regarding radiation exposure. However, a 15% reduction in the number of malignancies might affect epidemiologic studies with an external comparison as well as geographic or temporal comparisons

ITK: Enabling Reproducible Research and Open Science

Directory of Open Access Journals (Sweden)

Matthew Michael McCormick

2014-02-01

Full Text Available Reproducibility verification is essential to the practice of the scientific method. Researchers report their findings, which are strengthened as other independent groups in the scientific community share similar outcomes. In the many scientific fields where software has become a fundamental tool for capturing and analyzing data, this requirement of reproducibility implies that reliable and comprehensive software platforms and tools should be made available to the scientific community. The tools will empower them and the public to verify, through practice, the reproducibility of observations that are reported in the scientific literature.Medical image analysis is one of the fields in which the use of computational resources, both software and hardware, are an essential platform for performing experimental work. In this arena, the introduction of the Insight Toolkit (ITK in 1999 has transformed the field and facilitates its progress by accelerating the rate at which algorithmic implementations are developed, tested, disseminated and improved. By building on the efficiency and quality of open source methodologies, ITK has provided the medical image community with an effective platform on which to build a daily workflow that incorporates the true scientific practices of reproducibility verification.This article describes the multiple tools, methodologies, and practices that the ITK community has adopted, refined, and followed during the past decade, in order to become one of the research communities with the most modern reproducibility verification infrastructure. For example, 207 contributors have created over 2400 unit tests that provide over 84% code line test coverage. The Insight Journal, an open publication journal associated with the toolkit, has seen over 360,000 publication downloads. The median normalized closeness centrality, a measure of knowledge flow, resulting from the distributed peer code review system was high, 0.46.

MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation.

Science.gov (United States)

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

2016-05-01

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

A Web-based e-learning course: integration of pathophysiology into pharmacology.

Science.gov (United States)

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.

Jaundice associated pruritis: a review of pathophysiology and treatment.

Science.gov (United States)

Bassari, Ramez; Koea, Jonathan B

2015-02-07

To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and clinicaltrials.gov for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective.

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.

Science.gov (United States)

Morley, John E

2013-01-01

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

Pathophysiology of osteoporosis: new mechanistic insights.

Science.gov (United States)

Armas, Laura A G; Recker, Robert R

2012-09-01

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

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.

Highly reproducible polyol synthesis for silver nanocubes

Science.gov (United States)

Han, Hye Ji; Yu, Taekyung; Kim, Woo-Sik; Im, Sang Hyuk

2017-07-01

We could synthesize the Ag nanocubes highly reproducibly by conducting the polyol synthesis using HCl etchant in dark condition because the photodecomposition/photoreduction of AgCl nanoparticles formed at initial reaction stage were greatly depressed and consequently the selective self-nucleation of Ag single crystals and their selective growth reaction could be promoted. Whereas the reproducibility of the formation of Ag nanocubes were very poor when we synthesize the Ag nanocubes in light condition due to the photoreduction of AgCl to Ag.

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...

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

Science.gov (United States)

Watanabe, Ken

2009-01-01

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

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.

Reproducible Bioinformatics Research for Biologists

Science.gov (United States)

This book chapter describes the current Big Data problem in Bioinformatics and the resulting issues with performing reproducible computational research. The core of the chapter provides guidelines and summaries of current tools/techniques that a noncomputational researcher would need to learn to pe...

Shear wave elastography for breast masses is highly reproducible.

Science.gov (United States)

Cosgrove, David O; Berg, Wendie A; Doré, Caroline J; Skyba, Danny M; Henry, Jean-Pierre; Gay, Joel; Cohen-Bacrie, Claude

2012-05-01

To evaluate intra- and interobserver reproducibility of shear wave elastography (SWE) for breast masses. For intraobserver reproducibility, each observer obtained three consecutive SWE images of 758 masses that were visible on ultrasound. 144 (19%) were malignant. Weighted kappa was used to assess the agreement of qualitative elastographic features; the reliability of quantitative measurements was assessed by intraclass correlation coefficients (ICC). For the interobserver reproducibility, a blinded observer reviewed images and agreement on features was determined. Mean age was 50 years; mean mass size was 13 mm. Qualitatively, SWE images were at least reasonably similar for 666/758 (87.9%). Intraclass correlation for SWE diameter, area and perimeter was almost perfect (ICC ≥ 0.94). Intraobserver reliability for maximum and mean elasticity was almost perfect (ICC = 0.84 and 0.87) and was substantial for the ratio of mass-to-fat elasticity (ICC = 0.77). Interobserver agreement was moderate for SWE homogeneity (κ = 0.57), substantial for qualitative colour assessment of maximum elasticity (κ = 0.66), fair for SWE shape (κ = 0.40), fair for B-mode mass margins (κ = 0.38), and moderate for B-mode mass shape (κ = 0.58), orientation (κ = 0.53) and BI-RADS assessment (κ = 0.59). SWE is highly reproducible for assessing elastographic features of breast masses within and across observers. SWE interpretation is at least as consistent as that of BI-RADS ultrasound B-mode features. • Shear wave ultrasound elastography can measure the stiffness of breast tissue • It provides a qualitatively and quantitatively interpretable colour-coded map of tissue stiffness • Intraobserver reproducibility of SWE is almost perfect while intraobserver reproducibility of SWE proved to be moderate to substantial • The most reproducible SWE features between observers were SWE image homogeneity and maximum elasticity.

Reproducibility, controllability, and optimization of LENR experiments

Energy Technology Data Exchange (ETDEWEB)

Nagel, David J. [The George Washington University, Washington DC 20052 (United States)

2006-07-01

Low-energy nuclear reaction (LENR) measurements are significantly, and increasingly reproducible. Practical control of the production of energy or materials by LENR has yet to be demonstrated. Minimization of costly inputs and maximization of desired outputs of LENR remain for future developments. The paper concludes by underlying that it is now clearly that demands for reproducible experiments in the early years of LENR experiments were premature. In fact, one can argue that irreproducibility should be expected for early experiments in a complex new field. As emphasized in the paper and as often happened in the history of science, experimental and theoretical progress can take even decades. It is likely to be many years before investments in LENR experiments will yield significant returns, even for successful research programs. However, it is clearly that a fundamental understanding of the anomalous effects observed in numerous experiments will significantly increase reproducibility, improve controllability, enable optimization of processes, and accelerate the economic viability of LENR.

Reproducibility, controllability, and optimization of LENR experiments

International Nuclear Information System (INIS)

Nagel, David J.

2006-01-01

Low-energy nuclear reaction (LENR) measurements are significantly, and increasingly reproducible. Practical control of the production of energy or materials by LENR has yet to be demonstrated. Minimization of costly inputs and maximization of desired outputs of LENR remain for future developments. The paper concludes by underlying that it is now clearly that demands for reproducible experiments in the early years of LENR experiments were premature. In fact, one can argue that irreproducibility should be expected for early experiments in a complex new field. As emphasized in the paper and as often happened in the history of science, experimental and theoretical progress can take even decades. It is likely to be many years before investments in LENR experiments will yield significant returns, even for successful research programs. However, it is clearly that a fundamental understanding of the anomalous effects observed in numerous experiments will significantly increase reproducibility, improve controllability, enable optimization of processes, and accelerate the economic viability of LENR

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.

Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study.

Directory of Open Access Journals (Sweden)

Borah Kim

Full Text Available The frontal cortex might play an important role in the fear network, and white matter (WM integrity could be related to the pathophysiology of panic disorder (PD. A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI scores were assessed. Tract-based spatial statistics (TBSS was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.

Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drug candidate ZM241385.

Directory of Open Access Journals (Sweden)

Zhiyun Wang

2010-11-01

Full Text Available This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009 established that moderate strength static magnetic field (SMF exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A(2A receptor (A(2AR in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD.SMF reproduced several responses elicited by ZM241385, a selective A(2AR antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A(2AR agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A(2AR, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth.When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders.

Reproducing Kernels and Coherent States on Julia Sets

Energy Technology Data Exchange (ETDEWEB)

Thirulogasanthar, K., E-mail: santhar@cs.concordia.ca; Krzyzak, A. [Concordia University, Department of Computer Science and Software Engineering (Canada)], E-mail: krzyzak@cs.concordia.ca; Honnouvo, G. [Concordia University, Department of Mathematics and Statistics (Canada)], E-mail: g_honnouvo@yahoo.fr

2007-11-15

We construct classes of coherent states on domains arising from dynamical systems. An orthonormal family of vectors associated to the generating transformation of a Julia set is found as a family of square integrable vectors, and, thereby, reproducing kernels and reproducing kernel Hilbert spaces are associated to Julia sets. We also present analogous results on domains arising from iterated function systems.

Reproducing Kernels and Coherent States on Julia Sets

International Nuclear Information System (INIS)

Thirulogasanthar, K.; Krzyzak, A.; Honnouvo, G.

2007-01-01

We construct classes of coherent states on domains arising from dynamical systems. An orthonormal family of vectors associated to the generating transformation of a Julia set is found as a family of square integrable vectors, and, thereby, reproducing kernels and reproducing kernel Hilbert spaces are associated to Julia sets. We also present analogous results on domains arising from iterated function systems

Pathophysiological significance and therapeutic applications of snake venom protease inhibitors.

Science.gov (United States)

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.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

Science.gov (United States)

Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

2013-01-01

Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

Directory of Open Access Journals (Sweden)

James P. Kesby

2013-07-01

Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

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.

Reproduction alters oxidative status when it is traded-off against longevity.

Science.gov (United States)

Beaulieu, Michaël; Geiger, Rina E; Reim, Elisabeth; Zielke, Luisa; Fischer, Klaus

2015-07-01

Oxidative stress has been proposed to mediate one of the most important aspects of life-history evolution: the trade-off between reproduction and self-maintenance. However, empirical studies have cast doubt on the generality of this intriguing notion. Here, we hypothesize that reproduction alters oxidative status only when a trade-off between reproduction and self-maintenance occurs. Accordingly, in female Bicyclus anynana butterflies, we found that reproduction affected oxidative markers only under challenging thermal conditions that made the trade-off between reproduction and longevity emerge. Interestingly, under such conditions, butterflies favored longevity over reproduction, suggesting that self-maintenance mechanisms were activated. Accordingly, butterflies reproducing under challenging thermal conditions exhibited enhanced antioxidant defenses and stable oxidative damage. Altogether, our results indicate that a trade-off between reproduction and self-maintenance is indeed a necessary condition for reproduction to alter oxidative status, and that the effects of such a trade-off on oxidative status depend on whether priority is given to self-maintenance or reproduction. Assessing the existence of the trade-off between self-maintenance and reproduction, and whether self-maintenance is prioritized relative to reproduction is therefore crucial for understanding variation in oxidative status in reproducing animals, which may clarify the general implication of oxidative stress in the resolution of life-history trade-offs. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Reproducible diagnosis of Chronic Lymphocytic Leukemia by flow cytometry

DEFF Research Database (Denmark)

Rawstron, Andy C; Kreuzer, Karl-Anton; Soosapilla, Asha

2018-01-01

The diagnostic criteria for CLL rely on morphology and immunophenotype. Current approaches have limitations affecting reproducibility and there is no consensus on the role of new markers. The aim of this project was to identify reproducible criteria and consensus on markers recommended for the di...

Participant Nonnaiveté and the reproducibility of cognitive psychology

NARCIS (Netherlands)

R.A. Zwaan (Rolf); D. Pecher (Diane); G. Paolacci (Gabriele); S. Bouwmeester (Samantha); P.P.J.L. Verkoeijen (Peter); K. Dijkstra (Katinka); R. Zeelenberg (René)

2017-01-01

textabstractMany argue that there is a reproducibility crisis in psychology. We investigated nine well-known effects from the cognitive psychology literature—three each from the domains of perception/action, memory, and language, respectively—and found that they are highly reproducible. Not only can

Pathophysiology of MDS: genomic aberrations.

Science.gov (United States)

Ichikawa, Motoshi

2016-01-01

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

Encapsulating Peritoneal Sclerosis: A study on pathophysiology, clinical aspects and management

NARCIS (Netherlands)

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

A Framework for Reproducible Latent Fingerprint Enhancements.

Science.gov (United States)

Carasso, Alfred S

2014-01-01

Photoshop processing of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology.

Altered Regional Cerebral Blood Flow in Chronic Whiplash Associated Disorders.

Science.gov (United States)

Vállez García, David; Doorduin, Janine; Willemsen, Antoon T M; Dierckx, Rudi A J O; Otte, Andreas

2016-08-01

There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD). However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1) to validate previous results showing alterations of regional cerebral blood flow (rCBF) in cWAD, (2) to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3) to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H2(15)O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Altered Regional Cerebral Blood Flow in Chronic Whiplash Associated Disorders

Directory of Open Access Journals (Sweden)

David Vállez García

2016-08-01

Full Text Available There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD. However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1 to validate previous results showing alterations of regional cerebral blood flow (rCBF in cWAD, (2 to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3 to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H215O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.

Altered protein networks and cellular pathways in severe west nile disease in mice.

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Christophe Fraisier

Full Text Available BACKGROUND: The recent West Nile virus (WNV outbreaks in developed countries, including Europe and the United States, have been associated with significantly higher neuropathology incidence and mortality rate than previously documented. The changing epidemiology, the constant risk of (re-emergence of more virulent WNV strains, and the lack of effective human antiviral therapy or vaccines makes understanding the pathogenesis of severe disease a priority. Thus, to gain insight into the pathophysiological processes in severe WNV infection, a kinetic analysis of protein expression profiles in the brain of WNV-infected mice was conducted using samples prior to and after the onset of clinical symptoms. METHODOLOGY/PRINCIPAL FINDINGS: To this end, 2D-DIGE and gel-free iTRAQ labeling approaches were combined, followed by protein identification by mass spectrometry. Using these quantitative proteomic approaches, a set of 148 proteins with modified abundance was identified. The bioinformatics analysis (Ingenuity Pathway Analysis of each protein dataset originating from the different time-point comparisons revealed that four major functions were altered during the course of WNV-infection in mouse brain tissue: i modification of cytoskeleton maintenance associated with virus circulation; ii deregulation of the protein ubiquitination pathway; iii modulation of the inflammatory response; and iv alteration of neurological development and neuronal cell death. The differential regulation of selected host protein candidates as being representative of these biological processes were validated by western blotting using an original fluorescence-based method. CONCLUSION/SIGNIFICANCE: This study provides novel insights into the in vivo kinetic host reactions against WNV infection and the pathophysiologic processes involved, according to clinical symptoms. This work offers useful clues for anti-viral research and further evaluation of early biomarkers for the diagnosis

Capillary leak syndrome: etiologies, pathophysiology, and management.

Science.gov (United States)

Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai

2017-07-01

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

Postoperative ileus: Recent developments in pathophysiology and management.

Science.gov (United States)

Bragg, Damian; El-Sharkawy, Ahmed M; Psaltis, Emmanouil; Maxwell-Armstrong, Charles A; Lobo, Dileep N

2015-06-01

Postoperative ileus (POI) is a frequent occurrence after abdominal and other types of surgery, and is associated with significant morbidity and costs to health care providers. The aims of this narrative review were to provide an update of classification systems, preventive techniques, pathophysiological mechanisms, and treatment options for established POI. The Web of Science, MEDLINE, PubMed and Google Scholar databases were searched using the key phrases 'ileus', 'postoperative ileus' and 'definition', for relevant studies published in English from January 1997 to August 2014. POI is still a problematic and frequent complication of surgery. Fluid overload, exogenous opioids, neurohormonal dysfunction, and gastrointestinal stretch and inflammation are key mechanisms in the pathophysiology of POI. Evidence is supportive of thoracic epidural analgesia, avoidance of salt and water overload, alvimopan and gum chewing as measures for the prevention of POI, and should be incorporated into perioperative care protocols. Minimal access surgery and avoidance of nasogastric tubes may also help. Novel strategies are emerging, but further studies are required for the treatment of prolonged POI, where evidence is still lacking. Although POI is often inevitable, methods to reduce its duration and facilitate recovery of postoperative gastrointestinal function are evolving rapidly. Utilisation of standardised diagnostic classification systems will help improve applicability of future studies. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Retinovascular physiology and pathophysiology: new experimental approach/new insights

Science.gov (United States)

Puro, Donald G.

2012-01-01

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

Sepsis: Current Definition, Pathophysiology, Diagnosis, and Management.

Science.gov (United States)

Taeb, Abdalsamih M; Hooper, Michael H; Marik, Paul E

2017-06-01

Sepsis is a clinical syndrome that results from the dysregulated inflammatory response to infection that leads to organ dysfunction. The resulting losses to society in terms of financial burden, morbidity, and mortality are enormous. We provide a review of sepsis, its underlying pathophysiology, and guidance for diagnosis and management of this common disease. Current established treatments include appropriate antimicrobial agents to target the underlying infection, optimization of intravascular volume to improve stroke volume, vasopressors to counteract vasoplegic shock, and high-quality supportive care. Appropriate implementation of established treatments combined with novel therapeutic approaches promises to continue to decrease the impact of this disease.

Validation and reproducibility of an Australian caffeine food frequency questionnaire.

Science.gov (United States)

Watson, E J; Kohler, M; Banks, S; Coates, A M

2017-08-01

The aim of this study was to measure validity and reproducibility of a caffeine food frequency questionnaire (C-FFQ) developed for the Australian population. The C-FFQ was designed to assess average daily caffeine consumption using four categories of food and beverages including; energy drinks; soft drinks/soda; coffee and tea and chocolate (food and drink). Participants completed a seven-day food diary immediately followed by the C-FFQ on two consecutive days. The questionnaire was first piloted in 20 adults, and then, a validity/reproducibility study was conducted (n = 90 adults). The C-FFQ showed moderate correlations (r = .60), fair agreement (mean difference 63 mg) and reasonable quintile rankings indicating fair to moderate agreement with the seven-day food diary. To test reproducibility, the C-FFQ was compared to itself and showed strong correlations (r = .90), good quintile rankings and strong kappa values (κ = 0.65), indicating strong reproducibility. The C-FFQ shows adequate validity and reproducibility and will aid researchers in Australia to quantify caffeine consumption.

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...

Pathophysiology of Headaches with a Prominent Vascular Component

Directory of Open Access Journals (Sweden)

Juan A Pareja

1996-01-01

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

Static Magnetic Field Exposure Reproduces Cellular Effects of the Parkinson's Disease Drug Candidate ZM241385

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Wang, Zhiyun; Che, Pao-Lin; Du, Jian; Ha, Barbara; Yarema, Kevin J.

2010-01-01

Background This study was inspired by coalescing evidence that magnetic therapy may be a viable treatment option for certain diseases. This premise is based on the ability of moderate strength fields (i.e., 0.1 to 1 Tesla) to alter the biophysical properties of lipid bilayers and in turn modulate cellular signaling pathways. In particular, previous results from our laboratory (Wang et al., BMC Genomics, 10, 356 (2009)) established that moderate strength static magnetic field (SMF) exposure altered cellular endpoints associated with neuronal function and differentiation. Building on this background, the current paper investigated SMF by focusing on the adenosine A2A receptor (A2AR) in the PC12 rat adrenal pheochromocytoma cell line that displays metabolic features of Parkinson's disease (PD). Methodology and Principal Findings SMF reproduced several responses elicited by ZM241385, a selective A2AR antagonist, in PC12 cells including altered calcium flux, increased ATP levels, reduced cAMP levels, reduced nitric oxide production, reduced p44/42 MAPK phosphorylation, inhibited proliferation, and reduced iron uptake. SMF also counteracted several PD-relevant endpoints exacerbated by A2AR agonist CGS21680 in a manner similar to ZM241385; these include reduction of increased expression of A2AR, reversal of altered calcium efflux, dampening of increased adenosine production, reduction of enhanced proliferation and associated p44/42 MAPK phosphorylation, and inhibition of neurite outgrowth. Conclusions and Significance When measured against multiple endpoints, SMF elicited qualitatively similar responses as ZM241385, a PD drug candidate. Provided that the in vitro results presented in this paper apply in vivo, SMF holds promise as an intriguing non-invasive approach to treat PD and potentially other neurological disorders. PMID:21079735

Altered Expression of Endoplasmic Reticulum Stress Associated Genes in Hippocampus of Learned Helpless Rats: Relevance to Depression Pathophysiology

Directory of Open Access Journals (Sweden)

Matthew A. Timberlake

2016-01-01

Full Text Available The unfolded protein response (UPR is an evolutionarily conserved defensive mechanism that is used by cells to correct misfolded proteins that accumulate in the endoplasmic reticulum. These proteins are misfolded as a result of physical stress on a cell and initiate a host of downstream effects that govern processes ranging from inflammation to apoptosis. To examine whether UPR system plays a role in depression, we examined the expression of genes that are part of the three different pathways for UPR activation, namely GRP78, GRP94, ATF6, XBP-1, ATF4 and CHOP using an animal model system that distinguishes vulnerability (learned helpless, LH from resistance (non-learned helpless, NLH to develop depression. Rats were exposed to inescapable shock on day 1 and day 7 and were tested for escape latency on day 14. Rats not given shock but tested for escape latency were used as tested control (TC. Plasma corticosterone levels were measured. Expression levels of various UPR associated genes were determined in hippocampus using qPCR. We found that the corticosterone level was higher in LH rats compared with TC and NLH rats. Expression of GRP78, GRP94, ATF6 and XBP-1 were significantly upregulated in LH rats compared with TC or NLH rats, whereas NLH rats did not show such changes. Expression levels of ATF4 and CHOP showed trends towards upregulation but were not significantly altered in LH or NLH group. Our data show strong evidence of altered UPR system in depressed rats, which could be associated with development of depressive behavior.

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

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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.

Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease.

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Vilar-Pereira, Glaucia; Ruivo, Leonardo Alexandre de Souza; Lannes-Vieira, Joseli

2015-12-01

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis

Science.gov (United States)

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

Effectiveness of integrating case studies in online and face-to-face instruction of pathophysiology: a comparative study.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2018-05-14

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

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

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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.

Review article: the pathophysiology, differential diagnosis and management of rumination syndrome.

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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.

Reproducibility of temporomandibular joint tomography. Influence of shifted X-ray beam and tomographic focal plane on reproducibility

International Nuclear Information System (INIS)

Saito, Masashi

1999-01-01

Proper tomographic focal plane and x-ray beam direction are the most important factors to obtain accurate images of the temporomandibular joint (TMJ). In this study, to clarify the magnitude of effect of these two factors on the image quality. We evaluated the reproducibility of tomograms by measuring the distortion when the x-ray beam was shifted from the correct center of the object. The effects of the deviation of the tomographic focal plane on image quality were evaluated by the MTF (Modulation Transfer Function). Two types of tomograms, one the plane type, the other the rotational type were used in this study. A TMJ model was made from Teflon for the purpose of evaluation by shifting the x-ray beam. The x-ray images were obtained by tilting the model from 0 to 10 degrees 2-degree increments. These x-ray images were processed for computer image analysis, and then the distance between condyle and the joint space was measured. To evaluate the influence of the shifted tomographic focal plane on image sharpness, the x-ray images from each setting were analyzed by MTF. To obtain the MTF, ''knife-edge'' made from Pb was used. The images were scanned with a microdensitometer at the central focal plane, and 0, 0.5, 1 mm away respectively. The density curves were analyzed by Fourier analysis and the MTF was calculated. The reproducibility of images became worse by shifting the x-ray beam. This tendency was similar for both tomograms. Object characteristics such as anterior and posterior portion of the joint space affected the deterioration of reproducibility of the tomography. The deviation of the tomographic focal plane also decreased the reproducibility of the x-ray images. The rotational type showed a better MTF, but it became seriously unfavorable with slight changes of the tomographic focal plane. Contrarily, the plane type showed a lower MTF, but the image was stable with shifting of the tomographic focal plane. (author)

[Pathophysiology and treatment of orofacial pain.

Science.gov (United States)

Shinoda, Masamichi; Noma, Noboru

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

Metabolic syndrome, its pathophysiology and the role of melatonin.

Science.gov (United States)

Srinivasan, Venkataramanujam; Ohta, Yoshiji; Espino, Javier; Pariente, Jose A; Rodriguez, Ana B; Mohamed, Mahaneem; Zakaria, Rahimah

2013-01-01

Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.

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 ...

Dysplastic naevus: histological criteria and their inter-observer reproducibility.

Science.gov (United States)

Hastrup, N; Clemmensen, O J; Spaun, E; Søndergaard, K

1994-06-01

Forty melanocytic lesions were examined in a pilot study, which was followed by a final series of 100 consecutive melanocytic lesions, in order to evaluate the inter-observer reproducibility of the histological criteria proposed for the dysplastic naevus. The specimens were examined in a blind fashion by four observers. Analysis by kappa statistics showed poor reproducibility of nuclear features, while reproducibility of architectural features was acceptable, improving in the final series. Consequently, we cannot apply the combined criteria of cytological and architectural features with any confidence in the diagnosis of dysplastic naevus, and, until further studies have documented that architectural criteria alone will suffice in the diagnosis of dysplastic naevus, we, as pathologists, shall avoid this term.

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

Reproducible and controllable induction voltage adder for scaled beam experiments

Energy Technology Data Exchange (ETDEWEB)

Sakai, Yasuo; Nakajima, Mitsuo; Horioka, Kazuhiko [Department of Energy Sciences, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8502 (Japan)

2016-08-15

A reproducible and controllable induction adder was developed using solid-state switching devices and Finemet cores for scaled beam compression experiments. A gate controlled MOSFET circuit was developed for the controllable voltage driver. The MOSFET circuit drove the induction adder at low magnetization levels of the cores which enabled us to form reproducible modulation voltages with jitter less than 0.3 ns. Preliminary beam compression experiments indicated that the induction adder can improve the reproducibility of modulation voltages and advance the beam physics experiments.

Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells.

Science.gov (United States)

Fletcher, Anne L; Malhotra, Deepali; Acton, Sophie E; Lukacs-Kornek, Veronika; Bellemare-Pelletier, Angelique; Curry, Mark; Armant, Myriam; Turley, Shannon J

2011-01-01

Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs) between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

GeoTrust Hub: A Platform For Sharing And Reproducing Geoscience Applications

Science.gov (United States)

Malik, T.; Tarboton, D. G.; Goodall, J. L.; Choi, E.; Bhatt, A.; Peckham, S. D.; Foster, I.; Ton That, D. H.; Essawy, B.; Yuan, Z.; Dash, P. K.; Fils, G.; Gan, T.; Fadugba, O. I.; Saxena, A.; Valentic, T. A.

2017-12-01

Recent requirements of scholarly communication emphasize the reproducibility of scientific claims. Text-based research papers are considered poor mediums to establish reproducibility. Papers must be accompanied by "research objects", aggregation of digital artifacts that together with the paper provide an authoritative record of a piece of research. We will present GeoTrust Hub (http://geotrusthub.org), a platform for creating, sharing, and reproducing reusable research objects. GeoTrust Hub provides tools for scientists to create `geounits'--reusable research objects. Geounits are self-contained, annotated, and versioned containers that describe and package computational experiments in an efficient and light-weight manner. Geounits can be shared on public repositories such as HydroShare and FigShare, and also using their respective APIs reproduced on provisioned clouds. The latter feature enables science applications to have a lifetime beyond sharing, wherein they can be independently verified and trust be established as they are repeatedly reused. Through research use cases from several geoscience laboratories across the United States, we will demonstrate how tools provided from GeoTrust Hub along with Hydroshare as its public repository for geounits is advancing the state of reproducible research in the geosciences. For each use case, we will address different computational reproducibility requirements. Our first use case will be an example of setup reproducibility which enables a scientist to set up and reproduce an output from a model with complex configuration and development environments. Our second use case will be an example of algorithm/data reproducibility, where in a shared data science model/dataset can be substituted with an alternate one to verify model output results, and finally an example of interactive reproducibility, in which an experiment is dependent on specific versions of data to produce the result. Toward this we will use software and data

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

Reproducibility of the chamber scarification test

DEFF Research Database (Denmark)

Andersen, Klaus Ejner

1996-01-01

The chamber scarification test is a predictive human skin irritation test developed to rank the irritation potential of products and ingredients meant for repeated use on normal and diseased skin. 12 products or ingredients can be tested simultaneously on the forearm skin of each volunteer....... The test combines with the procedure scratching of the skin at each test site and subsequent closed patch tests with the products, repeated daily for 3 days. The test is performed on groups of human volunteers: a skin irritant substance or products is included in each test as a positive control...... high reproducibility of the test. Further, intra-individual variation in skin reaction to the 2 control products in 26 volunteers, who participated 2x, is shown, which supports the conclusion that the chamber scarification test is a useful short-term human skin irritation test with high reproducibility....

New insights into pathophysiology of vestibular migraine

Directory of Open Access Journals (Sweden)

Juan Manuel Espinosa-Sanchez

2015-02-01

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

Insights into Pathophysiology from Medication-induced Tremor

Directory of Open Access Journals (Sweden)

John C. Morgan

2017-10-01

Full Text Available Background: Medication-induced tremor (MIT is common in clinical practice and there are many medications/drugs that can cause or exacerbate tremors. MIT typically occurs by enhancement of physiological tremor (EPT, but not all drugs cause tremor in this way. In this manuscript, we review how some common examples of MIT have informed us about the pathophysiology of tremor.Methods: We performed a PubMed literature search for published articles dealing with MIT and attempted to identify articles that especially dealt with the medication’s mechanism of inducing tremor.Results: There is a paucity of literature that deals with the mechanisms of MIT, with most manuscripts only describing the frequency and clinical settings where MIT is observed. That being said, MIT emanates from multiple mechanisms depending on the drug and it often takes an individualized approach to manage MIT in a given patient.Discussion: MIT has provided some insight into the mechanisms of tremors we see in clinical practice. The exact mechanism of MIT is unknown for most medications that cause tremor, but it is assumed that in most cases physiological tremor is influenced by these medications. Some medications (epinephrine that cause EPT likely lead to tremor by peripheral mechanisms in the muscle (β-adrenergic agonists, but others may influence the central component (amitriptyline. Other drugs can cause tremor, presumably by blockade of dopamine receptors in the basal ganglia (dopamine-blocking agents, by secondary effects such as causing hyperthyroidism (amiodarone, or by other mechanisms. We will attempt to discuss what is known and unknown about the pathophysiology of the most common MITs.

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.

Science.gov (United States)

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.

Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.

Science.gov (United States)

Bumb, J M; Enning, F; Mueller, J K; van der List, Till; Rohleder, C; Findeisen, P; Noelte, I; Schwarz, E; Leweke, F M

2016-07-01

Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. In CSF, melatonin levels were significantly decreased in bipolar (Pdepressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimating the reproducibility of psychological science

NARCIS (Netherlands)

Anderson, Joanna E.; Aarts, Alexander A.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahník, Štěpán; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Brüning, Jovita; Calhoun-Sauls, Ann; Callahan, Shannon P.; Chagnon, Elizabeth; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Christopherson, Cody D.; Cillessen, Linda; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Conn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Alvarez, Leslie D Cramblet; Cremata, Ed; Crusius, Jan; DeCoster, Jamie; DeGaetano, Michelle A.; Penna, Nicolás Delia; Den Bezemer, Bobby; Deserno, Marie K.; Devitt, Olivia; Dewitte, Laura; Dobolyi, David G.; Dodson, Geneva T.; Donnellan, M. Brent; Donohue, Ryan; Dore, Rebecca A.; Dorrough, Angela; Dreber, Anna; Dugas, Michelle; Dunn, Elizabeth W.; Easey, Kayleigh; Eboigbe, Sylvia; Eggleston, Casey; Embley, Jo; Epskamp, Sacha; Errington, Timothy M.; Estel, Vivien; Farach, Frank J.; Feather, Jenelle; Fedor, Anna; Fernández-Castilla, Belén; Fiedler, Susann; Field, James G.; Fitneva, Stanka A.; Flagan, Taru; Forest, Amanda L.; Forsell, Eskil; Foster, Joshua D.; Frank, Michael C.; Frazier, Rebecca S.; Fuchs, Heather; Gable, Philip; Galak, Jeff; Galliani, Elisa Maria; Gampa, Anup; Garcia, Sara; Gazarian, Douglas; Gilbert, Elizabeth; Giner-Sorolla, Roger; Glöckner, Andreas; Goellner, Lars; Goh, Jin X.; Goldberg, Rebecca; Goodbourn, Patrick T.; Gordon-McKeon, Shauna; Gorges, Bryan; Gorges, Jessie; Goss, Justin; Graham, Jesse; Grange, James A.; Gray, Jeremy; Hartgerink, Chris; Hartshorne, Joshua; Hasselman, Fred; Hayes, Timothy; Heikensten, Emma; Henninger, Felix; Hodsoll, John; Holubar, Taylor; Hoogendoorn, Gea; Humphries, Denise J.; Hung, Cathy O Y; Immelman, Nathali; Irsik, Vanessa C.; Jahn, Georg; Jäkel, Frank; Jekel, Marc; Johannesson, Magnus; Johnson, Larissa G.; Johnson, David J.; Johnson, Kate M.; Johnston, William J.; Jonas, Kai; Joy-Gaba, Jennifer A.; Kappes, Heather Barry; Kelso, Kim; Kidwell, Mallory C.; Kim, Seung Kyung; Kirkhart, Matthew; Kleinberg, Bennett; Knežević, Goran; Kolorz, Franziska Maria; Kossakowski, Jolanda J.; Krause, Robert Wilhelm; Krijnen, Job; Kuhlmann, Tim; Kunkels, Yoram K.; Kyc, Megan M.; Lai, Calvin K.; Laique, Aamir; Lakens, Daniël|info:eu-repo/dai/nl/298811855; Lane, Kristin A.; Lassetter, Bethany; Lazarević, Ljiljana B.; Le Bel, Etienne P.; Lee, Key Jung; Lee, Minha; Lemm, Kristi; Levitan, Carmel A.; Lewis, Melissa; Lin, Lin; Lin, Stephanie; Lippold, Matthias; Loureiro, Darren; Luteijn, Ilse; MacKinnon, Sean; Mainard, Heather N.; Marigold, Denise C.; Martin, Daniel P.; Martinez, Tylar; Masicampo, E. J.; Matacotta, Josh; Mathur, Maya; May, Michael; Mechin, Nicole; Mehta, Pranjal; Meixner, Johannes; Melinger, Alissa; Miller, Jeremy K.; Miller, Mallorie; Moore, Katherine; Möschl, Marcus; Motyl, Matt; Müller, Stephanie M.; Munafo, Marcus; Neijenhuijs, Koen I.; Nervi, Taylor; Nicolas, Gandalf; Nilsonne, Gustav; Nosek, Brian A.; Nuijten, Michèle B.; Olsson, Catherine; Osborne, Colleen; Ostkamp, Lutz; Pavel, Misha; Penton-Voak, Ian S.; Perna, Olivia; Pernet, Cyril; Perugini, Marco; Pipitone, R. Nathan; Pitts, Michael; Plessow, Franziska; Prenoveau, Jason M.; Rahal, Rima Maria; Ratliff, Kate A.; Reinhard, David; Renkewitz, Frank; Ricker, Ashley A.; Rigney, Anastasia; Rivers, Andrew M.; Roebke, Mark; Rutchick, Abraham M.; Ryan, Robert S.; Sahin, Onur; Saide, Anondah; Sandstrom, Gillian M.; Santos, David; Saxe, Rebecca; Schlegelmilch, René; Schmidt, Kathleen; Scholz, Sabine; Seibel, Larissa; Selterman, Dylan Faulkner; Shaki, Samuel; Simpson, William B.; Sinclair, H. Colleen; Skorinko, Jeanine L M; Slowik, Agnieszka; Snyder, Joel S.; Soderberg, Courtney; Sonnleitner, Carina; Spencer, Nick; Spies, Jeffrey R.; Steegen, Sara; Stieger, Stefan; Strohminger, Nina; Sullivan, Gavin B.; Talhelm, Thomas; Tapia, Megan; Te Dorsthorst, Anniek; Thomae, Manuela; Thomas, Sarah L.; Tio, Pia; Traets, Frits; Tsang, Steve; Tuerlinckx, Francis; Turchan, Paul; Valášek, Milan; Van't Veer, Anna E.; Van Aert, Robbie; Van Assen, Marcel|info:eu-repo/dai/nl/407629971; Van Bork, Riet; Van De Ven, Mathijs; Van Den Bergh, Don; Van Der Hulst, Marije; Van Dooren, Roel; Van Doorn, Johnny; Van Renswoude, Daan R.; Van Rijn, Hedderik; Vanpaemel, Wolf; Echeverría, Alejandro Vásquez; Vazquez, Melissa; Velez, Natalia; Vermue, Marieke; Verschoor, Mark; Vianello, Michelangelo; Voracek, Martin; Vuu, Gina; Wagenmakers, Eric Jan; Weerdmeester, Joanneke; Welsh, Ashlee; Westgate, Erin C.; Wissink, Joeri; Wood, Michael; Woods, Andy; Wright, Emily; Wu, Sining; Zeelenberg, Marcel; Zuni, Kellylynn

2015-01-01

Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available.

Preeclampsia: from Pathophysiology to Treatment

Directory of Open Access Journals (Sweden)

Kaculini Enton

2016-12-01

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

Modelling of Pb release during Portland cement alteration

Energy Technology Data Exchange (ETDEWEB)

Benard, A. [INERIS Mediterrannee, F-13545 Aix En Provence 04 (France); Rose, J.; Borschneck, D.; Bottero, J.Y. [Univ Paul Cezanne, CNRS, UMR 6635, CEREGE, IFR PMSE 112, F-13545 Aix En Provence, (France); Hazemann, J.L. [CNRS, Cristallog Lab, F-38042 Grenoble 09 (France); Proux, O. [Univ Grenoble 1, CNRS, UMR, LGIT, F-38400 St Martin Dheres (France); Trotignon, L. [CEA Cadarache, DTN, SMTM, Lab Modelisat Transferts Environm, 13 - Saint Paul lez Durance (France); Nonat, A. [Univ Bourgogne, CNRS, UMR 5613, Fac Sci Mirande, Lab Rech Reactivite Solides, F-21078 Dijon (France); Chateau, L. [ADEME, F-49004 Angers (France)

2009-07-01

Complex cementitious matrices undergo weathering with environmental exchange and can release metallic pollutants during alteration. The molecular mechanisms responsible for metal release are difficult to identify, though this is necessary if such processes are to be controlled. The present study determines and models the molecular mechanisms of Pb release during Portland cement leaching. As Pb release is strongly related to its speciation (i.e. atomic environment and the nature of bearing phases), the first objective of the present study was to investigate the evolution of Pb retention sites together with the evolution of the cement mineralogy during leaching. Complementary and efficient investigation tools were used, namely X-ray diffraction, micro-X-ray fluorescence and X-ray absorption fine structures. The second objective was to reproduce our results with a reactive transport code (CHESS/HYTEC) in order to test the proposed speciation model of Pb. Combined results indicate that in both the unaltered core and the altered layer of the leached cement, Pb(II) would be retained through C-S-H 'nano-structure', probably linked to a Q(1) or Q(2P) silicate tetrahedra. Moreover in the altered layer, the presence of Fe atoms in the atomic environment of Pb is highly probable. Unfortunately little is known about Fe phases in cement, which makes the interpretation difficult. Can Fe-substituted hydrogranet (C(3)AH(6)) be responsible for Pb retention? Modelling results were consistent with Pb retention through C-S-H in layers and also in an additional, possibly Fe-containing, Pb-retention phase in the altered layer. (authors)

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

Science.gov (United States)

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.

Reproducibility problems of in-service ultrasonic testing results

International Nuclear Information System (INIS)

Honcu, E.

1974-01-01

The reproducibility of the results of ultrasonic testing is the basic precondition for its successful application in in-service inspection of changes in the quality of components of nuclear power installations. The results of periodic ultrasonic inspections are not satisfactory from the point of view of reproducibility. Regardless, the ultrasonic pulse-type method is suitable for evaluating the quality of most components of nuclear installations and often the sole method which may be recommended for inspection with regard to its technical and economic aspects. (J.B.)

Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

Directory of Open Access Journals (Sweden)

Catherine J. Andersen

2018-06-01

Full Text Available Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases. Research evaluating the effects of dietary cholesterol, often provided by eggs or as a component of Western-style diets, demonstrates that cholesterol-rich dietary patterns affect markers of immune inflammation and cellular cholesterol metabolism, while additionally modulating lipoprotein profiles and functional properties of HDL. Further, cholesterol-rich diets appear to differentially impact immunomodulatory lipid pathways across human populations of variable metabolic status, suggesting that these complex mechanisms may underlie the relationship between dietary cholesterol and immunity. Given the Dietary Guidelines for Americans 2015–2020 revision to no longer include limitations on dietary cholesterol, evaluation of dietary cholesterol recommendations beyond the context of cardiovascular disease risk is particularly timely. This review provides a comprehensive and comparative analysis of significant and controversial studies on the role of dietary cholesterol and lipid metabolism in the pathophysiology of infectious disease and autoimmune disorders, highlighting the need for further investigation in this developing area of research.

Pathophysiology of Portal Hypertension and Its Clinical Links

Science.gov (United States)

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

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

Science.gov (United States)

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

2015-09-29

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic-pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18-65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are

Effective Form of Reproducing the Total Financial Potential of Ukraine

Directory of Open Access Journals (Sweden)

Portna Oksana V.

2015-03-01

Full Text Available Development of scientific principles of reproducing the total financial potential of the country and its effective form is an urgent problem both in theoretical and practical aspects of the study, the solution of which is intended to ensure the active mobilization and effective use of the total financial potential of Ukraine, and as a result — its expanded reproduction as well, which would contribute to realization of the internal capacities for stabilization of the national economy. The purpose of the article is disclosing the essence of the effective form of reproducing the total financial potential of the country, analyzing the results of reproducing the total financial potential of Ukraine. It has been proved that the basis for the effective form of reproducing the total financial potential of the country is the volume and flow of resources, which are associated with the «real» economy, affect the dynamics of GDP and define it, i.e. resource and process forms of reproducing the total financial potential of Ukraine (which precede the effective one. The analysis of reproducing the total financial potential of Ukraine has shown that in the analyzed period there was an increase in the financial possibilities of the country, but steady dynamics of reduction of the total financial potential was observed. If we consider the amount of resources involved in production, creating a net value added and GDP, it occurs on a restricted basis. Growth of the total financial potential of Ukraine is connected only with extensive quantitative factors rather than intensive qualitative changes.

The MIMIC Code Repository: enabling reproducibility in critical care research.

Science.gov (United States)

Johnson, Alistair Ew; Stone, David J; Celi, Leo A; Pollard, Tom J

2018-01-01

Lack of reproducibility in medical studies is a barrier to the generation of a robust knowledge base to support clinical decision-making. In this paper we outline the Medical Information Mart for Intensive Care (MIMIC) Code Repository, a centralized code base for generating reproducible studies on an openly available critical care dataset. Code is provided to load the data into a relational structure, create extractions of the data, and reproduce entire analysis plans including research studies. Concepts extracted include severity of illness scores, comorbid status, administrative definitions of sepsis, physiologic criteria for sepsis, organ failure scores, treatment administration, and more. Executable documents are used for tutorials and reproduce published studies end-to-end, providing a template for future researchers to replicate. The repository's issue tracker enables community discussion about the data and concepts, allowing users to collaboratively improve the resource. The centralized repository provides a platform for users of the data to interact directly with the data generators, facilitating greater understanding of the data. It also provides a location for the community to collaborate on necessary concepts for research progress and share them with a larger audience. Consistent application of the same code for underlying concepts is a key step in ensuring that research studies on the MIMIC database are comparable and reproducible. By providing open source code alongside the freely accessible MIMIC-III database, we enable end-to-end reproducible analysis of electronic health records. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

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.

Science.gov (United States)

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.

Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects.

Science.gov (United States)

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.

Altered brain network measures in patients with primary writing tremor

Energy Technology Data Exchange (ETDEWEB)

Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant [National Institute of Mental Health and Neurosciences, Department of Clinical Neurosciences, Bangalore, Karnataka (India); National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India); Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn [National Institute of Mental Health and Neurosciences, Department of Neuroimaging and Interventional Radiology, Bangalore, Karnataka (India); Yadav, Ravi; Pal, Pramod Kumar [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India)

2017-10-15

Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results. (orig.)

Altered brain network measures in patients with primary writing tremor.

Science.gov (United States)

Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn; Yadav, Ravi; Pal, Pramod Kumar

2017-10-01

Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results.

Altered brain network measures in patients with primary writing tremor

International Nuclear Information System (INIS)

Lenka, Abhishek; Jhunjhunwala, Ketan Ramakant; Panda, Rajanikant; Saini, Jitender; Bharath, Rose Dawn; Yadav, Ravi; Pal, Pramod Kumar

2017-01-01

Primary writing tremor (PWT) is a rare task-specific tremor, which occurs only while writing or while adopting the hand in the writing position. The basic pathophysiology of PWT has not been fully understood. The objective of this study is to explore the alterations in the resting state functional brain connectivity, if any, in patients with PWT using graph theory-based analysis. This prospective case-control study included 10 patients with PWT and 10 age and gender matched healthy controls. All subjects underwent MRI in a 3-Tesla scanner. Several parameters of small-world functional connectivity were compared between patients and healthy controls by using graph theory-based analysis. There were no significant differences in age, handedness (all right handed), gender distribution (all were males), and MMSE scores between the patients and controls. The mean age at presentation of tremor in the patient group was 51.7 ± 8.6 years, and the mean duration of tremor was 3.5 ± 1.9 years. Graph theory-based analysis revealed that patients with PWT had significantly lower clustering coefficient and higher path length compared to healthy controls suggesting alterations in small-world architecture of the brain. The clustering coefficients were lower in PWT patients in left and right medial cerebellum, right dorsolateral prefrontal cortex (DLPFC), and left posterior parietal cortex (PPC). Patients with PWT have significantly altered small-world brain connectivity in bilateral medial cerebellum, right DLPFC, and left PPC. Further studies with larger sample size are required to confirm our results. (orig.)

Reproducibility of scoring emphysema by HRCT

International Nuclear Information System (INIS)

Malinen, A.; Partanen, K.; Rytkoenen, H.; Vanninen, R.; Erkinjuntti-Pekkanen, R.

2002-01-01

Purpose: We evaluated the reproducibility of three visual scoring methods of emphysema and compared these methods with pulmonary function tests (VC, DLCO, FEV1 and FEV%) among farmer's lung patients and farmers. Material and Methods: Three radiologists examined high-resolution CT images of farmer's lung patients and their matched controls (n=70) for chronic interstitial lung diseases. Intraobserver reproducibility and interobserver variability were assessed for three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as spirometry and diffusing capacity were measured. Results: Intraobserver -values for all three methods were good (0.51-0.74). Interobserver varied from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with pulmonary function tests, especially DLCO and FEV1. Conclusion: The Sanders' method proved to be reliable in evaluating emphysema, in terms of good consistency of interpretation and good correlation with pulmonary function tests

Using prediction markets to estimate the reproducibility of scientific research

Science.gov (United States)

Dreber, Anna; Pfeiffer, Thomas; Almenberg, Johan; Isaksson, Siri; Wilson, Brad; Chen, Yiling; Nosek, Brian A.; Johannesson, Magnus

2015-01-01

Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants’ individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a “statistically significant” finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications. PMID:26553988

Using prediction markets to estimate the reproducibility of scientific research.

Science.gov (United States)

Dreber, Anna; Pfeiffer, Thomas; Almenberg, Johan; Isaksson, Siri; Wilson, Brad; Chen, Yiling; Nosek, Brian A; Johannesson, Magnus

2015-12-15

Concerns about a lack of reproducibility of statistically significant results have recently been raised in many fields, and it has been argued that this lack comes at substantial economic costs. We here report the results from prediction markets set up to quantify the reproducibility of 44 studies published in prominent psychology journals and replicated in the Reproducibility Project: Psychology. The prediction markets predict the outcomes of the replications well and outperform a survey of market participants' individual forecasts. This shows that prediction markets are a promising tool for assessing the reproducibility of published scientific results. The prediction markets also allow us to estimate probabilities for the hypotheses being true at different testing stages, which provides valuable information regarding the temporal dynamics of scientific discovery. We find that the hypotheses being tested in psychology typically have low prior probabilities of being true (median, 9%) and that a "statistically significant" finding needs to be confirmed in a well-powered replication to have a high probability of being true. We argue that prediction markets could be used to obtain speedy information about reproducibility at low cost and could potentially even be used to determine which studies to replicate to optimally allocate limited resources into replications.

Composting in small laboratory pilots: Performance and reproducibility

International Nuclear Information System (INIS)

Lashermes, G.; Barriuso, E.; Le Villio-Poitrenaud, M.; Houot, S.

2012-01-01

Highlights: ► We design an innovative small-scale composting device including six 4-l reactors. ► We investigate the performance and reproducibility of composting on a small scale. ► Thermophilic conditions are established by self-heating in all replicates. ► Biochemical transformations, organic matter losses and stabilisation are realistic. ► The organic matter evolution exhibits good reproducibility for all six replicates. - Abstract: Small-scale reactors ( 2 consumption and CO 2 emissions, and characterising the biochemical evolution of organic matter. A good reproducibility was found for the six replicates with coefficients of variation for all parameters generally lower than 19%. An intense self-heating ensured the existence of a spontaneous thermophilic phase in all reactors. The average loss of total organic matter (TOM) was 46% of the initial content. Compared to the initial mixture, the hot water soluble fraction decreased by 62%, the hemicellulose-like fraction by 68%, the cellulose-like fraction by 50% and the lignin-like fractions by 12% in the final compost. The TOM losses, compost stabilisation and evolution of the biochemical fractions were similar to observed in large reactors or on-site experiments, excluding the lignin degradation, which was less important than in full-scale systems. The reproducibility of the process and the quality of the final compost make it possible to propose the use of this experimental device for research requiring a mass reduction of the initial composted waste mixtures.

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

Science.gov (United States)

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

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

Actin-Dependent Alterations of Dendritic Spine Morphology in Shankopathies

Directory of Open Access Journals (Sweden)

Tasnuva Sarowar

2016-01-01

Full Text Available Shank proteins (Shank1, Shank2, and Shank3 act as scaffolding molecules in the postsynaptic density of many excitatory neurons. Mutations in SHANK genes, in particular SHANK2 and SHANK3, lead to autism spectrum disorders (ASD in both human and mouse models. Shank3 proteins are made of several domains—the Shank/ProSAP N-terminal (SPN domain, ankyrin repeats, SH3 domain, PDZ domain, a proline-rich region, and the sterile alpha motif (SAM domain. Via various binding partners of these domains, Shank3 is able to bind and interact with a wide range of proteins including modulators of small GTPases such as RICH2, a RhoGAP protein, and βPIX, a RhoGEF protein for Rac1 and Cdc42, actin binding proteins and actin modulators. Dysregulation of all isoforms of Shank proteins, but especially Shank3, leads to alterations in spine morphogenesis, shape, and activity of the synapse via altering actin dynamics. Therefore, here, we highlight the role of Shank proteins as modulators of small GTPases and, ultimately, actin dynamics, as found in multiple in vitro and in vivo models. The failure to mediate this regulatory role might present a shared mechanism in the pathophysiology of autism-associated mutations, which leads to dysregulation of spine morphogenesis and synaptic signaling.

Reproducibility of esophageal scintigraphy using semi-solid yoghurt

Energy Technology Data Exchange (ETDEWEB)

Imai, Yukinori; Kinoshita, Manabu; Asakura, Yasushi; Kakinuma, Tohru; Shimoji, Katsunori; Fujiwara, Kenji; Suzuki, Kenji; Miyamae, Tatsuya [Saitama Medical School, Moroyama (Japan)

1999-10-01

Esophageal scintigraphy is a non-invasive method which evaluate esophageal function quantitatively. We applied new technique using semi-solid yoghurt, which can evaluate esophageal function in a sitting position. To evaluate the reproducibility of this method, scintigraphy were performed in 16 healthy volunteers. From the result of four swallows except the first one, the mean coefficients of variation in esophageal transit time and esophageal emptying time were 12.8% and 13.4% respectively (interday variation). As regards the interday variation, this method had also good reproducibility from the result on the 2 separate days. (author)

Estimating the reproducibility of psychological science

NARCIS (Netherlands)

Aarts, Alexander A.; Anderson, Joanna E.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahnik, Stepan; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Bruening, Jovita; Calhoun-Sauls, Ann; Chagnon, Elizabeth; Callahan, Shannon P.; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Cillessen, Linda; Christopherson, Cody D.; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Cohn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Hartgerink, Chris; Krijnen, Job; Nuijten, Michele B.; van 't Veer, Anna E.; Van Aert, Robbie; van Assen, M.A.L.M.; Wissink, Joeri; Zeelenberg, Marcel

2015-01-01

INTRODUCTION Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. Scientific claims should not gain credence because of the status or authority of their originator but by the replicability of their supporting evidence. Even research

CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

International Nuclear Information System (INIS)

Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

2011-01-01

CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

Reproducible insulin secretion from isolated rat pancreas preparations using an organ bath.

Science.gov (United States)

Morita, Asuka; Ouchi, Motoshi; Terada, Misao; Kon, Hiroe; Kishimoto, Satoko; Satoh, Keitaro; Otani, Naoyuki; Hayashi, Keitaro; Fujita, Tomoe; Inoue, Ken-Ichi; Anzai, Naohiko

2018-02-09

Diabetes mellitus is a lifestyle-related disease that is characterized by inappropriate or diminished insulin secretion. Ex vivo pharmacological studies of hypoglycemic agents are often conducted using perfused pancreatic preparations. Pancreas preparations for organ bath experiments do not require cannulation and are therefore less complex than isolated perfused pancreas preparations. However, previous research has generated almost no data on insulin secretion from pancreas preparations using organ bath preparations. The purpose of this study was to investigate the applicability of isolated rat pancreas preparations using the organ bath technique in the quantitative analysis of insulin secretion from β-cells. We found that insulin secretion significantly declined during incubation in the organ bath, whereas it was maintained in the presence of 1 µM GLP-1. Conversely, amylase secretion exhibited a modest increase during incubation and was not altered in the presence of GLP-1. These results demonstrate that the pancreatic organ bath preparation is a sensitive and reproducible method for the ex vivo assessment of the pharmacological properties of hypoglycemic agents.

Magnet stability and reproducibility

CERN Document Server

Marks, N

2010-01-01

Magnet stability and reproducibility have become increasingly important as greater precision and beams with smaller dimension are required for research, medical and other purpose. The observed causes of mechanical and electrical instability are introduced and the engineering arrangements needed to minimize these problems discussed; the resulting performance of a state-of-the-art synchrotron source (Diamond) is then presented. The need for orbit feedback to obtain best possible beam stability is briefly introduced, but omitting any details of the necessary technical equipment, which is outside the scope of the presentation.

Multi-disciplinary management of athletes with post-concussion syndrome: an evolving pathophysiological approach

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.

Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach.

Science.gov (United States)

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 Impact of Neuroimmune Alterations in Autism Spectrum Disorder

Science.gov (United States)

Gottfried, Carmem; Bambini-Junior, Victorio; Francis, Fiona; Riesgo, Rudimar; Savino, Wilson

2015-01-01

Autism spectrum disorder (ASD) involves a complex interplay of both genetic and environmental risk factors, with immune alterations and synaptic connection deficiency in early life. In the past decade, studies of ASD have substantially increased, in both humans and animal models. Immunological imbalance (including autoimmunity) has been proposed as a major etiological component in ASD, taking into account increased levels of pro-inflammatory cytokines observed in postmortem brain from patients, as well as autoantibody production. Also, epidemiological studies have established a correlation of ASD with family history of autoimmune diseases; associations with major histocompatibility complex haplotypes and abnormal levels of immunological markers in the blood. Moreover, the use of animal models to study ASD is providing increasing information on the relationship between the immune system and the pathophysiology of ASD. Herein, we will discuss the accumulating literature for ASD, giving special attention to the relevant aspects of factors that may be related to the neuroimmune interface in the development of ASD, including changes in neuroplasticity. PMID:26441683

Migraine aura pathophysiology: the role of blood vessels and microembolisation

OpenAIRE

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...

Reproducibility of scoring emphysema by HRCT

Energy Technology Data Exchange (ETDEWEB)

Malinen, A.; Partanen, K.; Rytkoenen, H.; Vanninen, R. [Kuopio Univ. Hospital (Finland). Dept. of Clinical Radiology; Erkinjuntti-Pekkanen, R. [Kuopio Univ. Hospital (Finland). Dept. of Pulmonary Diseases

2002-04-01

Purpose: We evaluated the reproducibility of three visual scoring methods of emphysema and compared these methods with pulmonary function tests (VC, DLCO, FEV1 and FEV%) among farmer's lung patients and farmers. Material and Methods: Three radiologists examined high-resolution CT images of farmer's lung patients and their matched controls (n=70) for chronic interstitial lung diseases. Intraobserver reproducibility and interobserver variability were assessed for three methods: severity, Sanders' (extent) and Sakai. Pulmonary function tests as spirometry and diffusing capacity were measured. Results: Intraobserver -values for all three methods were good (0.51-0.74). Interobserver varied from 0.35 to 0.72. The Sanders' and the severity methods correlated strongly with pulmonary function tests, especially DLCO and FEV1. Conclusion: The Sanders' method proved to be reliable in evaluating emphysema, in terms of good consistency of interpretation and good correlation with pulmonary function tests.

Additive Manufacturing: Reproducibility of Metallic Parts

Directory of Open Access Journals (Sweden)

Konda Gokuldoss Prashanth

2017-02-01

Full Text Available The present study deals with the properties of five different metals/alloys (Al-12Si, Cu-10Sn and 316L—face centered cubic structure, CoCrMo and commercially pure Ti (CP-Ti—hexagonal closed packed structure fabricated by selective laser melting. The room temperature tensile properties of Al-12Si samples show good consistency in results within the experimental errors. Similar reproducible results were observed for sliding wear and corrosion experiments. The other metal/alloy systems also show repeatable tensile properties, with the tensile curves overlapping until the yield point. The curves may then follow the same path or show a marginal deviation (~10 MPa until they reach the ultimate tensile strength and a negligible difference in ductility levels (of ~0.3% is observed between the samples. The results show that selective laser melting is a reliable fabrication method to produce metallic materials with consistent and reproducible properties.

Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

Directory of Open Access Journals (Sweden)

Christopher B Massa

2017-08-01

Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

Science.gov (United States)

Massa, Christopher B; Groves, Angela M; Jaggernauth, Smita U; Laskin, Debra L; Gow, Andrew J

2017-08-01

Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at

Studies on the Pathophysiology and Genetic Basis of Migraine

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

Pompili, Cecilia; Miserocchi, Giuseppe

2016-02-01

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

Recent developments in the pathophysiology of irritable bowel syndrome.

Science.gov (United States)

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.

The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder.

Science.gov (United States)

Kim, Yong-Ku; Won, Eunsoo

2017-06-30

Major depressive disorder (MDD) is a condition which has often been associated with chronic stress. The sympathetic nervous system is continuously activated without the normal counteraction of the parasympathetic nervous system under the influence of chronic stress. As a result, epinephrine and norepinephrine levels are increased, and acetylcholine levels are decreased, which in turn can increase the levels of pro-inflammatory cytokines. Peripheral inflammatory responses can access the brain, with neuroinflammation contributing to the increase in neurotoxic kynurenine pathway metabolites such as 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid, and decrease in neuroprotective metabolites such as kynurenic acid. Pro-inflammatory cytokines can also exert direct neurotoxic effects on specific brain regions. Previous imaging studies have reported associations between pro-inflammatory states and alterations in brain regions involved in emotional regulation, including the hippocampus, amygdala and anterior cingulate cortex. Alterations in structure and function of such brain areas due to the neurotoxic effects of increased inflammation may be associated with the pathophysiology of depression. This review focuses the influence of stress on neuroinflammation which may cause alterations in brain structure and function in MDD. Copyright © 2017. Published by Elsevier B.V.

Toxic AGE (TAGE Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD

Directory of Open Access Journals (Sweden)

Masayoshi Takeuchi

2017-06-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD and alcoholic liver disease (ALD are among the most common causes of chronic liver diseases in the westernized world. NAFLD and ALD are frequently accompanied by extrahepatic complications, including hepatocellular carcinoma and cardiovascular diseases, which have a negative impact on patient survival. The chronic ingestion of an excessive daily diet containing sugar/high-fructose corn syrup increases the level of the fructose/glucose metabolite, glyceraldehyde (GA, while the chronic consumption of an excessive number of alcoholic beverages increases the level of the alcohol metabolite, acetaldehyde (AA in the liver. GA and AA are known to react non-enzymatically with the ε- or α-amino groups of proteins, thereby generating advanced glycation end-products (AGEs, GA-AGEs, and AA-AGEs, respectively in vivo. The interaction between GA-AGEs and the receptor for AGEs (RAGE alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and also elicits the production of reactive oxygen species by human hepatocytes and hepatic stellate cells, all of which may contribute to the pathological changes associated with chronic liver diseases. We herein discuss the pathophysiological roles of GA-AGEs and AA-AGEs (toxic AGEs, TAGE and a related novel theory for preventing the onset/progression of NAFLD and ALD.

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...

Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity

Directory of Open Access Journals (Sweden)

Nathalie eCastanon

2015-07-01

Full Text Available Obesity is associated with a high prevalence of mood disorders and cognitive dysfunctions in addition to being a significant risk factor for important health complications such as cardiovascular diseases and type 2 diabetes. Identifying the pathophysiological mechanisms underlying these health issues is a major public health challenge. Based on recent findings, from studies conducted on animal models of obesity, it has been proposed that inflammatory processes may participate in both the peripheral and brain disorders associated with the obesity condition including the development of emotional and cognitive alterations. This is supported by the fact that obesity is characterized by peripheral low-grade inflammation, originating from increased adipose tissue mass and/or dysbiosis (changes in gut microbiota environment, both of which contribute to increased susceptibility to immune-mediated diseases. In this review, we provide converging evidence showing that obesity is associated with exacerbated neuroinflammation leading to dysfunction in vulnerable brain regions associated with mood regulation, learning and memory such as the hippocampus. These findings give new insights to the pathophysiological mechanisms contributing to the development of brain disorders in the context of obesity and provide valuable data for introducing new therapeutic strategies for the treatment of neuropsychiatric complications often reported in obese patients.

Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells

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Anne L Fletcher

2011-09-01

Full Text Available Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naïve T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture.

Pancreatitis in dogs and cats – definitions and pathophysiology

OpenAIRE

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...

Anhedonic behavior in cryptochrome 2-deficient mice is paralleled by altered diurnal patterns of amygdala gene expression.

Science.gov (United States)

Savalli, Giorgia; Diao, Weifei; Berger, Stefanie; Ronovsky, Marianne; Partonen, Timo; Pollak, Daniela D

2015-07-01

Mood disorders are frequently paralleled by disturbances in circadian rhythm-related physiological and behavioral states and genetic variants of clock genes have been associated with depression. Cryptochrome 2 (Cry2) is one of the core components of the molecular circadian machinery which has been linked to depression, both, in patients suffering from the disease and animal models of the disorder. Despite this circumstantial evidence, a direct causal relationship between Cry2 expression and depression has not been established. Here, a genetic mouse model of Cry2 deficiency (Cry2 (-/-) mice) was employed to test the direct relevance of Cry2 for depression-like behavior. Augmented anhedonic behavior in the sucrose preference test, without alterations in behavioral despair, was observed in Cry2 (-/-) mice. The novelty suppressed feeding paradigm revealed reduced hyponeophagia in Cry2 (-/-) mice compared to wild-type littermates. Given the importance of the amygdala in the regulation of emotion and their relevance for the pathophysiology of depression, potential alterations in diurnal patterns of basolateral amygdala gene expression in Cry2 (-/-) mice were investigated focusing on core clock genes and neurotrophic factor systems implicated in the pathophysiology of depression. Differential expression of the clock gene Bhlhe40 and the neurotrophic factor Vegfb were found in the beginning of the active (dark) phase in Cry2 (-/-) compared to wild-type animals. Furthermore, amygdala tissue of Cry2 (-/-) mice contained lower levels of Bdnf-III. Collectively, these results indicate that Cry2 exerts a critical role in the control of depression-related emotional states and modulates the chronobiological gene expression profile in the mouse amygdala.

Pathophysiological Mechanisms of Laser Correction in Critical Conditions

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V. L. Kozhura

2006-01-01

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

The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.

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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.

Altered cortical hubs in functional brain networks in amyotrophic lateral sclerosis.

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Ma, Xujing; Zhang, Jiuquan; Zhang, Youxue; Chen, Heng; Li, Rong; Wang, Jian; Chen, Huafu

2015-11-01

Cortical hubs are highly connected nodes in functional brain networks that play vital roles in the efficient transfer of information across brain regions. Although altered functional connectivity has been found in amyotrophic lateral sclerosis (ALS), the changing pattern in functional network hubs in ALS remains unknown. In this study, we applied a voxel-wise method to investigate the changing pattern of cortical hubs in ALS. Through resting-state fMRI, we constructed whole-brain voxel-wise functional networks by measuring the temporal correlations of each pair of brain voxels and identified hubs using the graph theory method. Specifically, a functional connectivity strength (FCS) map was derived from the data on 20 patients with ALS and 20 healthy controls. The brain regions with high FCS values were regarded as functional network hubs. Functional hubs were found mainly in the bilateral precuneus, parietal cortex, medial prefrontal cortex, and in several visual regions and temporal areas in both groups. Within the hub regions, the ALS patients exhibited higher FCS in the prefrontal cortex compared with the healthy controls. The FCS value in the significantly abnormal hub regions was correlated with clinical variables. Results indicated the presence of altered cortical hubs in the ALS patients and could therefore shed light on the pathophysiology mechanisms underlying ALS.

Reproducibility in cyclostratigraphy: initiating an intercomparison project

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Sinnesael, Matthias; De Vleeschouwer, David; Zeeden, Christian; Claeys, Philippe

2017-04-01

The study of astronomical climate forcing and the application of cyclostratigraphy have experienced a spectacular growth over the last decades. In the field of cyclostratigraphy a broad range in methodological approaches exist. However, comparative study between the different approaches is lacking. Different cases demand different approaches, but with the growing importance of the field, questions arise about reproducibility, uncertainties and standardization of results. The radioisotopic dating community, in particular, has done far-reaching efforts to improve reproducibility and intercomparison of radioisotopic dates and their errors. To satisfy this need in cyclostratigraphy, we initiate a comparable framework for the community. The aims are to investigate and quantify reproducibility of, and uncertainties related to cyclostratigraphic studies and to provide a platform to discuss the merits and pitfalls of different methodologies, and their applicabilities. With this poster, we ask the feedback from the community on how to design this comparative framework in a useful, meaningful and productive manner. In parallel, we would like to discuss how reproducibility should be tested and what uncertainties should stand for in cyclostratigraphy. On the other hand, we intend to trigger interest for a cyclostratigraphic intercomparison project. This intercomparison project would imply the analysis of artificial and genuine geological records by individual researchers. All participants would be free to determine their method of choice. However, a handful of criterions will be required for an outcome to be comparable. The different results would be compared (e.g. during a workshop or a special session), and the lessons learned from the comparison could potentially be reported in a review paper. The aim of an intercomparison project is not to rank the different methods according to their merits, but to get insight into which specific methods are most suitable for which

Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

OpenAIRE

Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

2017-01-01

Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

The quest for improved reproducibility in MALDI mass spectrometry.

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O'Rourke, Matthew B; Djordjevic, Steven P; Padula, Matthew P

2018-03-01

Reproducibility has been one of the biggest hurdles faced when attempting to develop quantitative protocols for MALDI mass spectrometry. The heterogeneous nature of sample recrystallization has made automated sample acquisition somewhat "hit and miss" with manual intervention needed to ensure that all sample spots have been analyzed. In this review, we explore the last 30 years of literature and anecdotal evidence that has attempted to address and improve reproducibility in MALDI MS. Though many methods have been attempted, we have discovered a significant publication history surrounding the use of nitrocellulose as a substrate to improve homogeneity of crystal formation and therefore reproducibility. We therefore propose that this is the most promising avenue of research for developing a comprehensive and universal preparation protocol for quantitative MALDI MS analysis. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:217-228, 2018. © 2016 Wiley Periodicals, Inc.

Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents.

NARCIS (Netherlands)

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

Reproducibility of the cutoff probe for the measurement of electron density

Energy Technology Data Exchange (ETDEWEB)

Kim, D. W.; Oh, W. Y. [Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); You, S. J., E-mail: sjyou@cnu.ac.kr [Department of Physics, Chungnam National University, Daejeon 305-701 (Korea, Republic of); Kwon, J. H.; You, K. H.; Seo, B. H.; Kim, J. H., E-mail: jhkim86@kriss.re.kr [Center for Vacuum Technology, Korea Research Institute of Standards and Science, Daejeon 305-306 (Korea, Republic of); Yoon, J.-S. [Plasma Technology Research Center, National Fusion Research Institute, Gunsan 573-540 (Korea, Republic of)

2016-06-15

Since a plasma processing control based on plasma diagnostics attracted considerable attention in industry, the reproducibility of the diagnostics using in this application has become a great interest. Because the cutoff probe is one of the potential candidates for this application, knowing the reproducibility of the cutoff probe measurement becomes quit important in the cutoff probe application research. To test the reproducibility of the cutoff probe measurement, in this paper, a comparative study among the different cutoff probe measurements was performed. The comparative study revealed remarkable result: the cutoff probe has a great reproducibility for the electron density measurement, i.e., there are little differences among measurements by different probes made by different experimenters. The discussion including the reason for the result was addressed via this paper by using a basic measurement principle of cutoff probe and a comparative experiment with Langmuir probe.

Reproducibility of the cutoff probe for the measurement of electron density

International Nuclear Information System (INIS)

Kim, D. W.; Oh, W. Y.; You, S. J.; Kwon, J. H.; You, K. H.; Seo, B. H.; Kim, J. H.; Yoon, J.-S.

2016-01-01

Since a plasma processing control based on plasma diagnostics attracted considerable attention in industry, the reproducibility of the diagnostics using in this application has become a great interest. Because the cutoff probe is one of the potential candidates for this application, knowing the reproducibility of the cutoff probe measurement becomes quit important in the cutoff probe application research. To test the reproducibility of the cutoff probe measurement, in this paper, a comparative study among the different cutoff probe measurements was performed. The comparative study revealed remarkable result: the cutoff probe has a great reproducibility for the electron density measurement, i.e., there are little differences among measurements by different probes made by different experimenters. The discussion including the reason for the result was addressed via this paper by using a basic measurement principle of cutoff probe and a comparative experiment with Langmuir probe.

Reproducibility between conventional and digital periapical radiography for bone height measurement

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Miguel Simancas Pallares

2015-10-01

Conclusions. Reproducibility between methods was considered poor, including subgroup analysis, therefore, reproducibility between methods is minimal. Usage of these methods in periodontics should be made implementing the whole knowledge of the technical features and the advantages of these systems.

Reproducibility Between Brain Uptake Ratio Using Anatomic Standardization and Patlak-Plot Methods.

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Shibutani, Takayuki; Onoguchi, Masahisa; Noguchi, Atsushi; Yamada, Tomoki; Tsuchihashi, Hiroko; Nakajima, Tadashi; Kinuya, Seigo

2015-12-01

The Patlak-plot and conventional methods of determining brain uptake ratio (BUR) have some problems with reproducibility. We formulated a method of determining BUR using anatomic standardization (BUR-AS) in a statistical parametric mapping algorithm to improve reproducibility. The objective of this study was to demonstrate the inter- and intraoperator reproducibility of mean cerebral blood flow as determined using BUR-AS in comparison to the conventional-BUR (BUR-C) and Patlak-plot methods. The images of 30 patients who underwent brain perfusion SPECT were retrospectively used in this study. The images were reconstructed using ordered-subset expectation maximization and processed using an automatic quantitative analysis for cerebral blood flow of ECD tool. The mean SPECT count was calculated from axial basal ganglia slices of the normal side (slices 31-40) drawn using a 3-dimensional stereotactic region-of-interest template after anatomic standardization. The mean cerebral blood flow was calculated from the mean SPECT count. Reproducibility was evaluated using coefficient of variation and Bland-Altman plotting. For both inter- and intraoperator reproducibility, the BUR-AS method had the lowest coefficient of variation and smallest error range about the Bland-Altman plot. Mean CBF obtained using the BUR-AS method had the highest reproducibility. Compared with the Patlak-plot and BUR-C methods, the BUR-AS method provides greater inter- and intraoperator reproducibility of cerebral blood flow measurement. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Reproducibility of 3.0 Tesla Magnetic Resonance Spectroscopy for Measuring Hepatic Fat Content

NARCIS (Netherlands)

van Werven, Jochem R.; Hoogduin, Johannes M.; Nederveen, Aart J.; van Vliet, Andre A.; Wajs, Ewa; Vandenberk, Petra; Stroes, Erik S. G.; Stoker, Jaap

Purpose: To investigate reproducibility of proton magnetic resonance spectroscopy (H-1-MRS) to measure hepatic triglyceride content (HTGC). Materials and Methods: In 24 subjects, HTGC was evaluated using H-1-MRS at 3.0 Tesla. We studied "between-weeks" reproducibility and reproducibility of H-1-MRS

Anthracycline-induced cardiotoxicity, a pathophysiology based approach for early detection and protective strategies

NARCIS (Netherlands)

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

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...

Epidemiology, genetics, pathophysiology, and prognostic classifications of cerebral arteriovenous malformations.

Science.gov (United States)

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.

Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment.

Science.gov (United States)

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.

Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review.

Science.gov (United States)

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.

Completely reproducible description of digital sound data with cellular automata

International Nuclear Information System (INIS)

Wada, Masato; Kuroiwa, Jousuke; Nara, Shigetoshi

2002-01-01

A novel method of compressive and completely reproducible description of digital sound data by means of rule dynamics of CA (cellular automata) is proposed. The digital data of spoken words and music recorded with the standard format of a compact disk are reproduced completely by this method with use of only two rules in a one-dimensional CA without loss of information

Symptoms in Inflammatory Bowel Disease: pathophysiologic aspects and their relation with disease activity

NARCIS (Netherlands)

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

Reproducibility of gene expression across generations of Affymetrix microarrays

Directory of Open Access Journals (Sweden)

Haslett Judith N

2003-06-01

Full Text Available Abstract Background The development of large-scale gene expression profiling technologies is rapidly changing the norms of biological investigation. But the rapid pace of change itself presents challenges. Commercial microarrays are regularly modified to incorporate new genes and improved target sequences. Although the ability to compare datasets across generations is crucial for any long-term research project, to date no means to allow such comparisons have been developed. In this study the reproducibility of gene expression levels across two generations of Affymetrix GeneChips® (HuGeneFL and HG-U95A was measured. Results Correlation coefficients were computed for gene expression values across chip generations based on different measures of similarity. Comparing the absolute calls assigned to the individual probe sets across the generations found them to be largely unchanged. Conclusion We show that experimental replicates are highly reproducible, but that reproducibility across generations depends on the degree of similarity of the probe sets and the expression level of the corresponding transcript.

Reproducibility of the Portuguese version of the PEDro Scale

Directory of Open Access Journals (Sweden)

Silvia Regina Shiwa

2011-10-01

Full Text Available The objective of this study was to test the inter-rater reproducibility of the Portuguese version of the PEDro Scale. Seven physiotherapists rated the methodological quality of 50 reports of randomized controlled trials written in Portuguese indexed on the PEDro database. Each report was also rated using the English version of the PEDro Scale. Reproducibility was evaluated by comparing two separate ratings of reports written in Portuguese and comparing the Portuguese PEDro score with the English version of the scale. Kappa coefficients ranged from 0.53 to 1.00 for individual item and an intraclass correlation coefficient (ICC of 0.82 for the total PEDro score was observed. The standard error of the measurement of the scale was 0.58. The Portuguese version of the scale was comparable with the English version, with an ICC of 0.78. The inter-rater reproducibility of the Brazilian Portuguese PEDro Scale is adequate and similar to the original English version.

Intra-and interobserver reproducibility of shear wave elastography for evaluation of the breast lesions

International Nuclear Information System (INIS)

Hong, Min Ji; Kim, Hak Hee

2017-01-01

To evaluate reproducibility of shear wave elastography (SWE) for breast lesions within and between observers and compare the reproducibility of SWE features. For intraobserver reproducibility, 225 masses with 208 patients were included; and two consecutive SWE images were acquired by each observer. For interobserver reproducibility, SWE images of the same mass were obtained by another observer before surgery in 40 patients. Intraclass correlation coefficients (ICC) were used to determine intra- and interobserver reproducibility. Intraobserver reliability for mean elasticity (Emean) and maximum elasticity (Emax) were excellent (ICC = 0.803, 0.799). ICC for SWE ratio and minimum elasticity (Emin) were fair to good (ICC = 0.703, 0.539). Emean showed excellent ICC regardless of histopathologic type and tumor size. Emax, SWE ratio and Emin represented excellent or fair to good reproducibility based on histopathologic type and tumor size. In interobserver study, ICC for Emean, Emax and SWE ratio were excellent. Emean, Emax and SWE ratio represented excellent ICC irrespective of histopathologic type. ICC for Emean was excellent regardless of tumor size. SWE ratio and Emax showed fair to good interobserver reproducibility based on tumor size. Emin represented poor interobserver reliability. Emean in SWE was highly reproducible within and between observers

Intra-and interobserver reproducibility of shear wave elastography for evaluation of the breast lesions

Energy Technology Data Exchange (ETDEWEB)

Hong, Min Ji [Dept. of Radiology, Gil Hospital, Gachon University of Medicine and Science, Incheon (Korea, Republic of); Kim, Hak Hee [Dept. of Radiology, and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

2017-03-15

To evaluate reproducibility of shear wave elastography (SWE) for breast lesions within and between observers and compare the reproducibility of SWE features. For intraobserver reproducibility, 225 masses with 208 patients were included; and two consecutive SWE images were acquired by each observer. For interobserver reproducibility, SWE images of the same mass were obtained by another observer before surgery in 40 patients. Intraclass correlation coefficients (ICC) were used to determine intra- and interobserver reproducibility. Intraobserver reliability for mean elasticity (Emean) and maximum elasticity (Emax) were excellent (ICC = 0.803, 0.799). ICC for SWE ratio and minimum elasticity (Emin) were fair to good (ICC = 0.703, 0.539). Emean showed excellent ICC regardless of histopathologic type and tumor size. Emax, SWE ratio and Emin represented excellent or fair to good reproducibility based on histopathologic type and tumor size. In interobserver study, ICC for Emean, Emax and SWE ratio were excellent. Emean, Emax and SWE ratio represented excellent ICC irrespective of histopathologic type. ICC for Emean was excellent regardless of tumor size. SWE ratio and Emax showed fair to good interobserver reproducibility based on tumor size. Emin represented poor interobserver reliability. Emean in SWE was highly reproducible within and between observers.

Reproducibility of abdominal fat assessment by ultrasound and computed tomography.

Science.gov (United States)

Mauad, Fernando Marum; Chagas-Neto, Francisco Abaeté; Benedeti, Augusto César Garcia Saab; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Carneiro, Antonio Adilton Oliveira; Muller, Enrico Mattana; Elias Junior, Jorge

2017-01-01

To test the accuracy and reproducibility of ultrasound and computed tomography (CT) for the quantification of abdominal fat in correlation with the anthropometric, clinical, and biochemical assessments. Using ultrasound and CT, we determined the thickness of subcutaneous and intra-abdominal fat in 101 subjects-of whom 39 (38.6%) were men and 62 (61.4%) were women-with a mean age of 66.3 years (60-80 years). The ultrasound data were correlated with the anthropometric, clinical, and biochemical parameters, as well as with the areas measured by abdominal CT. Intra-abdominal thickness was the variable for which the correlation with the areas of abdominal fat was strongest (i.e., the correlation coefficient was highest). We also tested the reproducibility of ultrasound and CT for the assessment of abdominal fat and found that CT measurements of abdominal fat showed greater reproducibility, having higher intraobserver and interobserver reliability than had the ultrasound measurements. There was a significant correlation between ultrasound and CT, with a correlation coefficient of 0.71. In the assessment of abdominal fat, the intraobserver and interobserver reliability were greater for CT than for ultrasound, although both methods showed high accuracy and good reproducibility.

An empirical analysis of journal policy effectiveness for computational reproducibility.

Science.gov (United States)

Stodden, Victoria; Seiler, Jennifer; Ma, Zhaokun

2018-03-13

A key component of scientific communication is sufficient information for other researchers in the field to reproduce published findings. For computational and data-enabled research, this has often been interpreted to mean making available the raw data from which results were generated, the computer code that generated the findings, and any additional information needed such as workflows and input parameters. Many journals are revising author guidelines to include data and code availability. This work evaluates the effectiveness of journal policy that requires the data and code necessary for reproducibility be made available postpublication by the authors upon request. We assess the effectiveness of such a policy by ( i ) requesting data and code from authors and ( ii ) attempting replication of the published findings. We chose a random sample of 204 scientific papers published in the journal Science after the implementation of their policy in February 2011. We found that we were able to obtain artifacts from 44% of our sample and were able to reproduce the findings for 26%. We find this policy-author remission of data and code postpublication upon request-an improvement over no policy, but currently insufficient for reproducibility.

Dyslipidemia alters sperm maturation and capacitation in LXR-null mice.

Science.gov (United States)

Whitfield, M; Guiton, R; Rispal, J; Acar, N; Kocer, A; Drevet, J R; Saez, F

2017-12-01

Lipid metabolism disorders (dyslipidemia) are causes of male infertility, but little is known about their impact on male gametes when considering post-testicular maturation events, given that studies concentrate most often on endocrine dysfunctions and testicular consequences. In this study, three-month-old wild-type ( wt ) and Liver-X-Receptors knock out ( Lxrα;β - / - ) males were fed four weeks with a control or a lipid-enriched diet containing 1.25% cholesterol (high cholesterol diet (HCD)). The HCD triggered a dyslipidemia leading to sperm post-testicular alterations and infertility. Sperm lipids were analyzed by LC-MS and those from Lxrα;β - / - males fed the HCD showed higher chol/PL and PC/PE ratios compared to wt -HCD ( P  pump (PMCA4) was decreased in Lxrα;β - / - males fed the HCD ( P  fertility prognostic markers in this pathophysiological situation, which could help clinicians to better understand male infertilities which are thus far classified as idiopathic. © 2017 Society for Reproduction and Fertility.

Reproducing Kernel Method for Solving Nonlinear Differential-Difference Equations

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Reza Mokhtari

2012-01-01

Full Text Available On the basis of reproducing kernel Hilbert spaces theory, an iterative algorithm for solving some nonlinear differential-difference equations (NDDEs is presented. The analytical solution is shown in a series form in a reproducing kernel space, and the approximate solution , is constructed by truncating the series to terms. The convergence of , to the analytical solution is also proved. Results obtained by the proposed method imply that it can be considered as a simple and accurate method for solving such differential-difference problems.

Archiving Reproducible Research with R and Dataverse

DEFF Research Database (Denmark)

Leeper, Thomas

2014-01-01

Reproducible research and data archiving are increasingly important issues in research involving statistical analyses of quantitative data. This article introduces the dvn package, which allows R users to publicly archive datasets, analysis files, codebooks, and associated metadata in Dataverse...

Reproducibility of cervical range of motion in patients with neck pain

NARCIS (Netherlands)

Pool, JJM; van Mameren, H; Deville, WJLM; Assendelft, WJJ; de Vet, HCW; de Winter, AF; Koes, BW; Bouter, LM; Hoving, J.L.

2005-01-01

Background: Reproducibility measurements of the range of motion are an important prerequisite for the interpretation of study results. The aim of the study is to assess the intra-rater and interrater reproducibility of the measurement of active Range of Motion ( ROM) in patients with neck pain using

Obesity and Pulmonary Hypertension: A Review of Pathophysiologic Mechanisms

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Scott E. Friedman

2012-01-01

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

Reproducibility of clinical research in critical care: a scoping review.

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Niven, Daniel J; McCormick, T Jared; Straus, Sharon E; Hemmelgarn, Brenda R; Jeffs, Lianne; Barnes, Tavish R M; Stelfox, Henry T

2018-02-21

The ability to reproduce experiments is a defining principle of science. Reproducibility of clinical research has received relatively little scientific attention. However, it is important as it may inform clinical practice, research agendas, and the design of future studies. We used scoping review methods to examine reproducibility within a cohort of randomized trials examining clinical critical care research and published in the top general medical and critical care journals. To identify relevant clinical practices, we searched the New England Journal of Medicine, The Lancet, and JAMA for randomized trials published up to April 2016. To identify a comprehensive set of studies for these practices, included articles informed secondary searches within other high-impact medical and specialty journals. We included late-phase randomized controlled trials examining therapeutic clinical practices in adults admitted to general medical-surgical or specialty intensive care units (ICUs). Included articles were classified using a reproducibility framework. An original study was the first to evaluate a clinical practice. A reproduction attempt re-evaluated that practice in a new set of participants. Overall, 158 practices were examined in 275 included articles. A reproduction attempt was identified for 66 practices (42%, 95% CI 33-50%). Original studies reported larger effects than reproduction attempts (primary endpoint, risk difference 16.0%, 95% CI 11.6-20.5% vs. 8.4%, 95% CI 6.0-10.8%, P = 0.003). More than half of clinical practices with a reproduction attempt demonstrated effects that were inconsistent with the original study (56%, 95% CI 42-68%), among which a large number were reported to be efficacious in the original study and to lack efficacy in the reproduction attempt (34%, 95% CI 19-52%). Two practices reported to be efficacious in the original study were found to be harmful in the reproduction attempt. A minority of critical care practices with research published

Reproducibility of Psychological Experiments as a Problem of Post-Nonclassical Science

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Vachkov I.V.,

2016-04-01

Full Text Available A fundamental project on reproducibility carried out in the USA by Brian Nosek in 2015 (the Reproducibility Project revealed a serious methodological problem in psychology: the issue of replication of psycho- logical experiments. Reproducibility has been traditionally perceived as one of the basic principles of the scientific method. However, methodological analysis of the modern post-nonclassical stage in the development of science suggests that this might be a bit too uncompromising as applied to psychology. It seems that the very criteria of scientific research need to be reconsidered with regard to the specifics of post-nonclassical science, and, as the authors put it, as a result, reproducibility might lose its key status or even be excluded at all. The reviewed problem and the proposed ways of coping with it are of high importance to research and practice in psychology as they define the strategies for organizing, conducting and evaluating experimental research.

Reproducibility study of TLD-100 micro-cubes at radiotherapy dose level

International Nuclear Information System (INIS)

Rosa, Luiz Antonio R. da; Regulla, Dieter F.; Fill, Ute A.

1999-01-01

The precision of the thermoluminescent response of Harshaw micro-cube dosimeters (TLD-100), evaluated in both Harshaw thermoluminescent readers 5500 and 3500, for 1 Gy dose value, was investigated. The mean reproducibility for micro-cubes, pre-readout annealed at 100 deg. C for 15 min, evaluated with the manual planchet reader 3500, is 0.61% (1 standard deviation). When micro-cubes are evaluated with the automated hot-gas reader 5500, reproducibility values are undoubtedly worse, mean reproducibility for numerically stabilised dosimeters being equal to 3.27% (1 standard deviation). These results indicate that the reader model 5500, or, at least, the instrument used for the present measurements, is not adequate for micro-cube evaluation, if precise and accurate dosimetry is required. The difference in precision is apparently due to geometry inconsistencies in the orientation of the imperfect micro-cube faces during readout, requiring careful and manual reproducible arrangement of the selected micro-cube faces in contact with the manual reader planchet

Relationships between Serotonin Transporter Binding in the Raphe Nuclei, Basal Ganglia, and Hippocampus with Clinical Symptoms in Cervical Dystonia : A [C]DASB Positron Emission Tomography Study

NARCIS (Netherlands)

Smit, Marenka; Vállez García, David; de Jong, Bauke M; Zoons, Evelien; Booij, Jan; Dierckx, Rudi A; Willemsen, Antoon T; de Vries, Erik F; Bartels, Anna L; Tijssen, Marina A

2018-01-01

Purpose: Alterations of the central serotonergic system have been implicated in the pathophysiology of dystonia. In this molecular imaging study, we assessed whether altered presynaptic serotonin transporter (SERT) binding contributes to the pathophysiology of cervical dystonia (CD), concerning both

Nutrient re-routing and altered gut-islet cell crosstalk may explain early relief of severe postprandial hypoglycaemia after reversal of Roux-en-Y gastric bypass

DEFF Research Database (Denmark)

Svane, M S; Toft-Nielsen, M B; Kristiansen, V B

2017-01-01

BACKGROUND: Roux-en-Y gastric bypass is associated with an increased risk of postprandial hyperinsulinaemic hypoglycaemia, but the underlying pathophysiology remains poorly understood. We therefore examined the effect of re-routing of nutrient delivery on gut-islet cell crosstalk in a person...... insulin and glucagon-like peptide-1 hypersecretion and eliminated postprandial hypoglycaemia, which emphasizes the importance of altered gut-islet cell crosstalk for glucose metabolism after Roux-en-Y gastric bypass. This article is protected by copyright. All rights reserved....

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.

Interactions of Mitochondria/Metabolism and Calcium Regulation in Alzheimer's Disease: A Calcinist Point of View.

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Gibson, Gary E; Thakkar, Ankita

2017-06-01

Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry. Similar anomalies in calcium result when AD-like changes in mitochondrial enzymes or oxidative stress are induced experimentally. The calcium abnormalities can be directly linked to the altered tau phosphorylation, amyloid precursor protein processing and synaptic dysfunction that are defining features of AD. A better understanding of these changes is required before using calcium abnormalities as therapeutic targets.

Protein-energy malnutrition alters thermoregulatory homeostasis and the response to brain ischemia.

Science.gov (United States)

Smith, Shari E; Prosser-Loose, Erin J; Colbourne, Frederick; Paterson, Phyllis G

2011-02-01

Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery. There was a rapid disruption in thermoregulatory function in rats fed the low protein diet as assessed by continuous recording of core temperature with bio-electrical sensor transmitters. Both daily temperature fluctuation and mean temperature increased within the first 24 hours, and these remained significantly elevated throughout the 7 day pre-ischemic period (p protein diet rapidly impairs the ability to maintain thermoregulatory homeostasis, and the resultant PEM also diminishes the ability to thermoregulate in response to a challenge. Since temperature regulation is a key determinant of brain injury following ischemia, these findings suggest that the pathophysiology of brain injury could be altered in stroke victims with coexisting PEM.

Scapular dyskinesis in trapezius myalgia and intraexaminer reproducibility of clinical tests

DEFF Research Database (Denmark)

Juul-Kristensen, Birgit; Hilt, Kenneth; Enoch, Flemming

2011-01-01

dyskinesis, general health, and work ability, and 19 cases and 14 controls participated in the reproducibility study. Intraexaminer reproducibility was good to excellent for 6 of 10 clinical variables (Intraclass Correlation Coefficient [ICC] 0.76-0.91; kappa 0.84-1.00), and fair to good for four variables...

Reproducibility of cervical range of motion in patients with neck pain

NARCIS (Netherlands)

Hoving, Jan Lucas; Pool, Jan J. M.; van Mameren, Henk; Devillé, Walter J. L. M.; Assendelft, Willem J. J.; de Vet, Henrica C. W.; de Winter, Andrea F.; Koes, Bart W.; Bouter, Lex M.

2005-01-01

BACKGROUND: Reproducibility measurements of the range of motion are an important prerequisite for the interpretation of study results. The aim of the study is to assess the intra-rater and inter-rater reproducibility of the measurement of active Range of Motion (ROM) in patients with neck pain using

Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

Science.gov (United States)

Robinson, Shenandoah

2013-01-01

Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is

Pathophysiology and clinical characteristics of pain in most common locations in cancer patients.

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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.

Quantized correlation coefficient for measuring reproducibility of ChIP-chip data

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Kuroda Mitzi I

2010-07-01

Full Text Available Abstract Background Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip is used to study protein-DNA interactions and histone modifications on a genome-scale. To ensure data quality, these experiments are usually performed in replicates, and a correlation coefficient between replicates is used often to assess reproducibility. However, the correlation coefficient can be misleading because it is affected not only by the reproducibility of the signal but also by the amount of binding signal present in the data. Results We develop the Quantized correlation coefficient (QCC that is much less dependent on the amount of signal. This involves discretization of data into set of quantiles (quantization, a merging procedure to group the background probes, and recalculation of the Pearson correlation coefficient. This procedure reduces the influence of the background noise on the statistic, which then properly focuses more on the reproducibility of the signal. The performance of this procedure is tested in both simulated and real ChIP-chip data. For replicates with different levels of enrichment over background and coverage, we find that QCC reflects reproducibility more accurately and is more robust than the standard Pearson or Spearman correlation coefficients. The quantization and the merging procedure can also suggest a proper quantile threshold for separating signal from background for further analysis. Conclusions To measure reproducibility of ChIP-chip data correctly, a correlation coefficient that is robust to the amount of signal present should be used. QCC is one such measure. The QCC statistic can also be applied in a variety of other contexts for measuring reproducibility, including analysis of array CGH data for DNA copy number and gene expression data.

Quantized correlation coefficient for measuring reproducibility of ChIP-chip data.

Science.gov (United States)

Peng, Shouyong; Kuroda, Mitzi I; Park, Peter J

2010-07-27

Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) is used to study protein-DNA interactions and histone modifications on a genome-scale. To ensure data quality, these experiments are usually performed in replicates, and a correlation coefficient between replicates is used often to assess reproducibility. However, the correlation coefficient can be misleading because it is affected not only by the reproducibility of the signal but also by the amount of binding signal present in the data. We develop the Quantized correlation coefficient (QCC) that is much less dependent on the amount of signal. This involves discretization of data into set of quantiles (quantization), a merging procedure to group the background probes, and recalculation of the Pearson correlation coefficient. This procedure reduces the influence of the background noise on the statistic, which then properly focuses more on the reproducibility of the signal. The performance of this procedure is tested in both simulated and real ChIP-chip data. For replicates with different levels of enrichment over background and coverage, we find that QCC reflects reproducibility more accurately and is more robust than the standard Pearson or Spearman correlation coefficients. The quantization and the merging procedure can also suggest a proper quantile threshold for separating signal from background for further analysis. To measure reproducibility of ChIP-chip data correctly, a correlation coefficient that is robust to the amount of signal present should be used. QCC is one such measure. The QCC statistic can also be applied in a variety of other contexts for measuring reproducibility, including analysis of array CGH data for DNA copy number and gene expression data.

Reproducibility of the dynamics of facial expressions in unilateral facial palsy.

Science.gov (United States)

Alagha, M A; Ju, X; Morley, S; Ayoub, A

2018-02-01

The aim of this study was to assess the reproducibility of non-verbal facial expressions in unilateral facial paralysis using dynamic four-dimensional (4D) imaging. The Di4D system was used to record five facial expressions of 20 adult patients. The system captured 60 three-dimensional (3D) images per second; each facial expression took 3-4seconds which was recorded in real time. Thus a set of 180 3D facial images was generated for each expression. The procedure was repeated after 30min to assess the reproducibility of the expressions. A mathematical facial mesh consisting of thousands of quasi-point 'vertices' was conformed to the face in order to determine the morphological characteristics in a comprehensive manner. The vertices were tracked throughout the sequence of the 180 images. Five key 3D facial frames from each sequence of images were analyzed. Comparisons were made between the first and second capture of each facial expression to assess the reproducibility of facial movements. Corresponding images were aligned using partial Procrustes analysis, and the root mean square distance between them was calculated and analyzed statistically (paired Student t-test, PFacial expressions of lip purse, cheek puff, and raising of eyebrows were reproducible. Facial expressions of maximum smile and forceful eye closure were not reproducible. The limited coordination of various groups of facial muscles contributed to the lack of reproducibility of these facial expressions. 4D imaging is a useful clinical tool for the assessment of facial expressions. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease.

Science.gov (United States)

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.

Reproducing kernel Hilbert spaces of Gaussian priors

NARCIS (Netherlands)

Vaart, van der A.W.; Zanten, van J.H.; Clarke, B.; Ghosal, S.

2008-01-01

We review definitions and properties of reproducing kernel Hilbert spaces attached to Gaussian variables and processes, with a view to applications in nonparametric Bayesian statistics using Gaussian priors. The rate of contraction of posterior distributions based on Gaussian priors can be described

Reproducibility, Controllability, and Optimization of Lenr Experiments

Science.gov (United States)

Nagel, David J.

2006-02-01

Low-energy nuclear reaction (LENR) measurements are significantly and increasingly reproducible. Practical control of the production of energy or materials by LENR has yet to be demonstrated. Minimization of costly inputs and maximization of desired outputs of LENR remain for future developments.

Metabolic syndrome pathophysiology and clinical presentation.

Science.gov (United States)

Handelsman, Yehuda

2009-01-01

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

Pathophysiology and Immune Dysfunction in Endometriosis

Science.gov (United States)

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

2015-01-01

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

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.)

Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine.

Science.gov (United States)

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.

Cervical vertebrae maturation method morphologic criteria: poor reproducibility.

Science.gov (United States)

Nestman, Trenton S; Marshall, Steven D; Qian, Fang; Holton, Nathan; Franciscus, Robert G; Southard, Thomas E

2011-08-01

The cervical vertebrae maturation (CVM) method has been advocated as a predictor of peak mandibular growth. A careful review of the literature showed potential methodologic errors that might influence the high reported reproducibility of the CVM method, and we recently established that the reproducibility of the CVM method was poor when these potential errors were eliminated. The purpose of this study was to further investigate the reproducibility of the individual vertebral patterns. In other words, the purpose was to determine which of the individual CVM vertebral patterns could be classified reliably and which could not. Ten practicing orthodontists, trained in the CVM method, evaluated the morphology of cervical vertebrae C2 through C4 from 30 cephalometric radiographs using questions based on the CVM method. The Fleiss kappa statistic was used to assess interobserver agreement when evaluating each cervical vertebrae morphology question for each subject. The Kendall coefficient of concordance was used to assess the level of interobserver agreement when determining a "derived CVM stage" for each subject. Interobserver agreement was high for assessment of the lower borders of C2, C3, and C4 that were either flat or curved in the CVM method, but interobserver agreement was low for assessment of the vertebral bodies of C3 and C4 when they were either trapezoidal, rectangular horizontal, square, or rectangular vertical; this led to the overall poor reproducibility of the CVM method. These findings were reflected in the Fleiss kappa statistic. Furthermore, nearly 30% of the time, individual morphologic criteria could not be combined to generate a final CVM stage because of incompatible responses to the 5 questions. Intraobserver agreement in this study was only 62%, on average, when the inconclusive stagings were excluded as disagreements. Intraobserver agreement was worse (44%) when the inconclusive stagings were included as disagreements. For the group of subjects

A nondestructive, reproducible method of measuring joint reaction force at the distal radioulnar joint.

Science.gov (United States)

Canham, Colin D; Schreck, Michael J; Maqsoodi, Noorullah; Doolittle, Madison; Olles, Mark; Elfar, John C

2015-06-01

To develop a nondestructive method of measuring distal radioulnar joint (DRUJ) joint reaction force (JRF) that preserves all periarticular soft tissues and more accurately reflects in vivo conditions. Eight fresh-frozen human cadaveric limbs were obtained. A threaded Steinmann pin was placed in the middle of the lateral side of the distal radius transverse to the DRUJ. A second pin was placed into the middle of the medial side of the distal ulna colinear to the distal radial pin. Specimens were mounted onto a tensile testing machine using a custom fixture. A uniaxial distracting force was applied across the DRUJ while force and displacement were simultaneously measured. Force-displacement curves were generated and a best-fit polynomial was solved to determine JRF. All force-displacement curves demonstrated an initial high slope where relatively large forces were required to distract the joint. This ended with an inflection point followed by a linear area with a low slope, where small increases in force generated larger amounts of distraction. Each sample was measured 3 times and there was high reproducibility between repeated measurements. The average baseline DRUJ JRF was 7.5 N (n = 8). This study describes a reproducible method of measuring DRUJ reaction forces that preserves all periarticular stabilizing structures. This technique of JRF measurement may also be suited for applications in the small joints of the wrist and hand. Changes in JRF can alter native joint mechanics and lead to pathology. Reliable methods of measuring these forces are important for determining how pathology and surgical interventions affect joint biomechanics. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

The role of beta-endorphin in the pathophysiology of major depression.

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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

Accuracy, reproducibility, and time efficiency of dental measurements using different technologies.

Science.gov (United States)

Grünheid, Thorsten; Patel, Nishant; De Felippe, Nanci L; Wey, Andrew; Gaillard, Philippe R; Larson, Brent E

2014-02-01

Historically, orthodontists have taken dental measurements on plaster models. Technological advances now allow orthodontists to take these measurements on digital models. In this study, we aimed to assess the accuracy, reproducibility, and time efficiency of dental measurements taken on 3 types of digital models. emodels (GeoDigm, Falcon Heights, Minn), SureSmile models (OraMetrix, Richardson, Tex), and AnatoModels (Anatomage, San Jose, Calif) were made for 30 patients. Mesiodistal tooth-width measurements taken on these digital models were timed and compared with those on the corresponding plaster models, which were used as the gold standard. Accuracy and reproducibility were assessed using the Bland-Altman method. Differences in time efficiency were tested for statistical significance with 1-way analysis of variance. Measurements on SureSmile models were the most accurate, followed by those on emodels and AnatoModels. Measurements taken on SureSmile models were also the most reproducible. Measurements taken on SureSmile models and emodels were significantly faster than those taken on AnatoModels and plaster models. Tooth-width measurements on digital models can be as accurate as, and might be more reproducible and significantly faster than, those taken on plaster models. Of the models studied, the SureSmile models provided the best combination of accuracy, reproducibility, and time efficiency of measurement. Copyright © 2014 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Experience with an Independent Study Program in Pathophysiology for Doctor of Pharmacy Students.

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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…

Altered Insular and Occipital Responses to Simulated Vertical Self-Motion in Patients with Persistent Postural-Perceptual Dizziness

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Roberta Riccelli

2017-10-01

Full Text Available BackgroundPersistent postural-perceptual dizziness (PPPD is a common functional vestibular disorder characterized by persistent symptoms of non-vertiginous dizziness and unsteadiness that are exacerbated by upright posture, self-motion, and exposure to complex or moving visual stimuli. Recent physiologic and neuroimaging data suggest that greater reliance on visual cues for postural control (as opposed to vestibular cues—a phenomenon termed visual dependence and dysfunction in central visuo-vestibular networks may be important pathophysiologic mechanisms underlying PPPD. Dysfunctions are thought to involve insular regions that encode recognition of the visual effects of motion in the gravitational field.MethodsWe tested for altered activity in vestibular and visual cortices during self-motion simulation obtained via a visual virtual-reality rollercoaster stimulation using functional magnetic resonance imaging in 15 patients with PPPD and 15 healthy controls (HCs. We compared between groups differences in brain responses to simulated displacements in vertical vs horizontal directions and correlated the difference in directional responses with dizziness handicap in patients with PPPD.ResultsHCs showed increased activity in the anterior bank of the central insular sulcus during vertical relative to horizontal motion, which was not seen in patients with PPPD. However, for the same comparison, dizziness handicap correlated positively with activity in the visual cortex (V1, V2, and V3 in patients with PPPD.ConclusionWe provide novel insight into the pathophysiologic mechanisms underlying PPPD, including functional alterations in brain processes that affect balance control and reweighting of space-motion inputs to favor visual cues. For patients with PPPD, difficulties using visual data to discern the effects of gravity on self-motion may adversely affect balance control, particularly for individuals who simultaneously rely too heavily on visual

Tinnitus: Network pathophysiology-network pharmacology

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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.

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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.

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.

A fresh look into the pathophysiology of ischemia-induced complications in patients with chronic kidney disease undergoing hemodialysis

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Honore PM

2015-03-01

Full Text Available Patrick M Honore,1 Rita Jacobs,1 Elisabeth De Waele,1 Viola Van Gorp,1 Jouke De Regt,1 Olivier Joannes-Boyau,2 Willem Boer,3 Herbert D Spapen1 1Intensive Care Department, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; 2Intensive Care Unit, Haut Leveque University Hospital of Bordeaux, University of Bordeaux 2, Pessac, France; 3Intensive Care Department, Ziekenhuis Oost Limburg, Genk, Belgium Abstract: Recent case reports of acute esophageal necrosis in patients with chronic kidney disease (CKD undergoing hemodialysis encouraged us to look beyond hypoperfusion/ischemia as a sole explanation for this dramatic complication. At least three intriguing pathways, ie, accumulation of protein-bound toxins, endotoxin translocation, and altered mucosal defense mechanisms, have been proposed to explain the inherent susceptibility of CKD patients to developing ischemia-related and cardiovascular events. Interestingly, all the proposed pathways can be potentially antagonized or attenuated. At present, however, it is not known whether one pathway predominates or if any interaction exists between these pathways. More solid experimental and clinical data are warranted to acquire a better insight into the complex pathogenesis of CKD-associated ischemia. Keywords: chronic kidney disease, ischemia, pathophysiology, cardiovascular events

Reproducibility of abdominal fat assessment by ultrasound and computed tomography

Energy Technology Data Exchange (ETDEWEB)

Mauad, Fernando Marum; Chagas-Neto, Francisco Abaete; Benedeti, Augusto Cesar Garcia Saab; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Carneiro, Antonio Adilton Oliveira; Muller, Enrico Mattana; Elias Junior, Jorge, E-mail: fernando@fatesa.edu.br [Faculdade de Tecnologia em Saude (FATESA), Ribeirao Preto, SP (Brazil); Universidade de Fortaleza (UNIFOR), Fortaleza, CE (Brazil). Departmento de Radiologia; Universidade de Sao Paulo (FMRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Departmento de Medicina Clinica; Universidade de Sao Paulo (FFCLRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras; Hospital Mae de Deus, Porto Alegre, RS (Brazil)

2017-05-15

Objective: To test the accuracy and reproducibility of ultrasound and computed tomography (CT) for the quantification of abdominal fat in correlation with the anthropometric, clinical, and biochemical assessments. Materials and Methods: Using ultrasound and CT, we determined the thickness of subcutaneous and intra-abdominal fat in 101 subjects-of whom 39 (38.6%) were men and 62 (61.4%) were women-with a mean age of 66.3 years (60-80 years). The ultrasound data were correlated with the anthropometric, clinical, and biochemical parameters, as well as with the areas measured by abdominal CT. Results: Intra-abdominal thickness was the variable for which the correlation with the areas of abdominal fat was strongest (i.e., the correlation coefficient was highest). We also tested the reproducibility of ultrasound and CT for the assessment of abdominal fat and found that CT measurements of abdominal fat showed greater reproducibility, having higher intraobserver and interobserver reliability than had the ultrasound measurements. There was a significant correlation between ultrasound and CT, with a correlation coefficient of 0.71. Conclusion: In the assessment of abdominal fat, the intraobserver and interobserver reliability were greater for CT than for ultrasound, although both methods showed high accuracy and good reproducibility. (author)

Structural alterations of the superior temporal gyrus in schizophrenia: Detailed subregional differences.

Science.gov (United States)

Ohi, K; Matsuda, Y; Shimada, T; Yasuyama, T; Oshima, K; Sawai, K; Kihara, H; Nitta, Y; Okubo, H; Uehara, T; Kawasaki, Y

2016-05-01

Reduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus. We acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification. As expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics. These findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome.

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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.

Empirical evaluation of cross-site reproducibility in radiomic features for characterizing prostate MRI

Science.gov (United States)

Chirra, Prathyush; Leo, Patrick; Yim, Michael; Bloch, B. Nicolas; Rastinehad, Ardeshir R.; Purysko, Andrei; Rosen, Mark; Madabhushi, Anant; Viswanath, Satish

2018-02-01

The recent advent of radiomics has enabled the development of prognostic and predictive tools which use routine imaging, but a key question that still remains is how reproducible these features may be across multiple sites and scanners. This is especially relevant in the context of MRI data, where signal intensity values lack tissue specific, quantitative meaning, as well as being dependent on acquisition parameters (magnetic field strength, image resolution, type of receiver coil). In this paper we present the first empirical study of the reproducibility of 5 different radiomic feature families in a multi-site setting; specifically, for characterizing prostate MRI appearance. Our cohort comprised 147 patient T2w MRI datasets from 4 different sites, all of which were first pre-processed to correct acquisition-related for artifacts such as bias field, differing voxel resolutions, as well as intensity drift (non-standardness). 406 3D voxel wise radiomic features were extracted and evaluated in a cross-site setting to determine how reproducible they were within a relatively homogeneous non-tumor tissue region; using 2 different measures of reproducibility: Multivariate Coefficient of Variation and Instability Score. Our results demonstrated that Haralick features were most reproducible between all 4 sites. By comparison, Laws features were among the least reproducible between sites, as well as performing highly variably across their entire parameter space. Similarly, the Gabor feature family demonstrated good cross-site reproducibility, but for certain parameter combinations alone. These trends indicate that despite extensive pre-processing, only a subset of radiomic features and associated parameters may be reproducible enough for use within radiomics-based machine learning classifier schemes.

Systematic review of type-specific pathophysiological symptoms of Sasang typology

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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.

Examining the Reproducibility of 6 Published Studies in Public Health Services and Systems Research.

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Harris, Jenine K; B Wondmeneh, Sarah; Zhao, Yiqiang; Leider, Jonathon P

2018-02-23

Research replication, or repeating a study de novo, is the scientific standard for building evidence and identifying spurious results. While replication is ideal, it is often expensive and time consuming. Reproducibility, or reanalysis of data to verify published findings, is one proposed minimum alternative standard. While a lack of research reproducibility has been identified as a serious and prevalent problem in biomedical research and a few other fields, little work has been done to examine the reproducibility of public health research. We examined reproducibility in 6 studies from the public health services and systems research subfield of public health research. Following the methods described in each of the 6 papers, we computed the descriptive and inferential statistics for each study. We compared our results with the original study results and examined the percentage differences in descriptive statistics and differences in effect size, significance, and precision of inferential statistics. All project work was completed in 2017. We found consistency between original and reproduced results for each paper in at least 1 of the 4 areas examined. However, we also found some inconsistency. We identified incorrect transcription of results and omitting detail about data management and analyses as the primary contributors to the inconsistencies. Increasing reproducibility, or reanalysis of data to verify published results, can improve the quality of science. Researchers, journals, employers, and funders can all play a role in improving the reproducibility of science through several strategies including publishing data and statistical code, using guidelines to write clear and complete methods sections, conducting reproducibility reviews, and incentivizing reproducible science.

Reproducibility in Research: Systems, Infrastructure, Culture

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Tom Crick

2017-11-01

Full Text Available The reproduction and replication of research results has become a major issue for a number of scientific disciplines. In computer science and related computational disciplines such as systems biology, the challenges closely revolve around the ability to implement (and exploit novel algorithms and models. Taking a new approach from the literature and applying it to a new codebase frequently requires local knowledge missing from the published manuscripts and transient project websites. Alongside this issue, benchmarking, and the lack of open, transparent and fair benchmark sets present another barrier to the verification and validation of claimed results. In this paper, we outline several recommendations to address these issues, driven by specific examples from a range of scientific domains. Based on these recommendations, we propose a high-level prototype open automated platform for scientific software development which effectively abstracts specific dependencies from the individual researcher and their workstation, allowing easy sharing and reproduction of results. This new e-infrastructure for reproducible computational science offers the potential to incentivise a culture change and drive the adoption of new techniques to improve the quality and efficiency – and thus reproducibility – of scientific exploration.

Altered Kinematics of Facial Emotion Expression and Emotion Recognition Deficits Are Unrelated in Parkinson's Disease.

Science.gov (United States)

Bologna, Matteo; Berardelli, Isabella; Paparella, Giulia; Marsili, Luca; Ricciardi, Lucia; Fabbrini, Giovanni; Berardelli, Alfredo

2016-01-01

Altered emotional processing, including reduced emotion facial expression and defective emotion recognition, has been reported in patients with Parkinson's disease (PD). However, few studies have objectively investigated facial expression abnormalities in PD using neurophysiological techniques. It is not known whether altered facial expression and recognition in PD are related. To investigate possible deficits in facial emotion expression and emotion recognition and their relationship, if any, in patients with PD. Eighteen patients with PD and 16 healthy controls were enrolled in this study. Facial expressions of emotion were recorded using a 3D optoelectronic system and analyzed using the facial action coding system. Possible deficits in emotion recognition were assessed using the Ekman test. Participants were assessed in one experimental session. Possible relationship between the kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients were evaluated using the Spearman's test and multiple regression analysis. The facial expression of all six basic emotions had slower velocity and lower amplitude in patients in comparison to healthy controls (all P s facial expression kinematics and emotion recognition deficits were unrelated in patients (all P s > 0.05). Finally, no relationship emerged between kinematic variables of facial emotion expression, the Ekman test scores, and clinical and demographic data in patients (all P s > 0.05). The results in this study provide further evidence of altered emotional processing in PD. The lack of any correlation between altered facial emotion expression kinematics and emotion recognition deficits in patients suggests that these abnormalities are mediated by separate pathophysiological mechanisms.

Serous tubal intraepithelial carcinoma: diagnostic reproducibility and its implications.

Science.gov (United States)

Carlson, Joseph W; Jarboe, Elke A; Kindelberger, David; Nucci, Marisa R; Hirsch, Michelle S; Crum, Christopher P

2010-07-01

Serous tubal intraepithelial carcinoma (STIC) is detected in between 5% and 7% of women undergoing risk-reduction salpingooophorectomy for mutations in the BRCA1 or 2 genes (BRCA+), and seems to play a role in the pathogenesis of many ovarian and "primary peritoneal" serous carcinomas. The recognition of STIC is germane to the management of BRCA+ women; however, the diagnostic reproducibility of STIC is unknown. Twenty-one cases were selected and classified as STIC or benign, using both hematoxylin and eosin and immunohistochemical stains for p53 and MIB-1. Digital images of 30 hematoxylin and eosin-stained STICs (n=14) or benign tubal epithelium (n=16) were photographed and randomized for blind digital review in a Powerpoint format by 6 experienced gynecologic pathologists and 6 pathology trainees. A generalized kappa statistic for multiple raters was calculated for all groups. For all reviewers, the kappa was 0.333, indicating poor reproducibility; kappa was 0.453 for the experienced gynecologic pathologists (fair-to-good reproducibility), and kappa=0.253 for the pathology residents (poor reproducibility). In the experienced group, 3 of 14 STICs were diagnosed by all 6 reviewers, and 9 of 14 by a majority of the reviewers. These results show that interobserver concordance in the recognition of STIC in high-quality digital images is at best fair-to-good for even experienced gynecologic pathologists, and a proportion cannot be consistently identified even among experienced observers. In view of these findings, a diagnosis of STIC should be corroborated by a second pathologist, if feasible.

Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective.

Science.gov (United States)

Zaccardi, Francesco; Webb, David R; Yates, Thomas; Davies, Melanie J

2016-02-01

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/

LHC Orbit Correction Reproducibility and Related Machine Protection

CERN Document Server

Baer, T; Schmidt, R; Wenninger, J

2012-01-01

The Large Hadron Collider (LHC) has an unprecedented nominal stored beam energy of up to 362 MJ per beam. In order to ensure an adequate machine protection by the collimation system, a high reproducibility of the beam position at collimators and special elements like the final focus quadrupoles is essential. This is realized by a combination of manual orbit corrections, feed forward and real time feedback. In order to protect the LHC against inconsistent orbit corrections, which could put the machine in a vulnerable state, a novel software-based interlock system for orbit corrector currents was developed. In this paper, the principle of the new interlock system is described and the reproducibility of the LHC orbit correction is discussed against the background of this system.

Understanding reproducibility of human IVF traits to predict next IVF cycle outcome.

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Wu, Bin; Shi, Juanzi; Zhao, Wanqiu; Lu, Suzhen; Silva, Marta; Gelety, Timothy J

2014-10-01

Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome. The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome. The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae. The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient's stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly.

Addition of electrophilic lipids to actin alters filament structure

International Nuclear Information System (INIS)

Gayarre, Javier; Sanchez, David; Sanchez-Gomez, Francisco J.; Terron, Maria C.; Llorca, Oscar; Perez-Sala, Dolores

2006-01-01

Pathophysiological processes associated with oxidative stress lead to the generation of reactive lipid species. Among them, lipids bearing unsaturated aldehyde or ketone moieties can form covalent adducts with cysteine residues and modulate protein function. Through proteomic techniques we have identified actin as a target for the addition of biotinylated analogs of the cyclopentenone prostaglandins 15-deoxy-Δ 12,14 -PGJ 2 (15d-PGJ 2 ) and PGA 1 in NIH-3T3 fibroblasts. This modification could take place in vitro and mapped to the protein C-terminal end. Other electrophilic lipids, like the isoprostane 8-iso-PGA 1 and 4-hydroxy-2-nonenal, also bound to actin. The C-terminal region of actin is important for monomer-monomer interactions and polymerization. Electron microscopy showed that actin treated with 15d-PGJ 2 or 4-hydroxy-2-nonenal formed filaments which were less abundant and displayed shorter length and altered structure. Streptavidin-gold staining allowed mapping of biotinylated 15d-PGJ 2 at sites of filament disruption. These results shed light on the structural implications of actin modification by lipid electrophiles

On the Reproducibility of Label-Free Quantitative Cross-Linking/Mass Spectrometry

Science.gov (United States)

Müller, Fränze; Fischer, Lutz; Chen, Zhuo Angel; Auchynnikava, Tania; Rappsilber, Juri

2018-02-01

Quantitative cross-linking/mass spectrometry (QCLMS) is an emerging approach to study conformational changes of proteins and multi-subunit complexes. Distinguishing protein conformations requires reproducibly identifying and quantifying cross-linked peptides. Here we analyzed the variation between multiple cross-linking reactions using bis[sulfosuccinimidyl] suberate (BS3)-cross-linked human serum albumin (HSA) and evaluated how reproducible cross-linked peptides can be identified and quantified by LC-MS analysis. To make QCLMS accessible to a broader research community, we developed a workflow that integrates the established software tools MaxQuant for spectra preprocessing, Xi for cross-linked peptide identification, and finally Skyline for quantification (MS1 filtering). Out of the 221 unique residue pairs identified in our sample, 124 were subsequently quantified across 10 analyses with coefficient of variation (CV) values of 14% (injection replica) and 32% (reaction replica). Thus our results demonstrate that the reproducibility of QCLMS is in line with the reproducibility of general quantitative proteomics and we establish a robust workflow for MS1-based quantitation of cross-linked peptides.

Dysmotility in Esophageal Atresia: Pathophysiology, Characterization, and Treatment

Science.gov (United States)

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...

AFFECT: Altered-Fidelity Framework for Enhancing Cognition and Training

Directory of Open Access Journals (Sweden)

Ryan Patrick McMahan

2016-11-01

Full Text Available In this paper, we present a new framework for analyzing and designing virtual reality (VR techniques. This framework is based on two concepts—system fidelity (i.e., the degree with which real-world experiences are reproduced by a system and memory (i.e., the formation and activation of perceptual, cognitive, and motor networks of neurons. The premise of the framework is to manipulate an aspect of system fidelity in order to assist a stage of memory. We call it the Altered-Fidelity Framework for Enhancing Cognition and Training (AFFECT. AFFECT provides nine categories of approaches to altering system fidelity to positively affect learning or training. These categories are based on the intersections of three aspects of system fidelity (interaction fidelity, scenario fidelity, and display fidelity and three stages of memory (encoding, implicit retrieval, and explicit retrieval. In addition to discussing the details of our new framework, we show how AFFECT can be used as a tool for analyzing and categorizing VR techniques designed to facilitate learning or training. We also demonstrate how AFFECT can be used as a design space for creating new VR techniques intended for educational and training systems.

Migraine and magnetic resonance spectroscopy

DEFF Research Database (Denmark)

Younis, Samaira; Hougaard, Anders; Vestergaard, Mark B.

2017-01-01

Purpose of review: To present an updated and streamlined overview of the metabolic and biochemical aspect of the migraine pathophysiology based on findings from phosphorous (31P) and hydrogen (1H) magnetic resonance spectroscopy (MRS) studies. Recent findings: Despite of the variation in the meth......Purpose of review: To present an updated and streamlined overview of the metabolic and biochemical aspect of the migraine pathophysiology based on findings from phosphorous (31P) and hydrogen (1H) magnetic resonance spectroscopy (MRS) studies. Recent findings: Despite of the variation...... in the methodology and quality of the MRS migraine studies over time, some results were consistent and reproducible. 31P-MRS studies suggested reduced availability of neuronal energy and implied a mitochondrial dysfunction in the migraine brain. 1H-MRS studies reported interictal abnormalities in the excitatory...... and inhibitory neurotransmitters, glutamate and g-aminobutyric acid (GABA), suggesting persistent altered excitability in migraine patients. N-Acetylaspartate levels were decreased in migraine, probably due to a mitochondrial dysfunction and abnormal energy metabolism. The reported abnormalities may increase...

Nuclear medicine to image applied pathophysiology: Evaluation of reserves by emission computerized tomography

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.)

Reproducibility of airway luminal size in asthma measured by HRCT.

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Brown, Robert H; Henderson, Robert J; Sugar, Elizabeth A; Holbrook, Janet T; Wise, Robert A

2017-10-01

Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability. NEW & NOTEWORTHY There is a surprising lack

A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD).

Science.gov (United States)

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.

Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia

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Battistella, Giovanni; Fuertinger, Stefan; Fleysher, Lazar; Ozelius, Laurie J.; Simonyan, Kristina

2017-01-01

Background Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. Methods We used a combination of independent component analysis and linear discriminant analysis of resting-state functional MRI data to investigate brain organization in different SD phenotypes (abductor vs. adductor type) and putative genotypes (familial vs. sporadic cases) and to characterize neural markers for genotype/phenotype categorization. Results We found abnormal functional connectivity within sensorimotor and frontoparietal networks in SD patients compared to healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortex. When categorizing between different forms of SD, the combination of measures from left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. Conclusions Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder. PMID:27346568

Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia.

Science.gov (United States)

Battistella, G; Fuertinger, S; Fleysher, L; Ozelius, L J; Simonyan, K

2016-10-01

Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. We used a combination of independent component analysis and linear discriminant analysis of resting-state functional magnetic resonance imaging data to investigate brain organization in different SD phenotypes (abductor versus adductor type) and putative genotypes (familial versus sporadic cases) and to characterize neural markers for genotype/phenotype categorization. We found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with SD compared with healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortices. When categorizing between different forms of SD, the combination of measures from the left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder. © 2016 EAN.

Gerbode defect: A comprehensive review of its history, anatomy, embryology, pathophysiology, diagnosis, and treatment

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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.

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

The Role of Mast Cells in Irritable Bowel Syndrome

OpenAIRE

Lee, Kang Nyeong; Lee, Oh Young

2016-01-01

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but its treatment is unsatisfactory as its pathophysiology is multifactorial. The putative factors of IBS pathophysiology are visceral hypersensitivity and intestinal dysmotility, also including psychological factors, dysregulated gut-brain axis, intestinal microbiota alterations, impaired intestinal permeability, and mucosal immune alterations. Recently, mucosal immune alterations have received mu...

Relevant principal factors affecting the reproducibility of insect primary culture.

Science.gov (United States)

Ogata, Norichika; Iwabuchi, Kikuo

2017-06-01

The primary culture of insect cells often suffers from problems with poor reproducibility in the quality of the final cell preparations. The cellular composition of the explants (cell number and cell types), surgical methods (surgical duration and surgical isolation), and physiological and genetic differences between donors may be critical factors affecting the reproducibility of culture. However, little is known about where biological variation (interindividual differences between donors) ends and technical variation (variance in replication of culture conditions) begins. In this study, we cultured larval fat bodies from the Japanese rhinoceros beetle, Allomyrina dichotoma, and evaluated, using linear mixed models, the effect of interindividual variation between donors on the reproducibility of the culture. We also performed transcriptome analysis of the hemocyte-like cells mainly seen in the cultures using RNA sequencing and ultrastructural analyses of hemocytes using a transmission electron microscope, revealing that the cultured cells have many characteristics of insect hemocytes.

Evaluation of multichannel reproduced sound

DEFF Research Database (Denmark)

Choisel, Sylvain; Wickelmaier, Florian Maria

2007-01-01

A study was conducted with the goal of quantifying auditory attributes which underlie listener preference for multichannel reproduced sound. Short musical excerpts were presented in mono, stereo and several multichannel formats to a panel of forty selected listeners. Scaling of auditory attributes......, as well as overall preference, was based on consistency tests of binary paired-comparison judgments and on modeling the choice frequencies using probabilistic choice models. As a result, the preferences of non-expert listeners could be measured reliably at a ratio scale level. Principal components derived...

Validity and reproducibility of a Spanish dietary history.

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Pilar Guallar-Castillón

Full Text Available To assess the validity and reproducibility of food and nutrient intake estimated with the electronic diet history of ENRICA (DH-E, which collects information on numerous aspects of the Spanish diet.The validity of food and nutrient intake was estimated using Pearson correlation coefficients between the DH-E and the mean of seven 24-hour recalls collected every 2 months over the previous year. The reproducibility was estimated using intraclass correlation coefficients between two DH-E made one year apart.The correlations coefficients between the DH-E and the mean of seven 24-hour recalls for the main food groups were cereals (r = 0.66, meat (r = 0.66, fish (r = 0.42, vegetables (r = 0.62 and fruits (r = 0.44. The mean correlation coefficient for all 15 food groups considered was 0.53. The correlations for macronutrients were: energy (r = 0.76, proteins (r= 0.58, lipids (r = 0.73, saturated fat (r = 0.73, monounsaturated fat (r = 0.59, polyunsaturated fat (r = 0.57, and carbohydrates (r = 0.66. The mean correlation coefficient for all 41 nutrients studied was 0.55. The intraclass correlation coefficient between the two DH-E was greater than 0.40 for most foods and nutrients.The DH-E shows good validity and reproducibility for estimating usual intake of foods and nutrients.

Reproducible positioning in chest X-ray radiography

International Nuclear Information System (INIS)

1974-01-01

A device is described that can be used to ensure reproducibility in the positioning of the patient during X-ray radiography of the thorax. Signals are taken from an electrocardiographic monitor and from a device recording the respiratory cycle. Radiography is performed only when two preselected signals coincide

Reproducibility of Manual Platelet Estimation Following Automated Low Platelet Counts

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Zainab S Al-Hosni

2016-11-01

Full Text Available Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20. Data were analyzed using intraclass correlation coefficient (ICC as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78. The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037. When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420. Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

Reproducibility in the assessment of acute pancreatitis with computed tomography

International Nuclear Information System (INIS)

Freire Filho, Edison de Oliveira; Vieira, Renata La Rocca; Yamada, Andre Fukunishi; Shigueoka, David Carlos; Bekhor, Daniel; Freire, Maxime Figueiredo de Oliveira; Ajzen, Sergio; D'Ippolito, Giuseppe

2007-01-01

Objective: To evaluate the reproducibility of unenhanced and contrast-enhanced computed tomography in the assessment of patients with acute pancreatitis. Materials and methods: Fifty-one unenhanced and contrast-enhanced abdominal computed tomography studies of patients with acute pancreatitis were blindly reviewed by two radiologists (observers 1 and 2). The morphological index was separately calculated for unenhanced and contrast-enhanced computed tomography and the disease severity index was established. Intraobserver and interobserver reproducibility of computed tomography was measured by means of the kappa index (κ). Results: Interobserver agreement was κ 0.666, 0.705, 0.648, 0.547 and 0.631, respectively for unenhanced and contrast-enhanced morphological index, presence of pancreatic necrosis, pancreatic necrosis extension, and disease severity index. Intraobserver agreement (observers 1 and 2, respectively) was κ = 0.796 and 0.732 for unenhanced morphological index; κ 0.725 and 0.802 for contrast- enhanced morphological index; κ = 0.674 and 0.849 for presence of pancreatic necrosis; κ = 0.606 and 0.770 for pancreatic necrosis extension; and κ = 0.801 and 0.687 for disease severity index at computed tomography. Conclusion: Computed tomography for determination of morphological index and disease severity index in the staging of acute pancreatitis is a quite reproducible method. The absence of contrast- enhancement does not affect the computed tomography morphological index reproducibility. (author)

Pathophysiology and multifactorial etiology of acquired vasospastic disease (Raynaud syndrome) in vibration-exposed workers.

Science.gov (United States)

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.

Amygdala alterations during an emotional conflict task in women recovered from anorexia nervosa.

Science.gov (United States)

Bang, Lasse; Rø, Øyvind; Endestad, Tor

2016-02-28

The pathophysiology of anorexia nervosa (AN) is not completely understood, but research suggests that alterations in brain circuits related to cognitive control and emotion are central. The aim of this study was to explore neural responses to an emotional conflict task in women recovered from AN. Functional magnetic resonance imaging was used to measure neural responses to an emotional conflict task in 22 women recovered from AN and 21 age-matched healthy controls. The task involved categorizing affective faces while ignoring affective words. Face and word stimuli were either congruent (non-conflict) or incongruent (conflict). Brain responses to emotional conflict did not differ between groups. However, in response to emotional non-conflict, women recovered from AN relative to healthy controls showed significantly less activation in the bilateral amygdala. Specifically, while emotional non-conflict evoked significant activations of the amygdala in healthy controls, recovered AN women did not show such activations. Similar significant group differences were also observed in the hippocampus and basal ganglia. These results suggest that women recovered from AN are characterized by alterations within emotion-related brain circuits. Recovered women's absence of amygdala and hippocampus activation during non-conflict trials possibly reflects an impaired ability to process emotional significant stimuli. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A comparison between the pathophysiology of multiple sclerosis and normal pressure hydrocephalus: is pulse wave encephalopathy a component of MS?

Science.gov (United States)

Bateman, Grant A; Lechner-Scott, Jeannette; Lea, Rodney A

2016-09-22

It has been suggested there is a chronic neurodegenerative disorder, underlying the pathophysiology of multiple sclerosis (MS), which is distinct from the more obvious immune-mediated attack on the white matter. Limited data exists indicating there is an alteration in pulse wave propagation within the craniospinal cavity in MS, similar to the findings in normal pressure hydrocephalus (NPH). It is hypothesized MS may harbor pulse wave encephalopathy. The purpose of this study is to compare blood flow and pulse wave measurements in MS patients with a cohort of NPH patients and control subjects, to test this hypothesis. Twenty patients with MS underwent magnetic resonance (MR) flow quantification techniques. Mean blood flow and stroke volume were measured in the arterial inflow and venous out flow from the sagittal (SSS) and straight sinus (ST). The arteriovenous delay (AVD) was defined. The results were compared with both age-matched controls and NPH patients. In MS there was a 35 % reduction in arteriovenous delay and a 5 % reduction in the percentage of the arterial inflow returning via the sagittal sinus compared to age matched controls. There was an alteration in pulse wave propagation, with a 26 % increase in arterial stroke volume but 30 % reduction in SSS and ST stroke volume. The AVD and blood flow changes were in the same direction to those of NPH patients. There are blood flow and pulsation propagation changes in MS patients which are similar to those of NPH patients. The findings would be consistent with an underlying pulse wave encephalopathy component in MS.

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

Science.gov (United States)

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

2012-10-01

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

Inter-examiner reproducibility of tests for lumbar motor control

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Elkjaer Arne

2011-05-01

Full Text Available Abstract Background Many studies show a relation between reduced lumbar motor control (LMC and low back pain (LBP. However, test circumstances vary and during test performance, subjects may change position. In other words, the reliability - i.e. reproducibility and validity - of tests for LMC should be based on quantitative data. This has not been considered before. The aim was to analyse the reproducibility of five different quantitative tests for LMC commonly used in daily clinical practice. Methods The five tests for LMC were: repositioning (RPS, sitting forward lean (SFL, sitting knee extension (SKE, and bent knee fall out (BKFO, all measured in cm, and leg lowering (LL, measured in mm Hg. A total of 40 subjects (14 males, 26 females 25 with and 15 without LBP, with a mean age of 46.5 years (SD 14.8, were examined independently and in random order by two examiners on the same day. LBP subjects were recruited from three physiotherapy clinics with a connection to the clinic's gym or back-school. Non-LBP subjects were recruited from the clinic's staff acquaintances, and from patients without LBP. Results The means and standard deviations for each of the tests were 0.36 (0.27 cm for RPS, 1.01 (0.62 cm for SFL, 0.40 (0.29 cm for SKE, 1.07 (0.52 cm for BKFO, and 32.9 (7.1 mm Hg for LL. All five tests for LMC had reproducibility with the following ICCs: 0.90 for RPS, 0.96 for SFL, 0.96 for SKE, 0.94 for BKFO, and 0.98 for LL. Bland and Altman plots showed that most of the differences between examiners A and B were less than 0.20 cm. Conclusion These five tests for LMC displayed excellent reproducibility. However, the diagnostic accuracy of these tests needs to be addressed in larger cohorts of subjects, establishing values for the normal population. Also cut-points between subjects with and without LBP must be determined, taking into account age, level of activity, degree of impairment and participation in sports. Whether reproducibility of these

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...

Pathophysiology of anorexia in the cancer cachexia syndrome.

Science.gov (United States)

Ezeoke, Chukwuemeka Charles; Morley, John E

2015-12-01

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

OpenAIRE

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...

Reproducibility of prompts in computer-aided detection (CAD) of breast cancer

International Nuclear Information System (INIS)

Taylor, C.G.; Champness, J.; Reddy, M.; Taylor, P.; Potts, H.W.W.; Given-Wilson, R.

2003-01-01

AIM: We evaluated the reproducibility of prompts using the R2 ImageChecker M2000 computer-aided detection (CAD) system. MATERIALS AND METHODS: Forty selected two-view mammograms of women with breast cancer were digitized and analysed using the ImageChecker on 10 separate occasions. The mammograms were chosen to provide both straightforward and subtle signs of malignancy. Data analysed included mammographic abnormality, pathology, and whether the cancer was prompted or given an emphasized prompt. RESULTS: Correct prompts were generated in 86 out of 100 occasions for screen-detected cancers. Reproducibility was less in the other categories of more subtle cancers: 21% for cancers previously missed by CAD, a group that contained more grade 1 and small (<10 mm) tumours. Prompts for calcifications were more reproducible than those for masses (76% versus 53%) and these cancers were more likely to have an emphasized prompt. CONCLUSIONS: Probably the most important cause of variability of prompts is shifts in film position between sequential digitizations. Consequently subtle lesions that are only just above the threshold for display may not be prompted on repeat scanning. However, users of CAD should be aware that even emphasized prompts are not consistently reproducible

Reproducing {sup 137}Cs vertical migration in Spanish soils - Reproducing {sup 137}Cs and {sup 90}Sr vertical migration in Spanish mainland

Energy Technology Data Exchange (ETDEWEB)

Olondo, C.; Legarda, F.; Herranz, M.; Idoeta, R. [The University of the Basque Country - UPV/EHU, Nuclear Engineering and Fluid Mechanics Dept. Faculty of Engineering, Alda. Urquijo 48013, Bilbao (Spain)

2014-07-01

As a result of caesium's and strontium's activity migration study developed in Spanish mainland soils, there has been obtained convective - diffusive migration equation that will reproduce adequately the movement that an activity deposit would follow in this land. Taking into account the dependence on rain that apparent convection velocity shows, it has been defined a new migration parameter that depends only on soil's properties. By means of a least square method and fitting the migration equation to experimental activity profiles, the values showed by the migration parameters in the studied soils, characteristics of that area, have been obtained. After that, there have been obtained the mean values of these parameters for each defined group that, depending on soil's texture, have been observed in the study performed about the movement of both radionuclides in soils and to whom these soils belong. Using these mean values and obtained equation, it has been properly reproduce those vertical activity profiles that were experimentally determined. In order to validate these values, a new sampling programme is carrying out in the north of Spain and, with obtained new sampling points' information, is going to verify if, indeed, obtained mean values also reproduce these new sampling points' activity vertical profile. (authors)

Histidine Decarboxylase Knockout Mice as a Model of the Pathophysiology of Tourette Syndrome and Related Conditions.

Science.gov (United States)

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.

Science.gov (United States)

McCrory, P R; Berkovic, S F

2001-12-26

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

[Refeeding syndrome : Pathophysiology, risk factors, prevention, and treatment].

Science.gov (United States)

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.

Reproducibility of liver position using active breathing coordinator for liver cancer radiotherapy

International Nuclear Information System (INIS)

Eccles, Cynthia; Brock, Kristy K.; Bissonnette, Jean-Pierre; Hawkins, Maria; Dawson, Laura A.

2006-01-01

Purpose: To measure the intrabreath-hold liver motion and the intrafraction and interfraction reproducibility of liver position relative to vertebral bodies using an active breathing coordinator (ABC) in patients with unresectable liver cancer treated with hypofractionated stereotactic body radiation therapy (SBRT). Methods: Tolerability of ABC and organ motion during ABC was assessed using kV fluoroscopy in 34 patients. For patients treated with ABC, repeat breath-hold CT scans in the ABC breath-hold position were acquired at simulation to estimate the volumetric intrafraction reproducibility of the liver relative to the vertebral bodies. In addition, preceding each radiation therapy fraction, with the liver immobilized using ABC, repeat anteroposterior (AP) megavoltage verification images were obtained. Off-line alignments were completed to determine intrafraction reproducibility (from repeat images obtained before one treatment) and interfraction reproducibility (from comparisons of the final image for each fraction with the AP) of diaphragm position relative to vertebral bodies. For each image set, the vertebral bodies were aligned, and the resultant craniocaudal (CC) offset in diaphragm position was measured. Liver position during ABC was also evaluated from kV fluoroscopy acquired at the time of simulation, kV fluoroscopy at the time of treatment, and from MV beam's-eye view movie loops acquired during treatment. Results: Twenty-one of 34 patients were screened to be suitable for ABC. The average free breathing range of these patients was 13 mm (range, 5-1 mm). Fluoroscopy revealed that the average maximal diaphragm motion during ABC breath-hold was 1.4 mm (range, 0-3.4 mm). The MV treatment movie loops confirmed diaphragm stability during treatment. For a measure of intrafraction reproducibility, an analysis of 36 repeat ABC computed tomography (CT) scans in 14 patients was conducted. The average mean difference in the liver surface position was -0.9 mm, -0

The pathophysiology of trauma-induced coagulopathy.

Science.gov (United States)

Frith, Daniel; Brohi, Karim

2012-12-01

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

Pathophysiology of AAA: heredity vs environment.

Science.gov (United States)

Björck, Martin; Wanhainen, Anders

2013-01-01

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

The reproducibility of random amplified polymorphic DNA (RAPD ...

African Journals Online (AJOL)

RAPD) profiles of Streptococcus thermophilus strains by using the polymerase chain reaction (PCR). Several factors can cause the amplification of false and non reproducible bands in the RAPD profiles. We tested three primers, OPI-02 MOD, ...

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.

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

Science.gov (United States)

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

2016-06-01

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

The Sphenopalatine Ganglion: Anatomy, Pathophysiology, and Therapeutic Targeting in Headache.

Science.gov (United States)

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.

Reproducibility and Transparency in Ocean-Climate Modeling

Science.gov (United States)

Hannah, N.; Adcroft, A.; Hallberg, R.; Griffies, S. M.

2015-12-01

Reproducibility is a cornerstone of the scientific method. Within geophysical modeling and simulation achieving reproducibility can be difficult, especially given the complexity of numerical codes, enormous and disparate data sets, and variety of supercomputing technology. We have made progress on this problem in the context of a large project - the development of new ocean and sea ice models, MOM6 and SIS2. Here we present useful techniques and experience.We use version control not only for code but the entire experiment working directory, including configuration (run-time parameters, component versions), input data and checksums on experiment output. This allows us to document when the solutions to experiments change, whether due to code updates or changes in input data. To avoid distributing large input datasets we provide the tools for generating these from the sources, rather than provide raw input data.Bugs can be a source of non-determinism and hence irreproducibility, e.g. reading from or branching on uninitialized memory. To expose these we routinely run system tests, using a memory debugger, multiple compilers and different machines. Additional confidence in the code comes from specialised tests, for example automated dimensional analysis and domain transformations. This has entailed adopting a code style where we deliberately restrict what a compiler can do when re-arranging mathematical expressions.In the spirit of open science, all development is in the public domain. This leads to a positive feedback, where increased transparency and reproducibility makes using the model easier for external collaborators, who in turn provide valuable contributions. To facilitate users installing and running the model we provide (version controlled) digital notebooks that illustrate and record analysis of output. This has the dual role of providing a gross, platform-independent, testing capability and a means to documents model output and analysis.

The "chloride theory", a unifying hypothesis for renal handling and body fluid distribution in heart failure pathophysiology.

Science.gov (United States)

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.

Properties of galaxies reproduced by a hydrodynamic simulation

Science.gov (United States)

Vogelsberger, M.; Genel, S.; Springel, V.; Torrey, P.; Sijacki, D.; Xu, D.; Snyder, G.; Bird, S.; Nelson, D.; Hernquist, L.

2014-05-01

Previous simulations of the growth of cosmic structures have broadly reproduced the `cosmic web' of galaxies that we see in the Universe, but failed to create a mixed population of elliptical and spiral galaxies, because of numerical inaccuracies and incomplete physical models. Moreover, they were unable to track the small-scale evolution of gas and stars to the present epoch within a representative portion of the Universe. Here we report a simulation that starts 12 million years after the Big Bang, and traces 13 billion years of cosmic evolution with 12 billion resolution elements in a cube of 106.5 megaparsecs a side. It yields a reasonable population of ellipticals and spirals, reproduces the observed distribution of galaxies in clusters and characteristics of hydrogen on large scales, and at the same time matches the `metal' and hydrogen content of galaxies on small scales.

Assessment of (patho)physiologic alterations in equine muscle metabolism

NARCIS (Netherlands)

Westermann, C.M.

2008-01-01

This thesis focussed on the diagnostic use of metabolic products and enzymes found in plasma, urine and muscle of the horse, the identification of which can reveal physiological or pathological changes in muscle metabolism. In this thesis analyses of carbohydrate-, lipid- and protein metabolites

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

Bridging from Cells to Cognition in Autism Pathophysiology: Biological Pathways to Defective Brain Function and Plasticity

Energy Technology Data Exchange (ETDEWEB)

Anderson, Matthew; Hooker, Brian S.; Herbert, Martha

2008-01-01

We review evidence to support the model that autism may begin when a maternal environmental, infectious, or autoantibody insult causes inflammation which increases reactive oxygen species (ROS) production in the fetus, leading to fetal DNA damage (nuclear and mitochondrial), and that these inflammatory and oxidative stressors persist beyond early development (with potential further exacerbations), producing ongoing functional consequences. In organs with a high metabolic demand such as the central nervous system, the continued use of mitochondria with DNA damage may generate additional ROS which will activate the innate immune system leading to more ROS production. Such a mechanism would self-sustain and possibly progressively worsen. The mitochondrial dysfunction and altered redox signal transduction pathways found in autism would conspire to activate both astroglia and microglia. These activated cells can then initiate a broad-spectrum proinflammatory gene response. Neurons may have acquired receptors for these inflammatory signals to inhibit neuronal signaling as a protection from excitotoxic damage during various pathologic insults (e.g., infection). In autism, over-zealous neuroinflammatory responses could not only influence neural developmental processes, but may more significantly impair neural signaling involved in cognition in an ongoing fashion. This model makes specific predictions in patients and experimental animal models and suggests a number of targets sites of intervention. Our model of potentially reversible pathophysiological mechanisms in autism motivates our hope that effective therapies may soon appear on the horizon.

The impact of technical conditions of X-ray imaging on reproducibility and precision of digital computer-assisted X-ray radiogrammetry (DXR)

International Nuclear Information System (INIS)

Malich, A.; Boettcher, J.; Pfeil, A.; Sauner, D.; Heyne, J.P.; Petrovitch, A.; Hansch, A.; Kaiser, W.A.; Linss, W.

2004-01-01

To evaluate the reproducibility of imaging and analysis for bone mineral density (BMD) determination using digital computer-assisted X-ray radiogrammetry (DXR; Pronosco X-posure, version V.2, Sectra Pronosco, Denmark); to verify potential factors that influence BMD extrapolation such as tube voltage, film-focus distance (FFD), film quality and brand (Kodak T-MAT-Plus, Konika SRH, Agfa Scopix), imaging technology (conventional, digital), imaging system (Kodak, Agfa) and exposure level (mAs); and to clarify whether DXR analysis based on printouts of digital images is comparable to analysis of conventional images. The hand of a cadaver was X-rayed using varied parameters: 4-8 mAs, 40-52 kV, 90-130 cm FFD. Radiographs under standardised conditions were performed 10 times using a conventional machine (Philips Super 80 CP) and the printouts of a digital system (Digital Diagnost Philips Optimus) for the analysis of reproducibility. One image was scanned and analysed 10 times additionally for imaging reproducibility. Reliability error of the system for the imaging process using conventional radiographs-rays was 0.49% (standard conditions: 6 mAs, 40 kV, 1 m FFD), using printouts of digital images was 2.89% (4 mAs, 42 kV, 1 m FFD) and regarding the analysis process was 0.22%. BMD calculation is not affected by alterations in FFD (precision error 1.21%), mAs (0.83%) or film quality/brand (0.38%), but differs significantly depending on tube voltage (2.70%). The system was not able to analyse conventional images with tube voltages of 49/52 kV. DXR technology is stable with most of the tested parameters. Normative data should exclusively be used for calculations using similar tube voltage or correction factors. All other parameters had no significant influence on the BMD calculation. Reproducibility is high. For technical reasons it is not recommended to use the printouts of digital images for BMD determination. (orig.)

Pathophysiology of anorexia in the cancer cachexia syndrome

Science.gov (United States)

Ezeoke, Chukwuemeka Charles; Morley, John E

2015-01-01

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients. PMID:26675762

Regulating Ultrasound Cavitation in order to Induce Reproducible Sonoporation

Science.gov (United States)

Mestas, J.-L.; Alberti, L.; El Maalouf, J.; Béra, J.-C.; Gilles, B.

2010-03-01

Sonoporation would be linked to cavitation, which generally appears to be a non reproducible and unstationary phenomenon. In order to obtain an acceptable trade-off between cell mortality and transfection, a regulated cavitation generator based on an acoustical cavitation measurement was developed and tested. The medium to be sonicated is placed in a sample tray. This tray is immersed in in degassed water and positioned above the face of a flat ultrasonic transducer (frequency: 445 kHz; intensity range: 0.08-1.09 W/cm2). This technical configuration was admitted to be conducive to standing-wave generation through reflection at the air/medium interface in the well thus enhancing the cavitation phenomenon. Laterally to the transducer, a homemade hydrophone was oriented to receive the acoustical signal from the bubbles. From this spectral signal recorded at intervals of 5 ms, a cavitation index was calculated as the mean of the cavitation spectrum integration in a logarithmic scale, and the excitation power is automatically corrected. The device generates stable and reproducible cavitation level for a wide range of cavitation setpoint from stable cavitation condition up to full-developed inertial cavitation. For the ultrasound intensity range used, the time delay of the response is lower than 200 ms. The cavitation regulation device was evaluated in terms of chemical bubble collapse effect. Hydroxyl radical production was measured on terephthalic acid solutions. In open loop, the results present a great variability whatever the excitation power. On the contrary the closed loop allows a great reproducibility. This device was implemented for study of sonodynamic effect. The regulation provides more reproducible results independent of cell medium and experimental conditions (temperature, pressure). Other applications of this regulated cavitation device concern internalization of different particles (Quantum Dot) molecules (SiRNA) or plasmids (GFP, DsRed) into different

Reproducibility of heart rate variability, blood pressure variability and baroreceptor sensitivity during rest and head-up tilt

DEFF Research Database (Denmark)

Højgaard, Michael V; Agner, Erik; Kanters, Jørgen K

2005-01-01

OBJECTIVE: Previous studies have indicated moderate-to-poor reproducibility of heart rate variability (HRV) but the reproducibility of blood pressure variability (BPV) and spectral measures of baroreceptor sensitivity (BRS) are not well established. METHODS: We measured normal-to-normal heart beat...... pressures were extracted for the assessment of day-to-day and short-term reproducibility. Power spectrum analysis (Fourier) and transfer function analysis was performed. Reproducibility was assessed using the coefficient of variation (CV). The reproducibility of the mean RR interval, mean systolic......, diastolic and mean blood pressure was good (CVspectral parameters of HRV (CV range 18-36%) and BPV (16-44%) and moderate reproducibility of BRS (14-20%). CONCLUSION: Spectral estimates of BRS had only moderate reproducibility although...

Metabolic alterations in dialysis patients

NARCIS (Netherlands)

Drechsler, Christiane

2010-01-01

Assessing metabolic risk in dialysis patients, three main aspects are important: a) the pathophysiologic effects of metabolic disturbances as known from the general population are unlikely to completely reverse once patients reach dialysis. b) Specific additional problems related to chronic kidney

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

Science.gov (United States)

Que, Y; Shen, X

2016-02-01

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

Reproducibility Test for Thermoluminescence Dosimeter (TLD) Using TLD Radpro

International Nuclear Information System (INIS)

Nur Khairunisa Zahidi; Ahmad Bazlie Abdul Kadir; Faizal Azrin Abdul Razalim

2016-01-01

Thermoluminescence dosimeters (TLD) as one type of dosimeter which are often used to substitute the film badge. Like a film badge, it is worn for a period of time and then must be processed to determine the dose received. This study was to test the reproducibility of TLD using Radpro reader. This study aimed to determine the dose obtained by TLD-100 chips when irradiated with Co-60 gamma source and to test the effectiveness of TLD Radpro reader as a machine to analyse the TLD. Ten chips of TLD -100 were irradiated using Eldorado machine with Co-60 source at a distance of 5 meters from the source with 2 mSv dose exposure. After the irradiation process, TLD-100 chips were read using the TLD Radpro reader. These steps will be repeated for nine times to obtain reproducibility coefficient, r i . The readings of dose obtained from experiment was almost equivalent to the actual dose. Results shows that the average value obtained for reproducibility coefficient, r i is 6.39 % which is less than 10 %. As conclusion, the dose obtained from experiment considered accurate because its value were almost equivalent to the actual dose and TLD Radpro was verified as a good reader to analyse the TLD. (author)

Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

Science.gov (United States)

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.

The Physiology of Female Sexual Function and the Pathophysiology of Female Sexual Dysfunction (Committee 13A).

Science.gov (United States)

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.

Repeatability and Reproducibility of Fibre-Based Nanogenerator Synthesized by Electrospinning Machine

International Nuclear Information System (INIS)

Suyitno; Huda, Sholiehul; Arifin, Zainal; Hadi, Syamsul; Lambang, Raymundus Lullus

2014-01-01

Zinc oxide fibres-based nanogenerators synthesized easily by electrospinning machine are promising to harvest electricity from mechanical energy. However, the repeatability and reproducibility were two major factors needed to be investigated to minimize product failure and to determine the feasibility of mass production of nanogenerators. The green fibres of zinc oxide were produced by electrospinning machine of zinc acetate and polyvinyl alcohol solution at a flow rate of 4 μL/min followed by sintering at temperature 550°C with heating rate 240°C/h. Each 10 nanogenerators was tested by three trained operators with three times of repetition at compressive load 0.5 kg. The nanogenerators revealed the maximum output voltage ranging from 203 to 217 mV. The value of repeatability and reproducibility of nanogenerators was approximately 24.29% showing that nanogenerators were still acceptable to be mass-produced. The relatively low reproducibility was mainly due to the operators, so that the checklist needed to be made easier and simpler for all the variables affecting to the quality of the fibres. Reducing the value of the repeatability and reproducibility is interesting to study further by creating a rotating collector so that the thickness and orientation of fibres can be arranged better

Assessing Cognitive Performance in Badminton Players: A Reproducibility and Validity Study

Directory of Open Access Journals (Sweden)

van de Water Tanja

2017-01-01

Full Text Available Fast reaction and good inhibitory control are associated with elite sports performance. To evaluate the reproducibility and validity of a newly developed Badminton Reaction Inhibition Test (BRIT, fifteen elite (25 ± 4 years and nine non-elite (24 ± 4 years Dutch male badminton players participated in the study. The BRIT measured four components: domain-general reaction time, badminton-specific reaction time, domain-general inhibitory control and badminton-specific inhibitory control. Five participants were retested within three weeks on the badminton-specific components. Reproducibility was acceptable for badminton-specific reaction time (ICC = 0.626, CV = 6% and for badminton-specific inhibitory control (ICC = 0.317, CV = 13%. Good construct validity was shown for badminton-specific reaction time discriminating between elite and non-elite players (F = 6.650, p 0.05. Concurrent validity for domain-general reaction time was good, as it was associated with a national ranking for elite (p = 0.70, p 0.05. In conclusion, reproducibility and validity of inhibitory control assessment was not confirmed, however, the BRIT appears a reproducible and valid measure of reaction time in badminton players. Reaction time measured with the BRIT may provide input for training programs aiming to improve badminton players’ performance.

Assessing Cognitive Performance in Badminton Players: A Reproducibility and Validity Study.

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van de Water, Tanja; Huijgen, Barbara; Faber, Irene; Elferink-Gemser, Marije

2017-01-01

Fast reaction and good inhibitory control are associated with elite sports performance. To evaluate the reproducibility and validity of a newly developed Badminton Reaction Inhibition Test (BRIT), fifteen elite (25 ± 4 years) and nine non-elite (24 ± 4 years) Dutch male badminton players participated in the study. The BRIT measured four components: domain-general reaction time, badminton-specific reaction time, domain-general inhibitory control and badminton-specific inhibitory control. Five participants were retested within three weeks on the badminton-specific components. Reproducibility was acceptable for badminton-specific reaction time (ICC = 0.626, CV = 6%) and for badminton-specific inhibitory control (ICC = 0.317, CV = 13%). Good construct validity was shown for badminton-specific reaction time discriminating between elite and non-elite players (F = 6.650, p 0.05). Concurrent validity for domain-general reaction time was good, as it was associated with a national ranking for elite (p = 0.70, p badminton-specific reaction time, nor both components of inhibitory control (p > 0.05). In conclusion, reproducibility and validity of inhibitory control assessment was not confirmed, however, the BRIT appears a reproducible and valid measure of reaction time in badminton players. Reaction time measured with the BRIT may provide input for training programs aiming to improve badminton players' performance.

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

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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.

Open and reproducible global land use classification

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Nüst, Daniel; Václavík, Tomáš; Pross, Benjamin

2015-04-01

Researchers led by the Helmholtz Centre for Environmental research (UFZ) developed a new world map of land use systems based on over 30 diverse indicators (http://geoportal.glues.geo.tu-dresden.de/stories/landsystemarchetypes.html) of land use intensity, climate and environmental and socioeconomic factors. They identified twelve land system archetypes (LSA) using a data-driven classification algorithm (self-organizing maps) to assess global impacts of land use on the environment, and found unexpected similarities across global regions. We present how the algorithm behind this analysis can be published as an executable web process using 52°North WPS4R (https://wiki.52north.org/bin/view/Geostatistics/WPS4R) within the GLUES project (http://modul-a.nachhaltiges-landmanagement.de/en/scientific-coordination-glues/). WPS4R is an open source collaboration platform for researchers, analysts and software developers to publish R scripts (http://www.r-project.org/) as a geo-enabled OGC Web Processing Service (WPS) process. The interoperable interface to call the geoprocess allows both reproducibility of the analysis and integration of user data without knowledge about web services or classification algorithms. The open platform allows everybody to replicate the analysis in their own environments. The LSA WPS process has several input parameters, which can be changed via a simple web interface. The input parameters are used to configure both the WPS environment and the LSA algorithm itself. The encapsulation as a web process allows integration of non-public datasets, while at the same time the publication requires a well-defined documentation of the analysis. We demonstrate this platform specifically to domain scientists and show how reproducibility and open source publication of analyses can be enhanced. We also discuss future extensions of the reproducible land use classification, such as the possibility for users to enter their own areas of interest to the system and

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

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Simona-Adriana Manea

2015-08-01

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

Altered intrinsic functional connectivity in the latent period of epileptogenesis in a temporal lobe epilepsy model.

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Lee, Hyoin; Jung, Seungmoon; Lee, Peter; Jeong, Yong

2017-10-01

The latent period, a seizure-free phase, is the duration between brain injury and the onset of spontaneous recurrent seizures (SRSs) during epileptogenesis. The latent period is thought to involve several progressive pathophysiological events that lead to the evolution of the chronic epilepsy phase. Hence, it is vital to investigate the changes in the latent period during epileptogenesis in order to better understand temporal lobe epilepsy (TLE), and to achieve early diagnosis and appropriate management of the condition. Accordingly, recent studies with patients with TLE using resting-state functional magnetic resonance imaging (rs-fMRI) have reported that alterations of resting-state functional connectivity (rsFC) during the chronic period are associated with some clinical manifestations, including learning and memory impairments, emotional instability, and social behavior deficits, in addition to repetitive seizure episodes. In contrast, the changes in the intrinsic rsFC during epileptogenesis, particularly during the latent period, remain unclear. In this study, we investigated the alterations in intrinsic rsFC during the latent and chronic periods in a pilocarpine-induced TLE mouse model using intrinsic optical signal imaging (IOSI). This technique can monitor the changes in the local hemoglobin concentration according to neuronal activity and can help investigate large-scale brain intrinsic networks. After seeding on the anatomical regions of interest (ROIs) and calculating the correlation coefficients between each ROI, we established and compared functional correlation matrices and functional connectivity maps during the latent and chronic periods of epilepsy. We found a decrease in the interhemispheric rsFC at the frontal and temporal regions during both the latent and chronic periods. Furthermore, a significant decrease in the interhemispheric rsFC was observed in the somatosensory area during the chronic period. Changes in network configurations during

Pathophysiological changes that affect drug disposition in protein-energy malnourished children

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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.

Model of Alteration of Matrix. Implementation of new approaches (influence of H{sub 2}); Modelo de Alteracion de la Matriz. Implementacion de nuevas aproximaciones (influencia del H{sub 2})

Energy Technology Data Exchange (ETDEWEB)

Rodriguez, N.; Iglesias, E.; Palomo, C.; Nieto, J.; Martinez Esparza, A.; Quinones, J.

2011-07-01

In order to improve the model and get reproduce the behavior observed in the laboratory in this paper present the changes incorporated in the model of altered matrix to model the catalytic effect of the particles in the activation of H{sub 2}.

Can cancer researchers accurately judge whether preclinical reports will reproduce?

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Daniel Benjamin

2017-06-01

Full Text Available There is vigorous debate about the reproducibility of research findings in cancer biology. Whether scientists can accurately assess which experiments will reproduce original findings is important to determining the pace at which science self-corrects. We collected forecasts from basic and preclinical cancer researchers on the first 6 replication studies conducted by the Reproducibility Project: Cancer Biology (RP:CB to assess the accuracy of expert judgments on specific replication outcomes. On average, researchers forecasted a 75% probability of replicating the statistical significance and a 50% probability of replicating the effect size, yet none of these studies successfully replicated on either criterion (for the 5 studies with results reported. Accuracy was related to expertise: experts with higher h-indices were more accurate, whereas experts with more topic-specific expertise were less accurate. Our findings suggest that experts, especially those with specialized knowledge, were overconfident about the RP:CB replicating individual experiments within published reports; researcher optimism likely reflects a combination of overestimating the validity of original studies and underestimating the difficulties of repeating their methodologies.