Bone marrow lesions and subchondral bone pathology of the knee.

PubMed

Kon, Elizaveta; Ronga, Mario; Filardo, Giuseppe; Farr, Jack; Madry, Henning; Milano, Giuseppe; Andriolo, Luca; Shabshin, Nogah

2016-06-01

Bone marrow lesions (BMLs) around the knee are a common magnetic resonance imaging (MRI) finding. However, despite the growing interest on BMLs in multiple pathological conditions, they remain controversial not only for the still unknown role in the etiopathological processes, but also in terms of clinical impact and treatment. The differential diagnosis includes a wide range of conditions: traumatic contusion and fractures, cyst formation and erosions, hematopoietic and infiltrated marrow, developmental chondroses, disuse and overuse, transient bone marrow oedema syndrome and, lastly, subchondral insufficiency fractures and true osteonecrosis. Regardless the heterogeneous spectrum of these pathologies, a key factor for patient management is the distinction between reversible and irreversible conditions. To this regard, MRI plays a major role, leading to the correct diagnosis based on recognizable typical patterns that have to be considered together with coexistent abnormalities, age, and clinical history. Several treatment options have been proposed, from conservative to surgical approaches. In this manuscript the main lesion patterns and their management have been analysed to provide the most updated evidence for the differential diagnosis and the most effective treatment.

A case with unexplained bleeding from multiple sites: munchausen syndrome by proxy.

PubMed

Tüfekçi, Özlem; Gözmen, Salih; Yılmaz, Şebnem; Hilkay Karapınar, Tuba; Çetin, Benhur; Burak Dursun, Onur; Emiroğlu, Neslihan; Ören, Hale; Irken, Gülersu

2011-08-01

Munchausen syndrome by proxy (MBP) is an extreme form of child abuse where children were unnecessarily treated or investigated for medical conditions that were falsified by their caregivers. Here the authors report a 16-year-old female with the complaints of bleeding from multiple and unusual sites, including hemoptysis, hematuria, bloody tears, and bloody nipple discharge, all of which are only witnessed by her mother. Extensive investigation revealed no organic etiologies for bleeding. The diagnosis of MBP was put by a multidisciplinary team. The diagnosis of MBP must be kept in mind in conditions where there is no underlying organic pathology in a bleeding patient.

Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

PubMed Central

Jope, Richard S.; Yuskaitis, Christopher J.; Beurel, Eléonore

2007-01-01

Deciphering what governs inflammation and its effects on tissues is vital for understanding many pathologies. The recent discovery that glycogen synthase kinase-3 (GSK3) promotes inflammation reveals a new component of its well-documented actions in several prevalent diseases which involve inflammation, including mood disorders, Alzheimer’s disease, diabetes, and cancer. Involvement in such disparate conditions stems from the widespread influences of GSK3 on many cellular functions, with this review focusing on its regulation of inflammatory processes. GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation, while GSK3 inhibition provides protection from inflammatory conditions in animal models. The involvement of GSK3 and inflammation in these diseases are highlighted. Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions. PMID:16944320

Polycystic kidneys in the red panda (Ailurus fulgens).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Koeppel, Katja N; Groenewald, Hermanus B

2013-09-01

An intact adult male 14.3-yr-old red panda (Ailurus fulgens) presented for health examination with a history of slowly progressing loss of body condition. Abdominal radiographs revealed a truncated abdomen with poor serosal abdominal detail and multiple areas of spondylosis with some collapsed intervertebral disc spaces. On computed tomography, multiple ovoid hypoattenuating lesions were seen in the left and right kidneys. Gross pathology and histopathology revealed multiple cystic lesions in the kidneys concurrent with pancreatic cysts on histopathology. To the best of the authors' knowledge, polycystic kidneys have not been reported in this species.

The Emerging Role of Inflammasomes as Central Mediators in Inflammatory Bladder Pathology

PubMed Central

Inouye, Brian M.; Hughes, Francis M.; Sexton, Stephanie J.; Purves, J. Todd

2018-01-01

Irritative voiding symptoms (e.g. increased frequency and urgency) occur in many common pathologic conditions such as urinary tract infections and bladder outlet obstruction, and these conditions are well-established to have underlying inflammation that directly triggers these symptoms. However, it remains unclear as to how such diverse stimuli individually generate a common inflammatory process. Jürg Tschopp provided substantial insight into this conundrum when, working with extracts from THP-1 cells, he reported the existence of the inflammasome. He described it as a structure that senses multiple diverse signals from intracellular/extracellular sources and pathogens and triggers inflammation by the maturation and release of the pro-inflammatory cytokines interleukin-1β and interleukin-18. Recently, many of these sensors were found in the bladder and the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, has been shown to be a central mediator of inflammation in several urological diseases. In this review, we introduce the nucleotide-binding domain, leucine-rich-containing family, pyrin domaincontaining-3 inflammasome, highlight its emerging role in several common urologic conditions, and speculate on the potential involvement of other inflammasomes in bladder pathology. PMID:29593464

Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis.

PubMed

Forrest, Osric A; Ingersoll, Sarah A; Preininger, Marcela K; Laval, Julie; Limoli, Dominique H; Brown, Milton R; Lee, Frances E; Bedi, Brahmchetna; Sadikot, Ruxana T; Goldberg, Joanna B; Tangpricha, Vin; Gaggar, Amit; Tirouvanziam, Rabindra

2018-05-09

Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies. We used multiple platforms (flow cytometry, bacteria-killing, and metabolic assays) to characterize functional properties of blood neutrophils recruited in a transepithelial migration model using airway milieu from CF subjects as an apical chemoattractant. Similarly to neutrophils recruited to CF airways in vivo, neutrophils migrated into CF airway milieu in vitro display depressed phagocytic receptor expression and bacterial killing, but enhanced granule release, immunoregulatory function (arginase-1 activation), and metabolic activities, including high Glut1 expression, glycolysis, and oxidant production. We also identify enhanced pinocytic activity as a novel feature of these cells. In vitro treatment with the leukotriene pathway inhibitor acebilustat reduces the number of transmigrating neutrophils, while the metabolic modulator metformin decreases metabolism and oxidant production, but fails to restore bacterial killing. Interestingly, we describe similar pathological conditioning of neutrophils in other inflammatory airway diseases. We successfully tested the hypothesis that recruitment of neutrophils into airway milieu from patients with CF in vitro induces similar pathological conditioning to that observed in vivo, opening new avenues for targeted therapeutic intervention. ©2018 Society for Leukocyte Biology.

Extracellular small heat shock proteins: exosomal biogenesis and function.

PubMed

Reddy, V Sudhakar; Madala, Satish K; Trinath, Jamma; Reddy, G Bhanuprakash

2018-05-01

Small heat shock proteins (sHsps) belong to the family of heat shock proteins (Hsps): some are induced in response to multiple stressful events to protect the cells while others are constitutively expressed. Until now, it was believed that Hsps, including sHsps, are present inside the cells and perform intracellular functions. Interestingly, several groups recently reported the extracellular presence of Hsps, and sHsps have also been detected in sera/cerebrospinal fluids in various pathological conditions. Secretion into the extracellular milieu during many pathological conditions suggests additional or novel functions of sHsps in addition to their intracellular properties. Extracellular sHsps are implicated in cell-cell communication, activation of immune cells, and promoting anti-inflammatory and anti-platelet responses. Interestingly, exogenous administration of sHsps showed therapeutic effects in multiple disease models implying that extracellular sHsps are beneficial in pathological conditions. sHsps do not possess signal sequence and, hence, are not exported through the classical Endoplasmic reticulum-Golgi complex (ER-Golgi) secretory pathway. Further, export of sHsps is not inhibited by ER-Golgi secretory pathway inhibitors implying the involvement of a nonclassical secretory pathway in sHsp export. In lieu, lysoendosomal and exosomal pathways have been proposed for the export of sHsps. Heat shock protein 27 (Hsp27), αB-crystallin (αBC), and Hsp20 are shown to be exported by exosomes. Exosomes packaged with sHsps have beneficial effects in in vivo disease models. However, secretion mechanisms and therapeutic use of sHsps have not been elucidated in detail. Therefore, this review aimed at highlighting the current understanding of sHsps (Hsp27, αBC, and Hsp20) in the extracellular medium.

The intestinal microenvironment in sepsis.

PubMed

Fay, Katherine T; Ford, Mandy L; Coopersmith, Craig M

2017-10-01

The gastrointestinal tract has long been hypothesized to function as "the motor" of multiple organ dysfunction syndrome. The gastrointestinal microenvironment is comprised of a single cell layer epithelia, a local immune system, and the microbiome. These three components of the intestine together play a crucial role in maintaining homeostasis during times of health. However, the gastrointestinal microenvironment is perturbed during sepsis, resulting in pathologic changes that drive both local and distant injury. In this review, we seek to characterize the relationship between the epithelium, gastrointestinal lymphocytes, and commensal bacteria during basal and pathologic conditions and how the intestinal microenvironment may be targeted for therapeutic gain in septic patients. Published by Elsevier B.V.

Role of the blood-brain barrier in multiple sclerosis.

PubMed

Ortiz, Genaro Gabriel; Pacheco-Moisés, Fermín Paul; Macías-Islas, Miguel Ángel; Flores-Alvarado, Luis Javier; Mireles-Ramírez, Mario A; González-Renovato, Erika Daniela; Hernández-Navarro, Vanessa Elizabeth; Sánchez-López, Angélica Lizeth; Alatorre-Jiménez, Moisés Alejandro

2014-11-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

DTIC Science & Technology

2014-09-01

and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI PRINCIPAL INVESTIGATOR: Dr. Caterina Mainero...studies in multiple sclerosis (MS) suggested that cortical demyelinating lesions, which are hardly detected in vivo on conventional magnetic resonance...disease progression in many MS cases. 15. SUBJECT TERMS Multiple sclerosis ; cortex; cortical sulci; neuroinflammation; microglia; cortical

Orthodontic treatment in patient with idiopathic root resorption: a case report.

PubMed

Rey, Diego; Smit, Rosana Martínez; Gamboa, Liliana

2015-01-01

Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results.

Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations

PubMed Central

Honce, Justin Morris

2013-01-01

It is abundantly clear that there is extensive gray matter pathology occurring in multiple sclerosis. While attention to gray matter pathology was initially limited to studies of autopsy specimens and biopsies, the development of new MRI techniques has allowed assessment of gray matter pathology in vivo. Current MRI techniques allow the direct visualization of gray matter demyelinating lesions, the quantification of diffuse damage to normal appearing gray matter, and the direct measurement of gray matter atrophy. Gray matter demyelination (both focal and diffuse) and gray matter atrophy are found in the very earliest stages of multiple sclerosis and are progressive over time. Accumulation of gray matter damage has substantial impact on the lives of multiple sclerosis patients; a growing body of the literature demonstrates correlations between gray matter pathology and various measures of both clinical disability and cognitive impairment. The effect of disease modifying therapies on the rate accumulation of gray matter pathology in MS has been investigated. This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage. PMID:23878736

Pediatric dysphagia.

PubMed

Kakodkar, Kedar; Schroeder, James W

2013-08-01

Feeding and swallowing disorders in the pediatric population are becoming more common, particularly in infants born prematurely and in children with chronic medical conditions. The normal swallowing mechanism is divided into 4 stages: the preparatory, the oral, the pharyngeal, and the esophageal phases. Feeding disorders have multiple causes: medical, nutritional, behavioral, psychological, and environmental factors can all contribute. Pathologic conditions involving any of the anatomic sites associated with the phases of swallowing can negatively impact the coordination of these phases and lead to symptoms of dysphagia and feeding intolerance. Copyright © 2013 Elsevier Inc. All rights reserved.

42 CFR 485.715 - Condition of participation: Speech pathology services.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Speech pathology... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.715 Condition of participation: Speech pathology services. If speech pathology services are offered, the...

42 CFR 485.715 - Condition of participation: Speech pathology services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition of participation: Speech pathology... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.715 Condition of participation: Speech pathology services. If speech pathology services are offered, the...

42 CFR 485.715 - Condition of participation: Speech pathology services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition of participation: Speech pathology... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.715 Condition of participation: Speech pathology services. If speech pathology services are offered, the...

42 CFR 485.715 - Condition of participation: Speech pathology services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition of participation: Speech pathology... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.715 Condition of participation: Speech pathology services. If speech pathology services are offered, the...

42 CFR 485.715 - Condition of participation: Speech pathology services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition of participation: Speech pathology... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.715 Condition of participation: Speech pathology services. If speech pathology services are offered, the...

Factors associated with vocal fold pathologies in teachers.

PubMed

Souza, Carla Lima de; Carvalho, Fernando Martins; Araújo, Tânia Maria de; Reis, Eduardo José Farias Borges Dos; Lima, Verônica Maria Cadena; Porto, Lauro Antonio

2011-10-01

To analyze factors associated with the prevalence of the medical diagnosis of vocal fold pathologies in teachers. A census-based epidemiological, cross-sectional study was conducted with 4,495 public primary and secondary school teachers in the city of Salvador, Northeastern Brazil, between March and April 2006. The dependent variable was the self-reported medical diagnosis of vocal fold pathologies and the independent variables were sociodemographic characteristics; professional activity; work organization/interpersonal relationships; physical work environment characteristics; frequency of common mental disorders, measured by the Self-Reporting Questionnaire-20 (SRQ-20 >7); and general health conditions. Descriptive statistical, bivariate and multiple logistic regression analysis techniques were used. The prevalence of self-reported medical diagnosis of vocal fold pathologies was 18.9%. In the logistic regression analysis, the variables that remained associated with this medical diagnosis were as follows: being female, having worked as a teacher for more than seven years, excessive voice use, reporting more than five unfavorable physical work environment characteristics and presence of common mental disorders. The presence of self-reported vocal fold pathologies was associated with factors that point out the need of actions that promote teachers' vocal health and changes in their work structure and organization.

Investigation and identification of etiologies involved in the development of acquired hydronephrosis in aged laboratory mice with the use of high-frequency ultrasound imaging

PubMed Central

Springer, Danielle A.; Allen, Michele; Hoffman, Victoria; Brinster, Lauren; Starost, Matthew F.; Bryant, Mark; Eckhaus, Michael

2014-01-01

Laboratory mice develop naturally occurring lesions that affect biomedical research. Hydronephrosis is a recognized pathologic abnormality of the mouse kidney. Acquired hydronephrosis can affect any mouse, as it is caused by any naturally occurring disease that impairs free urine flow. Many etiologies leading to this condition are of particular significance to aging mice. Non-invasive ultrasound imaging detects renal pelvic dilation, renal enlargement, and parenchymal loss for pre-mortem identification of this condition. High-frequency ultrasound transducers produce high-resolution images of small structures, ideal for detecting organ pathology in mice. Using a 40 MHz linear array transducer, we obtained high-resolution images of a diversity of pathologic lesions occurring within the abdomen of seven geriatric mice with acquired hydronephrosis that enabled a determination of the underlying etiology. Etiologies diagnosed from the imaging results include pyelonephritis, neoplasia, urolithiasis, mouse urologic syndrome, and spontaneous hydronephrosis, and were confirmed at necropsy. A retrospective review of abdominal scans from an additional 149 aging mice shows that the most common etiologies associated with acquired hydronephrosis are mouse urologic syndrome and abdominal neoplasia. This report highlights the utility of high-frequency ultrasound for surveying research mice for age-related pathology, and is the first comprehensive report of multiple cases of acquired hydronephrosis in mice. PMID:25143818

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

PubMed Central

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

Expanding the spectrum of neuronal pathology in multiple system atrophy

PubMed Central

Cykowski, Matthew D.; Coon, Elizabeth A.; Powell, Suzanne Z.; Jenkins, Sarah M.; Benarroch, Eduardo E.; Low, Phillip A.; Schmeichel, Ann M.

2015-01-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. See Halliday (doi:10.1093/brain/awv151) for a scientific commentary on this article. PMID:25981961

Hypothalamic demyelination causing panhypopituitarism.

PubMed

Dixon-Douglas, Julia; Burgess, John; Dreyer, Michael

2018-05-01

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed. © 2018 Royal Australasian College of Physicians.

Rotator Cuff Tear Arthropathy: Pathophysiology, Imaging Characteristics, and Treatment Options.

PubMed

Eajazi, Alireza; Kussman, Steve; LeBedis, Christina; Guermazi, Ali; Kompel, Andrew; Jawa, Andrew; Murakami, Akira M

2015-11-01

The purpose of this article is to review the biomechanical properties of the rotator cuff and glenohumeral joint and the pathophysiology, imaging characteristics, and treatment options of rotator cuff tear arthropathy (RCTA). Although multiple pathways have been proposed as causes of RCTA, the exact cause remains unclear. Increasing knowledge about the clinical diagnosis, imaging features, and indicators of severity improves recognition and treatment of this pathologic condition.

Homocysteinemia control by cysteine in cerebral vascular patients after methionine loading test: evidences in physiological and pathological conditions in cerebro-vascular and multiple sclerosis patients.

PubMed

Ulivelli, Monica; Priora, Raffaella; Di Giuseppe, Danila; Coppo, Lucia; Summa, Domenico; Margaritis, Antonios; Frosali, Simona; Bartalini, Sabina; Martini, Giuseppe; Cerase, Alfonso; Di Simplicio, Paolo

2016-06-01

The toxicity risk of hyperhomocysteinemia is prevented through thiol drug administration which reduces plasma total homocysteine (tHcy) concentrations by activating thiol exchange reactions. Assuming that cysteine (Cys) is a homocysteinemia regulator, the hypothesis was verified in healthy and pathological individuals after the methionine loading test (MLT). The plasma variations of redox species of Cys, Hcy, cysteinylglycine, glutathione and albumin (reduced, HS-ALB, and at mixed disulfide, XSS-ALB) were compared in patients with cerebral small vessels disease (CSVD) (n = 11), multiple sclerosis (MS) (n = 12) and healthy controls (n = 11) at 2-4-6 h after MLT. In MLT-treated subjects, the activation of thiol exchange reactions provoked significant changes over time in redox species concentrations of Cys, Hcy, and albumin. Significant differences between controls and pathological groups were also observed. In non-methionine-treated subjects, total Cys concentrations, tHcy and thiol-protein mixed disulfides (CSS-ALB, HSS-ALB) of CSVD patients were higher than controls. After MLT, all groups displayed significant cystine (CSSC) increases and CSS-ALB decreases, that in pathological groups were significantly higher than controls. These data would confirm the Cys regulatory role on the homocysteinemia; they also explain that the Cys-Hcy mixed disulfide excretion is an important point of hyperhomocysteinemia control. Moreover, in all groups after MLT, significant increases in albumin concentrations, named total albumin (tALB) and measured as sum of HS-ALB (spectrophometric), and XSS-ALB (assayed at HPLC) were observed. tALB increases, more pronounced in healthy than in the pathological subjects, could indicate alterations of albumin equilibria between plasma and other extracellular spaces, whose toxicological consequences deserve further studies.

Assessing the effects of cocaine dependence and pathological gambling using group-wise sparse representation of natural stimulus FMRI data.

PubMed

Ren, Yudan; Fang, Jun; Lv, Jinglei; Hu, Xintao; Guo, Cong Christine; Guo, Lei; Xu, Jiansong; Potenza, Marc N; Liu, Tianming

2017-08-01

Assessing functional brain activation patterns in neuropsychiatric disorders such as cocaine dependence (CD) or pathological gambling (PG) under naturalistic stimuli has received rising interest in recent years. In this paper, we propose and apply a novel group-wise sparse representation framework to assess differences in neural responses to naturalistic stimuli across multiple groups of participants (healthy control, cocaine dependence, pathological gambling). Specifically, natural stimulus fMRI (N-fMRI) signals from all three groups of subjects are aggregated into a big data matrix, which is then decomposed into a common signal basis dictionary and associated weight coefficient matrices via an effective online dictionary learning and sparse coding method. The coefficient matrices associated with each common dictionary atom are statistically assessed for each group separately. With the inter-group comparisons based on the group-wise correspondence established by the common dictionary, our experimental results demonstrated that the group-wise sparse coding and representation strategy can effectively and specifically detect brain networks/regions affected by different pathological conditions of the brain under naturalistic stimuli.

Current Strategies for Brain Drug Delivery

PubMed Central

Dong, Xiaowei

2018-01-01

The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature. PMID:29556336

The impact of malnutrition on the quality of life in the elderly.

PubMed

Vetta, F; Ronzoni, S; Taglieri, G; Bollea, M R

1999-10-01

Malnutrition is a frequent condition, both widely represented in geriatric population and underestimated in diagnostic and therapeutic work-up, and is known to affect health status and life expectancy of elderly people. The unexpected weight loss is a pathological condition, recently classified in three different ways (sarcopenia, wasting and cachexia) according to criteria of nutritional intake, functional abilities and age-related body composition modifications, that is caused by social psychological and medical factors. In this review, the authors highlight the ways that, through malnutrition, could lead to an impairment of quality of life in elderly people. Notwithstanding the great impreciseness and confusion that surrounds the term 'quality of life', the authors focus their attention on the correlation existing with the recently occurring changes to patients' health status and life-style, analysing the relationship with frailty, failure to thrive and homeostatic balance failure syndrome. With the latter term, the authors introduce a pathological condition widely represented in the late stages of malnutrition that often evolves in multiple organ failure and lastly in the death.

42 CFR 415.130 - Conditions for payment: Physician pathology services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Conditions for payment: Physician pathology... Physician Services to Beneficiaries in Providers § 415.130 Conditions for payment: Physician pathology... of physician pathology services to fee-for-service Medicare beneficiaries who were hospital...

42 CFR 493.853 - Condition: Pathology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes of...

42 CFR 493.853 - Condition: Pathology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes of...

42 CFR 493.853 - Condition: Pathology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes of...

Challenges of multimorbidity of the aging brain: a critical update.

PubMed

Jellinger, Kurt A; Attems, Johannes

2015-04-01

A major problem in elderly patients is the high incidence of multiple pathologies, referred to as multimorbidity, in the aging brain. It has been increasingly recognized that co-occurrence of neurodegenerative proteinopathies and other pathologies including cerebrovascular disorders is a frequent event in the brains of both cognitively intact and impaired aged subjects. Although clinical and neuropathological diagnostic criteria of the major neurodegenerative diseases have been improved, major challenges arise from cerebral multimorbidity, and the thresholds to cause clinical overt dementia are ill defined. More than 80% of aged human brains show neurodegenerative non-Alzheimer type proteinopathies and other pathologies which, however, frequently have been missed clinically and are even difficult to identify at neuropathological examination. Autopsy studies differ in selection criteria and the applied evaluation methods. Therefore, irrespective of the clinical symptoms, the frequency of cerebral pathologies vary considerably: Alzheimer-related pathology is seen in 19-100%, with "pure" Alzheimer's disease (AD) in 17-72%, Lewy pathology in 6-39% (AD + Lewy disease 9-28%), vascular pathologies in 28-93% (10.7-78% "pure" vascular dementia), TDP-43 proteinopathy in 6-39%, hippocampal sclerosis in 8-1%, and mixed pathologies in 10-93%. These data clearly suggest that pathologically deposited proteins in neurodegenerating diseases mutually interact and are influenced by other factors, in particular cardiovascular and cerebrovascular ones, to promote cognitive decline and other clinical symptoms. It is obvious that cognitive and other neuropsychiatric impairment in the aged result from a multimorbid condition in the CNS rather than from a single disease and that the number of complex pathologies progresses with increasing age. These facts have implications for improvement of the clinical diagnosis and prognosis, the development of specific biomarkers, preventive strategies and better treatment of cerebral multimorbidity.

Rare case of primary spinal ependymomatosis occurring in a 26-year-old man: a case report

PubMed Central

2009-01-01

Introduction The authors report a rare case of primary spinal ependymomatosis in a young adult man. Multiple primary ependymomatous lesions were seen on magnetic resonance imaging and no anaplasia was identified on the surgical-pathological analysis. The aetio-pathological mechanism and surgical significance of this rare occurrence is discussed. Case presentation A 26-year-old man of Polish origin presented with a ten-day history of pain in the left leg and lower back. This was followed by difficulty in urinating and a decrease in sensation in both legs. Examination revealed pyramidal signs and mild weakness in both lower limbs. He had early sphincter involvement requiring catheterization. Magnetic resonance imaging of the brain was normal. However, that of the spinal cord revealed multiple intradural spinal lesions, both intra- and extramedullary, extending from the cervical cord down to the cauda equina roots. T12-L1 laminectomy was performed. Multiple intradural, extra- and intra-medullary tumors were seen. After the operation, the patient deteriorated with a sensory level at T4. Post-operative cranio-spinal radiotherapy was administered but there was no clinical improvement in the lower limbs. Conclusion Primary spinal ependymomatosis is a rare phenomenon involving multiple spinal segments in the absence of a primary intracranial tumor. Radical excision is unrealistic in this condition. Biopsy followed by radiotherapy is the preferred method of treatment. PMID:19946548

42 CFR 493.1220 - Condition: Oral pathology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Oral pathology. 493.1220 Section 493....1220 Condition: Oral pathology. If the laboratory provides services in the subspecialty of Oral pathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

42 CFR 493.1220 - Condition: Oral pathology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Oral pathology. 493.1220 Section 493....1220 Condition: Oral pathology. If the laboratory provides services in the subspecialty of Oral pathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

42 CFR 493.1220 - Condition: Oral pathology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Oral pathology. 493.1220 Section 493....1220 Condition: Oral pathology. If the laboratory provides services in the subspecialty of Oral pathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

42 CFR 493.1220 - Condition: Oral pathology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Oral pathology. 493.1220 Section 493....1220 Condition: Oral pathology. If the laboratory provides services in the subspecialty of Oral pathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

42 CFR 493.1220 - Condition: Oral pathology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Oral pathology. 493.1220 Section 493....1220 Condition: Oral pathology. If the laboratory provides services in the subspecialty of Oral pathology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

Expanding the spectrum of neuronal pathology in multiple system atrophy.

PubMed

Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

2015-08-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Physiological and pathological functions of acid-sensing ion channels in the central nervous system

PubMed Central

Chu, Xiang-Ping; Xiong, Zhi-Gang

2012-01-01

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS. PMID:22204324

Evidence of intermetastatic heterogeneity for pathological response and genetic mutations within colorectal liver metastases following preoperative chemotherapy.

PubMed

Sebagh, Mylène; Allard, Marc-Antoine; Bosselut, Nelly; Dao, Myriam; Vibert, Eric; Lewin, Maïté; Lemoine, Antoinette; Cherqui, Daniel; Adam, René; Sa Cunha, Antonio

2016-04-19

In patients receiving preoperative chemotherapy, colorectal liver metastases (CLM) are expected to demonstrate a similar behaviour because of similar organ microenvironment and tumour cell chemosensitivity. We focused on the occurrence of pathological and genetic heterogeneity within CLM. Patients resected for multiple CLM between 2004 and 2011 after > three cycles of chemotherapy were included. Pathological heterogeneity was arbitrarily defined as a > 50% difference in the percentage of remaining tumour cells between individual CLM. In patients with pathological heterogeneity, the mutational genotyping (KRAS, NRAS, BRAF and PIK3CA) was determined from the most heterogeneous CLM. Pathological heterogeneity was observed in 31 of 157 patients with multiple CLM (median = 4, range, 2-32) (19.7%). In 72.4% of them, we found a concordance of the mutation status between the paired CLM: both wild-type in 55%, and both mutated in 17.2%. We observed a discordance of the mutation status of 27.6% between CLM: one mutated and the other wild-type. The mutated CLM was the less florid one in 75% of patients with genetic heterogeneity. Pathological heterogeneity is present in 19.7% of patients with multiple CLM. Genetic heterogeneity is present in 27.6% of patients with pathological heterogeneity. Heterogeneity could refine guide management for tissue sampling.

The transformative potential of an integrative approach to pregnancy.

PubMed

Eidem, Haley R; McGary, Kriston L; Capra, John A; Abbot, Patrick; Rokas, Antonis

2017-09-01

Complex traits typically involve diverse biological pathways and are shaped by numerous genetic and environmental factors. Pregnancy-associated traits and pathologies are further complicated by extensive communication across multiple tissues in two individuals, interactions between two genomes-maternal and fetal-that obscure causal variants and lead to genetic conflict, and rapid evolution of pregnancy-associated traits across mammals and in the human lineage. Given the multi-faceted complexity of human pregnancy, integrative approaches that synthesize diverse data types and analyses harbor tremendous promise to identify the genetic architecture and environmental influences underlying pregnancy-associated traits and pathologies. We review current research that addresses the extreme complexities of traits and pathologies associated with human pregnancy. We find that successful efforts to address the many complexities of pregnancy-associated traits and pathologies often harness the power of many and diverse types of data, including genome-wide association studies, evolutionary analyses, multi-tissue transcriptomic profiles, and environmental conditions. We propose that understanding of pregnancy and its pathologies will be accelerated by computational platforms that provide easy access to integrated data and analyses. By simplifying the integration of diverse data, such platforms will provide a comprehensive synthesis that transcends many of the inherent challenges present in studies of pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skeletal pathology and variable anatomy in elephant feet assessed using computed tomography

PubMed Central

Dixon, Jonathon J.I.; Warren-Smith, Chris; Hutchinson, John R.; Weller, Renate

2017-01-01

Foot problems are a major cause of morbidity and mortality in elephants, but are underreported due to difficulties in diagnosis, particularly of conditions affecting the bones and internal structures. Here we evaluate post-mortem computer tomographic (CT) scans of 52 feet from 21 elephants (seven African Loxodonta africana and 14 Asian Elephas maximus), describing both pathology and variant anatomy (including the appearance of phalangeal and sesamoid bones) that could be mistaken for disease. We found all the elephants in our study to have pathology of some type in at least one foot. The most common pathological changes observed were bone remodelling, enthesopathy, osseous cyst-like lesions, and osteoarthritis, with soft tissue mineralisation, osteitis, infectious osteoarthriti, subluxation, fracture and enostoses observed less frequently. Most feet had multiple categories of pathological change (81% with two or more diagnoses, versus 10% with a single diagnosis, and 9% without significant pathology). Much of the pathological change was focused over the middle/lateral digits, which bear most weight and experience high peak pressures during walking. We found remodelling and osteoarthritis to be correlated with increasing age, more enthesopathy in Asian elephants, and more cyst-like lesions in females. We also observed multipartite, missing and misshapen phalanges as common and apparently incidental findings. The proximal (paired) sesamoids can appear fused or absent, and the predigits (radial/tibial sesamoids) can be variably ossified, though are significantly more ossified in Asian elephants. Our study reinforces the need for regular examination and radiography of elephant feet to monitor for pathology and as a tool for improving welfare. PMID:28123909

Pathological manifestations of feline immunodeficiency virus (FIV) infection in wild African lions.

PubMed

Roelke, Melody E; Brown, Meredith A; Troyer, Jennifer L; Winterbach, Hanlie; Winterbach, Christiaan; Hemson, Graham; Smith, Dahlem; Johnson, Randall C; Pecon-Slattery, Jill; Roca, Alfred L; Alexander, Kathleen A; Klein, Lin; Martelli, Paolo; Krishnasamy, Karthiyani; O'Brien, Stephen J

2009-07-20

Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple-infected lions and anecdotal reports of lion morbidity associated with FIV seroprevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple-negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple-infected lions displayed a significant elevation in the prevalence of AIDS-defining conditions: lymphadenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters, depressed serum albumin, and elevated liver enzymes and gamma globulin. Spleen and lymph node biopsies from free-ranging FIVple-infected lions (N=9) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodeficiency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca).

PATHOLOGICAL MANIFESTATIONS OF FELINE IMMUNODEFICIENCY VIRUS (FIV) INFECTION IN WILD AFRICAN LIONS

PubMed Central

Roelke, Melody E.; Brown, Meredith A.; Troyer, Jennifer L.; Winterbach, Hanlie; Winterbach, Christiaan; Hemson, Graham; Smith, Dahlem; Johnson, Randall C.; Pecon-Slattery, Jill; Roca, Alfred L.; Alexander, Katherine; Klein, Lin; Martinelli, Paulo; Krishnasamu, Karthiuani; O'Brien, Stephen J.

2009-01-01

Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple infected lions and anecdotal reports of lion morbidity associated with FIV sero-prevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple infected lions displayed a significant elevation in the prevalence of AIDS defining conditions: lymphandenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters and elevated liver enzymes and serum proteins. Spleen and lymph node laparoscopic biopsies from free-ranging FIVple infected lions (N=8) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodefieciency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca). PMID:19464039

Autophagy in alcohol-induced liver diseases

PubMed Central

Dolganiuc, Angela; Thomes, Paul G.; Ding, Wen-Xing; Lemasters, John J.; Donohue, Terrence M.

2013-01-01

Alcohol is the most abused substance worldwide and a significant source of liver injury; the mechanisms of alcohol-induced liver disease are not fully understood. Significant cellular toxicity and impairment of protein synthesis and degradation occur in alcohol-exposed liver cells, along with changes in energy balance and modified responses to pathogens. Autophagy is the process of cellular catabolism through the lysosomal-dependent machinery, which maintains a balance among protein synthesis, degradation, and recycling of self. Autophagy is part of normal homeostasis and it can be triggered by multiple factors that threaten cell integrity including starvation, toxins, or pathogens. Multiple factors regulate autophagy; survival and preservation of cellular integrity at the expense of inadequately-folded proteins and damaged high energy-generating intracellular organelles are prominent targets of autophagy in pathologic conditions. Coincidentally, inadequately-folded proteins accumulate and high energy-generating intracellular organelles, such as mitochondria, are damaged by alcohol abuse; these alcohol-induced pathological findings prompted investigation of the role of autophagy in the pathogenesis of alcohol-induced liver damage. Our review summarizes the current knowledge about the role and implications of autophagy in alcohol-induced liver disease. PMID:22551004

Basic principles of fracture treatment in children.

PubMed

Ömeroğlu, Hakan

2018-04-01

This review aims to summarize the basic treatment principles of fractures according to their types and general management principles of special conditions including physeal fractures, multiple fractures, open fractures, and pathologic fractures in children. Definition of the fracture is needed for better understanding the injury mechanism, planning a proper treatment strategy, and estimating the prognosis. As the healing process is less complicated, remodeling capacity is higher and non-union is rare, the fractures in children are commonly treated by non-surgical methods. Surgical treatment is preferred in children with multiple injuries, in open fractures, in some pathologic fractures, in fractures with coexisting vascular injuries, in fractures which have a history of failed initial conservative treatment and in fractures in which the conservative treatment has no/little value such as femur neck fractures, some physeal fractures, displaced extension and flexion type humerus supracondylar fractures, displaced humerus lateral condyle fractures, femur, tibia and forearm shaft fractures in older children and adolescents and unstable pelvis and acetabulum fractures. Most of the fractures in children can successfully be treated by non-surgical methods.

Relationships between pathologic subjective halitosis, olfactory reference syndrome, and social anxiety in young Japanese women.

PubMed

Tsuruta, Miho; Takahashi, Toru; Tokunaga, Miki; Iwasaki, Masanori; Kataoka, Shota; Kakuta, Satoko; Soh, Inho; Awano, Shuji; Hirata, Hiromi; Kagawa, Masaharu; Ansai, Toshihiro

2017-03-14

Pathologic subjective halitosis is known as a halitosis complaint without objective confirmation of halitosis by others or by halitometer measurements; it has been reported to be associated with social anxiety disorder. Olfactory reference syndrome is a preoccupation with the false belief that one emits a foul and offensive body odor. Generally, patients with olfactory reference syndrome are concerned with multiple body parts. However, the mouth is known to be the most common source of body odor for those with olfactory reference syndrome, which could imply that the two conditions share similar features. Therefore, we investigated potential causal relationships among pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupations with body part odors. A total of 1360 female students (mean age 19.6 ± 1.1 years) answered a self-administered questionnaire regarding pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupation with odors of body parts such as mouth, body, armpits, and feet. The scale for pathologic subjective halitosis followed that developed by Tsunoda et al.; participants were divided into three groups based on their scores (i.e., levels of pathologic subjective halitosis). A Bayesian network was used to analyze causal relationships between pathologic subjective halitosis, olfactory reference syndrome, social anxiety, and preoccupations with body part odors. We found statistically significant differences in the results for olfactory reference syndrome and social anxiety among the various levels of pathologic subjective halitosis (P < 0.001). Residual analyses indicated that students with severe levels of pathologic subjective halitosis showed greater preoccupations with mouth and body odors (P < 0.05). Bayesian network analysis showed that social anxiety directly influenced pathologic subjective halitosis and olfactory reference syndrome. Preoccupations with mouth and body odors also influenced pathologic subjective halitosis. Social anxiety may be a causal factor of pathologic subjective halitosis and olfactory reference syndrome.

Mammalian Polyamine Metabolism and Function

PubMed Central

Pegg, Anthony E.

2009-01-01

Summary Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism. PMID:19603518

Delving into foot mechanics and related problems.

PubMed

Zanni, Guido R; Wick, Jeannette Y

2011-12-01

Foot problems are common in elders, stemming from age-related podiatric mechanical problems or disease-induced pathology. Common mechanical problems include hammertoe, arthritis, bunions, and metatarsalgia. Disease-induced conditions include onychomycosis, athlete's foot, plantar warts, gout, and diabetes. Treatment is case-specific and often involves multiple interventions, including lifestyle changes. Prevention and treatment strategies are presented. Patient education on proper foot care is effective.When patients are unable to reach or see their feet, staff assumes responsibility for foot care.

Idiopathic granulomatous mastitis: a mimicking disease in a pregnant woman: a case report

PubMed Central

2013-01-01

Background Idiopathic granulomatous mastitis is a rare, benign, inflammatory chronic condition of unclear etiology. This case is reported because it illustrates how idiopathic granulomatous mastitis can mimic other diseases, making it difficult to associate the presenting symptoms and the correct diagnosis; This disease is a challenge for clinicians to diagnose, manage and avoid iatrogenic complications, and requires consultation with experts in several specialties. Case presentation The patient was 30 years old, South-American, eleven weeks pregnant, and with an apparent infectious mastitis. She presented with progressive worsening of her breast symptoms and multiple negative laboratory tests. She suffered different side effects from several prescribed treatments and endured a prolonged recovery. The article emphasizes the need for ruling out common pathologies to arrive at the correct diagnosis such as bacterial and fungal infections; granulomatous conditions like tuberculosis and sarcoidosis; and inflammatory breast carcinoma. It also describes frequently used pharmacological and supplementary forms of treatment for patients with this condition. Conclusion Idiopathic granulomatous mastitis is a rare unusual condition of unknown etiology. Pathological confirmation is required for its diagnosis and optimal management is still unclear. The presentation and management of this case is intended to advance its awareness to physicians from different specialties. PMID:23497626

Radionuclide bone imaging: an illustrative review.

PubMed

Love, Charito; Din, Anabella S; Tomas, Maria B; Kalapparambath, Tomy P; Palestro, Christopher J

2003-01-01

Bone scintigraphy with technetium-99m-labeled diphosphonates is one of the most frequently performed of all radionuclide procedures. Radionuclide bone imaging is not specific, but its excellent sensitivity makes it useful in screening for many pathologic conditions. Moreover, some conditions that are not clearly depicted on anatomic images can be diagnosed with bone scintigraphy. Bone metastases usually appear as multiple foci of increased activity, although they occasionally manifest as areas of decreased uptake. Traumatic processes can often be detected, even when radiographic findings are negative. Most fractures are scintigraphically detectable within 24 hours, although in elderly patients with osteopenia, further imaging at a later time is sometimes indicated. Athletic individuals are prone to musculoskeletal trauma, and radionuclide bone imaging is useful for identifying pathologic conditions such as plantar fasciitis, stress fractures, "shin splints," and spondylolysis, for which radiographs may be nondiagnostic. A combination of focal hyperperfusion, focal hyperemia, and focally increased bone uptake is virtually diagnostic for osteomyelitis in patients with nonviolated bone. Bone scintigraphy is also useful for evaluating disease extent in Paget disease and for localizing avascular necrosis in patients with negative radiographs. Radionuclide bone imaging will likely remain a popular and important imaging modality for years to come. Copyright RSNA, 2003

Spontaneous hemothorax caused by ruptured multiple mycotic aortic aneurysms: a case report and literature review.

PubMed

Li, Po-Sung; Tsai, Chung-Lin; Hu, Sung-Yuan; Lin, Tzu-Chieh; Chang, Yao-Tien

2017-12-02

Mycotic aortic aneurysm (MAA) is a rare clinical entity with an incidence of 1-3%, but it is a life-threatening infection of aorta characterized by dilatation of aorta with false lumen. Multiple MAAs have been reported rarely with an incidence of 0.03% and associated with a high mortality rate of 80% if ruptured. A hypertensive and diabetic 78-year-old man visited our emergency department complaining intermittent dull and tingled pain over the left flank region for 1 week. Chest X-ray showed left pleural effusion and hemothorax was confirmed by thoracocentesis. Computed tomography (CT) of chest demonstrated multiple thoracic aortic aneurysms and the pathological findings disclosed the diagnosis of multiple MAAs. He was discharged under an uneventful condition post-surgical aortic repair with adequate intravenous antibiotics for 4 weeks. CT scan may make a definite diagnosis of multiple MAAs and management with surgical debridement, aortic repair and full-course antibiotics for Gram-positive coccus and/or Gram-negative bacillus is recommended.

Clinical, pathological and thin-section CT features of persistent multiple ground-glass opacity nodules: comparison with solitary ground-glass opacity nodule.

PubMed

Kim, Tae Jung; Goo, Jin Mo; Lee, Kyung Won; Park, Chang Min; Lee, Hyun Ju

2009-05-01

To retrospectively compare the clinical, pathological, and thin-section CT features of persistent multiple ground-glass opacity (GGO) nodules with those of solitary GGO nodules. Histopathologic specimens were obtained from 193 GGO nodules in 136 patients (87 women, 49 men; mean age, 57; age range 33-81). The clinical data, pathologic findings, and thin-section CT features of multiple and solitary GGO nodules were compared by using t-test or Fisher's exact test. Multiple GGO nodules (n=105) included atypical adenomatous hyperplasia (AAH) (n=31), bronchioloalveolar carcinoma (BAC) (n=33), adenocarcinoma (n=34) and focal interstitial fibrosis (n=7). Solitary GGO nodules included AAH (n=8), BAC (n=15), adenocarcinoma (n=55) and focal interstitial fibrosis (n=10). AAH (P=.001) and BAC (P=.029) were more frequent in multiple GGO nodules, whereas adenocarcinoma (P<.001) was more frequent in solitary GGO nodules. Female sex (P<.001), nonsmoker (P=.012) and multiple primary lung cancers (P<.001) were more frequent for multiple GGO nodules, which were smaller (12 mm+/-7.9) than solitary GGO nodules (17 mm+/-8.1) (P<.001). Air-bronchogram (P=.019), bubble-lucency (P=.004), and pleural retraction (P<.001) were more frequent in solitary GGO nodules. There was no postoperative recurrence except for one patient with multiple GGO nodules and one with solitary GGO nodule. Clinical, pathological, and thin-section CT features of persistent multiple GGO nodules were found to differ from those of solitary GGO nodules. Nevertheless, the two nodule types can probably be followed up and managed in a similar manner because their prognoses were found to be similar.

Drastic stability change of X-X mismatch in d(CXG) trinucleotide repeat disorders under molecular crowding condition.

PubMed

Teng, Ye; Pramanik, Smritimoy; Tateishi-Karimata, Hisae; Ohyama, Tatsuya; Sugimoto, Naoki

2018-02-05

The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence causing repeat expansion disorders. The formation of non-canonical structures, such as hairpin structures with X-X mismatches, has been proposed to affect gene expression and regulation, which are important in pathological studies of these devastating neurological diseases. However, little information is available regarding the thermodynamics of the repeat sequence under crowded cellular conditions where many non-canonical structures such as G-quadruplexes are highly stabilized, while duplexes are destabilised. In this study, we investigated the different stabilities of X-X mismatches in the context of internal d(CXG) self-complementary sequences in an environment with a high concentration of cosolutes to mimic the crowding conditions in cells. The stabilities of full-matched duplexes and duplexes with A-A, G-G, and T-T mismatched base pairs under molecular crowding conditions were notably decreased compared to under dilute conditions. However, the stability of the DNA duplex with a C-C mismatch base pair was only slightly destabilised. Investigating different stabilities of X-X mismatches in d(CXG) sequences is important for improving our understanding of the formation and transition of multiple non-canonical structures in trinucleotide repeat diseases, and may provide insights for pathological studies and drug development. Copyright © 2018 Elsevier Inc. All rights reserved.

42 CFR 415.130 - Conditions for payment: Physician pathology services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Conditions for payment: Physician pathology... pathology services. (a) Definitions. The following definitions are used in this section. (1) Covered... technical component of physician pathology services to fee-for-service Medicare beneficiaries who were...

42 CFR 415.130 - Conditions for payment: Physician pathology services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Conditions for payment: Physician pathology... pathology services. (a) Definitions. The following definitions are used in this section. (1) Covered... technical component of physician pathology services to fee-for-service Medicare beneficiaries who were...

42 CFR 415.130 - Conditions for payment: Physician pathology services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Conditions for payment: Physician pathology... pathology services. (a) Definitions. The following definitions are used in this section. (1) Covered... technical component of physician pathology services to fee-for-service Medicare beneficiaries who were...

Mitochondrial protein Fus1/Tusc2 in premature aging and age-related pathologies: critical roles of calcium and energy homeostasis.

PubMed

Uzhachenko, Roman; Boyd, Kelli; Olivares-Villagomez, Danyvid; Zhu, Yueming; Goodwin, J Shawn; Rana, Tanu; Shanker, Anil; Tan, Winston J T; Bondar, Tanya; Medzhitov, Ruslan; Ivanova, Alla V

2017-03-26

Decreased energy production and increased oxidative stress are considered to be major contributors to aging and aging-associated pathologies. The role of mitochondrial calcium homeostasis has also been highlighted as an important factor affecting different pathological conditions. Here, we present evidence that loss of a small mitochondrial protein Fus1 that maintains mitochondrial homeostasis results in premature aging, aging-associated pathologies, and decreased survival. We showed that Fus1KO mice develop multiple early aging signs including lordokyphosis, lack of vigor, inability to accumulate fat, reduced ability to tolerate stress, and premature death. Other prominent pathological changes included low sperm counts, compromised ability of adult stem cells to repopulate tissues, and chronic inflammation. At the molecular level, we demonstrated that mitochondria of Fus1 KO cells have low reserve respiratory capacity (the ability to produce extra energy during sudden energy demanding situations), and show significantly altered dynamics of cellular calcium response.Our recent studies on early hearing and memory loss in Fus1 KO mice combined with the new data presented here suggest that calcium and energy homeostasis controlled by Fus1 may be at the core of its aging-regulating activities. Thus, Fus1 protein and Fus1-dependent pathways and processes may represent new tools and targets for anti-aging strategies.

Mitochondrial protein Fus1/Tusc2 in premature aging and age-related pathologies: critical roles of calcium and energy homeostasis

PubMed Central

Uzhachenko, Roman; Boyd, Kelli; Olivares-Villagomez, Danyvid; Zhu, Yueming; Goodwin, J. Shawn; Rana, Tanu; Shanker, Anil; Tan, Winston J.T.; Bondar, Tanya; Medzhitov, Ruslan; Ivanova, Alla V.

2017-01-01

Decreased energy production and increased oxidative stress are considered to be major contributors to aging and aging-associated pathologies. The role of mitochondrial calcium homeostasis has also been highlighted as an important factor affecting different pathological conditions. Here, we present evidence that loss of a small mitochondrial protein Fus1 that maintains mitochondrial homeostasis results in premature aging, aging-associated pathologies, and decreased survival. We showed that Fus1KO mice develop multiple early aging signs including lordokyphosis, lack of vigor, inability to accumulate fat, reduced ability to tolerate stress, and premature death. Other prominent pathological changes included low sperm counts, compromised ability of adult stem cells to repopulate tissues, and chronic inflammation. At the molecular level, we demonstrated that mitochondria of Fus1 KO cells have low reserve respiratory capacity (the ability to produce extra energy during sudden energy demanding situations), and show significantly altered dynamics of cellular calcium response. Our recent studies on early hearing and memory loss in Fus1 KO mice combined with the new data presented here suggest that calcium and energy homeostasis controlled by Fus1 may be at the core of its aging-regulating activities. Thus, Fus1 protein and Fus1-dependent pathways and processes may represent new tools and targets for anti-aging strategies. PMID:28351997

Upper Extremity Function in Multiple Sclerosis Patients With Advanced Disability Treated With Ocrevus

ClinicalTrials.gov

2018-06-18

Multiple Sclerosis; Pathologic Processes; Demyelinating Diseases; Demyelinating Autoimmune Diseases; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Primary Progressive Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis

HLA-DRB*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis.

PubMed

Yaldizli, Özgür; Sethi, Varun; Pardini, Matteo; Tur, Carmen; Mok, Kin Y; Muhlert, Nils; Liu, Zheng; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Yousry, Tarek A; Houlden, Henry; Hardy, John; Miller, David H; Chard, Declan T

2016-05-01

The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology. To assess HLA-DRB(*)1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology. Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB(*)1501 haplotype was determined by genotyping (rs3135388). No significant differences were observed in MRI measures between the HLA-DRB(*)1501 subgroups. The HLA-DRB(*)1501 haplotype is not strongly associated with MRI-visible grey matter pathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Sigma-1 (σ1) Receptor in Memory and Neurodegenerative Diseases.

PubMed

Maurice, Tangui; Goguadze, Nino

2017-01-01

The sigma-1 (σ 1 ) receptor has been associated with regulation of intracellular Ca 2+ homeostasis, several cellular signaling pathways, and inter-organelle communication, in part through its chaperone activity. In vivo, agonists of the σ 1 receptor enhance brain plasticity, with particularly well-described impact on learning and memory. Under pathological conditions, σ 1 receptor agonists can induce cytoprotective responses. These protective responses comprise various complementary pathways that appear to be differentially engaged according to pathological mechanism. Recent studies have highlighted the efficacy of drugs that act through the σ 1 receptor to mitigate symptoms associated with neurodegenerative disorders with distinct mechanisms of pathogenesis. Here, we will review genetic and pharmacological evidence of σ 1 receptor engagement in learning and memory disorders, cognitive impairment, and neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease.

Tubal telocytes: factor infertility reason?

PubMed

Aleksandrovych, Veronika; Sajewicz, Marek; Walocha, Jerzy A; Gil, Krzysztof

Infertility is actually widespread pathological condition, which affected one in every four couples in developing countries. Approximately one third of all cases are connected with tubal factor infertility, o en accompanies by endometriosis, acute salpingitis, urogenital infections etc. The newly identified telocytes (TCs) have multiple potential bio-functions and might participate in the fertility problems. They influence on structural and functional integrity of oviduct tissue. Despite recent discovery, TCs involvement in the majority of physiological and pathological processes is still unclear and require significant increasing of deep observations and data analysis. Focusing on female reproductive system help better understands the main reasons of infertility, while evaluation of TCs impact on Fallopian tube and uterus contractility might be a key point of its correction. The article summarizes the main features of telocytes in Fallopian tubes, emphasizing their involvement in pathophysiological processes and tubal factor infertility.

Modulation of PPAR-γ by Nutraceutics as Complementary Treatment for Obesity-Related Disorders and Inflammatory Diseases

PubMed Central

Ortuño Sahagún, D.; Márquez-Aguirre, A. L.; Quintero-Fabián, S.; López-Roa, R. I.; Rojas-Mayorquín, A. E.

2012-01-01

A direct correlation between adequate nutrition and health is a universally accepted truth. The Western lifestyle, with a high intake of simple sugars, saturated fat, and physical inactivity, promotes pathologic conditions. The main adverse consequences range from cardiovascular disease, type 2 diabetes, and metabolic syndrome to several cancers. Dietary components influence tissue homeostasis in multiple ways and many different functional foods have been associated with various health benefits when consumed. Natural products are an important and promising source for drug discovery. Many anti-inflammatory natural products activate peroxisome proliferator-activated receptors (PPAR); therefore, compounds that activate or modulate PPAR-gamma (PPAR-γ) may help to fight all of these pathological conditions. Consequently, the discovery and optimization of novel PPAR-γ agonists and modulators that would display reduced side effects is of great interest. In this paper, we present some of the main naturally derived products studied that exert an influence on metabolism through the activation or modulation of PPAR-γ, and we also present PPAR-γ-related diseases that can be complementarily treated with nutraceutics from functional foods. PMID:23251142

Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection.

PubMed

Flieger, Miroslav; Bandouchova, Hana; Cerny, Jan; Chudíčková, Milada; Kolarik, Miroslav; Kovacova, Veronika; Martínková, Natália; Novák, Petr; Šebesta, Ondřej; Stodůlková, Eva; Pikula, Jiri

2016-09-13

Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml(-1), indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats' primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay.

Vitamin B2 as a virulence factor in Pseudogymnoascus destructans skin infection

PubMed Central

Flieger, Miroslav; Bandouchova, Hana; Cerny, Jan; Chudíčková, Milada; Kolarik, Miroslav; Kovacova, Veronika; Martínková, Natália; Novák, Petr; Šebesta, Ondřej; Stodůlková, Eva; Pikula, Jiri

2016-01-01

Pathogenic and non-pathogenic related microorganisms differ in secondary metabolite production. Here we show that riboflavin overproduction by a fungal pathogen and its hyperaccumulation in affected host tissue exacerbates a skin infection to necrosis. In white-nose syndrome (WNS) skin lesions caused by Pseudogymnoascus destructans, maximum riboflavin concentrations reached up to 815 μg ml−1, indicating bioaccumulation and lack of excretion. We found that high riboflavin concentrations are cytotoxic under conditions specific for hibernation, affect bats’ primary fibroblasts and induce cell detachment, loss of mitochondrial membrane potential, polymerization of cortical actin, and cell necrosis. Our results explain molecular pathology of WNS, where a skin infection becomes fatal. Hyperaccumulation of vitamin B2 coupled with reduced metabolism and low tissue oxygen saturation during hibernation prevents removal of excess riboflavin in infected bats. Upon reperfusion, oxygen reacts with riboflavin resulting in dramatic pathology after arousal. While multiple molecules enable invasive infection, riboflavin-associated extensive necrosis likely contributes to pathophysiology and altered arousal pattern in infected bats. Bioaccumulation of a vitamin under natural infection represents a novel condition in a complex host-pathogen interplay. PMID:27620349

Use of magnetic micro-cantilevers to study the dynamics of 3D engineered smooth muscle constructs

NASA Astrophysics Data System (ADS)

Liu, Alan; Zhao, Ruogang; Copeland, Craig; Chen, Christopher; Reich, Daniel

2013-03-01

The normal and pathological response of arterial tissue to mechanical stimulus sheds important light on such conditions as atherosclerosis and hypertension. While most previous methods of determining the biomechanical properties of arteries have relied on excised tissue, we have devised a system that enables the growth and in situ application of forces to arrays of stable suspended microtissues consisting of arterial smooth muscle cells (SMCs). Briefly, this magnetic microtissue tester system consists of arrays of pairs of elastomeric magnetically actuated micro-cantilevers between which SMC-infused 3D collagen gels self-assemble and remodel into aligned microtissue constructs. These devices allow us to simultaneously apply force and track stress-strain relationships of multiple microtissues per substrate. We have studied the dilatory capacity and subsequent response of the tissues and find that the resulting stress-strain curves show viscoelastic behavior as well as a linear dynamic recovery. These results provide a foundation for elucidating the mechanical behavior of this novel model system as well as further experiments that simulate pathological conditions. Supported in part by NIH grant HL090747.

CADASIL accelerated by acute hypotension: Arterial and venous contribution to leukoaraiosis.

PubMed

Pettersen, Jacqueline A; Keith, Julia; Gao, Fuqiang; Spence, J David; Black, Sandra E

2017-03-14

To underline the importance of blood pressure regulation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to describe changes that occur in the veins in this condition, specifically venous collagenosis associated with leukoaraiosis. Case report with neuroimaging and pathologic data. A 61-year-old man with genetically confirmed CADASIL was initially lucid following a motor vehicle accident but subsequently became hypotensive (60/40 mm Hg) due to an open femur fracture and required intubation. Multiple new white matter infarcts appeared on brain imaging. A second hypotensive episode days later was associated with new coin-sized infarcts in the bilateral corona radiata and cerebellar peduncles, and resulted in quadriplegia. No embolic source was found on cardiac or vascular imaging. He died 5 weeks post trauma. Autopsy revealed extensive subcortical and periventricular leukoencephalopathy and multiple cavitations involving deep subcortical gray and white matter. Small arteries had thickened walls, disruption of the muscularis, and intimal periodic acid-Schiff (PAS)-positive material. Both larger periventricular and small caliber veins had thickened walls that were PAS-negative and trichrome-positive, consistent with venous collagenosis. There was no pathologic evidence of global hypoxia or diffuse axonal injury. The findings suggest rapid acceleration of CADASIL pathology from acute hypotension in the setting of impaired vasoreactivity. In addition, collagenosis of veins in the affected white matter regions suggests that the veins may play an important, though largely overlooked, role in maintaining white matter integrity. © 2017 American Academy of Neurology.

42 CFR 485.719 - Condition of participation: Arrangements for physical therapy and speech pathology services to be...

Code of Federal Regulations, 2011 CFR

2011-10-01

... physical therapy and speech pathology services to be performed by other than salaried organization... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.719 Condition of participation: Arrangements for physical therapy and speech pathology services to be performed...

42 CFR 485.719 - Condition of participation: Arrangements for physical therapy and speech pathology services to be...

Code of Federal Regulations, 2010 CFR

2010-10-01

... physical therapy and speech pathology services to be performed by other than salaried organization... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.719 Condition of participation: Arrangements for physical therapy and speech pathology services to be performed...

42 CFR 485.719 - Condition of participation: Arrangements for physical therapy and speech pathology services to be...

Code of Federal Regulations, 2013 CFR

2013-10-01

... physical therapy and speech pathology services to be performed by other than salaried organization... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.719 Condition of participation: Arrangements for physical therapy and speech pathology services to be performed...

42 CFR 485.719 - Condition of participation: Arrangements for physical therapy and speech pathology services to be...

Code of Federal Regulations, 2014 CFR

2014-10-01

... physical therapy and speech pathology services to be performed by other than salaried organization... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.719 Condition of participation: Arrangements for physical therapy and speech pathology services to be performed...

42 CFR 485.719 - Condition of participation: Arrangements for physical therapy and speech pathology services to be...

Code of Federal Regulations, 2012 CFR

2012-10-01

... physical therapy and speech pathology services to be performed by other than salaried organization... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.719 Condition of participation: Arrangements for physical therapy and speech pathology services to be performed...

Endocannabinoid System in Neurological Disorders.

PubMed

Ranieri, Roberta; Laezza, Chiara; Bifulco, Maurizio; Marasco, Daniela; Malfitano, Anna M

2016-01-01

Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others. In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies. Despite different etiologies, neurodegenerative disorders exhibit similar mechanisms like neuro-inflammation, excitotoxicity, deregulation of intercellular communication, mitochondrial dysfunction and disruption of brain tissue homeostasis. Current treatments ameliorate the symptoms but are not curative. Interfering with the endocannabinoid signaling might be a valid therapeutic option in neuro-degeneration. To this aim, pharmacological intervention to modulate the endocannabinoid system and the use of natural and synthetic cannabimimetic drugs have been assessed. CB1 and CB2 receptor signaling contributes to the control of Ca2+ homeostasis, trophic support, mitochondrial activity, and inflammatory conditions. Several studies and patents suggest that the endocannabinoid system has neuro-protective properties and might be a target in neurodegenerative diseases.

Assessing the interplay of childhood adversities with more recent stressful life events and conditions in predicting panic pathology among adults from the general population.

PubMed

Asselmann, E; Stender, J; Grabe, H J; König, J; Schmidt, C O; Hamm, A O; Pané-Farré, C A

2018-01-01

Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology. Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age). Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities. Data were assessed retrospectively and might be subject to recall biases. Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events. Copyright © 2017. Published by Elsevier B.V.

Pathological features of polyneuropathy in three dogs.

PubMed

Tsuboi, Masaya; Uchida, Kazuyuki; Ide, Tetsuya; Ogawa, Mizue; Inagaki, Takehiko; Tamura, Shinji; Saito, Miyoko; Chambers, James K; Nakayama, Hiroyuki

2013-01-01

Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested.

The clinical spectrum of phaeochromocytoma: analysis of 115 patients.

PubMed

Safwat, Ahmed S; Bissada, Nabil K; Seyam, Raouf M; Al Sobhi, Saif; Hanash, Kamal A

2008-06-01

To analyse the presentation, manifestations and outcome in consecutive patients with phaeochromocytoma, as this disease has a wide range of pathological and clinical expressions. The records of 115 patients with phaeochromocytoma were analysed retrospectively, recording the patients' age, sex, presenting symptoms and clinical signs, chemical, radiological and pathological findings and associated conditions. Of the 115 patients, 90 had adrenal tumours, 18 extra-adrenal and seven combined adrenal and extra-adrenal tumours. Ten patients had malignant and 105 had benign phaeochromocytoma. Eighty-six patients had sporadic and 29 had familial phaeochromocytoma, comprising eight with von Hippel-Lindau (VHL) disease, 17 with multiple endocrine neoplasia type II (MEN II) and four with von Recklinghausen disease. Two patients with sporadic phaeochromocytoma had Grave's disease. Ten patients (8.7%) had malignant phaeochromocytoma, of whom two had MEN II. A pregnant woman required prolonged intensive-care management before adrenalectomy and lost a fetus. Phaeochromocytoma is an interesting clinical entity with a wide spectrum of pathological and clinical manifestations. The diagnosis of phaeochromocytoma is confirmed by chemical methods, and located using imaging techniques, with computed tomography, magnetic resonance imaging and (131)I-meta-iodobenzyl guanidine radioisotope scanning being the most common. This series reflects the pathological and clinical spectrum of phaeochromocytoma. The presence of other manifestations of familial phaeochromocytoma influenced the presentation and prognosis of these patients.

Histone deacetylases (HDAC) in physiological and pathological bone remodelling.

PubMed

Cantley, M D; Zannettino, A C W; Bartold, P M; Fairlie, D P; Haynes, D R

2017-02-01

Histone deacetylases (HDACs) 2 play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi) 3 that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders.

PubMed

Ikonomovic, Milos D; Mi, Zhiping; Abrahamson, Eric E

2017-03-01

Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE). The pathology of TBI is complex and dependent on injury severity, age-at-injury, and length of time between injury and neuropathological evaluation. In addition, the mechanisms influencing pathology and recovery after TBI likely involve genetic/epigenetic factors as well as additional disorders or comorbid states related to age and central and peripheral vascular health. In this regard, dysfunction of the aging neurovascular system could be an important link between TBI and chronic neurodegenerative diseases, either as a precipitating event or related to accumulation of AD-like pathology which is amplified in the context of aging. Thus with advanced age and vascular dysfunction, TBI can trigger self-propagating cycles of neuronal injury, pathological protein aggregation, and synaptic loss resulting in chronic neurodegenerative disease. In this review we discuss evidence supporting TBI and aging as dual, interacting risk factors for AD, and the role of Aβ and cerebral vascular dysfunction in this relationship. Evidence is discussed that Aβ is involved in cyto- and synapto-toxicity after severe TBI, and that its chronic effects are potentiated by aging and impaired cerebral vascular function. From a therapeutic perspective, we emphasize that in the fields of TBI- and aging-related neurodegeneration protective strategies should include preservation of neurovascular function. Published by Elsevier B.V.

42 CFR 484.38 - Condition of participation: Qualifying to furnish outpatient physical therapy or speech pathology...

Code of Federal Regulations, 2013 CFR

2013-10-01

... outpatient physical therapy or speech pathology services. 484.38 Section 484.38 Public Health CENTERS FOR... furnish outpatient physical therapy or speech pathology services. An HHA that wishes to furnish outpatient physical therapy or speech pathology services must meet all the pertinent conditions of this part and also...

42 CFR 484.38 - Condition of participation: Qualifying to furnish outpatient physical therapy or speech pathology...

Code of Federal Regulations, 2014 CFR

2014-10-01

... outpatient physical therapy or speech pathology services. 484.38 Section 484.38 Public Health CENTERS FOR... furnish outpatient physical therapy or speech pathology services. An HHA that wishes to furnish outpatient physical therapy or speech pathology services must meet all the pertinent conditions of this part and also...

42 CFR 484.38 - Condition of participation: Qualifying to furnish outpatient physical therapy or speech pathology...

Code of Federal Regulations, 2011 CFR

2011-10-01

... outpatient physical therapy or speech pathology services. 484.38 Section 484.38 Public Health CENTERS FOR... furnish outpatient physical therapy or speech pathology services. An HHA that wishes to furnish outpatient physical therapy or speech pathology services must meet all the pertinent conditions of this part and also...

42 CFR 484.38 - Condition of participation: Qualifying to furnish outpatient physical therapy or speech pathology...

Code of Federal Regulations, 2012 CFR

2012-10-01

... outpatient physical therapy or speech pathology services. 484.38 Section 484.38 Public Health CENTERS FOR... furnish outpatient physical therapy or speech pathology services. An HHA that wishes to furnish outpatient physical therapy or speech pathology services must meet all the pertinent conditions of this part and also...

42 CFR 484.38 - Condition of participation: Qualifying to furnish outpatient physical therapy or speech pathology...

Code of Federal Regulations, 2010 CFR

2010-10-01

... outpatient physical therapy or speech pathology services. 484.38 Section 484.38 Public Health CENTERS FOR... furnish outpatient physical therapy or speech pathology services. An HHA that wishes to furnish outpatient physical therapy or speech pathology services must meet all the pertinent conditions of this part and also...

Prediction of anthropometric foot characteristics in children.

PubMed

Morrison, Stewart C; Durward, Brian R; Watt, Gordon F; Donaldson, Malcolm D C

2009-01-01

The establishment of growth reference values is needed in pediatric practice where pathologic conditions can have a detrimental effect on the growth and development of the pediatric foot. This study aims to use multiple regression to evaluate the effects of multiple predictor variables (height, age, body mass, and gender) on anthropometric characteristics of the peripubescent foot. Two hundred children aged 9 to 12 years were recruited, and three anthropometric measurements of the pediatric foot were recorded (foot length, forefoot width, and navicular height). Multiple regression analysis was conducted, and coefficients for gender, height, and body mass all had significant relationships for the prediction of forefoot width and foot length (P < or = .05, r > or = 0.7). The coefficients for gender and body mass were not significant for the prediction of navicular height (P > or = .05), whereas height was (P < or = .05). Normative growth reference values and prognostic regression equations are presented for the peripubescent foot.

Epithelial Integrity Is Maintained by a Matriptase-Dependent Proteolytic Pathway

PubMed Central

List, Karin; Kosa, Peter; Szabo, Roman; Bey, Alexandra L.; Wang, Chao Becky; Molinolo, Alfredo; Bugge, Thomas H.

2009-01-01

A pericellular proteolytic pathway initiated by the transmembrane serine protease matriptase plays a critical role in the terminal differentiation of epidermal tissues. Matriptase is constitutively expressed in multiple other epithelia, suggesting a putative role of this membrane serine protease in general epithelial homeostasis. Here we generated mice with conditional deletion of the St14 gene, encoding matriptase, and show that matriptase indeed is essential for the maintenance of multiple types of epithelia in the mouse. Thus, embryonic or postnatal ablation of St14 in epithelial tissues of diverse origin and function caused severe organ dysfunction, which was often associated with increased permeability, loss of tight junction function, mislocation of tight junction-associated proteins, and generalized epithelial demise. The study reveals that the homeostasis of multiple simple and stratified epithelia is matriptase-dependent, and provides an important animal model for the exploration of this membrane serine protease in a range of physiological and pathological processes. PMID:19717635

Update on conjunctival pathology

PubMed Central

Mudhar, Hardeep Singh

2017-01-01

Conjunctival biopsies constitute a fairly large number of cases in a typical busy ophthalmic pathology practice. They range from a single biopsy through multiple mapping biopsies to assess the extent of a particular pathological process. Like most anatomical sites, the conjunctiva is subject to a very wide range of pathological processes. This article will cover key, commonly encountered nonneoplastic and neoplastic entities. Where relevant, sections will include recommendations on how best to submit specimens to the ophthalmic pathology laboratory and the relevance of up-to-date molecular techniques. PMID:28905821

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Pathological Gambling and Associated Drug and Alcohol Abuse, Emotion Regulation, and Anxious-Depressive Symptomatology.

PubMed

Jauregui, Paula; Estévez, Ana; Urbiola, Irache

2016-06-01

Background and aims Pathological gambling is associated with comorbid disorders, such as anxiety, depression, and drug and alcohol abuse. Difficulties of emotion regulation may be one of the factors related to the presence of addictive disorders, along with comorbid symptomatology in pathological gamblers. Therefore, the aim of this study was to evaluate the difficulties of emotion regulation, drug and alcohol abuse, and anxious and depressive symptomatology in pathological gamblers, and the mediating role of difficulties of emotion regulation between anxiety and pathological gambling. Methods The study sample included 167 male pathological gamblers (mean age = 39.29 years) and 107 non-gamblers (mean age = 33.43 years). Pathological gambling (SOGS), difficulties of emotion regulation (DERS), drug and alcohol abuse (MUTICAGE CAD-4), and anxious and depressive symptomatology (SA-45) were measured. Student's t, Pearson's r, stepwise multiple linear regression and multiple mediation analyses were conducted. The study was approved by an Investigational Review Board. Results Relative to non-gamblers, pathological gamblers exhibited greater difficulties of emotion regulation, as well as more anxiety, depression, and drug abuse. Moreover, pathological gambling correlated with emotion regulation difficulties, anxiety, depression, and drug abuse. Besides, emotion regulation difficulties correlated with and predicted pathological gambling, drug and alcohol abuse, and anxious and depressive symptomatology. Finally, emotion regulation difficulties mediated the relationship between anxiety and pathological gambling controlling the effect of age, both when controlling and not controlling for the effect of other abuses. Discussion and conclusions These results suggest that difficulties of emotion regulation may provide new keys to understanding and treating pathological gambling and comorbid disorders.

The biology of IL-23 and IL-17 and their therapeutic targeting in rheumatic diseases.

PubMed

Sherlock, Jonathan P; Taylor, Peter C; Buckley, Christopher D

2015-01-01

Interleukin (IL)-23 and the related cytokine IL-17 play vital roles in immune-mediated inflammatory pathology. In the years since its discovery, IL-23 has been implicated as a central pathogenic factor in multiple rheumatic conditions and has been shown to act via a wide range of immune cells including type 17 T-helper (Th17) cells and innate-like immune cells. We review here the pivotal role of these cytokines and IL-23-responsive cells in both the bona fide autoimmune rheumatic diseases rheumatoid arthritis and systemic lupus erythematosus, as well as the spondyloarthropathies which more closely resemble the auto-inflammatory conditions. IL-23 and related cytokines have been found to be up-regulated in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy, and preclinical models suggest that they play important pathological roles in these conditions. It is anticipated that agents which target the IL-23 pathway will have profound roles in modifying the natural history of these diseases and in preventing the structural damage which occurs secondary to such chronic inflammation. This is especially relevant in the case of spondyloarthropathy in which case prevention of the novel bone formation is a particular challenge. It is also potentially pertinent for patients with rheumatoid arthritis, particularly those who do not respond to other biological therapies.

Dopamine Receptors and Neurodegeneration

PubMed Central

Rangel-Barajas, Claudia; Coronel, Israel; Florán, Benjamín

2015-01-01

Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson’s disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases. PMID:26425390

A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.

PubMed

Geminiani, Alice; Casellato, Claudia; Antonietti, Alberto; D'Angelo, Egidio; Pedrocchi, Alessandra

2018-06-01

The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.

Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism.

PubMed

Ardestani, Amin; Lupse, Blaz; Maedler, Kathrin

2018-05-05

The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer. In this review we summarize the connection between key Hippo components and metabolism, and how this interplay regulates cellular metabolism and metabolic pathways. The emerging function of Hippo in the regulation of metabolic homeostasis under physiological and pathological conditions is highlighted. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative analysis of whole mount processing and systematic sampling of radical prostatectomy specimens: pathological outcomes and risk of biochemical recurrence.

PubMed

Salem, Shady; Chang, Sam S; Clark, Peter E; Davis, Rodney; Herrell, S Duke; Kordan, Yakup; Wills, Marcia L; Shappell, Scott B; Baumgartner, Roxelyn; Phillips, Sharon; Smith, Joseph A; Cookson, Michael S; Barocas, Daniel A

2010-10-01

Whole mount processing is more resource intensive than routine systematic sampling of radical retropubic prostatectomy specimens. We compared whole mount and systematic sampling for detecting pathological outcomes, and compared the prognostic value of pathological findings across pathological methods. We included men (608 whole mount and 525 systematic sampling samples) with no prior treatment who underwent radical retropubic prostatectomy at Vanderbilt University Medical Center between January 2000 and June 2008. We used univariate and multivariate analysis to compare the pathological outcome detection rate between pathological methods. Kaplan-Meier curves and the log rank test were used to compare the prognostic value of pathological findings across pathological methods. There were no significant differences between the whole mount and the systematic sampling groups in detecting extraprostatic extension (25% vs 30%), positive surgical margins (31% vs 31%), pathological Gleason score less than 7 (49% vs 43%), 7 (39% vs 43%) or greater than 7 (12% vs 13%), seminal vesicle invasion (8% vs 10%) or lymph node involvement (3% vs 5%). Tumor volume was higher in the systematic sampling group and whole mount detected more multiple surgical margins (each p <0.01). There were no significant differences in the likelihood of biochemical recurrence between the pathological methods when patients were stratified by pathological outcome. Except for estimated tumor volume and multiple margins whole mount and systematic sampling yield similar pathological information. Each method stratifies patients into comparable risk groups for biochemical recurrence. Thus, while whole mount is more resource intensive, it does not appear to result in improved detection of clinically important pathological outcomes or prognostication. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla

PubMed Central

Hametner, Simon; Yao, Bing; van Gelderen, Peter; Merkle, Hellmut; Cantor, Fredric K.; Lassmann, Hans; Duyn, Jeff H.

2011-01-01

Previous authors have shown that the transverse relaxivity R2* and frequency shifts that characterize gradient echo signal decay in magnetic resonance imaging are closely associated with the distribution of iron and myelin in the brain's white matter. In multiple sclerosis, iron accumulation in brain tissue may reflect a multiplicity of pathological processes. Hence, iron may have the unique potential to serve as an in vivo magnetic resonance imaging tracer of disease pathology. To investigate the ability of iron in tracking multiple sclerosis-induced pathology by magnetic resonance imaging, we performed qualitative histopathological analysis of white matter lesions and normal-appearing white matter regions with variable appearance on gradient echo magnetic resonance imaging at 7 Tesla. The samples used for this study derive from two patients with multiple sclerosis and one non-multiple sclerosis donor. Magnetic resonance images were acquired using a whole body 7 Tesla magnetic resonance imaging scanner equipped with a 24-channel receive-only array designed for tissue imaging. A 3D multi-gradient echo sequence was obtained and quantitative R2* and phase maps were reconstructed. Immunohistochemical stainings for myelin and oligodendrocytes, microglia and macrophages, ferritin and ferritin light polypeptide were performed on 3- to 5-µm thick paraffin sections. Iron was detected with Perl's staining and 3,3′-diaminobenzidine-tetrahydrochloride enhanced Turnbull blue staining. In multiple sclerosis tissue, iron presence invariably matched with an increase in R2*. Conversely, R2* increase was not always associated with the presence of iron on histochemical staining. We interpret this finding as the effect of embedding, sectioning and staining procedures. These processes likely affected the histopathological analysis results but not the magnetic resonance imaging that was obtained before tissue manipulations. Several cellular sources of iron were identified. These sources included oligodendrocytes in normal-appearing white matter and activated macrophages/microglia at the edges of white matter lesions. Additionally, in white matter lesions, iron precipitation in aggregates typical of microbleeds was shown by the Perl's staining. Our combined imaging and pathological study shows that multi-gradient echo magnetic resonance imaging is a sensitive technique for the identification of iron in the brain tissue of patients with multiple sclerosis. However, magnetic resonance imaging-identified iron does not necessarily reflect pathology and may also be seen in apparently normal tissue. Iron identification by multi-gradient echo magnetic resonance imaging in diseased tissues can shed light on the pathological processes when coupled with topographical information and patient disease history. PMID:22171355

Analysis of Extracellular Vesicles in the Tumor Microenvironment.

PubMed

Al-Nedawi, Khalid; Read, Jolene

2016-01-01

Extracellular vesicles (ECV) are membrane compartments shed from all types of cells in various physiological and pathological states. In recent years, ECV have gained an increasing interest from the scientific community for their role as an intercellular communicator that plays important roles in modifying the tumor microenvironment. Multiple techniques have been established to collect ECV from conditioned media of cell culture or physiological fluids. The gold standard methodology is differential centrifugation. Although alternative techniques exist to collect ECV, these techniques have not proven suitable as a substitution for the ultracentrifugation procedure.

PML nuclear bodies: regulation, function and therapeutic perspectives.

PubMed

Sahin, Umut; Lallemand-Breitenbach, Valérie; de Thé, Hugues

2014-11-01

PML nuclear bodies (NBs) were first described by electron microscopy and rediscovered through their treatment-reversible disruption in a rare leukaemia. They recruit multiple partner proteins and now emerge as interferon- and oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced viral restriction, enhance proteolysis, finely tune metabolism and enforce stress-induced senescence. Apart from being markers of cellular stress, PML NBs could be harnessed pharmacologically in a number of conditions, including cancer, viral infection or neurodegenerative diseases. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Storage and distribution of pathology digital images using integrated web-based viewing systems.

PubMed

Marchevsky, Alberto M; Dulbandzhyan, Ronda; Seely, Kevin; Carey, Steve; Duncan, Raymond G

2002-05-01

Health care providers have expressed increasing interest in incorporating digital images of gross pathology specimens and photomicrographs in routine pathology reports. To describe the multiple technical and logistical challenges involved in the integration of the various components needed for the development of a system for integrated Web-based viewing, storage, and distribution of digital images in a large health system. An Oracle version 8.1.6 database was developed to store, index, and deploy pathology digital photographs via our Intranet. The database allows for retrieval of images by patient demographics or by SNOMED code information. The Intranet of a large health system accessible from multiple computers located within the medical center and at distant private physician offices. The images can be viewed using any of the workstations of the health system that have authorized access to our Intranet, using a standard browser or a browser configured with an external viewer or inexpensive plug-in software, such as Prizm 2.0. The images can be printed on paper or transferred to film using a digital film recorder. Digital images can also be displayed at pathology conferences by using wireless local area network (LAN) and secure remote technologies. The standardization of technologies and the adoption of a Web interface for all our computer systems allows us to distribute digital images from a pathology database to a potentially large group of users distributed in multiple locations throughout a large medical center.

Seminal Plasma Proteins as Androgen Receptor Corregulators Promote Prostate Cancer Growth

DTIC Science & Technology

2015-10-01

functional analyses of semenogelins in pathological conditions have been reported and their roles in prostate cancer outgrowth remain uncertain. In...1Departments of Pathology and Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Pathology and Laboratory... pathological conditions have been reported and their roles in prostate cancer growth remain uncertain. In the current study, we aim to determine the

Augmented Reality Technology Using Microsoft HoloLens in Anatomic Pathology.

PubMed

Hanna, Matthew G; Ahmed, Ishtiaque; Nine, Jeffrey; Prajapati, Shyam; Pantanowitz, Liron

2018-05-01

Context Augmented reality (AR) devices such as the Microsoft HoloLens have not been well used in the medical field. Objective To test the HoloLens for clinical and nonclinical applications in pathology. Design A Microsoft HoloLens was tested for virtual annotation during autopsy, viewing 3D gross and microscopic pathology specimens, navigating whole slide images, telepathology, as well as real-time pathology-radiology correlation. Results Pathology residents performing an autopsy wearing the HoloLens were remotely instructed with real-time diagrams, annotations, and voice instruction. 3D-scanned gross pathology specimens could be viewed as holograms and easily manipulated. Telepathology was supported during gross examination and at the time of intraoperative consultation, allowing users to remotely access a pathologist for guidance and to virtually annotate areas of interest on specimens in real-time. The HoloLens permitted radiographs to be coregistered on gross specimens and thereby enhanced locating important pathologic findings. The HoloLens also allowed easy viewing and navigation of whole slide images, using an AR workstation, including multiple coregistered tissue sections facilitating volumetric pathology evaluation. Conclusions The HoloLens is a novel AR tool with multiple clinical and nonclinical applications in pathology. The device was comfortable to wear, easy to use, provided sufficient computing power, and supported high-resolution imaging. It was useful for autopsy, gross and microscopic examination, and ideally suited for digital pathology. Unique applications include remote supervision and annotation, 3D image viewing and manipulation, telepathology in a mixed-reality environment, and real-time pathology-radiology correlation.

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2015-02-01

Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive neurological and...11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain injuries 15-17...To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing efforts include

Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

DTIC Science & Technology

2016-02-01

14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for delayed, progressive...pugilistica 3, 11 or ‘punch drunk’ syndrome 9, 12. US military personnel 13, 14 and others who have sustained multiple concussive traumatic brain...Progress to date: To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in mice has been optimal. Ongoing

Role of Proangiogenic Factors in Immunopathogenesis of Multiple Sclerosis.

PubMed

Hamid, Kabir Magaji; Mirshafiey, Abbas

2016-02-01

Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear. In this study, the link between proangiogenic factors and multiple sclerosis pathogenesis was examined by conducting a systemic review. Thus we searched the English medical literature via PubMed, ISI web of knowledge, Medline and virtual health library (VHL) databases. In this review, we describe direct and indirect roles of some proangiogenic factors in MS pathogenesis and report the association of these factors with pathological and inflammatory angiogenesis.

Pathological Gambling and Associated Drug and Alcohol Abuse, Emotion Regulation, and Anxious-Depressive Symptomatology

PubMed Central

Jauregui, Paula; Estévez, Ana; Urbiola, Irache

2016-01-01

Background and aims Pathological gambling is associated with comorbid disorders, such as anxiety, depression, and drug and alcohol abuse. Difficulties of emotion regulation may be one of the factors related to the presence of addictive disorders, along with comorbid symptomatology in pathological gamblers. Therefore, the aim of this study was to evaluate the difficulties of emotion regulation, drug and alcohol abuse, and anxious and depressive symptomatology in pathological gamblers, and the mediating role of difficulties of emotion regulation between anxiety and pathological gambling. Methods The study sample included 167 male pathological gamblers (mean age = 39.29 years) and 107 non-gamblers (mean age = 33.43 years). Pathological gambling (SOGS), difficulties of emotion regulation (DERS), drug and alcohol abuse (MUTICAGE CAD-4), and anxious and depressive symptomatology (SA-45) were measured. Student’s t, Pearson’s r, stepwise multiple linear regression and multiple mediation analyses were conducted. The study was approved by an Investigational Review Board. Results Relative to non-gamblers, pathological gamblers exhibited greater difficulties of emotion regulation, as well as more anxiety, depression, and drug abuse. Moreover, pathological gambling correlated with emotion regulation difficulties, anxiety, depression, and drug abuse. Besides, emotion regulation difficulties correlated with and predicted pathological gambling, drug and alcohol abuse, and anxious and depressive symptomatology. Finally, emotion regulation difficulties mediated the relationship between anxiety and pathological gambling controlling the effect of age, both when controlling and not controlling for the effect of other abuses. Discussion and conclusions These results suggest that difficulties of emotion regulation may provide new keys to understanding and treating pathological gambling and comorbid disorders. PMID:27348555

A gradient in cortical pathology in multiple sclerosis by in vivo quantitative 7 T imaging

PubMed Central

Louapre, Céline; Govindarajan, Sindhuja T.; Giannì, Costanza; Nielsen, A. Scott; Cohen-Adad, Julien; Sloane, Jacob; Kinkel, Revere P.

2015-01-01

We used a surface-based analysis of T2* relaxation rates at 7 T magnetic resonance imaging, which allows sampling quantitative T2* throughout the cortical width, to map in vivo the spatial distribution of intracortical pathology in multiple sclerosis. Ultra-high resolution quantitative T2* maps were obtained in 10 subjects with clinically isolated syndrome/early multiple sclerosis (≤3 years disease duration), 18 subjects with relapsing-remitting multiple sclerosis (≥4 years disease duration), 13 subjects with secondary progressive multiple sclerosis, and in 17 age-matched healthy controls. Quantitative T2* maps were registered to anatomical cortical surfaces for sampling T2* at 25%, 50% and 75% depth from the pial surface. Differences in laminar quantitative T2* between each patient group and controls were assessed using general linear model (P < 0.05 corrected for multiple comparisons). In all 41 multiple sclerosis cases, we tested for associations between laminar quantitative T2*, neurological disability, Multiple Sclerosis Severity Score, cortical thickness, and white matter lesions. In patients, we measured, T2* in intracortical lesions and in the intracortical portion of leukocortical lesions visually detected on 7 T scans. Cortical lesional T2* was compared with patients’ normal-appearing cortical grey matter T2* (paired t-test) and with mean cortical T2* in controls (linear regression using age as nuisance factor). Subjects with multiple sclerosis exhibited relative to controls, independent from cortical thickness, significantly increased T2*, consistent with cortical myelin and iron loss. In early disease, T2* changes were focal and mainly confined at 25% depth, and in cortical sulci. In later disease stages T2* changes involved deeper cortical laminae, multiple cortical areas and gyri. In patients, T2* in intracortical and leukocortical lesions was increased compared with normal-appearing cortical grey matter (P < 10−10 and P < 10−7), and mean cortical T2* in controls (P < 10−5 and P < 10−6). In secondary progressive multiple sclerosis, T2* in normal-appearing cortical grey matter was significantly increased relative to controls (P < 0.001). Laminar T2* changes may, thus, result from cortical pathology within and outside focal cortical lesions. Neurological disability and Multiple Sclerosis Severity Score correlated each with the degree of laminar quantitative T2* changes, independently from white matter lesions, the greatest association being at 25% depth, while they did not correlate with cortical thickness and volume. These findings demonstrate a gradient in the expression of cortical pathology throughout stages of multiple sclerosis, which was associated with worse disability and provides in vivo evidence for the existence of a cortical pathological process driven from the pial surface. PMID:25681411

Imaging and histology in the diagnosis of multiple papillary fibroelastomas in a patient with hypertrophic obstructive cardiomyopathy. Case report.

PubMed

Ionescu, Alin Alexandru; Radulescu, Bogdan; Herlea, Vlad; Miclea, Ioan; Parepa, Irinel; Bubenek, Serban; Popescu, Bogdan Alexandru; Ginghina, Carmen; Jurcut, Ruxandra

2017-11-29

Papillary fibroelastomas (PFEs) are one of the most frequent primary cardiac tumors and occur more often in patients with hypertrophic obstructive cardiomyopathy (HOCM). PFEs have been linked to an increased risk of neurological events. We report a case of a 59-year-old woman with HOCM in whom echocardiography (transthoracic and transesophageal, using 2D and 3D techniques) revealed multiple masses in various locations in the left cardiac chambers. Surgical excision of the cardiac tumors and aortic valve replacement was performed and the pathologic report confirmed the diagnosis of PFEs. Patient followup using ultrasonography is crucial since recurrence is a possibility. Current cardiac ultrasound techniques are essential for diagnosing and for guiding the management of these conditions.

Methylation and microRNA-mediated epigenetic regulation of SOCS3

PubMed Central

Boosani, Chandra S.; Agrawal, Devendra K.

2017-01-01

Epigenetic gene silencing of several genes causes different pathological conditions in humans, and DNA methylation has been identified as one of the key mechanisms that underlie this evolutionarily conserved phenomenon associated with developmental and pathological gene regulation. Recent advances in the miRNA technology with high throughput analysis of gene regulation further increased our understanding on the role of miRNAs regulating multiple gene expression. There is increasing evidence supporting that the miRNAs not only regulate gene expression but they also are involved in the hypermethylation of promoter sequences, which cumulatively contributes to the epigenetic gene silencing. Here, we critically evaluated the recent progress on the transcriptional regulation of an important suppressor protein that inhibits cytokine-mediated signaling, SOCS3, whose expression is directly regulated both by promoter methylation and also by microRNAs, affecting its vital cell regulating functions. SOCS3 was identified as a potent inhibitor of Jak/STAT signaling pathway which is frequently upregulated in several pathologies, including cardiovascular disease, cancer, diabetes, viral infections, and the expression of SOCS3 was inhibited or greatly reduced due to hypermethylation of the CpG islands in its promoter region or suppression of its expression by different microRNAs. Additionally, we discuss key intracellular signaling pathways regulated by SOCS3 involving cellular events, including cell proliferation, cell growth, cell migration and apoptosis. Identification of the pathway intermediates as specific targets would not only aid in the development of novel therapeutic drugs, but, would also assist in developing new treatment strategies that could successfully be employed in combination therapy to target multiple signaling pathways. PMID:25682267

An iterative Riemann solver for systems of hyperbolic conservation law s, with application to hyperelastic solid mechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Gregory H.

2003-08-06

In this paper we present a general iterative method for the solution of the Riemann problem for hyperbolic systems of PDEs. The method is based on the multiple shooting method for free boundary value problems. We demonstrate the method by solving one-dimensional Riemann problems for hyperelastic solid mechanics. Even for conditions representative of routine laboratory conditions and military ballistics, dramatic differences are seen between the exact and approximate Riemann solution. The greatest discrepancy arises from misallocation of energy between compressional and thermal modes by the approximate solver, resulting in nonphysical entropy and temperature estimates. Several pathological conditions arise in commonmore » practice, and modifications to the method to handle these are discussed. These include points where genuine nonlinearity is lost, degeneracies, and eigenvector deficiencies that occur upon melting.« less

Grey matter damage in progressive multiple sclerosis versus amyotrophic lateral sclerosis: a voxel-based morphometry MRI study.

PubMed

Tavazzi, Eleonora; Laganà, Maria Marcella; Bergsland, Niels; Tortorella, Paola; Pinardi, Giovanna; Lunetta, Christian; Corbo, Massimo; Rovaris, Marco

2015-03-01

Primary progressive multiple sclerosis (PPMS) and amyotrophic lateral sclerosis (ALS) seem to share some clinical and pathological features. MRI studies revealed the presence of grey matter (GM) atrophy in both diseases, but no comparative data are available. The objective was to compare the regional patterns of GM tissue loss in PPMS and ALS with voxel-based morphometry (VBM). Eighteen PPMS patients, 20 ALS patients, and 31 healthy controls (HC) were studied with a 1.5 Tesla scanner. VBM was performed to assess volumetric GM differences with age and sex as covariates. Threshold-free cluster enhancement analysis was used to obtain significant clusters. Group comparisons were tested with family-wise error correction for multiple comparisons (p < 0.05) except for HC versus MND which was tested at a level of p < 0.001 uncorrected and a cluster threshold of 20 contiguous voxels. Compared to HC, ALS patients showed GM tissue reduction in selected frontal and temporal areas, while PPMS patients showed a widespread bilateral GM volume decrease, involving both deep and cortical regions. Compared to ALS, PPMS patients showed tissue volume reductions in both deep and cortical GM areas. This preliminary study confirms that PPMS is characterized by a more diffuse cortical and subcortical GM atrophy than ALS and that, in the latter condition, brain damage is present outside the motor system. These results suggest that PPMS and ALS may share pathological features leading to GM tissue loss.

Spontaneous abortion in multiple pregnancy: focus on fetal pathology.

PubMed

Joó, József Gábor; Csaba, Ákos; Szigeti, Zsanett; Rigó, János

2012-08-15

Multiple pregnancy with its wide array of medical consequences poses an important condition during pregnancy. We performed perinatal autopsy in 49 cases of spontaneous abortion resulting from multiple pregnancies during the study period. Twenty-seven of the 44 twin pregnancies ending in miscarriage were conceived naturally, whereas 17 were conceived through assisted reproductive techniques. Each of the 5 triplet pregnancies ending in miscarriage was conceived through assisted reproductive techniques. There was a positive history of miscarriage in 22.4% of the cases. Monochorial placentation occurred more commonly in multiple pregnancies terminating with miscarriage than in multiple pregnancies without miscarriage. A fetal congenital malformation was found in 8 cases. Three of these cases were conceived through assisted reproductive techniques, and 5 were conceived naturally. Miscarriage was due to intrauterine infection in 36% of the cases. Our study confirms that spontaneous abortion is more common in multiple than in singleton pregnancies. Monochorial placentation predicted a higher fetal morbidity and mortality. In pregnancies where all fetuses were of male gender, miscarriage was more common than in pregnancies where all fetuses were female. Assisted reproductive techniques do not predispose to the development of fetal malformations. Copyright © 2012 Elsevier GmbH. All rights reserved.

Chaos theory for clinical manifestations in multiple sclerosis.

PubMed

Akaishi, Tetsuya; Takahashi, Toshiyuki; Nakashima, Ichiro

2018-06-01

Multiple sclerosis (MS) is a demyelinating disease which characteristically shows repeated relapses and remissions irregularly in the central nervous system. At present, the pathological mechanism of MS is unknown and we do not have any theories or mathematical models to explain its disseminated patterns in time and space. In this paper, we present a new theoretical model from a viewpoint of complex system with chaos model to reproduce and explain the non-linear clinical and pathological manifestations in MS. First, we adopted a discrete logistic equation with non-linear dynamics to prepare a scalar quantity for the strength of pathogenic factor at a specific location of the central nervous system at a specific time to reflect the negative feedback in immunity. Then, we set distinct minimum thresholds in the above-mentioned scalar quantity for demyelination possibly causing clinical relapses and for cerebral atrophy. With this simple model, we could theoretically reproduce all the subtypes of relapsing-remitting MS, primary progressive MS, and secondary progressive MS. With the sensitivity to initial conditions and sensitivity to minute change in parameters of the chaos theory, we could also reproduce the spatial dissemination. Such chaotic behavior could be reproduced with other similar upward-convex functions with appropriate set of initial conditions and parameters. In conclusion, by applying chaos theory to the three-dimensional scalar field of the central nervous system, we can reproduce the non-linear outcome of the clinical course and explain the unsolved disseminations in time and space of the MS patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

The α‐synuclein gene in multiple system atrophy

PubMed Central

Ozawa, T; Healy, D G; Abou‐Sleiman, P M; Ahmadi, K R; Quinn, N; Lees, A J; Shaw, K; Wullner, U; Berciano, J; Moller, J C; Kamm, C; Burk, K; Josephs, K A; Barone, P; Tolosa, E; Goldstein, D B; Wenning, G; Geser, F; Holton, J L; Gasser, T; Revesz, T; Wood, N W

2006-01-01

Background The formation of α‐synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested. Method The linkage disequilibrium (LD) structure of the α‐synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated. Results and conclusion In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag‐defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases. PMID:16543523

Deep gluteal space problems: piriformis syndrome, ischiofemoral impingement and sciatic nerve release.

PubMed

Carro, Luis Perez; Hernando, Moises Fernandez; Cerezal, Luis; Navarro, Ivan Saenz; Fernandez, Ana Alfonso; Castillo, Alexander Ortiz

2016-01-01

Deep gluteal syndrome (DGS) is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip or posterior thigh and/or radicular pain due to a non-discogenic sciatic nerve entrapment in the subgluteal space. Multiple pathologies have been incorporated in this all-included "piriformis syndrome", a term that has nothing to do with the presence of fibrous bands, obturator internus/gemellus syndrome, quadratus femoris/ischiofemoral pathology, hamstring conditions, gluteal disorders and orthopedic causes. This article describes the subgluteal space anatomy, reviews known and new etiologies of DGS, and assesses the role of the radiologist and orthopaedic surgeons in the diagnosis, treatment and postoperative evaluation of sciatic nerve entrapments. DGS is an under-recognized and multifactorial pathology. The development of periarticular hip endoscopy has led to an understanding of the pathophysiological mechanisms underlying piriformis syndrome, which has supported its further classification. The whole sciatic nerve trajectory in the deep gluteal space can be addressed by an endoscopic surgical technique. Endoscopic decompression of the sciatic nerve appears useful in improving function and diminishing hip pain in sciatic nerve entrapments, but requires significant experience and familiarity with the gross and endoscopic anatomy. IV.

Tricuspid Regurgitation – Medical Management and Evolving Interventional Concepts

PubMed Central

Beckhoff, Frederik; Alushi, Brunilda; Jung, Christian; Navarese, Eliano; Franz, Marcus; Kretzschmar, Daniel; Wernly, Bernhard; Lichtenauer, Michael; Lauten, Alexander

2018-01-01

Severe tricuspid regurgitation (TR) is a complex condition of the right ventricle (RV) and tricuspid valve apparatus and is frequently associated with symptomatic heart failure and a significant morbidity and mortality. In these patients, left heart pathologies lead to chronic pressure overload of the RV, eventually causing progressive RV dilatation and functional TR. Therefore, TR cannot be considered as isolated heart valve disease pathology but has to be understood and treated as one component of a complex structural RV pathology and is frequently also a marker of an advanced stage of cardiac disease. In these patients, medical therapy restricted to diuretics and heart failure medication is frequently ineffective. Also, severe TR in the setting of advanced heart failure constitutes a high risk for cardiac surgery. Neither one of these treatment options has demonstrated a beneficial effect on long-term prognosis. The recent innovations in transcatheter technology led to efforts to develop interventional approaches to severe TR. Multiple innovative treatment concepts are currently under preclinical and clinical investigation to replace or repair TV function. However, up to date none of these approaches is established and there is still a lack of clinical data to support the efficacy of transcatheter TR treatment. PMID:29892601

Tissue engineering strategies applied in the regeneration of the human intervertebral disk.

PubMed

Silva-Correia, Joana; Correia, Sandra I; Oliveira, Joaquim M; Reis, Rui L

2013-12-01

Low back pain (LBP) is one of the most common painful conditions that lead to work absenteeism, medical visits, and hospitalization. The majority of cases showing signs of LBP are due to age-related degenerative changes in the intervertebral disk (IVD), which are, in fact, associated with multiple spine pathologies. Traditional and more conservative procedures/clinical approaches only treat the symptoms of disease and not the underlying pathology, thus limiting their long-term efficiency. In the last few years, research and development of new approaches aiming to substitute the nucleus pulposus and annulus fibrosus tissue and stimulate its regeneration has been conducted. Regeneration of the damaged IVD using tissue engineering strategies appears particularly promising in pre-clinical studies. Meanwhile, surgical techniques must be adapted to this new approach in order to be as minimally invasive as possible, reducing recovering time and side effects associated to traditional surgeries. In this review, the current knowledge on IVD, its associated pathologies and current surgical procedures are summarized. Furthermore, it also provides a succinct and up-to-date overview on regenerative medicine research, especially on the newest tissue engineering strategies for IVD regeneration. © 2013.

Assessment of Renal Pathological Changes in Lupus Nephritis Using Diffusion Weighted Imaging: A Multiple Correspondence Analysis.

PubMed

Zheng, Zhenfeng; Yan, Tiekun; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

2018-05-30

Renal pathological changes affect the motion of water molecules, which can be detected using diffusion-weighted imaging (DWI). The current study was performed to explore the correlation between renal tissue pathological injuries and DWI iconographical parameters in lupus nephritis (LN). Twenty adult patients with LN and 11 healthy volunteers were recruited. Patients with LN received renal biopsies and renal DWI-MRI inspections. The renal biopsy tissues were characterized based on the ISN/RPS 2003 classification. The volunteers, who were of comparable gender and age, only underwent renal DWI-MRI inspection. Four DWI parameters, namely, apparent diffusion coefficient (ADC), pure diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (fp), were calculated using monoexponential and biexponential functions, respectively. Data from different renal areas and pathological pattern groups were compared. Multiple correspondence analysis (MCA) was performed to explore the correlation between each DWI index and multiple pathological features. ADC, Dt, and fp values were lower in the LN group compared to the controls (P < 0.001) regardless of the renal area in the cortex and medulla. Dp values were higher in the LN group (P = 0.004). A difference in mean DWI parameters was found between three LN subgroups and the healthy volunteers, with the exception of the Dp index in the renal cortex. MCA showed that serious proliferative pathological injuries and lower ADC and Dt values were located in the same quadrant. The MCA plots of Dp and fp provided similar results. Higher Dp and fp values were located in the MCA plot quadrant with more serious proliferative pathological changes. DWI is a noninvasive technique that may be used to detect renal pathophysiological changes. Renal cell proliferation and intestinal fibrosis may impact the movement of water in certain microenvironments. Enhanced perfusion may be a compensatory mechanism that is associated with renal pathological injuries. © 2018 The Author(s). Published by S. Karger AG, Basel.

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

PubMed Central

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-01-01

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states. PMID:26154191

MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis

PubMed Central

Lecca, Davide; Marangon, Davide; Coppolino, Giusy T.; Méndez, Aida Menéndez; Finardi, Annamaria; Costa, Gloria Dalla; Martinelli, Vittorio; Furlan, Roberto; Abbracchio, Maria P.

2016-01-01

In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here, we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of oligodendroglial maturation, that, in the mammalian CNS regulates the expression of myelin genes by simultaneously acting on several of its already validated targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the cerebrospinal fluid of MS patients bearing active demyelinating lesions, suggesting that its pathological upregulation may contribute to MS development, at least in part by blockade of OPC differentiation leading to impaired repair of demyelinated lesions. PMID:27698367

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency.

PubMed

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-07-08

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer's disease and Parkinson's disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

NASA Astrophysics Data System (ADS)

Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

2015-07-01

Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

D’Andrea’s disease (angiomegaly): a currently well-defined nosological entitys.

PubMed

Taurone, S; Spoletini, M; Di Matteo, F M; Mele, R; Tromba, L; Grippaudo, F R; Minni, A; Artico, M

2017-01-01

In 1997 D’Andrea et al. described a new nosological entity the characteristics of which consisted of lengthening, dilation and tortuosity of blood vessels, arteries or veins, less prominent, but also less circumscribed than an aneurysm. This condition does not necessarily imply specific aneurysm formation although aneurysms at multiple sites are a frequent observation. The term used by authors for angiomegaly of the venous system was venomegaly and the analogous condition of the arterial system was termed arteriomegaly. Although tortuosity and dilation of arteries and veins have been widely reported, suggesting a systemic disorder which affects the structural integrity of all vessels, most papers dealing with this intriguing condition did not describe any alterations in the components of vessel walls. In the present paper, the authors describe a well-defined condition, D’Andrea’s Disease (or DD, in this article), analyzing its salient morphological and clinical features and clarifying this pathological condition as a distinct and now well-defined nosological entity.

HRCT findings of collagen vascular disease-related interstitial pneumonia (CVD-IP): a comparative study among individual underlying diseases.

PubMed

Tanaka, N; Kunihiro, Y; Kubo, M; Kawano, R; Oishi, K; Ueda, K; Gondo, T

2018-05-29

To identify characteristic high-resolution computed tomography (CT) findings for individual collagen vascular disease (CVD)-related interstitial pneumonias (IPs). The HRCT findings of 187 patients with CVD, including 55 patients with rheumatoid arthritis (RA), 50 with systemic sclerosis (SSc), 46 with polymyositis/dermatomyositis (PM/DM), 15 with mixed connective tissue disease, 11 with primary Sjögren's syndrome, and 10 with systemic lupus erythematosus, were evaluated. Lung parenchymal abnormalities were compared among CVDs using χ 2 test, Kruskal-Wallis test, and multiple logistic regression analysis. A CT-pathology correlation was performed in 23 patients. In RA-IP, honeycombing was identified as the significant indicator based on multiple logistic regression analyses. Traction bronchiectasis (81.8%) was further identified as the most frequent finding based on χ 2 test. In SSc IP, lymph node enlargement and oesophageal dilatation were identified as the indicators based on multiple logistic regression analyses, and ground-glass opacity (GGO) was the most extensive based on Kruskal-Wallis test, which reflects the higher frequency of the pathological nonspecific interstitial pneumonia (NSIP) pattern present in the CT-pathology correlation. In PM/DM IP, airspace consolidation and the absence of honeycombing were identified as the indicators based on multiple logistic regression analyses, and predominance of consolidation over GGO (32.6%) and predominant subpleural distribution of GGO/consolidation (41.3%) were further identified as the most frequent findings based on χ 2 test, which reflects the higher frequency of the pathological NSIP and/or the organising pneumonia patterns present in the CT-pathology correlation. Several characteristic high-resolution CT findings with utility for estimating underlying CVD were identified. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

PubMed

Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

2017-04-01

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

PubMed

Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

2018-03-09

This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.

Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

PubMed Central

Takeuchi, Hideyuki; Suzumura, Akio

2014-01-01

Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g., minocycline) have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases. PMID:25228858

Similar mandibular osseous lesions in Tyrannosaurus rex and man.

PubMed

Neiburger, E J

2005-01-01

This report identifies several cases of similar-appearing multiple lesions in the mandibles of both humans and the dinosaur Tyrannosaurus rex (T. rex). A diagnosis and potential etiologies are discussed. The appearance of these lesions in prehistoric fossils suggests that this pathology is an ancient affliction which predates humans and our mammalian ancestors. Lytic lesions of the oral structures have occurred in man and higher animals throughout time. The causes range from congenital anomalies, trauma, and infections to benign and metastatic neoplasms. Not only mammals suffer from these conditions; reptiles and birds experience similar diseases.

Manipulations of the features of standard video lottery terminal (VLT) games: effects in pathological and non-pathological gamblers.

PubMed

Loba, P; Stewart, S H; Klein, R M; Blackburn, J R

2001-01-01

The present study was conducted to identify game parameters that would reduce the risk of abuse of video lottery terminals (VLTs) by pathological gamblers, while exerting minimal effects on the behavior of non-pathological gamblers. Three manipulations of standard VLT game features were explored. Participants were exposed to: a counter which displayed a running total of money spent; a VLT spinning reels game where participants could no longer "stop" the reels by touching the screen; and sensory feature manipulations. In control conditions, participants were exposed to standard settings for either a spinning reels or a video poker game. Dependent variables were self-ratings of reactions to each set of parameters. A set of 2(3) x 2 x 2 (game manipulation [experimental condition(s) vs. control condition] x game [spinning reels vs. video poker] x gambler status [pathological vs. non-pathological]) repeated measures ANOVAs were conducted on all dependent variables. The findings suggest that the sensory manipulations (i.e., fast speed/sound or slow speed/no sound manipulations) produced the most robust reaction differences. Before advocating harm reduction policies such as lowering sensory features of VLT games to reduce potential harm to pathological gamblers, it is important to replicate findings in a more naturalistic setting, such as a real bar.

Clinical multiple sclerosis occurs at one end of a spectrum of CNS pathology: a modified threshold liability model leads to new ways of thinking about the cause of clinical multiple sclerosis.

PubMed

Haegert, David G

2005-01-01

Multiple sclerosis (MS) is a complex trait, the causes of which are elusive. A threshold liability model influences thinking about the causes of this disorder. According to this model, a population has a normal distribution of genetic liability to MS. In addition, a threshold exists, so that MS begins when an individual's liability exceeds the MS threshold; environmental and other causative factors may increase or decrease an individual's MS liability. It is argued here, however, that this model is misleading, as it is based on the incorrect assumption that MS is a disorder that one either has or does not have. This paper hypothesizes, instead, that patients with a diagnosis of MS share identical CNS pathology, termed MS pathology, with some individuals who have a diagnosis of possible MS and with some apparently healthy individuals, who may never have a diagnosis of MS. In order to accommodate this hypothesis, the current threshold liability model is modified as follows. (1) In addition to a normal distribution of MS liability within a population, a spectrum of MS pathology occurs in some who have a high MS liability. (2) A clinical MS threshold exists at a point on this liability distribution, where the burden and distribution of MS pathology permits a diagnosis of clinical MS. (3) Additional thresholds exist that correspond to a lower MS liability and a lesser burden of MS pathology than occur at the clinical MS threshold. This modified threshold model leads to the postulate that causes act at various time points to increase MS liability and induce MS pathology. The accumulation of MS pathology sometimes leads to a diagnosis of clinical MS. One implication of this model is that the MS pathology in clinical MS and in some with possible MS differs only in the extent but not in the type of CNS injury. Thus, it may be possible to obtain insight into the causative environmental factors that increase MS liability and induce MS pathology by focusing on patients who have clinical MS; some environmental factors that induce new lesions in patients with clinical MS may be identical to those that induce MS pathology in genetically susceptible individuals who do not have clinical MS. Identification of these causative factors has importance, as specific treatment may prevent the accumulation of MS pathology that leads to the significant CNS damage associated with clinical MS.

Extramedullary plasmacytoma of the testicle.

PubMed

Carrion, Diego M; Álvarez-Maestro, Mario; Gómez Rivas, Juan; González-Peramato, Pilar; Cisneros Ledo, Jesús

2017-12-01

We present the case of a patient diagnosed with a testicular extramedullary plasmacytoma (EMP), and perform a brief review of the literature of this pathology. A 64 year-old male patient, with history of multiple myeloma successfully treated three years before, presented with left testicular swelling. Initial work-up was compatible with a testicular tumor and radical inguinal orchiectomy was performed. Histologic examination of the testis revealed extensive intertubular infiltration by CD138 and CD56 atypical plasma cells, with diffuse staining for IgA, compatible with EMP. Invasion of the testis in multiple myeloma patients as a recurrence of the disease is an extremely rare condition, as EMPs are more common in other organ systems. Initial treatment should be the same as a primary testicular tumor with radical inguinal orchiectomy, and definitive diagnosis is established in histologic analysis.

Anti-IL-23 and Anti-IL-17 Biologic Agents for the Treatment of Immune-Mediated Inflammatory Conditions.

PubMed

Frieder, Jillian; Kivelevitch, Dario; Haugh, Isabel; Watson, Ian; Menter, Alan

2018-01-01

Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here we review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Reduced Virulence of Azoxystrobin-Resistant Zymoseptoria tritici Populations in Greenhouse Assays.

PubMed

Hagerty, Christina H; Mundt, Christopher C

2016-08-01

The development of resistance to multiple fungicide classes is currently limiting disease management options for many pathogens, while the discovery of new fungicide classes may become less frequent. In light of this, more research is needed to quantify virulence trade-offs of fungicide resistance in order to more fully understand the implications of fungicide resistance on pathogen fitness. The purpose of this study was to measure the virulence of azoxystrobin-resistant and -sensitive Zymoseptoria tritici populations collected from North and South Willamette Valley, Oregon, in 2012 and 2015. Inoculum mixtures of known fungicide-resistant phenotypes were used to simulate natural field conditions, where multiple genotypes exist and interact in close proximity. Six greenhouse inoculations were conducted over 2 years, and virulence of the isolate mixtures was evaluated in planta. We considered virulence to be "the degree of pathology caused by the organism" and visually estimated the percent area of leaf necrosis as a measure of virulence. In greenhouse conditions, a consistent association of reduced virulence with azoxystrobin-resistant Z. tritici isolate mixtures was observed. North Willamette Valley and South Willamette Valley populations did not differ in virulence.

Cellular IRES-mediated translation: the war of ITAFs in pathophysiological states.

PubMed

Komar, Anton A; Hatzoglou, Maria

2011-01-15

Translation of cellular mRNAs via initiation at Internal Ribosome Entry Sites (IRESs) has received increased attention during recent years due to its emerging significance for many physiological and pathological stress conditions in eukaryotic cells. Expression of genes bearing IRES elements in their mRNAs is controlled by multiple molecular mechanisms, with IRES-mediated translation favored under conditions when cap-dependent translation is compromised. In this review, we discuss recent advances in the field and future directions that may bring us closer to understanding the complex mechanisms that guide cellular IRES-mediated expression. We present examples in which the competitive action of IRES-transacting factors (ITAFs) plays a pivotal role in IRES-mediated translation and thereby controls cell-fate decisions leading to either pro-survival stress adaptation or cell death.

Imagined futures in living with multiple conditions: Positivity, relationality and hopelessness.

PubMed

Coyle, Lindsay-Ann; Atkinson, Sarah

2018-02-01

Hope serves as an overarching concept for a range of engagements that demonstrate the benefits of a positive outlook for coping with chronic conditions of ill-health and disability. A dominant engagement through medicine has positioned hope as a desirable attribute and its opposite, hopelessness, as pathological. In this engagement hope is individual, internally located and largely cognitive and able to be learned. Attaining hope reflects a process of coming to terms with the losses associated with long-term conditions and of imagining new meanings and purposes for the future ahead. This process is characterised by a set of linear temporal stages, from loss and denial to acceptance and reappraising the life-course, by an emphasis on the morally desirable exercise of self-care and by a desired outcome that, in the absence of cure, is hope. Through interviews, we aim to unsettle the privileged status given to a positive outlook through examining the expressions, contexts and negotiations of hopelessness of people living with multiple conditions of ill-health and/or disability. These narratives of hopelessness disclose the ways in which realistic imagined possibilities for the future are constrained by external structures of time and function that demand complex negotiations with places, bodies and other people. As a situated and relational narrative, hopelessness draws our attention to the need to rebalance the exclusive attention to individual, internal resources with a renewed attention to contexts and settings. Moreover, hopelessness can be generative for those living with multiple conditions in shaping alternatively framed priorities with respect to their temporal and interpersonal relations. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases.

PubMed

Brkic, Marjana; Balusu, Sriram; Libert, Claude; Vandenbroucke, Roosmarijn E

2015-01-01

Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

Neuronal network disintegration: common pathways linking neurodegenerative diseases.

PubMed

Ahmed, Rebekah M; Devenney, Emma M; Irish, Muireann; Ittner, Arne; Naismith, Sharon; Ittner, Lars M; Rohrer, Jonathan D; Halliday, Glenda M; Eisen, Andrew; Hodges, John R; Kiernan, Matthew C

2016-11-01

Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration. 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/.

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

PubMed

Javid, Ashkan; Zlotnikov, Nataliya; Pětrošová, Helena; Tang, Tian Tian; Zhang, Yang; Bansal, Anil K; Ebady, Rhodaba; Parikh, Maitry; Ahmed, Mijhgan; Sun, Chunxiang; Newbigging, Susan; Kim, Yae Ram; Santana Sosa, Marianna; Glogauer, Michael; Moriarty, Tara J

2016-01-01

Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

PubMed Central

Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

2013-01-01

One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

Modifications of pancreatic diffusion MRI by tissue characteristics: what are we weighting for?

PubMed

Nissan, Noam

2017-08-01

Diffusion-weighted imaging holds the potential to improve the diagnosis and biological characterization of pancreatic disease, and in particular pancreatic cancer, which exhibits decreased values of the apparent diffusion coefficient (ADC). Yet, variable and overlapping ADC values have been reported for the healthy and the pathological pancreas, including for cancer and other benign conditions. This controversy reflects the complexity of probing the water-diffusion process in the pancreas, which is dependent upon multiple biological factors within this organ's unique physiological environment. In recent years, extensive studies have investigated the correlation between tissue properties including cellularity, vascularity, fibrosis, secretion and microstructure and pancreatic diffusivity. Understanding how the various physiological and pathological features and the underlying functional processes affect the diffusion measurement may serve to optimize the method for improved diagnostic gain. Therefore, the aim of the present review article is to elucidate the relationship between pancreatic tissue characteristics and diffusion MRI measurement. Copyright © 2017 John Wiley & Sons, Ltd.

Cell-oriented modeling of angiogenesis.

PubMed

Guidolin, Diego; Rebuffat, Piera; Albertin, Giovanna

2011-01-01

Due to its significant involvement in various physiological and pathological conditions, angiogenesis (the development of new blood vessels from an existing vasculature) represents an important area of the actual biological research and a field in which mathematical modeling proved particularly useful in supporting the experimental work. In this paper, we focus on a specific modeling strategy, known as "cell-centered" approach. This type of mathematical models work at a "mesoscopic scale," assuming the cell as the natural level of abstraction for computational modeling of development. They treat cells phenomenologically, considering their essential behaviors to study how tissue structure and organization emerge from the collective dynamics of multiple cells. The main contributions of the cell-oriented approach to the study of the angiogenic process will be described. From one side, they have generated "basic science understanding" about the process of capillary assembly during development, growth, and pathology. On the other side, models were also developed supporting "applied biomedical research" for the purpose of identifying new therapeutic targets and clinically relevant approaches for either inhibiting or stimulating angiogenesis.

[The Value of High Frequency Color Doppler Ultrasonography in the Diagnosis of Solid Skin Tumorsa-a Preliminary Study].

PubMed

Zhong, Lin; Tang, Yuan-Jiao; Yang, Yu-Jia; Qiu, Li

2017-01-01

To explore the value of high frequency color doppler ultrasonography in differentiating benign and malignant skin solid tumors. Clinical and ultrasonic data of cutaneous solid tumors confirmed by pathology in our hospital were collected. The differences in clinical and sonographic features between benign and malignant tumors were statistically analyzed. A total of 512 patients, involving 527 cases of skin solid tumors, were enrolled in this study. The ultrasonic detected 99.43% of the cases, with 99.02% accuracy in locating the lesions. The benign and malignant tumors showed differences in patient age, location, multiple occurance, location and depth, surface skin condition, tumor size, echo, morphology, uniformity, calcification, blood flow status, tumor rear area and peripheral echo, and pathological requests ( P <0.05). High frequency ultrasound has excellent detection rate of skin tumors, which can locate invasion depth of skin accurately. Benign and malignant skin tumors show differences in a number of clinical and ultrasound features.

Ubiquitinated Sirtuin 1 (SIRT1) Function Is Modulated during DNA Damage-induced Cell Death and Survival*

PubMed Central

Peng, Lirong; Yuan, Zhigang; Li, Yixuan; Ling, Hongbo; Izumi, Victoria; Fang, Bin; Fukasawa, Kenji; Koomen, John; Chen, Jiandong; Seto, Edward

2015-01-01

Downstream signaling of physiological and pathological cell responses depends on post-translational modification such as ubiquitination. The mechanisms regulating downstream DNA damage response (DDR) signaling are not completely elucidated. Sirtuin 1 (SIRT1), the founding member of Class III histone deacetylases, regulates multiple steps in DDR and is closely associated with many physiological and pathological processes. However, the role of post-translational modification or ubiquitination of SIRT1 during DDR is unclear. We show that SIRT1 is dynamically and distinctly ubiquitinated in response to DNA damage. SIRT1 was ubiquitinated by the MDM2 E3 ligase in vitro and in vivo. SIRT1 ubiquitination under normal conditions had no effect on its enzymatic activity or rate of degradation; hypo-ubiquitination, however, reduced SIRT1 nuclear localization. Ubiquitination of SIRT1 affected its function in cell death and survival in response to DNA damage. Our results suggest that ubiquitination is required for SIRT1 function during DDR. PMID:25670865

MR imaging evaluation of abdominal pain during pregnancy: appendicitis and other nonobstetric causes.

PubMed

Spalluto, Lucy B; Woodfield, Courtney A; DeBenedectis, Carolynn M; Lazarus, Elizabeth

2012-01-01

Clinical diagnosis of the cause of abdominal pain in a pregnant patient is particularly difficult because of multiple confounding factors related to normal pregnancy. Magnetic resonance (MR) imaging is useful in evaluation of abdominal pain during pregnancy, as it offers the benefit of cross-sectional imaging without ionizing radiation or evidence of harmful effects to the fetus. MR imaging is often performed specifically for diagnosis of possible appendicitis, which is the most common illness necessitating emergency surgery in pregnant patients. However, it is important to look for pathologic processes outside the appendix that may be an alternative source of abdominal pain. Numerous entities other than appendicitis can cause abdominal pain during pregnancy, including processes of gastrointestinal, hepatobiliary, genitourinary, vascular, and gynecologic origin. MR imaging is useful in diagnosing the cause of abdominal pain in a pregnant patient because of its ability to safely demonstrate a wide range of pathologic conditions in the abdomen and pelvis beyond appendicitis. © RSNA, 2012.

Neuronopathic Lysosomal Storage Diseases: Clinical and Pathologic Findings

ERIC Educational Resources Information Center

Prada, Carlos E.; Grabowski, Gregory A.

2013-01-01

Background: The lysosomal--autophagocytic system diseases (LASDs) affect multiple body systems including the central nervous system (CNS). The progressive CNS pathology has its onset at different ages, leading to neurodegeneration and early death. Methods: Literature review provided insight into the current clinical neurological findings,…

Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

PubMed

Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

2015-04-21

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Cancer biology and genomics: translating discoveries, transforming pathology.

PubMed

Ladanyi, Marc; Hogendoorn, Pancras C W

2011-01-01

Advances in our understanding of cancer biology and discoveries emerging from cancer genomics are being translated into real clinical benefits for patients with cancer. The 2011 Journal of Pathology Annual Review Issue provides a snapshot of recent rapid progress on multiple fronts in the war on cancer or, more precisely, the wars on cancers. Indeed, perhaps the most notable recent shift is reflected by the sharp increase in understanding the biology of multiple specific cancers and using these new insights to inform rationally targeted therapies, with often striking successes. These recent developments, as reviewed in this issue, show how the long-term investments in basic cancer research are finally beginning to bear fruit. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Surgical pathology to describe the clinical margin of debridement of chronic wounds using a wound electronic medical record.

PubMed

Golinko, Michael S; Joffe, Renata; de Vinck, David; Chandrasekaran, Eashwar; Stojadinovic, Olivera; Barrientos, Stephan; Vukelic, Sasa; Tomic-Canic, Marjana; Brem, Harold

2009-08-01

Chronic wounds, including diabetic foot ulcers (DFU), pressure ulcers (PU), and venous ulcers (VU) result from multiple physiologic impairments. Operative debridement is a mainstay of treatment to remove nonviable tissue and to stimulate wound healing. Unlike tumor resection, however, operative wound specimens are not routinely sent for pathology. The objective of this study was to describe the pathology present in chronic wounds. Pathology reports of the skin edge and wound base from 397 initial debridements in 336 consecutive patients with chronic wounds were retrospectively reviewed. All data were entered and stored in a Wound Electronic Medical Record. Pathology data were extracted from the Wound Electronic Medical Record, coded, and quantified. Up to 15 distinct histopathologic findings across 7 tissue types were observed after review of pathology reports from chronic wounds. Specifically, the pathology of epidermis revealed hyperkeratosis: 66% in DFUs, 31% in PUs, and 29% in VUs. Dermal pathology revealed fibrosis in 49% of DFUs, 30% of PUs, and 15% of VUs. Wound bed pathology revealed necrosis in the subcutaneous tissue in 67% of DFUs, 55% of PUs, and 19% of VUs. Fibrosis was reported in between 19% and 52% of all wound types. Acute osteomyelitis was present in 39% of DFUs, 33% of PUs, and 29% of VUs. This observational study of the histopathology of initial surgical debridement of chronic wounds revealed a wide range of findings across multiple tissue levels. Although certain findings such as osteomyelitis and gangrene have been shown to directly relate to impaired wound healing and amputation, other findings require additional investigation. To rigorously define a margin of debridement, a prospective study relating histopathology and clinical outcomes such as healing rates and amputation is needed.

Spiking Neural Network With Distributed Plasticity Reproduces Cerebellar Learning in Eye Blink Conditioning Paradigms.

PubMed

Antonietti, Alberto; Casellato, Claudia; Garrido, Jesús A; Luque, Niceto R; Naveros, Francisco; Ros, Eduardo; D' Angelo, Egidio; Pedrocchi, Alessandra

2016-01-01

In this study, we defined a realistic cerebellar model through the use of artificial spiking neural networks, testing it in computational simulations that reproduce associative motor tasks in multiple sessions of acquisition and extinction. By evolutionary algorithms, we tuned the cerebellar microcircuit to find out the near-optimal plasticity mechanism parameters that better reproduced human-like behavior in eye blink classical conditioning, one of the most extensively studied paradigms related to the cerebellum. We used two models: one with only the cortical plasticity and another including two additional plasticity sites at nuclear level. First, both spiking cerebellar models were able to well reproduce the real human behaviors, in terms of both "timing" and "amplitude", expressing rapid acquisition, stable late acquisition, rapid extinction, and faster reacquisition of an associative motor task. Even though the model with only the cortical plasticity site showed good learning capabilities, the model with distributed plasticity produced faster and more stable acquisition of conditioned responses in the reacquisition phase. This behavior is explained by the effect of the nuclear plasticities, which have slow dynamics and can express memory consolidation and saving. We showed how the spiking dynamics of multiple interactive neural mechanisms implicitly drive multiple essential components of complex learning processes.  This study presents a very advanced computational model, developed together by biomedical engineers, computer scientists, and neuroscientists. Since its realistic features, the proposed model can provide confirmations and suggestions about neurophysiological and pathological hypotheses and can be used in challenging clinical applications.

A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model

PubMed Central

’t Hart, Bert A.; Dunham, Jordon; Faber, Bart W.; Laman, Jon D.; van Horssen, Jack; Bauer, Jan; Kap, Yolanda S.

2017-01-01

The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund’s adjuvant (IFA)]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes. PMID:28744286

Intra-articular findings in symptomatic minor instability of the lateral elbow (SMILE).

PubMed

Arrigoni, Paolo; Cucchi, Davide; D'Ambrosi, Riccardo; Butt, Usman; Safran, Marc R; Denard, Patrick; Randelli, Pietro

2017-07-01

Lateral epicondylitis is generally considered an extra-articular condition. The role of minor instability in the aetiology of lateral elbow pain has rarely been considered. The aim of this study was to evaluate the correlation of lateral ligamentous laxity with aspects of intra-articular lateral elbow pathology and investigate the role of minor instability in lateral elbow pain. Thirty-five consecutive patients aged between 20 and 60 years with recalcitrant lateral epicondylitis who had failed conservative therapy and had no previous trauma or overt instability, were included. The presence of three signs of lateral ligamentous patholaxity and five intra-articular findings were documented during arthroscopy. The relative incidence of each of these was calculated, and the correlation between patholaxity and intra-articular pathology was evaluated. At least one sign of lateral ligamentous laxity was observed in 48.6% of the studied cohort, and 85.7% demonstrated at least one intra-articular abnormal finding. Radial head ballottement was the most common sign of patholaxity (42.9%). Synovitis was the most common intra-articular aspect of pathology (77.1%), followed by lateral capitellar chondropathy (40.0%). A significant correlation was found between the presence of lateral ligamentous patholaxity signs and capitellar chondropathy (p = 0.0409), as well as anteromedial synovitis (p = 0.0408). Almost one half of patients suffering from recalcitrant lateral epicondylitis display signs of lateral ligamentous patholaxity, and over 85% demonstrate at least one intra-articular abnormality. The most frequent intra-articular findings are synovitis and lateral capitellar chondropathy, which correlate significantly with the presence of lateral ligamentous patholaxity. The fact that several patients demonstrated multiple intra-articular findings in relation to laxity provides support to a sequence of pathologic changes that may result from a symptomatic minor instability of the lateral elbow (SMILE) condition. III.

Deep gluteal space problems: piriformis syndrome, ischiofemoral impingement and sciatic nerve release

PubMed Central

Carro, Luis Perez; Hernando, Moises Fernandez; Cerezal, Luis; Navarro, Ivan Saenz; Fernandez, Ana Alfonso; Castillo, Alexander Ortiz

2016-01-01

Summary Background Deep gluteal syndrome (DGS) is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip or posterior thigh and/or radicular pain due to a non-discogenic sciatic nerve entrapment in the subgluteal space. Multiple pathologies have been incorporated in this all-included “piriformis syndrome”, a term that has nothing to do with the presence of fibrous bands, obturator internus/gemellus syndrome, quadratus femoris/ischiofemoral pathology, hamstring conditions, gluteal disorders and orthopedic causes. Methods This article describes the subgluteal space anatomy, reviews known and new etiologies of DGS, and assesses the role of the radiologist and orthopaedic surgeons in the diagnosis, treatment and postoperative evaluation of sciatic nerve entrapments. Conclusion DGS is an under-recognized and multifactorial pathology. The development of periarticular hip endoscopy has led to an understanding of the pathophysiological mechanisms underlying piriformis syndrome, which has supported its further classification. The whole sciatic nerve trajectory in the deep gluteal space can be addressed by an endoscopic surgical technique. Endoscopic decompression of the sciatic nerve appears useful in improving function and diminishing hip pain in sciatic nerve entrapments, but requires significant experience and familiarity with the gross and endoscopic anatomy. Level of evidence IV. PMID:28066745

Augmenting College Students' Study of Speech-Language Pathology Using Computer-Based Mini Quiz Games.

PubMed

Vinney, Lisa A; Howles, Les; Leverson, Glen; Connor, Nadine P

2016-08-01

This study examined whether undergraduate college students' immediate recall and longer-term retention of introductory voice disorder concepts improved by using mini quiz games (MQGs; interactive knowledge tests in game format) compared with (a) traditional study alone, (b) MQGs and traditional study together, or (c) a no-study control condition. Ninety-three college students participated in proctored sessions in which they were given a pretest, viewed an online lecture on introductory voice disorder concepts, and then engaged in either no intervention or interventions including traditional study, MQG play, or both MQG play and traditional study, followed by an immediate recall posttest and longer-term retention follow-up test. Analyses suggested that the effects of all interventions (traditional study, MQG play, and the combination of the 2) were equivalent and resulted in significantly greater improvements from pretest to immediate recall posttest performance than the control condition. In contrast, MQGs and MQGs with traditional study, but not traditional study alone, showed better results for long-term retention than no study. Results provide preliminary support for the idea that there may be multiple effective learning modes, beyond traditional study, that enhance recall and retention of knowledge foundational to speech-language pathology clinical training and practice.

Loss of Sigma-1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense

PubMed Central

Weng, Tzu-Yu; Hung, Denise T.; Su, Tsung-Ping

2017-01-01

Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins. Astrogliosis was also observed in the neuron-glia culture. Upon proteasome or autophagy inhibitor treatments, the pronounced ubiquitinated proteins were further increased in Sig-1R KO neurons, indicating that the Sig-1R regulates both protein degradation and quality control systems. We found that Nrf2 (nuclear factor erythroid 2-related factor 2), which functions to overcome the stress condition, was enhanced in the Sig-1R KO systems especially when cells were under stressful conditions. Mutation or deficiency of Sig-1Rs has been observed in neurodegenerative models. Our study identifies the critical roles of Sig-1R in CNS homeostasis and supports the idea that functional complementation pathways are triggered in the Sig-1R KO pathology. PMID:28883901

Loss of Sigma-1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense.

PubMed

Weng, Tzu-Yu; Hung, Denise T; Su, Tsung-Ping; Tsai, Shang-Yi A

2017-01-01

Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins. Astrogliosis was also observed in the neuron-glia culture. Upon proteasome or autophagy inhibitor treatments, the pronounced ubiquitinated proteins were further increased in Sig-1R KO neurons, indicating that the Sig-1R regulates both protein degradation and quality control systems. We found that Nrf2 (nuclear factor erythroid 2-related factor 2), which functions to overcome the stress condition, was enhanced in the Sig-1R KO systems especially when cells were under stressful conditions. Mutation or deficiency of Sig-1Rs has been observed in neurodegenerative models. Our study identifies the critical roles of Sig-1R in CNS homeostasis and supports the idea that functional complementation pathways are triggered in the Sig-1R KO pathology.

Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated.

PubMed

Robinson, John L; Lee, Edward B; Xie, Sharon X; Rennert, Lior; Suh, EunRan; Bredenberg, Colin; Caswell, Carrie; Van Deerlin, Vivianna M; Yan, Ning; Yousef, Ahmed; Hurtig, Howard I; Siderowf, Andrew; Grossman, Murray; McMillan, Corey T; Miller, Bruce; Duda, John E; Irwin, David J; Wolk, David; Elman, Lauren; McCluskey, Leo; Chen-Plotkin, Alice; Weintraub, Daniel; Arnold, Steven E; Brettschneider, Johannes; Lee, Virginia M-Y; Trojanowski, John Q

2018-06-05

Lewy bodies commonly occur in Alzheimer's disease, and Alzheimer's disease pathology is frequent in Lewy body diseases, but the burden of co-pathologies across neurodegenerative diseases is unknown. We assessed the extent of tau, amyloid-β, α-synuclein and TDP-43 proteinopathies in 766 autopsied individuals representing a broad spectrum of clinical neurodegenerative disease. We interrogated pathological Alzheimer's disease (n = 247); other tauopathies (n = 95) including Pick's disease, corticobasal disease and progressive supranuclear palsy; the synucleinopathies (n = 164) including multiple system atrophy and Lewy body disease; the TDP-43 proteinopathies (n = 188) including frontotemporal lobar degeneration with TDP-43 inclusions and amyotrophic lateral sclerosis; and a minimal pathology group (n = 72). Each group was divided into subgroups without or with co-pathologies. Age and sex matched logistic regression models compared co-pathology prevalence between groups. Co-pathology prevalence was similar between the minimal pathology group and most neurodegenerative diseases for each proteinopathy: tau was nearly universal (92-100%), amyloid-β common (20-57%); α-synuclein less common (4-16%); and TDP-43 the rarest (0-16%). In several neurodegenerative diseases, co-pathology increased: in Alzheimer's disease, α-synuclein (41-55%) and TDP-43 (33-40%) increased; in progressive supranuclear palsy, α-synuclein increased (22%); in corticobasal disease, TDP-43 increased (24%); and in neocortical Lewy body disease, amyloid-β (80%) and TDP-43 (22%) increased. Total co-pathology prevalence varied across groups (27-68%), and was increased in high Alzheimer's disease, progressive supranuclear palsy, and neocortical Lewy body disease (70-81%). Increased age at death was observed in the minimal pathology group, amyotrophic lateral sclerosis, and multiple system atrophy cases with co-pathologies. In amyotrophic lateral sclerosis and neocortical Lewy body disease, co-pathologies associated with APOE ɛ4. Lewy body disease cases with Alzheimer's disease co-pathology had substantially lower Mini-Mental State Examination scores than pure Lewy body disease. Our data imply that increased age and APOE ɛ4 status are risk factors for co-pathologies independent of neurodegenerative disease; that neurodegenerative disease severity influences co-pathology as evidenced by the prevalence of co-pathology in high Alzheimer's disease and neocortical Lewy body disease, but not intermediate Alzheimer's disease or limbic Lewy body disease; and that tau and α-synuclein strains may also modify co-pathologies since tauopathies and synucleinopathies had differing co-pathologies and burdens. These findings have implications for clinical trials that focus on monotherapies targeting tau, amyloid-β, α-synuclein and TDP-43.

Practical Applications of Digital Pathology.

PubMed

Saeed-Vafa, Daryoush; Magliocco, Anthony M

2015-04-01

Virtual microscopy and advances in machine learning have paved the way for the ever-expanding field of digital pathology. Multiple image-based computing environments capable of performing automated quantitative and morphological analyses are the foundation on which digital pathology is built. The applications for digital pathology in the clinical setting are numerous and are explored along with the digital software environments themselves, as well as the different analytical modalities specific to digital pathology. Prospective studies, case-control analyses, meta-analyses, and detailed descriptions of software environments were explored that pertained to digital pathology and its use in the clinical setting. Many different software environments have advanced platforms capable of improving digital pathology and potentially influencing clinical decisions. The potential of digital pathology is vast, particularly with the introduction of numerous software environments available for use. With all the digital pathology tools available as well as those in development, the field will continue to advance, particularly in the era of personalized medicine, providing health care professionals with more precise prognostic information as well as helping them guide treatment decisions.

Myofibroblastoma of the male breast: a rare entity with radiologic-pathologic correlation

PubMed Central

Comer, John D.; Cui, Xiaoyan; Eisen, Carolyn Sharyn; Abbey, Genevieve; Arleo, Elizabeth Kagan

2016-01-01

A 73-year old man with a history of multiple genitourinary malignancies was found to have a left retroareolar soft tissue mass on CT assessment of disease, and dedicated breast imaging was recommended. Diagnostic mammography and ultrasonography confirmed a solid mass, for which biopsy was recommended. Pathologic analysis demonstrated a spindle cell neoplasm with an immunoreactivity pattern consistent with myofibroblastoma. While this entity is benign, nonspecific imaging features necessitate tissue sampling for pathologic diagnosis, and, given pathologic rarity, open communication between the radiologist and pathologist is important to establish the correct diagnosis and to recommend appropriate management. PMID:27936420

Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases).

PubMed

El-Azami-El-Idrissi, Mohammed; Lakhdar-Idrissi, Mounia; Chaouki, Sanae; Atmani, Samir; Bouharrou, Abdelhak; Hida, Moustapha

2016-01-01

Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified.

The Spine in Patients With Osteogenesis Imperfecta.

PubMed

Wallace, Maegen J; Kruse, Richard W; Shah, Suken A

2017-02-01

Osteogenesis imperfecta is a genetic disorder of type I collagen. Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of diphosphonates has been found to decrease the rate of progression of scoliosis in patients with osteogenesis imperfecta. A lateral cervical radiograph is recommended in patients with this condition before age 6 years for surveillance of craniocervical junction abnormalities, such as basilar impression. Intraoperative and anesthetic considerations in patients with osteogenesis imperfecta include challenges related to fracture risk, airway management, pulmonary function, and blood loss.

Multiproteinopathy, neurodegeneration and old age: a case study.

PubMed

Rojas, Julio C; Stephens, Melanie L; Rabinovici, Gil D; Kramer, Joel H; Miller, Bruce L; Seeley, William W

2018-02-01

A complex spectrum of mixed brain pathologies is common in older people. This clinical pathologic conference case study illustrates the challenges of formulating clinicopathologic correlations in late-onset neurodegenerative diseases featuring cognitive-behavioral syndromes with underlying multiple proteinopathy. Studies on the co-existence and interactions of Alzheimer's disease (AD) with neurodegenerative non-AD pathologies in the aging brain are needed to understand the pathogenesis of neurodegeneration and to support the development of diagnostic biomarkers and therapies.

Multiproteinopathy, neurodegeneration and old age: a case study

PubMed Central

Rojas, Julio C.; Stephens, Melanie L.; Rabinovici, Gil D.; Kramer, Joel H.; Miller, Bruce L.; Seeley, William W.

2018-01-01

A complex spectrum of mixed brain pathologies is common in older people. This clinical pathologic conference case study illustrates the challenges of formulating clinicopathologic correlations in late-onset neurodegenerative diseases featuring cognitive-behavioral syndromes with underlying multiple proteinopathy. Studies on the co-existence and interactions of Alzheimer’s disease (AD) with neurodegenerative non-AD pathologies in the aging brain are needed to understand the pathogenesis of neurodegeneration and to support the development of diagnostic biomarkers and therapies. PMID:29307276

[Traumatic tricuspid insufficiency].

PubMed

Vayre, F; Richard, P; Ollivier, J P

1996-04-01

Traumatic tricuspid insufficiency is a rare condition. The diagnosis is difficult because of the slow progression of this pathology and the presence of more clinically acute lesions. Non-penetrating chest trauma is responsible for 90% of cases. Echocardiography is the investigation of choice for assessing the mechanism of the tricuspid regurgitation and for diagnosing associated lesions. It should be performed systematically in patients with multiple trauma. The surgical indications are difficult to determine and depend on the patients' symptoms and the type of anatomical lesions. It should be undertaken before right ventricular myocardial dysfunction. Several techniques may be used from valvuloplasty to valve replacement mainly with bioprostheses in symptomatic patients.

Update in TSH Receptor Agonists and Antagonists

PubMed Central

Neumann, Susanne

2012-01-01

The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, “drug-like” TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands. PMID:23019348

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

PubMed

Tobin, W O; Popescu, B F; Lowe, V; Pirko, I; Parisi, J E; Kantarci, K; Fields, J A; Bruns, M B; Boeve, B F; Lucchinetti, C F

2016-04-01

We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry. © The Author(s), 2015.

42 CFR 418.72 - Condition of participation: Physical therapy, occupational therapy, and speech-language pathology.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., occupational therapy, and speech-language pathology. 418.72 Section 418.72 Public Health CENTERS FOR MEDICARE...: Physical therapy, occupational therapy, and speech-language pathology. Physical therapy services, occupational therapy services, and speech-language pathology services must be available, and when provided...

42 CFR 418.72 - Condition of participation: Physical therapy, occupational therapy, and speech-language pathology.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., occupational therapy, and speech-language pathology. 418.72 Section 418.72 Public Health CENTERS FOR MEDICARE...: Physical therapy, occupational therapy, and speech-language pathology. Physical therapy services, occupational therapy services, and speech-language pathology services must be available, and when provided...

42 CFR 418.72 - Condition of participation: Physical therapy, occupational therapy, and speech-language pathology.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., occupational therapy, and speech-language pathology. 418.72 Section 418.72 Public Health CENTERS FOR MEDICARE...: Physical therapy, occupational therapy, and speech-language pathology. Physical therapy services, occupational therapy services, and speech-language pathology services must be available, and when provided...

42 CFR 418.72 - Condition of participation: Physical therapy, occupational therapy, and speech-language pathology.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., occupational therapy, and speech-language pathology. 418.72 Section 418.72 Public Health CENTERS FOR MEDICARE... therapy, occupational therapy, and speech-language pathology. Physical therapy services, occupational therapy services, and speech-language pathology services must be available, and when provided, offered in...

42 CFR 418.72 - Condition of participation: Physical therapy, occupational therapy, and speech-language pathology.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., occupational therapy, and speech-language pathology. 418.72 Section 418.72 Public Health CENTERS FOR MEDICARE... therapy, occupational therapy, and speech-language pathology. Physical therapy services, occupational therapy services, and speech-language pathology services must be available, and when provided, offered in...

Magnetic resonance techniques for investigation of multiple sclerosis

NASA Astrophysics Data System (ADS)

MacKay, Alex; Laule, Cornelia; Li, David K. B.; Meyers, Sandra M.; Russell-Schulz, Bretta; Vavasour, Irene M.

2014-11-01

Multiple sclerosis (MS) is a common neurological disease which can cause loss of vision and balance, muscle weakness, impaired speech, fatigue, cognitive dysfunction and even paralysis. The key pathological processes in MS are inflammation, edema, myelin loss, axonal loss and gliosis. Unfortunately, the cause of MS is still not understood and there is currently no cure. Magnetic resonance imaging (MRI) is an important clinical and research tool for MS. 'Conventional' MRI images of MS brain reveal bright lesions, or plaques, which demark regions of severe tissue damage. Conventional MRI has been extremely valuable for the diagnosis and management of people who have MS and also for the assessment of therapies designed to reduce inflammation and promote repair. While conventional MRI is clearly valuable, it lack pathological specificity and, in some cases, sensitivity to non-lesional pathology. Advanced MR techniques have been developed to provide information that is more sensitive and specific than what is available with clinical scanning. Diffusion tensor imaging and magnetization transfer provide a general but non-specific measure of the pathological state of brain tissue. MR spectroscopy provides concentrations of brain metabolites which can be related to specific pathologies. Myelin water imaging was designed to assess brain myelination and has proved useful for measuring myelin loss in MS. To combat MS, it is crucial that the pharmaceutical industry finds therapies which can reverse the neurodegenerative processes which occur in the disease. The challenge for magnetic resonance researchers is to design imaging techniques which can provide detailed pathological information relating to the mechanisms of MS therapies. This paper briefly describes the pathologies of MS and demonstrates how MS-associated pathologies can be followed using both conventional and advanced MR imaging protocols.

Surgical Management of Carney Complex-Associated Pituitary Pathology.

PubMed

Lonser, Russell R; Mehta, Gautam U; Kindzelski, Bogdan A; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O; Dickerman, Robert; Oldfield, Edward H

2017-05-01

Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. Copyright © 2017 by the Congress of Neurological Surgeons

Surgical Management of Carney Complex–Associated Pituitary Pathology

PubMed Central

Mehta, Gautam U.; Kindzelski, Bogdan A.; Ray-Chaudhury, Abhik; Vortmeyer, Alexander O.; Dickerman, Robert; Oldfield, Edward H.

2017-01-01

Abstract BACKGROUND: Carney complex (CNC) is a familial neoplasia syndrome that is associated with pituitary-associated hypersecretion of growth hormone (GH) (acromegaly). The underlying cause of pituitary GH hypersecretion and its management have been incompletely defined. OBJECTIVE: To provide biological insight into CNC-associated pituitary pathology and improve management, we analyzed findings in CNC patients who underwent transsphenoidal surgery. METHODS: Consecutive CNC patients at the National Institutes of Health with acromegaly and imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal resection of tumor(s) were included. Prospectively acquired magnetic resonance imaging and biochemical, surgical, and histological data were analyzed. RESULTS: Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years (range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas patients with single discrete pituitary adenomas underwent selective adenomectomy, patients with multiple adenomas underwent selective adenomectomy of multiple tumors, as well as partial or total hypophysectomy. All adenomas were either GH and prolactin positive or exclusively prolactin positive. Pituitary tissue surrounding the adenomas in patients with multiple adenomas revealed hyperplastic GH- and prolactin-positive tissue. CONCLUSION: CNC-associated acromegaly results from variable pituitary pathology, including a single GH-secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of the pituitary gland surrounding multiple adenomas. Although selective adenomectomy is the preferred treatment for cases of GH-secreting adenomas, multiple adenomas with associated pituitary gland GH hypersecretion may require partial or complete hypophysectomy to achieve biochemical remission. PMID:27509071

Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits

PubMed Central

Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

2015-01-01

Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis. PMID:25847999

Is synaptic loss a unique hallmark of Alzheimer's disease?

PubMed Central

Scheff, Stephen W.; Neltner, Janna H.; Nelson, Peter T.

2014-01-01

Synapses may represent a key nidus for dementia including Alzheimer's disease (AD) pathogenesis. Here we review published studies and present new ideas related to the question of the specificity of synapse loss in AD. Currently, AD is defined by the regional presence of neuritic plaques and neurofibrillary tangles in the brain. The severity of involvement by those pathological hallmarks tends to correlate both with antemortem cognitive status, and also with synapse loss in multiple brain areas. Recent studies from large autopsy series have led to a new standard of excellence with regard to clinical–pathological correlation and to improved comprehension of the numerous brain diseases of the elderly. These studies have provided evidence that it is the rule rather than the exception for brains of aged individuals to demonstrate pathologies (often multiple) other than AD plaques and tangles. For many of these comorbid pathologies, the extent of synapse loss is imperfectly understood but could be substantial. These findings indicate that synapse loss is probably not a hallmark specific to AD but rather a change common to many diseases associated with dementia. PMID:24412275

Multiple schwannomatosis caused by the recently described INI1 gene--molecular pathology, and implications for prognosis.

PubMed

Brennan, Paul M; Barlow, Antonio; Geraghty, Alistair; Summers, David; Fitzpatrick, Michael M

2011-06-01

The most common genetic predisposition to multiple schwannoma growth is mutation of the neurofibromatosis type 2 gene. We describe a patient with multiple schwannomas and mutation in the recently described INI1 gene, which also predisposes to the disease. We explore the implications for prognosis and outcome.

42 CFR 493.853 - Condition: Pathology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Performing Tests of Moderate Complexity (including the Subcategory), High Complexity, Or Any Combination of...

42 CFR 493.853 - Condition: Pathology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Performing Tests of Moderate Complexity (including the Subcategory), High Complexity, Or Any Combination of...

Time-frequency analysis of pediatric murmurs

NASA Astrophysics Data System (ADS)

Lombardo, Joseph S.; Blodgett, Lisa A.; Rosen, Ron S.; Najmi, Amir-Homayoon; Thompson, W. Reid

1998-05-01

Technology has provided many new tools to assist in the diagnosis of pathologic conditions of the heart. Echocardiography, Ultrafast CT, and MRI are just a few. While these tools are a valuable resource, they are typically too expensive, large and complex in operation for use in rural, homecare, and physician's office settings. Recent advances in computer performance, miniaturization, and acoustic signal processing, have yielded new technologies that when applied to heart sounds can provide low cost screening for pathologic conditions. The short duration and transient nature of these signals requires processing techniques that provide high resolution in both time and frequency. Short-time Fourier transforms, Wigner distributions, and wavelet transforms have been applied to signals form hearts with various pathologic conditions. While no single technique provides the ideal solution, the combination of tools provides a good representation of the acoustic features of the pathologies selected.

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?

PubMed

Washington, Patricia M; Villapol, Sonia; Burns, Mark P

2016-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should it be classified together as traumatic encephalopathy?

PubMed Central

Washington, Patricia M.; Villapol, Sonia; Burns, Mark P.

2015-01-01

Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer’s disease (AD), while mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position—examining epidemiological and case-control human studies, neuropathological evidence, and preclinical studies. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson’s disease. Further, human post-mortem studies on either single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a ‘polypathology’. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI are viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI. PMID:26091850

Comorbidity, family history and personality traits in pathological gamblers compared with healthy controls.

PubMed

Mann, K; Lemenager, T; Zois, E; Hoffmann, S; Nakovics, H; Beutel, M; Vogelgesang, M; Wölfling, K; Kiefer, F; Fauth-Bühler, M

2017-05-01

While DSM-5 classified pathological gambling as an addictive disorder, there is debate as to whether ICD-11 should follow suit. The debate hinges on scientific evidence such as neurobiological findings, family history of psychiatric disorders, psychiatric comorbidity, and personality variables. In the "Baden-Württemberg Study of Pathological Gambling", we compared a group of 515 male pathological gamblers receiving treatment with 269 matched healthy controls. We studied differences in sociodemographic characteristics, gambling-related variables, psychiatric comorbidity (lifetime), family history of psychiatric conditions, as well as personality traits such as impulsivity (Barratt Impulsiveness Scale), sensation seeking (Zuckerman's Sensation Seeking Scale) and the NEO-FFI big five. Personality traits were validated in an age- and ethnicity-matched subsample of "pure" gamblers without any psychiatric comorbidity (including nicotine dependence). Data were analyzed using two-sample t-tests, Chi 2 analyses, Fisher's exact test and Pearson correlation analysis, as appropriate. Bonferroni correction was applied to correct for multiple comparisons. Only 1% of the gamblers had been diagnosed with an impulse control disorder other than gambling (ICD-10). Notably, 88% of the gamblers in our sample had a comorbid diagnosis of substance dependence. The highest axis I comorbidity rate was for nicotine dependence (80%), followed by alcohol dependence (28%). Early age of first gambling experience was correlated with gambling severity. Compared to first-degree relatives of controls, first-degree relatives of pathological gamblers were more likely to suffer from alcohol dependence (27.0% vs. 7.4%), pathological gambling (8.3% vs. 0.7%) and suicide attempts (2.7% vs. 0.4%). Significant group differences were observed for the NEO-FFI factors neuroticism, agreeableness and conscientiousness. Gamblers were also more impulsive than controls, but did not differ from controls in terms of sensation seeking. Our findings support classifying pathological gambling as a behavioural addiction in the ICD-11. This decision will have a significant impact on the approaches available for prevention (e.g. age limits) and treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Distinctive Epstein-Barr virus variants associated with benign and malignant pediatric pathologies: LMP1 sequence characterization and linkage with other viral gene polymorphisms.

PubMed

Lorenzetti, Mario Alejandro; Gantuz, Magdalena; Altcheh, Jaime; De Matteo, Elena; Chabay, Paola Andrea; Preciado, María Victoria

2012-03-01

The ubiquitous Epstein-Barr virus (EBV) is related to the development of lymphoma and is also the etiological agent for infectious mononucleosis (IM). Sequence variations in the gene encoding LMP1 have been deeply studied in different pathologies and geographic regions. Controversial results propose the existence of tumor-related variants, while others argued in favor of a geographical distribution of these variants. Reports assessing EBV variants in IM were performed in adult patients who displayed multiple variant infections. In the present study, LMP1 variants in 15 pediatric patients with IM and 20 pediatric patients with EBV-associated lymphomas from Argentina were analyzed as representatives of benign and malignant infections in children, respectively. A 3-month follow-up study of LMP1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. Moreover, an integrated linkage analysis was performed with variants of EBNA1 and the promoter region of BZLF1. Similar sequence polymorphisms were detected in both pathological conditions, IM and lymphoma, but these differ from those previously described in healthy donors from Argentina and Brazil. The results suggest that certain LMP1 polymorphisms, namely, the 30-bp deletion and high copy number of the 33-bp repeats, are associated with EBV-related pathologies, either benign or malignant, instead of just being tumor related. Additionally, this is the first study to describe the Alaskan variant in EBV-related lymphomas that previously was restricted to nasopharyngeal carcinomas from North America.

Distinctive Epstein-Barr Virus Variants Associated with Benign and Malignant Pediatric Pathologies: LMP1 Sequence Characterization and Linkage with Other Viral Gene Polymorphisms

PubMed Central

Gantuz, Magdalena; Altcheh, Jaime; De Matteo, Elena; Chabay, Paola Andrea; Preciado, María Victoria

2012-01-01

The ubiquitous Epstein-Barr virus (EBV) is related to the development of lymphoma and is also the etiological agent for infectious mononucleosis (IM). Sequence variations in the gene encoding LMP1 have been deeply studied in different pathologies and geographic regions. Controversial results propose the existence of tumor-related variants, while others argued in favor of a geographical distribution of these variants. Reports assessing EBV variants in IM were performed in adult patients who displayed multiple variant infections. In the present study, LMP1 variants in 15 pediatric patients with IM and 20 pediatric patients with EBV-associated lymphomas from Argentina were analyzed as representatives of benign and malignant infections in children, respectively. A 3-month follow-up study of LMP1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. Moreover, an integrated linkage analysis was performed with variants of EBNA1 and the promoter region of BZLF1. Similar sequence polymorphisms were detected in both pathological conditions, IM and lymphoma, but these differ from those previously described in healthy donors from Argentina and Brazil. The results suggest that certain LMP1 polymorphisms, namely, the 30-bp deletion and high copy number of the 33-bp repeats, are associated with EBV-related pathologies, either benign or malignant, instead of just being tumor related. Additionally, this is the first study to describe the Alaskan variant in EBV-related lymphomas that previously was restricted to nasopharyngeal carcinomas from North America. PMID:22205789

Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease.

PubMed

Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi

2016-01-01

3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.

Analysis of tau post-translational modifications in rTg4510 mice, a model of tau pathology.

PubMed

Song, Lixin; Lu, Sherry X; Ouyang, Xuesong; Melchor, Jerry; Lee, Julie; Terracina, Giuseppe; Wang, Xiaohai; Hyde, Lynn; Hess, J Fred; Parker, Eric M; Zhang, Lili

2015-03-26

Microtubule associated protein tau is the major component of the neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and several other neurodegenerative diseases. Tau mutations are associated with frontotemperal dementia with parkinsonism on chromosome 17 (FTDP-17). rTg4510 mice overexpress human tau carrying the P301L FTDP-17 mutation and develop robust NFT-like pathology at 4-5 months of age. The current study is aimed at characterizing the rTg4510 mice to better understand the genesis of tau pathology and to better enable the use of this model in drug discovery efforts targeting tau pathology. Using a panel of immunoassays, we analyzed the age-dependent formation of pathological tau in rTg4510 mice and our data revealed a steady age-dependent accumulation of pathological tau in the insoluble fraction of brain homogenates. The pathological tau was associated with multiple post-translational modifications including aggregation, phosphorylation at a wide variety of sites, acetylation, ubiquitination and nitration. The change of most tau species reached statistical significance at the age of 16 weeks. There was a strong correlation between the different post-translationally modified tau species in this heterogeneous pool of pathological tau. Total tau in the cerebrospinal fluid (CSF) displayed a multiphasic temporal profile distinct from the steady accumulation of pathological tau in the brain. Female rTg4510 mice displayed significantly more aggressive accumulation of pathological tau in the brain and elevation of total tau in CSF than their male littermates. The immunoassays described here were used to generate the most comprehensive description of the changes in various tau species across the lifespan of the rTg4510 mouse model. The data indicate that development of tauopathy in rTg4510 mice involves the accumulation of a pool of pathological tau that carries multiple post-translational modifications, a process that can be detected well before the histological detection of NFTs. Therapeutic treatment targeting tau should therefore aim to reduce all tau species associated with the pathological tau pool rather than reduce specific post-translational modifications. There is still much to learn about CSF tau in physiological and pathological processes in order to use it as a translational biomarker in drug discovery.

Altering Response Chains in Pathological Gamblers Using a Response-Cost Procedure

ERIC Educational Resources Information Center

Johnson, Taylor E.; Dixon, Mark R.

2009-01-01

Two pathological gamblers could choose between emitting or having the dealer emit the response options when playing each of three casino games. A response-cost procedure was introduced in a multiple baseline design across games in which the participant had to pay to perform the responses himself, which was somewhat effective at reducing many of…

Wildfire risk as a socioecological pathology

Treesearch

A Paige Fischer; Thomas A Spies; Toddi A Steelman; Cassandra Moseley; Bart R Johnson; John D Bailey; Alan A Ager; Patrick Bourgeron; Susan Charnley; Brandon M Collins; Jeff Kline; Jessica E Leahy; Jeremy S Littell; James DA Millington; Max Nielsen-Pincus; Christine S Olsen; Travis B Paveglio; Christopher I Roos; Michelle M Steen-Adams; Forrest R Stevens; Jelena Vukomanovic; Eric White; David MJS Bowman

2016-01-01

Wildfire risk in temperate forests has become a nearly intractable problem that can be characterized as a socioecological “pathology”: that is, a set of complex and problematic interactions among social and ecological systems across multiple spatial and temporal scales. Assessments of wildfire risk could benefit from recognizing and accounting for these interactions in...

When your arm becomes mine: pathological embodiment of alien limbs using tools modulates own body representation.

PubMed

Garbarini, Francesca; Fossataro, Carlotta; Berti, Anna; Gindri, Patrizia; Romano, Daniele; Pia, Lorenzo; della Gatta, Francesco; Maravita, Angelo; Neppi-Modona, Marco

2015-04-01

Previous evidence has shown that active tool-use can reshape one's own body schema, extend peripersonal space and modulate the representation of related body parts. Here we investigate the effect of tool-use training on length representation of the contralesional forearm in brain-damaged hemiplegic patients who manifested a pathological embodiment of other people body parts. Four patients and 20 aged-matched healthy-controls were asked to estimate the mid-point of their contralesional forearm before and after 15 min of tool-use training (i.e. retrieving targets with a garbage plier). In the case of patients, training was always performed by the examiner's (alien) arm acting in two different positions, aligned (where the pathological embodiment occurs; E+ condition) or misaligned (where the pathological embodiment does not occur; E- condition) relative to the patients' shoulder. Healthy controls performed tool-use training either with their own arm (action condition) or observing the examiner's arm performing the task (observation condition), handling (observation with-tool condition) or not (observation without-tool condition) a similar tool. Crucially, in the E+ condition, when patients were convinced to perform the tool-use training with their own paralyzed arm, a significant overestimation effect was found (as in the Action condition with normal subjects): patients mislocated their forearm midpoint more proximally to the hand in the post- than in the pre-training phase. Conversely, in the E- condition, they did not show any overestimation effect, similarly to healthy subjects in the observation condition (neither in the with-tool nor in the without-tool condition significant overestimation effects were found). These findings show the existence of a tight link between spatial, motor and bodily representations and provide strong evidence that a pathological sense of body ownership can extend to intentional motor processes and modulate the sensory map of action-related body parts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis

PubMed Central

Lee, Inchul

2014-01-01

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach. PMID:24914362

Critical pathogenic steps to high risk Helicobacter pylori gastritis and gastric carcinogenesis.

PubMed

Lee, Inchul

2014-06-07

Helicobacter pylori (H. pylori) gastritis may progress to high risk gastropathy and cancer. However, the pathological progression has not been characterized in detail. H. pylori induce persistent inflammatory infiltration. Neutrophils are unique in that they directly infiltrate into foveolar epithelium aiming the proliferative zone specifically. Neutrophilic proliferative zone foveolitis is a critical pathogenic step in H. pylori gastritis inducing intensive epithelial damage. Epithelial cells carrying accumulated genomic damage and mutations show the Malgun (clear) cell change, characterized by large clear nucleus and prominent nucleolus. Malgun cells further undergo atypical changes, showing nuclear folding, coarse chromatin, and multiple nucleoli. The atypical Malgun cell (AMC) change is a novel premalignant condition in high risk gastropathy, which may progress and undergo malignant transformation directly. The pathobiological significance of AMC in gastric carcinogenesis is reviewed. A new diagnosis system of gastritis is proposed based on the critical pathologic steps classifying low and high risk gastritis for separate treatment modality. It is suggested that the regulation of H. pylori-induced neutrophilic foveolitis might be a future therapeutic goal replacing bactericidal antibiotics approach.

Interdisciplinary periodontics: the multidisciplinary approach to the planning and treatment of complex cases.

PubMed

Lyons, Karl M; Darby, Ivan

2017-06-01

Periodontics cannot be practiced in isolation as frequently many patients have multiple dental needs or medical health issues requiring management. In addition, pathology may manifest in the periodontal tissues, and the onset and progression of periodontitis can be affected by systemic conditions, such as diabetes, and vice versa. The focus of this volume of Periodontology 2000 is interdisciplinary periodontics, and the articles included discuss the interactions and the interrelationshipbetween periodontal tissues/periodontal diseases and endodontics, fixed prosthodontics, implant dentistry, esthetics, gerodontology, radiology, orthodontics, pediatric dentistry, oral and maxillofacial surgery, oral pathology, special needs dentistry and general medicine. Previous volumes of Periodontology 2000 have covered some of the interactions between periodontal diseases and other dental disciplines, especially implant dentistry, 'and the interaction between periodontal disease and systemic disease', but there has not been a volume on interdisciplinary periodontics. The intention therefore is to show how and why periodontics should be interdisciplinary, as well as the benefits of an interdisciplinary approach; in addition, the potential consequences of using a discipline in isolation are discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease.

PubMed

Daher, Raed; Manceau, Hana; Karim, Zoubida

2017-12-01

Although iron is vital, its free form is likely to be involved in oxidation-reduction reactions, leading to the formation of free radicals and oxidative stress. Living organisms have developed protein systems to transport free iron through the cell membranes and biological fluids and store it in a non-toxic and readily mobilizable form to avoid iron toxicity. Hepcidin plays a crucial role in maintaining iron homeostasis. Hepcidin expression is directly regulated by variations in iron intake and its repression leads to an increase in bioavailable serum iron level. However, in pathological situations, prolonged repression often leads to pathological iron overload. In this review, we describe the different molecular mechanisms responsible for the maintenance of iron metabolism and the consequences of iron overload. Indeed, genetic hemochromatosis and post-transfusional siderosis are the two main conditions responsible for iron overload. Long-term iron overload is deleterious, and treatment relies on venesection therapy for genetic hemochromatosis and chelation therapy for iron overload resulting from multiple transfusions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

EMMPRIN, an upstream regulator of MMPs, in CNS biology.

PubMed

Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee

2015-01-01

Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

The Manifestation of Vortical and Secondary Flow in the Cerebral Venous Outflow Tract: An In Vivo MR Velocimetry Study

PubMed Central

Kefayati, Sarah; Amans, Matthew; Faraji, Farshid; Ballweber, Megan; Kao, Evan; Ahn, Sinyeob; Meisel, Karl; Halbach, Van; Saloner, David

2016-01-01

Aberrations in flow in the cerebral venous outflow tract (CVOT) have been implicated as the cause of several pathologic conditions including idiopathic intracranial hypertension (IIH), multiple sclerosis (MS), and pulsatile tinnitus (PT). The advent of 4D Flow magnetic resonance imaging (4D-Flow MRI) has recently allowed researchers to evaluate blood flow patterns in the arterial structures with great success. We utilized similar imaging techniques and found several distinct flow characteristics in the CVOT of subjects with and without lumenal irregularities. We present the flow patterns of 8 out of 38 subjects who have varying heights of the internal jugular bulb and varying lumenal irregularities including stenosis and diverticulum. In the internal jugular vein (IJV) with an elevated jugular bulb (JB), 4DFlow MRI revealed a characteristic spiral flow that was dependent on the level of JB elevation. Vortical flow was also observed in the diverticula of the venous sinuses and IJV. The diversity of flow complexity in the CVOT illustrates the potential importance of hemodynamic investigations in elucidating venous pathologies. PMID:27894675

Neural Correlates of Alerting and Orienting Impairment in Multiple Sclerosis Patients

PubMed Central

Vázquez-Marrufo, Manuel; Galvao-Carmona, Alejandro; González-Rosa, Javier J.; Hidalgo-Muñoz, Antonio R.; Borges, Mónica; Ruiz-Peña, Juan Luis; Izquierdo, Guillermo

2014-01-01

Background A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. Results After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (p<0.05). ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05) and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01). With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01) and an ERP parameter (CNV amplitude). Conclusions Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients. PMID:24820333

Neural correlates of alerting and orienting impairment in multiple sclerosis patients.

PubMed

Vázquez-Marrufo, Manuel; Galvao-Carmona, Alejandro; González-Rosa, Javier J; Hidalgo-Muñoz, Antonio R; Borges, Mónica; Ruiz-Peña, Juan Luis; Izquierdo, Guillermo

2014-01-01

A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (p<0.05). ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05) and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01). With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01) and an ERP parameter (CNV amplitude). Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients.

42 CFR 415.130 - Conditions for payment: Physician pathology services.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-inclusive care for the elderly (PACE) under 1894 of the Act; or (iv) A social health maintenance... 42 Public Health 3 2010-10-01 2010-10-01 false Conditions for payment: Physician pathology services. 415.130 Section 415.130 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF...

The Use of Tympanometry to Detect Aerotitis Media in Hypobaric Chamber Operations

DTIC Science & Technology

1990-03-01

1972; 81:1654-78. for transient pathologic conditions of the middle ear 3. Brookler KH. Etiologic factors in non-supperotive otitis media . such as upper...Bluestone CD, Fria TJ,. Stool SE, Quinter CB, Sabo post-flight residual pathological conditions. These DL. Identification of otitis media with

Multiple sclerosis pathogenesis: missing pieces of an old puzzle.

PubMed

Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali

2018-06-08

Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

Trigeminal Neuralgia and Multiple Sclerosis: A Historical Perspective.

PubMed

Burkholder, David B; Koehler, Peter J; Boes, Christopher J

2017-09-01

Trigeminal neuralgia (TN) associated with multiple sclerosis (MS) was first described in Lehrbuch der Nervenkrankheiten für Ärzte und Studirende in 1894 by Hermann Oppenheim, including a pathologic description of trigeminal root entry zone demyelination. Early English-language translations in 1900 and 1904 did not so explicitly state this association compared with the German editions. The 1911 English-language translation described a more direct association. Other later descriptions were clinical with few pathologic reports, often referencing Oppenheim but citing the 1905 German or 1911 English editions of Lehrbuch. This discrepancy in part may be due to the translation differences of the original text.

AMPK at the Nexus of Energetics and Aging

PubMed Central

Burkewitz, Kristopher; Zhang, Yue; Mair, William B.

2014-01-01

When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both pro-longevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting towards substrates involved in longevity-assurance. PMID:24726383

Blast-Induced Color Change in Photonic Crystals Corresponds with Brain Pathology

PubMed Central

Cullen, D. Kacy; Browne, Kevin D.; Xu, Yongan; Adeeb, Saleena; Wolf, John A.; McCarron, Richard M.; Yang, Shu; Chavko, Mikulas

2011-01-01

Abstract A high incidence of blast exposure is a 21st century reality in counter-insurgency warfare. However, thresholds for closed-head blast-induced traumatic brain injury (bTBI) remain unknown. Moreover, without objective information about relative blast exposure, warfighters with bTBI may not receive appropriate medical care and may remain in harm's way. Accordingly, we have engineered a blast injury dosimeter (BID) using a photonic crystalline material that changes color following blast exposure. The photonic crystals are fabricated using SU-8 via multi-beam interference laser lithography. The final BID is similar in appearance to an array of small colored stickers that may be affixed to uniforms or helmets in multiple locations. Although durable under normal conditions, the photonic crystalline micro- and nano-structure are precisely altered by blast to create a color change. These BIDs were evaluated using a rat model of bTBI, for which blast shockwave exposure was generated via a compressed air-driven shock tube. With prototype BID arrays affixed to the animals, we found that BID color changes corresponded with subtle brain pathologies, including neuronal degeneration and reactive astrocytosis. These subtle changes were most notable in the dentate gyrus of the hippocampus, cerebral cortex, and cerebellum. These data demonstrate the feasibility of using a materials-based, power-free colorimetric BID as the first self-contained blast sensor calibrated to correspond with brain pathology. PMID:22082449

Monoacylglycerol signalling and ABHD6 in health and disease.

PubMed

Poursharifi, Pegah; Madiraju, Sri Ramachandra Murthy; Prentki, Marc

2017-09-01

Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues. Recent studies indicated the importance of the ubiquitously expressed serine hydrolase α/β-hydrolase domain 6 (ABHD6), which is a MAG hydrolase, in regulating signalling competent MAG in both central and peripheral tissues. The central and peripheral function of the endocannabinoid 2-arachidonoylglycerol, which is a 2-MAG, and its breakdown by both ABHD6 and classical MAG lipase has been well documented. ABHD6 and its substrate MAG appear to be involved in the regulation of various physiological and pathological processes including insulin secretion, adipose browning, food intake, neurotransmission, autoimmune disorders, neurological and metabolic diseases as well as cancer. Diverse cellular targets such as mammalian unc13-1 (Munc13-1), PPARs, GPR119 and CB1/2 receptors, for MAG-mediated signalling processes have been proposed in different cell types. The purpose of this review is to provide a comprehensive summary of the current state of knowledge regarding ABHD6/MAG signalling and its possible therapeutic implications. © 2017 John Wiley & Sons Ltd.

Multiple Immune-Inflammatory and Oxidative and Nitrosative Stress Pathways Explain the Frequent Presence of Depression in Multiple Sclerosis.

PubMed

Morris, Gerwyn; Reiche, Edna Maria Vissoci; Murru, Andrea; Carvalho, André F; Maes, Michael; Berk, Michael; Puri, Basant K

2018-01-02

Patients with a diagnosis of multiple sclerosis (MS) or major depressive disorder (MDD) share a wide array of biological abnormalities which are increasingly considered to play a contributory role in the pathogenesis and pathophysiology of both illnesses. Shared abnormalities include peripheral inflammation, neuroinflammation, chronic oxidative and nitrosative stress, mitochondrial dysfunction, gut dysbiosis, increased intestinal barrier permeability with bacterial translocation into the systemic circulation, neuroendocrine abnormalities and microglial pathology. Patients with MS and MDD also display a wide range of neuroimaging abnormalities and patients with MS who display symptoms of depression present with different neuroimaging profiles compared with MS patients who are depression-free. The precise details of such pathology are markedly different however. The recruitment of activated encephalitogenic Th17 T cells and subsequent bidirectional interaction leading to classically activated microglia is now considered to lie at the core of MS-specific pathology. The presence of activated microglia is common to both illnesses although the pattern of such action throughout the brain appears to be different. Upregulation of miRNAs also appears to be involved in microglial neurotoxicity and indeed T cell pathology in MS but does not appear to play a major role in MDD. It is suggested that the antidepressant lofepramine, and in particular its active metabolite desipramine, may be beneficial not only for depressive symptomatology but also for the neurological symptoms of MS. One clinical trial has been carried out thus far with, in particular, promising MRI findings.

[Pathogenetic associations of periodontal diseases with somatic therapeutic pathology, comorbid conditions in patients of advanced and senile age: state-of-the-art review. Part 1. Associations of periodontal diseases with somatic therapeutic pathology in patients of advanced and senile age].

PubMed

Ar'eva, G T; Solov'ev, M M; Ar'ev, A L; Ryzhak, G A

2014-01-01

The state-of-the-art review of literature on existing views on the association of periodontal diseases with somatic therapeutic pathology (first part of the review) and comorbid conditions (second part of the review) is submitted. The conclusion about need of carrying out the further multicenter researches which purpose is development of new integrated indicators, in a complex and comprehensively characterizing not only the periodontal status, but also set of available somatic therapeutic pathology, especially at pa- tients of advanced and senile age is drawn.

Neuromuscular conditions for physicians - what you need to know.

PubMed

Edwards, Laura; Phillips, Margaret

2016-06-01

The Royal College of Physicians (RCP) and the British Society of Rehabilitation Medicine co-hosted a meeting entitled 'Neuromuscular conditions for physicians - what you need to know' at the RCP on 30 November 2015. There was a series of talks, ranging from in-depth genetic and molecular descriptions of pathology to multidisciplinary management of chronic neuromuscular conditions, which stimulated lively debate and discussion. Some overarching themes emerged from the day, most notably: i) the changing expectations and survival rates in Duchenne muscular dystrophy (DMD), which are transforming this disorder into an adult as much as a paediatric condition; ii) the need for integrated management and good communication -between services - whether primary, secondary and tertiary care, medical teams and intensivists, or the multiple teams involved in providing treatment to neuromuscular patients; and iii) in line with the above, the essential need for streamlining care such that patients can avoid spending most of their time attending outpatient appointments, and instead concentrate on living full lives and exploring educational, occupational, leisure and social opportunities. © 2016 Royal College of Physicians.

Systems and precision medicine approaches to diabetes heterogeneity: a Big Data perspective.

PubMed

Capobianco, Enrico

2017-12-01

Big Data, and in particular Electronic Health Records, provide the medical community with a great opportunity to analyze multiple pathological conditions at an unprecedented depth for many complex diseases, including diabetes. How can we infer on diabetes from large heterogeneous datasets? A possible solution is provided by invoking next-generation computational methods and data analytics tools within systems medicine approaches. By deciphering the multi-faceted complexity of biological systems, the potential of emerging diagnostic tools and therapeutic functions can be ultimately revealed. In diabetes, a multidimensional approach to data analysis is needed to better understand the disease conditions, trajectories and the associated comorbidities. Elucidation of multidimensionality comes from the analysis of factors such as disease phenotypes, marker types, and biological motifs while seeking to make use of multiple levels of information including genetics, omics, clinical data, and environmental and lifestyle factors. Examining the synergy between multiple dimensions represents a challenge. In such regard, the role of Big Data fuels the rise of Precision Medicine by allowing an increasing number of descriptions to be captured from individuals. Thus, data curations and analyses should be designed to deliver highly accurate predicted risk profiles and treatment recommendations. It is important to establish linkages between systems and precision medicine in order to translate their principles into clinical practice. Equivalently, to realize their full potential, the involved multiple dimensions must be able to process information ensuring inter-exchange, reducing ambiguities and redundancies, and ultimately improving health care solutions by introducing clinical decision support systems focused on reclassified phenotypes (or digital biomarkers) and community-driven patient stratifications.

Conformational properties of serine proteinase inhibitors (serpins) confer multiple pathophysiological roles.

PubMed

Janciauskiene, S

2001-03-26

Serine proteinase inhibitors (Serpins) are irreversible suicide inhibitors of proteases that regulate diverse physiological processes such as coagulation, fibrinolysis, complement activation, angiogenesis, apoptosis, inflammation, neoplasia and viral pathogenesis. The molecular structure and physical properties of serpins permit these proteins to adopt a number of variant conformations under physiological conditions including the native inhibitory form and several inactive, non-inhibitory forms, such as complexes with protease or other ligands, cleaved, polymerised and oxidised. Alterations of a serpin which affect its structure and/or secretion and thus reduce its functional levels may result in pathology. Serpin dysfunction has been implicated in thrombosis, emphysema, liver cirrhosis, immune hypersensitivity and mental disorders. The loss of inhibitory activity of serpins necessarily results in an imbalance between proteases and their inhibitors, but it may also have other physiological effects through the generation of abnormal concentrations of modified, non-inhibitory forms of serpins. Although these forms of inhibitory serpins are detected in tissues and fluids recovered from inflammatory sites, the important questions of which conditions result in generation of different molecular forms of serpins, what biological function these forms have, and which of them are directly linked to pathologies and/or may be useful markers for characterisation of disease states, remain to be answered. Elucidation of the biological activities of non-inhibitory forms of serpins may provide useful insights into the pathogenesis of diseases and suggest new therapeutic strategies.

Preferred Names, Preferred Pronouns, and Gender Identity in the Electronic Medical Record and Laboratory Information System: Is Pathology Ready?

PubMed

Imborek, Katherine L; Nisly, Nicole L; Hesseltine, Michael J; Grienke, Jana; Zikmund, Todd A; Dreyer, Nicholas R; Blau, John L; Hightower, Maia; Humble, Robert M; Krasowski, Matthew D

2017-01-01

Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology.

Preferred Names, Preferred Pronouns, and Gender Identity in the Electronic Medical Record and Laboratory Information System: Is Pathology Ready?

PubMed Central

Imborek, Katherine L.; Nisly, Nicole L.; Hesseltine, Michael J.; Grienke, Jana; Zikmund, Todd A.; Dreyer, Nicholas R.; Blau, John L.; Hightower, Maia; Humble, Robert M.; Krasowski, Matthew D.

2017-01-01

Background: Electronic medical records (EMRs) and laboratory information systems (LISs) commonly utilize patient identifiers such as legal name, sex, medical record number, and date of birth. There have been recommendations from some EMR working groups (e.g., the World Professional Association for Transgender Health) to include preferred name, pronoun preference, assigned sex at birth, and gender identity in the EMR. These practices are currently uncommon in the United States. There has been little published on the potential impact of these changes on pathology and LISs. Methods: We review the available literature and guidelines on the use of preferred name and gender identity on pathology, including data on changes in laboratory testing following gender transition treatments. We also describe pathology and clinical laboratory challenges in the implementation of preferred name at our institution. Results: Preferred name, pronoun preference, and gender identity have the most immediate impact on the areas of pathology with direct patient contact such as phlebotomy and transfusion medicine, both in terms of interaction with patients and policies for patient identification. Gender identity affects the regulation and policies within transfusion medicine including blood donor risk assessment and eligibility. There are limited studies on the impact of gender transition treatments on laboratory tests, but multiple studies have demonstrated complex changes in chemistry and hematology tests. A broader challenge is that, even as EMRs add functionality, pathology computer systems (e.g., LIS, middleware, reference laboratory, and outreach interfaces) may not have functionality to store or display preferred name and gender identity. Conclusions: Implementation of preferred name, pronoun preference, and gender identity presents multiple challenges and opportunities for pathology. PMID:29114436

Profile of cognitive impairment and underlying pathology in multiple system atrophy.

PubMed

Koga, Shunsuke; Parks, Adam; Uitti, Ryan J; van Gerpen, Jay A; Cheshire, William P; Wszolek, Zbigniew K; Dickson, Dennis W

2017-03-01

The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients. We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank. The burden of glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were semiquantitatively scored in the limbic regions and middle frontal gyrus. We also assessed concurrent pathologies potentially causing dementia including Alzheimer's disease, hippocampal sclerosis, and cerebrovascular pathology. Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia. MSA patients with cognitive impairment had a greater burden of neuronal cytoplasmic inclusions in the dentate gyrus than patients without cognitive impairment, both including and excluding patients with concurrent pathologies of dementia. The cognitive deficits observed in this study were more evident on neuropsychological assessment than with cognitive screens. Based on these findings, we recommend that clinicians consider more in-depth neuropsychological assessments if patients with MSA present with cognitive complaints. Although we did not identify the correlation between cognitive deficits and responsible neuroanatomical regions, a greater burden of neuronal cytoplasmic inclusions in the limbic regions was associated with cognitive impairment in MSA. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Dietary fatty acids linking postprandial metabolic response and chronic diseases.

PubMed

Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

2012-01-01

Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

Methotrexate-associated lymphoproliferative disorder complicated by severe acute respiratory failure and ileal perforation: a case report.

PubMed

Suzuki, Eiji; Kanno, Takashi; Kimura, Satoru; Irie, Takumi; Odajima, Hajime; Migita, Kiyoshi

2018-06-19

Lymphoproliferative disorder (LPD) is a potentially severe adverse effect of methotrexate (MTX) administration in patients with rheumatoid arthritis (RA). We report a case of MTX-associated LPD (MTX-LPD) in a patient with RA who developed severe pulmonary failure complicated by perforation of the terminal ileum. A 61-year-old woman with RA receiving MTX complained of dyspnea and abdominal pain. She was diagnosed with intestinal perforation and peritonitis, and underwent immediate abdominal surgery. Pathological examinations of the specimen obtained from the resected ileum and a bone marrow aspirate revealed diffuse large B-cell lymphoma. Steroid therapy failed to improve her respiratory failure, but her condition improved after abdominal surgery and suspension of MTX. MTX-LPD can result in multiple life-threatening conditions; however, the symptoms are highly variable. RA patients receiving MTX should thus be monitored carefully, and MTX administration should be stopped immediately on suspicion of MTX-LPD.

Methods for Posttranslational Induction of Polyreactivity of Antibodies.

PubMed

Lecerf, Maxime; Jarossay, Annaelle; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien; Dimitrov, Jordan D

2017-01-01

An antibody molecule that recognizes multiple unrelated antigens is defined as polyreactive. Polyreactivity is an intrinsic characteristic of immune repertoires. Degenerated antigen binding diversifies the repertoire of specificities, thus contributing to immune defense and immune regulation. Immune repertoire contains also a fraction of immunoglobulins, which acquire polyreactivity only following contact with various protein-destabilizing or pro-oxidative substances. Posttranslational induction of the antibody polyreactivity may have important repercussion for laboratory practice, as well as in cases of pathological conditions accompanied by liberation of large quantities of pro-oxidative substances such as heme, labile iron, or reactive oxygen species. Antibodies with induced polyreactivity have been demonstrated to exert pathogen neutralization and immune regulatory potential in inflammatory conditions, suggesting that this phenomenon may be exploited for design of therapeutic strategies. In this article, we provide description of the basic procedures for uncovering of the cryptic polyreactivity of antibodies by heme, ferrous ions, and acid pH solution.

Interbrachial Pinch by Trapezius Transfer in Amyoplasia Congenita: A Case Report

PubMed Central

Thione, Alessandro; Cavadas, Pedro C.; Rubi, Carlo G.

2017-01-01

Summary: Amyoplasia congenita, or “classic distal arthrogryposis,” is the most common disorder among the congenital, non-progressive, multiple joint contractural conditions named arthrogryposis. The cause remains unknown, and it occurs sporadically. Abnormal neurological examination indicates that movement in utero was diminished as a result of an abnormality of the central or peripheral nervous system, the motor end plate, or muscle. The absence of central neural pathology indicates the origin in akinetic fetal condition. Three weeks are enough to cause muscle weakness and joint fibrosis. Joint contractures in amyoplasia are often rigid and refractory to nonoperative treatment such as passive stretching. Surgery is focused on each patient's need respecting adaptive maneuvers to accomplish daily tasks. We present a case in which pectoral major muscle had no strength for pinching; a trapezius muscle transfer was planned to obtain an interbrachial pinch useful for grasping. PMID:28607845

Catastrophic antiphospholipid syndrome (Ronald Asherson syndrome) and obstetric pathology.

PubMed

Makatsariya, Alexander D; Khizroeva, Jamilya; Bitsadze, Viktoriya O

2018-05-24

Catastrophic antiphospholipid syndrome (CAPS) is an uncommon, often fatal, variant of the antiphospholipid syndrome (APS) that results in a widespread coagulopathy and high titres of antiphospholipid antibodies (aPL) and affects predominantly small vessels supplying organs with the development of multiorgan failure. It remains unclear why some patients develop the typical clinical picture of APS (thrombosis of large vessels), whereas others show the development of progressive microthrombosis, which the authors called "thrombotic storm" and multiple organ failure, that is, CAPS. Since 2001-2016, we discovered 17 patients with CAPS development. CAPS is life-threatening condition, but optimal treatment for CAPS is not developed yet and the mortality rate is as high as 30%-40%.

Isolated ileal ganglioneuromatosis in an 11-year-old boy: Case report and review of literature.

PubMed

Mitra, Subhashis; Mukherjee, Sanghamitra; Chakraborty, Hema

2016-01-01

Ganglioneuromatous proliferation in the gastrointestinal tract is a rare occurrence and is usually associated with specific syndrome complexes such as multiple endocrine neoplasia Type 2B or von Recklinghausen's disease. We report here a case of diffuse intestinal ganglioneuromatosis, presenting as intestinal obstruction and chronic constipation in an 11-year-old boy. Sporadic cases of intestinal ganglioneuromatosis in the absence of any systemic manifestations are a very rare cause of enteric motility disorders in childhood, and we discuss the pathological and clinical significance of this finding. Histopathological identification of this uncommon cause of a common pediatric problem is important since the condition is amenable to surgical treatment.

Using the International Classification of Functioning, Disability and Health Framework to Achieve Interprofessional Functional Outcomes for Young Children: A Speech-Language Pathology Perspective.

PubMed

McNeilly, Lemmietta G

2018-02-01

The International Classification of Functioning, Disability and Health (ICF) framework is an excellent tool to facilitate the writing of functional goals for children who exhibit communication disorders and other developmental problems that require services from professionals in multiple therapeutic areas. The holistic view of children provides each professional with an approach that integrates how one's specific health conditions and contextual factors influence a child's functioning and participation in daily activities. This allows the interprofessional team to view the child as a person, recognizing how one need influences another within his or her environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Phytic Acid: From Antinutritional to Multiple Protection Factor of Organic Systems.

PubMed

Silva, Elisângela O; Bracarense, Ana Paula F R L

2016-06-01

Several studies have shown the benefits of natural antioxidants on health and food preservation. Phytic acid (IP6) is a natural antioxidant that is found mainly in cereals and vegetables and, for a long period of time, was considered an antinutritional factor. However, in vitro and in vivo studies have demonstrated its beneficial effects in the prevention and treatment of several pathological conditions and cancer. Despite the numerous benefits of IP6, the signs and intracellular interactions mediated by this antioxidant remain poorly understood. This review describes the main chemical and biological aspects of IP6, as well as its actions in the prevention and treatment of various diseases. © 2016 Institute of Food Technologists®

"It Ain't Over 'til It's Over" (a) -The Search for Treatments and Cures for Alzheimer's Disease.

PubMed

Hargreaves, Richard J

2012-11-08

In the neuroscience landscape, there is no condition with higher unmet medical and societal need than Alzheimer's disease (AD). There are significant opportunities to improve upon symptomatic treatments in AD, and as yet, there are no treatments to modify (slow, stop, or prevent) underlying disease progression. Our goals are to discover new symptomatic AD therapies with improved efficacy and longevity; to complete definitive studies that refute or prove the amyloid hypothesis, potentially opening multiple avenues to new therapeutic modalities; and to initiate tests of novel mechanisms that can prevent tau pathology and neurodegeneration. It's a critical time in the testing of novel AD therapeutics-let's hope we succeed.

[A case of intragastric wall abscess formation during bevacizumab combined chemotherapy].

PubMed

Mori, Ayano; Kogawa, Takahiro; Arihara, Youhei; Abe, Masakazu; Tamura, Fumito; Abe, Seiichirou; Kukitsu, Takehiro; Ihara, Hideyuki; Sumiyoshi, Tetsuya; Yoshizaki, Naoto; Kondou, Hitoshi; Tsuji, Yasushi

2013-05-01

A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.

Identification of Prevotella in pedal osteomyelitis of a diabetic patient.

PubMed

Dominiak, Barbara J; Oxberry, William; Chen, Patrick C

2003-01-01

Osteomyelitis in a diabetic patient with a nonhealing foot ulcer, multiple medical conditions, and recurrent hospitalization for antibiotic therapy was found to be associated with gram-negative bacteria Prevotella melanginoganica and Prevotella melaninoganica hemagglutinating variant. Those organisms were identified due to the morphologically distinct features in electron microscopy and sequencing of the genes after Polymerase chain reaction amplification from the pathological material. The bacteria invaded the bone and resided in osteocyte, osteoblast, and endothelial cells. The bacteria are usually associated with periodontal plaques, causing inflammation and destruction of gingival tissue and resorption of the alveolar bone. This is the first ultrastructural and molecular study of a diabetic bone lesion with anaerobic bacterial infection.

Consensus guidelines for the use and interpretation of angiogenesis assays.

PubMed

Nowak-Sliwinska, Patrycja; Alitalo, Kari; Allen, Elizabeth; Anisimov, Andrey; Aplin, Alfred C; Auerbach, Robert; Augustin, Hellmut G; Bates, David O; van Beijnum, Judy R; Bender, R Hugh F; Bergers, Gabriele; Bikfalvi, Andreas; Bischoff, Joyce; Böck, Barbara C; Brooks, Peter C; Bussolino, Federico; Cakir, Bertan; Carmeliet, Peter; Castranova, Daniel; Cimpean, Anca M; Cleaver, Ondine; Coukos, George; Davis, George E; De Palma, Michele; Dimberg, Anna; Dings, Ruud P M; Djonov, Valentin; Dudley, Andrew C; Dufton, Neil P; Fendt, Sarah-Maria; Ferrara, Napoleone; Fruttiger, Marcus; Fukumura, Dai; Ghesquière, Bart; Gong, Yan; Griffin, Robert J; Harris, Adrian L; Hughes, Christopher C W; Hultgren, Nan W; Iruela-Arispe, M Luisa; Irving, Melita; Jain, Rakesh K; Kalluri, Raghu; Kalucka, Joanna; Kerbel, Robert S; Kitajewski, Jan; Klaassen, Ingeborg; Kleinmann, Hynda K; Koolwijk, Pieter; Kuczynski, Elisabeth; Kwak, Brenda R; Marien, Koen; Melero-Martin, Juan M; Munn, Lance L; Nicosia, Roberto F; Noel, Agnes; Nurro, Jussi; Olsson, Anna-Karin; Petrova, Tatiana V; Pietras, Kristian; Pili, Roberto; Pollard, Jeffrey W; Post, Mark J; Quax, Paul H A; Rabinovich, Gabriel A; Raica, Marius; Randi, Anna M; Ribatti, Domenico; Ruegg, Curzio; Schlingemann, Reinier O; Schulte-Merker, Stefan; Smith, Lois E H; Song, Jonathan W; Stacker, Steven A; Stalin, Jimmy; Stratman, Amber N; Van de Velde, Maureen; van Hinsbergh, Victor W M; Vermeulen, Peter B; Waltenberger, Johannes; Weinstein, Brant M; Xin, Hong; Yetkin-Arik, Bahar; Yla-Herttuala, Seppo; Yoder, Mervin C; Griffioen, Arjan W

2018-05-15

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Social Media and Pathology: Where Are We Now and Why Does it Matter?

PubMed

Isom, James; Walsh, Meggen; Gardner, Jerad M

2017-09-01

Social media has exploded in popularity in recent years. It is a powerful new tool for networking, collaborating, and for the communication and evolution of ideas. It has been increasingly used for business purposes and is now being embraced by physicians including pathologists. Pathology professional organizations and even peer-reviewed pathology journals are now beginning to use social media, as well. There are multiple social media platforms, including Twitter, Facebook, Instagram, LinkedIn, and others. Each platform has different audiences and different ways to share content and interact with other users. This paper discusses the different social media platforms and how they are being used in pathology currently.

The use of thermovision camera to observe physiological and pathological conditions of oral cavity mucous membrane

NASA Astrophysics Data System (ADS)

Dąbrowski, M.; Dulski, R.; Żmuda, S.; Zaborowski, P.; Pogorzelski, C.

2002-06-01

This article presents initial results of investigations of the temperature distribution changes in oral cavity mucous membrane. The investigations aimed to prepare a model of temperature changes existing within mucosal membrane in physiological conditions and to compare those changes with those under pathological conditions. Our investigations were carried out using an infrared imaging system. A representative group of patients was tested.

Cardiac function in muscular dystrophy associates with abdominal muscle pathology.

PubMed

Gardner, Brandon B; Swaggart, Kayleigh A; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M

The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients.

Pathologic Aerophagia: A Rare but Important Medical Condition in People with Intellectual Disabilities

ERIC Educational Resources Information Center

Wong, Wendy; Sajith, Sreedharan Geetha

2017-01-01

Background: Pathologic aerophagia (PA) is characterised by excessive swallowing of air resulting in significant abdominal distension or belching. This is a relatively rare condition in general population but has been reported in up to 8.8% of institutionalised patients with intellectual disability. In severe cases, this can cause volvulus and…

The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging

PubMed Central

Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A.; Ciol, Marcia A.; Ritchey, Jerry; Liggitt, Denny

2016-01-01

Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations. PMID:26243216

Imaging biomarkers in multiple Sclerosis: From image analysis to population imaging.

PubMed

Barillot, Christian; Edan, Gilles; Commowick, Olivier

2016-10-01

The production of imaging data in medicine increases more rapidly than the capacity of computing models to extract information from it. The grand challenges of better understanding the brain, offering better care for neurological disorders, and stimulating new drug design will not be achieved without significant advances in computational neuroscience. The road to success is to develop a new, generic, computational methodology and to confront and validate this methodology on relevant diseases with adapted computational infrastructures. This new concept sustains the need to build new research paradigms to better understand the natural history of the pathology at the early phase; to better aggregate data that will provide the most complete representation of the pathology in order to better correlate imaging with other relevant features such as clinical, biological or genetic data. In this context, one of the major challenges of neuroimaging in clinical neurosciences is to detect quantitative signs of pathological evolution as early as possible to prevent disease progression, evaluate therapeutic protocols or even better understand and model the natural history of a given neurological pathology. Many diseases encompass brain alterations often not visible on conventional MRI sequences, especially in normal appearing brain tissues (NABT). MRI has often a low specificity for differentiating between possible pathological changes which could help in discriminating between the different pathological stages or grades. The objective of medical image analysis procedures is to define new quantitative neuroimaging biomarkers to track the evolution of the pathology at different levels. This paper illustrates this issue in one acute neuro-inflammatory pathology: Multiple Sclerosis (MS). It exhibits the current medical image analysis approaches and explains how this field of research will evolve in the next decade to integrate larger scale of information at the temporal, cellular, structural and morphological levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Digital Pathology Evaluation in the Multicenter Nephrotic Syndrome Study Network (NEPTUNE)

PubMed Central

Nast, Cynthia C.; Jennette, J. Charles; Hodgin, Jeffrey B.; Herzenberg, Andrew M.; Lemley, Kevin V.; Conway, Catherine M.; Kopp, Jeffrey B.; Kretzler, Matthias; Lienczewski, Christa; Avila-Casado, Carmen; Bagnasco, Serena; Sethi, Sanjeev; Tomaszewski, John; Gasim, Adil H.

2013-01-01

Summary Pathology consensus review for clinical trials and disease classification has historically been performed by manual light microscopy with sequential section review by study pathologists, or multi-headed microscope review. Limitations of this approach include high intra- and inter-reader variability, costs, and delays for slide mailing and consensus reviews. To improve this, the Nephrotic Syndrome Study Network (NEPTUNE) is systematically applying digital pathology review in a multicenter study using renal biopsy whole slide imaging (WSI) for observation-based data collection. Study pathology materials are acquired, scanned, uploaded, and stored in a web-based information system that is accessed through a web-browser interface. Quality control includes metadata and image quality review. Initially, digital slides are annotated, with each glomerulus identified, given a unique number, and maintained in all levels until the glomerulus disappears or sections end. The software allows viewing and annotation of multiple slide sections concurrently. Analysis utilizes “descriptors” for patterns of injury, rather than diagnoses, in renal parenchymal compartments. This multidimensional representation via WSI, allows more accurate glomerular counting and identification of all lesions in each glomerulus, with data available in a searchable database. The use of WSI brings about efficiency critical to pathology review in a clinical trial setting, including independent review by multiple pathologists, improved intraobserver and interobserver reproducibility, efficiencies and risk reduction in slide circulation and mailing, centralized management of data integrity and slide images for current or future studies, and web-based consensus meetings. The overall effect is improved incorporation of pathology review in a budget neutral approach. PMID:23393107

TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease

PubMed Central

Mishra, Manjari; Hatanpaa, Kimmo J.; White, Charles L.; Johnson, Nancy; Rademaker, Alfred; Weitner, Bing Bing; Deng, Han-Xiang; Dubner, Steven D.; Weintraub, Sandra; Mesulam, Marsel

2010-01-01

The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain–behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinicoanatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies. PMID:20361198

Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis.

PubMed

Albert, Monika; Barrantes-Freer, Alonso; Lohrberg, Melanie; Antel, Jack P; Prineas, John W; Palkovits, Miklós; Wolff, Joachim R; Brück, Wolfgang; Stadelmann, Christine

2017-11-01

In multiple sclerosis, cerebellar symptoms are associated with clinical impairment and an increased likelihood of progressive course. Cortical atrophy and synaptic dysfunction play a prominent role in cerebellar pathology and although the dentate nucleus is a predilection site for lesion development, structural synaptic changes in this region remain largely unexplored. Moreover, the mechanisms leading to synaptic dysfunction have not yet been investigated at an ultrastructural level in multiple sclerosis. Here, we report on synaptic changes of dentate nuclei in post-mortem cerebella of 16 multiple sclerosis patients and eight controls at the histological level as well as an electron microscopy evaluation of afferent synapses of the cerebellar dentate and pontine nuclei of one multiple sclerosis patient and one control. We found a significant reduction of afferent dentate synapses in multiple sclerosis, irrespective of the presence of demyelination, and a close relationship between glial processes and dentate synapses. Ultrastructurally, we show autophagosomes containing degradation products of synaptic vesicles within dendrites, residual bodies within intact-appearing axons and free postsynaptic densities opposed to astrocytic appendages. Our study demonstrates loss of dentate afferent synapses and provides, for the first time, ultrastructural evidence pointing towards neuron-autonomous and neuroglia-mediated mechanisms of synaptic degradation in chronic multiple sclerosis. © 2016 International Society of Neuropathology.

Quantum Dots for Molecular Pathology

PubMed Central

True, Lawrence D.; Gao, Xiaohu

2007-01-01

Assessing malignant tumors for expression of multiple biomarkers provides data that are critical for patient management. Quantum dot-conjugated probes to specific biomarkers are powerful tools that can be applied in a multiplex manner to single tissue sections of biopsies to measure expression levels of multiple biomarkers. PMID:17251330

Multiple functions of neuronal plasma membrane neurotransmitter transporters.

PubMed

Raiteri, Luca; Raiteri, Maurizio

2015-11-01

Removal from receptors of neurotransmitters just released into synapses is one of the major steps in neurotransmission. Transporters situated on the plasma membrane of nerve endings and glial cells perform the process of neurotransmitter (re)uptake. Because the density of transporters in the membranes can fluctuate, transporters can determine the transmitter concentrations at receptors, thus modulating indirectly the excitability of neighboring neurons. Evidence is accumulating that neurotransmitter transporters can exhibit multiple functions. Being bidirectional, neurotransmitter transporters can mediate transmitter release by working in reverse, most often under pathological conditions that cause ionic gradient dysregulations. Some transporters reverse to release transmitters, like dopamine or serotonin, when activated by 'indirectly acting' substrates, like the amphetamines. Some transporters exhibit as one major function the ability to capture transmitters into nerve terminals that perform insufficient synthesis. Transporter activation can generate conductances that regulate directly neuronal excitability. Synaptic and non-synaptic transporters play different roles. Cytosolic Na(+) elevations accompanying transport can interact with plasmalemmal or/and mitochondrial Na(+)/Ca(2+) exchangers thus generating calcium signals. Finally, neurotransmitter transporters can behave as receptors mediating releasing stimuli able to cause transmitter efflux through multiple mechanisms. Neurotransmitter transporters are therefore likely to play hitherto unknown roles in multiple therapeutic treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automatic identification of resting state networks: an extended version of multiple template-matching

NASA Astrophysics Data System (ADS)

Guaje, Javier; Molina, Juan; Rudas, Jorge; Demertzi, Athena; Heine, Lizette; Tshibanda, Luaba; Soddu, Andrea; Laureys, Steven; Gómez, Francisco

2015-12-01

Functional magnetic resonance imaging in resting state (fMRI-RS) constitutes an informative protocol to investigate several pathological and pharmacological conditions. A common approach to study this data source is through the analysis of changes in the so called resting state networks (RSNs). These networks correspond to well-defined functional entities that have been associated to different low and high brain order functions. RSNs may be characterized by using Independent Component Analysis (ICA). ICA provides a decomposition of the fMRI-RS signal into sources of brain activity, but it lacks of information about the nature of the signal, i.e., if the source is artifactual or not. Recently, a multiple template-matching (MTM) approach was proposed to automatically recognize RSNs in a set of Independent Components (ICs). This method provides valuable information to assess subjects at individual level. Nevertheless, it lacks of a mechanism to quantify how much certainty there is about the existence/absence of each network. This information may be important for the assessment of patients with severely damaged brains, in which RSNs may be greatly affected as a result of the pathological condition. In this work we propose a set of changes to the original MTM that improves the RSNs recognition task and also extends the functionality of the method. The key points of this improvement is a standardization strategy and a modification of method's constraints that adds flexibility to the approach. Additionally, we also introduce an analysis to the trustworthiness measurement of each RSN obtained by using template-matching approach. This analysis consists of a thresholding strategy applied over the computed Goodness-of-Fit (GOF) between the set of templates and the ICs. The proposed method was validated on 2 two independent studies (Baltimore, 23 healthy subjects and Liege, 27 healthy subjects) with different configurations of MTM. Results suggest that the method will provide complementary information for characterization of RSNs at individual level.

[Pathologic conditions in pregnancy. Preliminary evaluation of the effectiveness of magnetic resonance].

PubMed

Beomonte Zobel, B; Tella, S; Innacoli, M; D'Archivio, C; Cardone, G; Masciocchi, C; Gallucci, M; Cappa, F; Passariello, R

1991-03-01

Some authors suggested that MR imaging could represent an effective diagnostic alternative in the study of pathologic conditions of mother and fetus during pregnancy. To verify the actual role of MR imaging, we examined 20 patients in the 2nd and 3rd trimester of gestation, after a preliminary US examination. Fifteen patients presented fetal or placental pathologies; in 4 patients the onset of the pathologic condition occurred during pregnancy; in 1 case of US diagnosis of fetal ascites, MR findings were normal and the newborn was healthy. As for placental pathologies, our series included a case of placental cyst, two hematomas between placenta and uterine wall, and two cases of partial placenta previa. As for fetal malformations, we evaluated a case of omphalocele, one of Prune-Belly syndrome, a case of femoral asymmetry, one of thanatophoric dwarfism, a case of thoracopagus twins with cardiovascular abnormalities, two fetal hydrocephali, and three cases of pyelo-ureteral stenosis. As for maternal pathologies during pregnancy, we observed a case of subserous uterine fibromyoma, one of right hydronephrosis, one of protrusion of lumbar intervertebral disk, and a large ovarian cyst. In our experience, MR imaging exhibited high sensitivity and a large field of view, which were both useful in the investigation of the different conditions occurring during pregnancy. In the evaluation of fetal and placental abnormalities, especially during the 3rd trimester, the diagnostic yield of MR imaging suggested it as a complementary technique to US for the evaluation of fetal malformations and of intrauterine growth retardation.

Cortical pathology in multiple sclerosis detected by the T1/T2‐weighted ratio from routine magnetic resonance imaging

PubMed Central

Righart, Ruthger; Biberacher, Viola; Jonkman, Laura E.; Klaver, Roel; Schmidt, Paul; Buck, Dorothea; Berthele, Achim; Kirschke, Jan S.; Zimmer, Claus; Hemmer, Bernhard; Geurts, Jeroen J. G.

2017-01-01

Objective In multiple sclerosis, neuropathological studies have shown widespread changes in the cerebral cortex. In vivo imaging is critical, because the histopathological substrate of most measurements is unknown. Methods Using a novel magnetic resonance imaging analysis technique, based on the ratio of T1‐ and T2‐weighted signal intensities, we studied the cerebral cortex of a large cohort of patients in early stages of multiple sclerosis. A total of 168 patients with clinically isolated syndrome or relapsing–remitting multiple sclerosis (Expanded Disability Status Scale: median = 1, range = 0–3.5) and 80 age‐ and sex‐matched healthy controls were investigated. We also searched for the histopathological substrate of the T1/T2‐weighted ratio by combining postmortem imaging and histopathology in 9 multiple sclerosis brain donors. Results Patients showed lower T1/T2‐weighted ratio values in parietal and occipital areas. The 4 most significant clusters appeared in the medial occipital and posterior cingulate cortex (each left and right). The decrease of the T1/T2‐weighted ratio in the posterior cingulate was related to performance in attention. Analysis of the T1/T2‐weighted ratio values of postmortem imaging yielded a strong correlation with dendrite density but none of the other parameters including myelin. Interpretation The T1/T2‐weighted ratio decreases in early stages of multiple sclerosis in a widespread manner, with a preponderance of posterior areas and with a contribution to attentional performance; it seems to reflect dendrite pathology. As the method is broadly available and applicable to available clinical scans, we believe that it is a promising candidate for studying and monitoring cortical pathology or therapeutic effects in multiple sclerosis. Ann Neurol 2017;82:519–529 PMID:28833433

Simultaneous antegrade/retrograde upper urinary tract access: Bart's modified lateral position for complex upper tract endourologic pathologic features.

PubMed

Moraitis, Konstantinos; Philippou, Prodromos; El-Husseiny, Tamer; Wazait, Hassan; Masood, Junaid; Buchholz, Noor

2012-02-01

To determine whether the Bart's modified lateral position is safe and effective for achieving simultaneous anterograde and retrograde access in complex upper urinary tract pathologic features. From November 2006 to September 2010, 45 procedures were performed, with the patients in the modified lateral position. The indication for these procedures was the presence of complex unilateral upper urinary tract pathologic features. The patients with muscular and/or skeletal abnormalities were excluded. All procedures were performed using simultaneous anterograde and retrograde access with the patient under general anesthesia. The preoperative investigation protocol included assessment of the stone burden and location using enhanced abdominal computed tomography. The patients were routinely examined 6 weeks after the procedure with a combination of plain abdominal radiography and renal ultrasonography. For patients treated for conditions causing upper urinary tract obstruction (pelviureteral junction obstruction and/or ureteral strictures), a mercaptoacetyltriglycine renography was performed at 4, 12, and 24 months postoperatively. The mean patient age was 51.2 years (range 17-79). Stone clearance was achieved by a single combined procedure in 36 patients (80%). Successful recanalization was achieved in all patients with pelviureteral junction obstruction and ureteral strictures. In 4 patients (8.8%), persistent hematuria was noted, and 2 patients (4.4%) developed postoperative urinary sepsis and were treated conservatively. Modification to the lateral position compares equally with contemporary percutaneous nephrolithotomy series. It provides wide exposure of the flank, allowing the choice of multiple access sites, enhanced control, and a wide angle for handling of the antegrade instruments. Two surgeons can work simultaneously, addressing complex endourologic pathologic features in high-risk patients. Copyright © 2012. Published by Elsevier Inc.

Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

PubMed Central

Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

2017-01-01

Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

Systematic Review of International Colposcopy Quality Improvement Guidelines.

PubMed

Mayeaux, Edward J; Novetsky, Akiva P; Chelmow, David; Choma, Kim; Garcia, Francisco; Liu, Angela H; Papasozomenos, Theognosia; Einstein, Mark H

2017-10-01

The American Society for Colposcopy and Cervical Pathology Colposcopy Standards Committee organized multiple working groups to draft colposcopy standards for the United States. As part of this project, international quality assurance and improvement measures were examined. The quality improvement working group performed a systematic review of the literature to collate international guidelines related to quality improvement. Source guidelines were collected using searches in Medline, Google Scholar, the International Federation of Cervical Pathology and Colposcopy Web site, other regional colposcopy group's Web sites, and communications with International Federation of Cervical Pathology and Colposcopy board of directors' members and other expert members of various national groups. Once identified, the sources were reviewed by multiple workgroup members for potential guideline materials. Fifty-six unique documents were identified, of which 18 met inclusion criteria and contributed data to the analysis. Information was abstracted and grouped by related subject. Wide variation exists in colposcopy guidance and quality indicators from regional and national colposcopy societies. Abstracted international guidelines are presented.

Different EGFR gene mutations in two patients with synchronous multiple lung cancers: A case report

PubMed Central

Sakai, Hiroki; Kimura, Hiroyuki; Tsuda, Masataka; Wakiyama, Yoichi; Miyazawa, Tomoyuki; Marushima, Hideki; Kojima, Koji; Hoshikawa, Masahiro; Takagi, Masayuki; Nakamura, Haruhiko

2017-01-01

Routine clinical and pathological evaluations to determine the relationship between different lesions are often not completely conclusive. Interestingly, detailed genetic analysis of tumor samples may provide important additional information and identify second primary lung cancers. In the present study, we report cases of two synchronous lung adenocarcinomas composed of two distinct pathological subtypes with different EGFR gene mutations: a homozygous deletion in exon 19 of the papillary adenocarcinoma subtype and a point mutation of L858R in exon 21 of the tubular adenocarcinoma. The present report highlights the clinical importance of molecular cancer biomarkers to guide management decisions in cases involving multiple lung tumors. PMID:29090842

VISUALIZING IRON IN MULTIPLE SCLEROSIS

PubMed Central

Bagnato, Francesca; Hametner, Simon; Welch, Edward Brian

2012-01-01

Magnetic resonance imaging (MRI) protocols that are designed to be sensitive to iron typically take advantage of (1) iron effects on the relaxation of water protons and/or (2) iron-induced local magnetic field susceptibility changes. Increasing evidence sustains the notion that imaging iron in brain of patients with multiple sclerosis (MS) may add some specificity toward the identification of the disease pathology. The present review summarizes currently reported in vivo and post mortem MRI evidence of (1) iron detection in white matter and grey matter of MS brains, (2) pathological and physiological correlates of iron as disclosed by imaging and (3) relations between iron accumulation and disease progression as measured by clinical metrics. PMID:23347601

Sonographic evaluation of athletic pubalgia.

PubMed

Morley, Nicholas; Grant, Thomas; Blount, Kevin; Omar, Imran

2016-05-01

Athletic pubalgia, or "sports hernia", represents a constellation of pathologic conditions occurring at and around the pubic symphysis. These injuries are primarily seen in athletes or those involved in athletic activity. In this article, we review the sonographic appearance of the relevant complex anatomy, scanning technique for ultrasound evaluation of athletic pubalgia, and the sonographic appearances of associated pathologic conditions.

Human immunodeficiency virus (HIV) is highly associated with giant idiopathic esophageal ulcers in acquired immunodeficiency syndrome (AIDS) patients.

PubMed

Lv, Bei; Cheng, Xin; Gao, Jackson; Zhao, Hong; Chen, Liping; Wang, Liwei; Huang, Shaoping; Fan, Zhenyu; Zhang, Renfang; Shen, Yinzhong; Li, Lei; Liu, Baochi; Qi, Tangkai; Wang, Jing; Cheng, Jilin

2016-01-01

This study aimed to determine whether the human immunodeficiency virus (HIV) exists in giant idiopathic esophageal ulcers in the patients with acquired immune deficiency syndrome (AIDS). 16 AIDS patients with a primary complaint of epigastric discomfort were examined by gastroscopy. Multiple and giant esophageal ulcers were biopsied and analyzed with pathology staining and reverse transcription-polymerase chain reaction (RT-PCR) to determine the potential pathogenic microorganisms, including HIV, cytomegalovirus (CMV) and herpes simplex viruses (HSV). HIV was detected in ulcer samples from 12 out of these 16 patients. Ulcers in 2 patients were infected with CMV and ulcers in another 2 patients were found HSV positive. No obvious cancerous pathological changes were found in these multiple giant esophageal ulcer specimens. HIV may be one of the major causative agents of multiple benign giant esophageal ulcers in AIDS patients.

Human immunodeficiency virus (HIV) is highly associated with giant idiopathic esophageal ulcers in acquired immunodeficiency syndrome (AIDS) patients

PubMed Central

Lv, Bei; Cheng, Xin; Gao, Jackson; Zhao, Hong; Chen, Liping; Wang, Liwei; Huang, Shaoping; Fan, Zhenyu; Zhang, Renfang; Shen, Yinzhong; Li, Lei; Liu, Baochi; Qi, Tangkai; Wang, Jing; Cheng, Jilin

2016-01-01

Objective: This study aimed to determine whether the human immunodeficiency virus (HIV) exists in giant idiopathic esophageal ulcers in the patients with acquired immune deficiency syndrome (AIDS). Methods: 16 AIDS patients with a primary complaint of epigastric discomfort were examined by gastroscopy. Multiple and giant esophageal ulcers were biopsied and analyzed with pathology staining and reverse transcription-polymerase chain reaction (RT-PCR) to determine the potential pathogenic microorganisms, including HIV, cytomegalovirus (CMV) and herpes simplex viruses (HSV). Results: HIV was detected in ulcer samples from 12 out of these 16 patients. Ulcers in 2 patients were infected with CMV and ulcers in another 2 patients were found HSV positive. No obvious cancerous pathological changes were found in these multiple giant esophageal ulcer specimens. Conclusion: HIV may be one of the major causative agents of multiple benign giant esophageal ulcers in AIDS patients. PMID:27830031

JointMMCC: Joint Maximum-Margin Classification and Clustering of Imaging Data

PubMed Central

Filipovych, Roman; Resnick, Susan M.; Davatzikos, Christos

2012-01-01

A number of conditions are characterized by pathologies that form continuous or nearly-continuous spectra spanning from the absence of pathology to very pronounced pathological changes (e.g., normal aging, Mild Cognitive Impairment, Alzheimer's). Moreover, diseases are often highly heterogeneous with a number of diagnostic subcategories or subconditions lying within the spectra (e.g., Autism Spectrum Disorder, schizophrenia). Discovering coherent subpopulations of subjects within the spectrum of pathological changes may further our understanding of diseases, and potentially identify subconditions that require alternative or modified treatment options. In this paper, we propose an approach that aims at identifying coherent subpopulations with respect to the underlying MRI in the scenario where the condition is heterogeneous and pathological changes form a continuous spectrum. We describe a Joint Maximum-Margin Classification and Clustering (JointMMCC) approach that jointly detects the pathologic population via semi-supervised classification, as well as disentangles heterogeneity of the pathological cohort by solving a clustering subproblem. We propose an efficient solution to the non-convex optimization problem associated with JointMMCC. We apply our proposed approach to an MRI study of aging, and identify coherent subpopulations (i.e., clusters) of cognitively less stable adults. PMID:22328179

Hunter-gatherer dental pathology: Do historic accounts of Aboriginal Australians correspond to the archeological record of dental disease?

PubMed

Littleton, Judith

2018-03-01

Studies of hunter-gatherer oral pathology, particularly in Australia, often focus upon dental wear and caries or assume that historic studies of Aboriginal people reflect the precontact past. Consequently the range of population variation has been underestimated. In this paper dental pathology from human remains from Roonka are compared with a model of dental pathology derived from historic studies. The aim is to identify aspects of dental pathology indicative of regional or intra-population diversity. Adult dentitions (n = 115) dating from the mid to late Holocene were recorded for the following conditions: dental wear, caries, periapical voids, calculus, periodontal disease and antemortem tooth loss. Statistical analysis was used to identify patterns of dental pathology and to identify causal relationships between conditions. Dental wear is marked while dental caries rates are extremely low. Other indications of dental pathology are uncommon (<7% of teeth affected). Temporal heterogeneity is apparent: there are 3 young adults with caries who died in the postcontact period. There is also a small group of middle age to old adults with disproportionate abscessing and pulp exposure who may represent temporal variation or heterogeneity in individual frailty. The results confirm dental wear as the major cause of dental pathology in this group and that, at a general level, historic accounts do correspond with this archeological sample. However, intra-sample heterogeneity is apparent while 2 dental conditions, calculus and periodontal disease, along with the pattern of sex differences deviate from expectation, demonstrating that to identify regional variation attention needs to be paid to the dentoalveolar complex as a whole. © 2017 Wiley Periodicals, Inc.

Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip

PubMed Central

Samadani, Uzma; Farooq, Sameer; Ritlop, Robert; Warren, Floyd; Reyes, Marleen; Lamm, Elizabeth; Alex, Anastasia; Nehrbass, Elena; Kolecki, Radek; Jureller, Michael; Schneider, Julia; Chen, Agnes; Shi, Chen; Mendhiratta, Neil; Huang, Jason H.; Qian, Meng; Kwak, Roy; Mikheev, Artem; Rusinek, Henry; George, Ajax; Fergus, Robert; Kondziolka, Douglas; Huang, Paul P.; Smith, R. Theodore

2015-01-01

OBJECT Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. METHODS The authors recorded subjects’ eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. RESULTS In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. CONCLUSIONS This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma. PMID:25495739

Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip.

PubMed

Samadani, Uzma; Farooq, Sameer; Ritlop, Robert; Warren, Floyd; Reyes, Marleen; Lamm, Elizabeth; Alex, Anastasia; Nehrbass, Elena; Kolecki, Radek; Jureller, Michael; Schneider, Julia; Chen, Agnes; Shi, Chen; Mendhiratta, Neil; Huang, Jason H; Qian, Meng; Kwak, Roy; Mikheev, Artem; Rusinek, Henry; George, Ajax; Fergus, Robert; Kondziolka, Douglas; Huang, Paul P; Smith, R Theodore

2015-03-01

Automated eye movement tracking may provide clues to nervous system function at many levels. Spatial calibration of the eye tracking device requires the subject to have relatively intact ocular motility that implies function of cranial nerves (CNs) III (oculomotor), IV (trochlear), and VI (abducent) and their associated nuclei, along with the multiple regions of the brain imparting cognition and volition. The authors have developed a technique for eye tracking that uses temporal rather than spatial calibration, enabling detection of impaired ability to move the pupil relative to normal (neurologically healthy) control volunteers. This work was performed to demonstrate that this technique may detect CN palsies related to brain compression and to provide insight into how the technique may be of value for evaluating neuropathological conditions associated with CN palsy, such as hydrocephalus or acute mass effect. The authors recorded subjects' eye movements by using an Eyelink 1000 eye tracker sampling at 500 Hz over 200 seconds while the subject viewed a music video playing inside an aperture on a computer monitor. The aperture moved in a rectangular pattern over a fixed time period. This technique was used to assess ocular motility in 157 neurologically healthy control subjects and 12 patients with either clinical CN III or VI palsy confirmed by neuro-ophthalmological examination, or surgically treatable pathological conditions potentially impacting these nerves. The authors compared the ratio of vertical to horizontal eye movement (height/width defined as aspect ratio) in normal and test subjects. In 157 normal controls, the aspect ratio (height/width) for the left eye had a mean value ± SD of 1.0117 ± 0.0706. For the right eye, the aspect ratio had a mean of 1.0077 ± 0.0679 in these 157 subjects. There was no difference between sexes or ages. A patient with known CN VI palsy had a significantly increased aspect ratio (1.39), whereas 2 patients with known CN III palsy had significantly decreased ratios of 0.19 and 0.06, respectively. Three patients with surgically treatable pathological conditions impacting CN VI, such as infratentorial mass effect or hydrocephalus, had significantly increased ratios (1.84, 1.44, and 1.34, respectively) relative to normal controls, and 6 patients with supratentorial mass effect had significantly decreased ratios (0.27, 0.53, 0.62, 0.45, 0.49, and 0.41, respectively). These alterations in eye tracking all reverted to normal ranges after surgical treatment of underlying pathological conditions in these 9 neurosurgical cases. This proof of concept series of cases suggests that the use of eye tracking to detect CN palsy while the patient watches television or its equivalent represents a new capacity for this technology. It may provide a new tool for the assessment of multiple CNS functions that can potentially be useful in the assessment of awake patients with elevated intracranial pressure from hydrocephalus or trauma.

Review of Amyotrophic Lateral Sclerosis, Parkinson's and Alzheimer's diseases helps further define pathology of the novel paradigm for Alzheimer's with heavy metals as primary disease cause.

PubMed

Cavaleri, Franco

2015-12-01

Pathologies of neurological diseases are increasingly recognized to have common structural and molecular events that can fit, sometimes loosely, into a central pathological theme. A better understanding of the genetic, proteomic and metabolic similarities between three common neurodegenerative diseases - Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) - and how these similarities relate to their unique pathological features may shed more light on the underlying pathology of each. These are complex multigenic neuroinflammatory diseases caused by a combined action by multiple genetic mutations, lifestyle factors and environmental elements including a proposed contribution by transition metals. This comprehensive dynamic makes disease decoding and treatment difficult. One case of ALS, for example, can manifest from a very different pool of genetic mutations than another. In the case of ALS multiple genes in addition to SOD1 are implicated in the pathogenesis of both sporadic and familial variants of the disease. These genes play different roles in the processing and trafficking of signalling, metabolic and structural proteins. However, many of these genetic mutations or the cellular machinery they regulate can play a role in one form or another in PD and AD as well. In addition, the more recent understanding of how TREM-2 mutations factor into inflammatory response has shed new light on how chronic inflammatory activity can escalate to uncontrolled systemic levels in a variety of inflammatory diseases from neurodegenerative, auto-inflammatory and autoimmune diseases. TREM-2 mutations represent yet another complicating element in these multigenic disease pathologies. This review takes us one step back to discuss basic pathological features of these neurodegenerative diseases known to us for some time. However, the objective is to discuss the possibility of related or linked mechanisms that may exist through these basic disease hallmarks that we often classify as absolute signatures of one disease. These new perspectives will be discussed in the context of a new paradigm for Alzheimer's disease that implicates heavy metals as a primary cause. Plausible links between these distinctly different pathologies are presented showing intersections of their distinct pathologies that hinge on metal interactions.

Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease.

PubMed

Yamamoto, Shinji; Yamashina, Kota; Ishikawa, Masaki; Gotoh, Mari; Yagishita, Sosuke; Iwasa, Kensuke; Maruyama, Kei; Murakami-Murofushi, Kimiko; Yoshikawa, Keisuke

2017-07-21

Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. We designed, chemically synthesized, and metabolically stabilized derivatives of cPA: 2-carba-cPA (2ccPA), a synthesized compound in which one of the phosphate oxygen molecules is replaced with a methylene group at the sn-2 position. In the present study, we investigated whether 2ccPA exerts protective effects in oligodendrocytes and suppresses pathology in the two most common mouse models of multiple sclerosis. To evaluate whether 2ccPA has potential beneficial effects on the pathology of multiple sclerosis, we investigated the effects of 2ccPA on oligodendrocyte cell death in vitro and administrated 2ccPA to mouse models of experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination. We demonstrated that 2ccPA suppressed the CoCl 2 -induced increase in the Bax/Bcl-2 protein expression ratio and phosphorylation levels of p38MAPK and JNK protein. 2ccPA treatment reduced cuprizone-induced demyelination, microglial activation, NLRP3 inflammasome, and motor dysfunction. Furthermore, 2ccPA treatment reduced autoreactive T cells and macrophages, spinal cord injury, and pathological scores in EAE, the autoimmune multiple sclerosis mouse model. We demonstrated that 2ccPA protected oligodendrocytes via suppression of the mitochondrial apoptosis pathway. Also, we found beneficial effects of 2ccPA in the multiperiod of cuprizone-induced demyelination and the pathology of EAE. These data indicate that 2ccPA may be a promising compound for the development of new drugs to treat demyelinating disease and ameliorate the symptoms of multiple sclerosis.

Genetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis

PubMed Central

Mkhikian, Haik; Grigorian, Ani; Li, Carey F.; Chen, Hung-Lin; Newton, Barbara; Zhou, Raymond W.; Beeton, Christine; Torossian, Sevan; Tatarian, Gevork Grikor; Lee, Sung-Uk; Lau, Ken; Walker, Erin; Siminovitch, Katherine A.; Chandy, K. George; Yu, Zhaoxia; Dennis, James W.; Demetriou, Michael

2011-01-01

How environmental factors combine with genetic risk at the molecular level to promote complex trait diseases such as multiple sclerosis (MS) is largely unknown. In mice, N-glycan branching by the Golgi enzymes Mgat1 and/or Mgat5 prevents T cell hyperactivity, cytotoxic T-lymphocyte antigen 4 (CTLA-4) endocytosis, spontaneous inflammatory demyelination and neurodegeneration, the latter pathologies characteristic of MS. Here we show that MS risk modulators converge to alter N-glycosylation and/or CTLA-4 surface retention conditional on metabolism and vitamin D3, including genetic variants in interleukin-7 receptor-α (IL7RA*C), interleukin-2 receptor-α (IL2RA*T), MGAT1 (IVAVT−T) and CTLA-4 (Thr17Ala). Downregulation of Mgat1 by IL7RA*C and IL2RA*T is opposed by MGAT1 (IVAVT−T) and vitamin D3, optimizing branching and mitigating MS risk when combined with enhanced CTLA-4 N-glycosylation by CTLA-4 Thr17. Our data suggest a molecular mechanism in MS whereby multiple environmental and genetic inputs lead to dysregulation of a final common pathway, namely N-glycosylation. PMID:21629267

Next-Generation Pathology.

PubMed

Caie, Peter D; Harrison, David J

2016-01-01

The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

Interpersonal perception of pathological narcissism: a social relations analysis.

PubMed

Lukowitsky, Mark R; Pincus, Aaron L

2013-01-01

Impairments in self and interpersonal functioning are core features of personality pathology. Clinical theory and research indicate that compromised self-awareness and distorted interpersonal perceptions are particularly prominent in individuals exhibiting pathological narcissism and Narcissistic Personality Disorder. Therefore we conducted a study to gain a better understanding of interpersonal perception of pathological narcissism. A large sample (N=437) of moderately acquainted individuals assigned to 1 of 93 small mixed-sex groups completed self- and informant ratings on the Pathological Narcissism Inventory (PNI) in a round-robin design. The social relations model (SRM) was used to partition the variance in dyadic ratings to investigate several hypotheses about interpersonal perception of pathological narcissism. SRM analyses demonstrated evidence of assimilation (the tendency to perceive and rate others similarly) and consensus (the extent to which multiple observers form similar impressions of another person) in interpersonal perception of pathological narcissism. Results also indicated modest self-other agreement and assumed similarity (the tendency for people to perceive others as similar to themselves) for PNI higher order factors and subscale ratings. Finally, results suggested that individuals high in pathological narcissism had some awareness of how peers would rate them (metaperception) but believed that others would rate them similarly to how they rated themselves.

Postmortem examination of Australian sea snakes ( Hydrophiinae): Anatomy and common pathologic conditions.

PubMed

Gillett, Amber K; Ploeg, Richard; Flint, Mark; Mills, Paul C

2017-09-01

There is limited published information about disease in wild sea snakes and no standardized guideline for postmortem examination of sea snakes. Identifying causes of morbidity and mortality of marine vertebrate species has been pivotal to understanding disease factors implicated in stranding events and assisting with the formulation of conservation plans. Additionally, postmortem findings can provide valuable information on life history traits and the ecology of these reclusive species. Sick, moribund, or dead sea snakes are intermittently washed ashore along Australian and international beaches and provide an opportunity to examine a subset of the population and identify causes of population decline. We present an illustrated description of sea snake anatomy and describe a systematic approach to postmortem examination of sea snakes. We describe common pathologic conditions identified from clinical and postmortem examinations of stranded Australian sea snakes from southeast Queensland. Notable pathologic conditions include traumatic injury, inflammatory conditions, parasitic infections, and neoplasia.

Raymond's Paragraph System: an alternative format for the organization of gross pathology reports and its implementation in an academic teaching hospital.

PubMed

Dayton, Annette S; Ro, Jae Y; Schwartz, Mary R; Ayala, Alberto G; Raymond, A Kevin

2009-02-01

Traditionally organized gross pathology reports, which are widely used in pathology resident and pathologists' assistant training programs, may not offer the most efficient method of communicating pertinent information to treating physicians. Instructional materials for teaching gross pathology dictation are limited and the teaching methods used are inconsistent. Raymond's Paragraph System, a gross pathology report formatting system, was developed for use at a cancer center and has been implemented at The Methodist Hospital, Houston, Tex, an academic medical center. Unlike traditionally organized reports in which everything is normally dictated in 1 long paragraph, this system separates the dictation into multiple paragraphs creating an organized and comprehensible report. Recent literature regarding formatting of pathology reports focuses primarily on the organization of specimen diagnoses and overall report layout. However, little literature is available that highlights organization of the specimen gross descriptions. To provide instruction to pathologists, pathology residents and fellows, and pathologists' assistant students about an alternative method of organizing gross pathology reports. Review of pertinent literature relating to preparation of gross pathology reports, report formatting, and pathology laboratory credentialing requirements. The paragraph system offers a viable alternative to traditionally organized pathology reports. Primarily, it provides a working model for medical professionals-in-training. It helps create user-friendly pathology reports by giving precise and concise information in a standardized format. This article provides an overview of the system and discusses our experience in its implementation.

Inhibiting poly(ADP-ribose) polymerase: a potential therapy against oligodendrocyte death

PubMed Central

Veto, Sara; Acs, Peter; Bauer, Jan; Lassmann, Hans; Berente, Zoltan; Setalo, Gyorgy; Borgulya, Gabor; Sumegi, Balazs; Komoly, Samuel; Gallyas, Ferenc; Illes, Zsolt

2010-01-01

Oligodendrocyte loss and demyelination are major pathological hallmarks of multiple sclerosis. In pattern III lesions, inflammation is minor in the early stages, and oligodendrocyte apoptosis prevails, which appears to be mediated at least in part through mitochondrial injury. Here, we demonstrate poly(ADP-ribose) polymerase activation and apoptosis inducing factor nuclear translocation within apoptotic oligodendrocytes in such multiple sclerosis lesions. The same morphological and molecular pathology was observed in an experimental model of primary demyelination, induced by the mitochondrial toxin cuprizone. Inhibition of poly(ADP-ribose) polymerase in this model attenuated oligodendrocyte depletion and decreased demyelination. Poly(ADP-ribose) polymerase inhibition suppressed c-Jun N-terminal kinase and p38 mitogen-activated protein kinase phosphorylation, increased the activation of the cytoprotective phosphatidylinositol-3 kinase-Akt pathway and prevented caspase-independent apoptosis inducing factor-mediated apoptosis. Our data indicate that poly(ADP-ribose) polymerase activation plays a crucial role in the pathogenesis of pattern III multiple sclerosis lesions. Since poly(ADP-ribose) polymerase inhibition was also effective in the inflammatory model of multiple sclerosis, it may target all subtypes of multiple sclerosis, either by preventing oligodendrocyte death or attenuating inflammation. PMID:20157013

The molecular basis of jaundice: An old symptom revisited.

PubMed

Gazzin, Silvia; Masutti, Flora; Vitek, Libor; Tiribelli, Claudio

2017-08-01

Increased serum bilirubin level is a widely used diagnostic marker for hepatic illnesses. Nevertheless, mild elevation of unconjugated serum bilirubin (such as in Gilbert syndrome) has been recently demonstrated to correlate with low risk of chronic inflammatory and/or oxidative stress-mediated diseases. In accord, a low serum bilirubin level has emerged as an important predisposing factor or a biomarker of these pathologic conditions including cardiovascular, tumour, and possibly neurodegenerative diseases. Bilirubin possesses multiple biological actions with interaction in a complex network of enzymatic and signalling pathways. The fact that the liver is the main organ controlling the bioavailability of bilirubin emphasizes the central role of this organ in human health. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Successful management of angiolymphoid hyperplasia with eosinophilia in a split-face trial of topical tacrolimus and timolol solution.

PubMed

Chacon, Anna; Mercer, Jessica

2016-08-01

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign condition characterized by multiple benign angiomatous nodules or plaques. Cutaneous lesions can be painful, pruritic, pulsatile, or potentially disfiguring resulting in significant morbidity. ALHE is a pathologic diagnosis featuring proliferations of capillary-sized vessels with epithelioid endothelial cells surrounded by larger, thick-walled vessels and accompanying eosinophils and lymphocytes. Surgery is generally required, however the skin lesions often recur after excision. ALHE is notoriously difficult to treat and many physicians would prefer a non-invasive treatment of choice. We report a case of ALHE that was successfully treated with the novel use of topical tacrolimus in a split-face trial with topical timolol solution.

A flame burning within.

PubMed

Ferrucci, Luigi; Ble, Alessandro; Bandinelli, Stefania; Lauretani, Fulvio; Suthers, Kristen; Guralnik, Jack M

2004-06-01

Inflammation is a human being's primary defense against threats to homeostasis that are encountered every day. Especially in old age, when regulatory mechanisms responsible for inflammatory responses may be ineffective or damaged, the result can be adverse pathological conditions, and an increased risk of morbidity and mortality. The inflammation response is a plastic network composed of redundant signaling among several different mediators. These mediators have a reciprocal relationship with other biological sub-systems, including hormone regulation, the autonomic nervous system, and oxidative/anti-oxidant balance. Studying this complex architecture requires parallel and multiple research strategies from epidemiological to biochemical level, from observational studies to innovative intervention approaches. Given that the inflammatory response is a critical age-related process, understanding its regulatory action is essential in avoiding hazardous consequences in old age.

Nonbacterial Thrombotic Endocarditis in a Patient with Bowel Infarction due to Mesenteric Vein Thrombosis.

PubMed

Kim, Hyue Mee; Kim, Hack-Lyoung; Lee, Hak Seung; Jung, Ji-Hyun; Kim, Chee Hae; Oh, Sooyeon; Kim, Jung Ho; Zo, Joo-Hee

2014-05-01

Ante mortem cases of venous thrombosis in patients with nonbacterial thrombotic endocarditis (NBTE) have not yet been reported. We describe a rare case of NBTE in a patient with mesenteric vein thrombosis. A healthy 37-year-old man with abdominal pain and fever underwent emergency small bowel resection due to bowel ischemia resulting from mesenteric vein thrombosis. Transthoracic echocardiography revealed multiple mobile masses attached to the anterior leaflet of the mitral valves and their chordae tendineae. On suspicion of infective endocarditis, the cardiac masses were excised through open-heart surgery. However, pathologic reviews were compatible with NBTE. The patient was stable after the cardiac surgery and was treated with warfarin. Laboratory and imaging findings regarding his hypercoagulable condition were all negative.

Visual function affects prosocial behaviors in older adults.

PubMed

Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

2016-02-01

Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

White-nose syndrome pathology grading in Nearctic and Palearctic bats

PubMed Central

Pikula, Jiri; Amelon, Sybill K.; Bandouchova, Hana; Bartonička, Tomáš; Berkova, Hana; Brichta, Jiri; Hooper, Sarah; Kokurewicz, Tomasz; Kolarik, Miroslav; Köllner, Bernd; Kovacova, Veronika; Linhart, Petr; Piacek, Vladimir; Turner, Gregory G.; Zukal, Jan; Martínková, Natália

2017-01-01

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity. PMID:28767673

White-nose syndrome pathology grading in Nearctic and Palearctic bats.

PubMed

Pikula, Jiri; Amelon, Sybill K; Bandouchova, Hana; Bartonička, Tomáš; Berkova, Hana; Brichta, Jiri; Hooper, Sarah; Kokurewicz, Tomasz; Kolarik, Miroslav; Köllner, Bernd; Kovacova, Veronika; Linhart, Petr; Piacek, Vladimir; Turner, Gregory G; Zukal, Jan; Martínková, Natália

2017-01-01

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity.

The Effect of Diazoxide and Dimethyl Sulfoxide on Behavioral Outcomes and Markers of Pathology Following Controlled Cortical Impact

DTIC Science & Technology

2012-07-16

Over the last 30 years, preclinical research focused on evaluating potential pharmacologic therapeutic agents has produced multiple promising... potential therapeutic targets are being identified at a staggering rate as technology advances and our understanding of the pathology behind brain injury... potential therapeutic windows for interventional therapy. VI THE EFFECT OF DIAZOXIDE AND DIMETHYL SULFOXIDE ON BEHAVIORAL OUTCOMES AND MARKERS OF

Imaging in multiple sclerosis: A new spin on lesions.

PubMed

Bou Fakhredin, Rayan; Saade, Charbel; Kerek, Racha; El-Jamal, Lara; Khoury, Samia J; El-Merhi, Fadi

2016-10-01

This article evaluates the most relevant state-of-the-art magnetic resonance (MR) techniques that are clinically available to investigate multiple sclerosis (MS). The presence of hypo- and hyperintense lesions on T1- and T2-weighted magnetic resonance imaging (MRI) sequences in white matter (WM) is a common finding that is occasionally a diagnostic challenge for the radiologist. The technical requirements and how they may help to understand, classify or follow-up these pathologies are briefly summarized. The gold standard for MS diagnosis is pathological correlation. Yet due to limited availability of biopsy and autopsy material, there is a high demand for imaging as a diagnostic as well as prognostic indicator. With the progress in MRI during the last decade, MRI now plays a leading role in the diagnosis and follow-up of MS. A number of correlative pathological and MR studies have helped to define pathological substrates of MS in focal lesions and normal appearing white matter (NAWM). Vascular spaces mimicking MS lesions have been minimized by the enhanced differentiation of WM and grey (GM) matter parenchyma. The aim of this article is to enhance the current understanding of histopathology and radiological characteristics of MS lesions in space and time. © 2016 The Royal Australian and New Zealand College of Radiologists.

Pathological and Ecological Host Consequences of Infection by an Introduced Fish Parasite

PubMed Central

Britton, J. Robert; Pegg, Josephine; Williams, Chris F.

2011-01-01

The infection consequences of the introduced cestode fish parasite Bothriocephalus acheilognathi were studied in a cohort of wild, young-of-the-year common carp Cyprinus carpio that lacked co-evolution with the parasite. Within the cohort, parasite prevalence was 42% and parasite burdens were up to 12% body weight. Pathological changes within the intestinal tract of parasitized carp included distension of the gut wall, epithelial compression and degeneration, pressure necrosis and varied inflammatory changes. These were most pronounced in regions containing the largest proportion of mature proglottids. Although the body lengths of parasitized and non-parasitized fish were not significantly different, parasitized fish were of lower body condition and reduced weight compared to non-parasitized conspecifics. Stable isotope analysis (δ15N and δ13C) revealed trophic impacts associated with infection, particularly for δ15N where values for parasitized fish were significantly reduced as their parasite burden increased. In a controlled aquarium environment where the fish were fed ad libitum on an identical food source, there was no significant difference in values of δ15N and δ13C between parasitized and non-parasitized fish. The growth consequences remained, however, with parasitized fish growing significantly slower than non-parasitized fish, with their feeding rate (items s−1) also significantly lower. Thus, infection by an introduced parasite had multiple pathological, ecological and trophic impacts on a host with no experience of the parasite. PMID:22022606

Relationship between energy dense diets and white adipose tissue inflammation in metabolic syndrome.

PubMed

Alemany, Marià

2013-01-01

Metabolic syndrome (MS) is a widespread pathologic state that manifests as multiple intertwined diseases affecting the entire body. This review analyzes the contribution of adipose tissue inflammation to its development. The main factor in the appearance of MS is an excess of dietary energy (largely fats), eliciting insulin resistance and creating the problem of excess energy disposal. Under these conditions, amino acid catabolism is diminished, which indirectly alters the production of nitric oxide and affects blood flow regulation. The oxidation of nitric oxide to nitrite and nitrate affects microbiota composition and functions. Adipose tissue cannot incorporate excessive nutrients after cell enlargement and loss of function. Tissue damage is a form of aggression, and the response is proinflammatory cytokine release. Cytokines favor the massive penetration of immune system cells, such as macrophages, which unsuccessfully try to fight an elusive danger for which they are not prepared. The consequence is low-level maintenance of the inflammatory state, which affects endoplasmic reticulum function and the endothelial response to excess regulatory mechanisms affecting blood flow and substrate/oxygen supply. When inflammation becomes chronic, the pathologic consequences are disseminated throughout the body because unused substrates and signals from adipose tissue affect energy partitioning and organ function. This maintenance of an unbalanced state ultimately results in the establishment of MS and associated pathologies. New research should focus on identifying ways to disarm the inflammatory response of adipose tissue when the dangers of dietary excess have already been controlled. Copyright © 2013. Published by Elsevier Inc.

Relationships Between Problem-Gambling Severity and Psychopathology as Moderated by Income.

PubMed

Sanacora, Rachel L; Whiting, Seth W; Pilver, Corey E; Hoff, Rani A; Potenza, Marc N

2016-09-01

Background and aims Problem and pathological gambling have been associated with elevated rates of both Axis-I and Axis-II psychiatric disorders. Although both problem gambling and psychiatric disorders have been reported as being more prevalent among lower income vs. middle/higher income groups, how income might moderate the relationship between problem-gambling severity and psychopathology is incompletely understood. To examine the associations between problem-gambling severity and psychopathology in lower income and middle/higher income groups. Methods Data from the first wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093) were analyzed in adjusted logistic regression models to investigate the relationships between problem-gambling severity and psychiatric disorders within and across income groups. Results Greater problem-gambling severity was associated with increased odds of multiple psychiatric disorders for both lower income and middle/higher income groups. Income moderated the association between problem/pathological gambling and alcohol abuse/dependence, with a stronger association seen among middle/higher income respondents than among lower income respondents. Discussion and conclusions The findings that problem-gambling severity is related to psychopathology across income groups suggest a need for public health initiatives across social strata to reduce the impact that problem/pathological gambling may have in relation to psychopathology. Middle/higher income populations, perhaps owing to the availability of more "disposable income," may be at greater risk for co-occurring gambling and alcohol-use psychopathology and may benefit preferentially from interventions targeting both gambling and alcohol use.

The nexus between periodontics and oral pathology.

PubMed

Rich, Alison M; Seo, Benedict; Parachuru, Venkata; Hussaini, Haizal M

2017-06-01

A wide variety of lesions may arise from the oral mucosa, fibrous connective tissue, bone and cementum of the periodontium. The commonest pathology occurs as a result of bacterial infection and is very well known to dentists and periodontists, but rarer conditions present as gingival pathology. The pathogenesis of these conditions ranges from genetic to traumatic to immunological to neoplastic, and includes benign, malignant and metastatic lesions. This paper outlines some of these conditions and describes how the periodontist and oral pathologist can work together using a framework, and how with careful consideration of the clinical features and the use of appropriate special tests, including obtaining an adequate tissue specimen, a timely and accurate diagnosis can be obtained. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GORE Flow Reversal System and GORE Embolic Filter Extension Study

ClinicalTrials.gov

2016-01-22

Carotid Stenosis; Constriction, Pathologic; Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical

Alterity: Learning Polyvalent Selves, Resisting Disabling Notions of the Self

ERIC Educational Resources Information Center

Walker, Wayland

2011-01-01

This article queries how one type of human difference--alterity, the experience of multiple distinct consciousnesses, or "alters," by one person--is pathologized in American culture. This experience is inscribed as a mental illness, labeled now as dissociative identity disorder (DID) and formerly known as multiple personality disorder (MPD). In…

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

PubMed Central

Williams, Jonathan M.

2017-01-01

ABSTRACT Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. PMID:28151409

The effectiveness of annotated (vs. non-annotated) digital pathology slides as a teaching tool during dermatology and pathology residencies.

PubMed

Marsch, Amanda F; Espiritu, Baltazar; Groth, John; Hutchens, Kelli A

2014-06-01

With today's technology, paraffin-embedded, hematoxylin & eosin-stained pathology slides can be scanned to generate high quality virtual slides. Using proprietary software, digital images can also be annotated with arrows, circles and boxes to highlight certain diagnostic features. Previous studies assessing digital microscopy as a teaching tool did not involve the annotation of digital images. The objective of this study was to compare the effectiveness of annotated digital pathology slides versus non-annotated digital pathology slides as a teaching tool during dermatology and pathology residencies. A study group composed of 31 dermatology and pathology residents was asked to complete an online pre-quiz consisting of 20 multiple choice style questions, each associated with a static digital pathology image. After completion, participants were given access to an online tutorial composed of digitally annotated pathology slides and subsequently asked to complete a post-quiz. A control group of 12 residents completed a non-annotated version of the tutorial. Nearly all participants in the study group improved their quiz score, with an average improvement of 17%, versus only 3% (P = 0.005) in the control group. These results support the notion that annotated digital pathology slides are superior to non-annotated slides for the purpose of resident education. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia

PubMed Central

Lim, Young H.; Ovejero, Diana; Sugarman, Jeffrey S.; DeKlotz, Cynthia M.C.; Maruri, Ann; Eichenfield, Lawrence F.; Kelley, Patrick K.; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J.; Gafni, Rachel I.; Boyce, Alison M.; Cowen, Edward W.; Bhattacharyya, Nisan; Guthrie, Lori C.; Gahl, William A.; Golas, Gretchen; Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.; Levy, Moise L.; Collins, Michael T.; Choate, Keith A.

2014-01-01

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23. PMID:24006476

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.

PubMed

Lim, Young H; Ovejero, Diana; Sugarman, Jeffrey S; Deklotz, Cynthia M C; Maruri, Ann; Eichenfield, Lawrence F; Kelley, Patrick K; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J; Gafni, Rachel I; Boyce, Alison M; Cowen, Edward W; Bhattacharyya, Nisan; Guthrie, Lori C; Gahl, William A; Golas, Gretchen; Loring, Erin C; Overton, John D; Mane, Shrikant M; Lifton, Richard P; Levy, Moise L; Collins, Michael T; Choate, Keith A

2014-01-15

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.

A pathologist-designed imaging system for anatomic pathology signout, teaching, and research.

PubMed

Schubert, E; Gross, W; Siderits, R H; Deckenbaugh, L; He, F; Becich, M J

1994-11-01

Pathology images are derived from gross surgical specimens, light microscopy, immunofluorescence, electron microscopy, molecular diagnostic gels, flow cytometry, image analysis data, and clinical laboratory data in graphic form. We have implemented a network of desktop personal computers (PCs) that allow us to easily capture, store, and retrieve gross and microscopic, anatomic, and research pathology images. System architecture involves multiple image acquisition and retrieval sites and a central file server for storage. The digitized images are conveyed via a local area network to and from image capture or display stations. Acquisition sites consist of a high-resolution camera connected to a frame grabber card in a 486-type personal computer, equipped with 16 MB (Table 1) RAM, a 1.05-gigabyte hard drive, and a 32-bit ethernet card for access to our anatomic pathology reporting system. We have designed a push-button workstation for acquiring and indexing images that does not significantly interfere with surgical pathology sign-out. Advantages of the system include the following: (1) Improving patient care: the availability of gross images at time of microscopic sign-out, verification of recurrence of malignancy from archived images, monitoring of bone marrow engraftment and immunosuppressive intervention after bone marrow/solid organ transplantation on repeat biopsies, and ability to seek instantaneous consultation with any pathologist on the network; (2) enhancing the teaching environment: building a digital surgical pathology atlas, improving the availability of images for conference support, and sharing cases across the network; (3) enhancing research: case study compilation, metastudy analysis, and availability of digitized images for quantitative analysis and permanent/reusable image records for archival study; and (4) other practical and economic considerations: storing case requisition images and hand-drawn diagrams deters the spread of gross room contaminants and results in considerable cost savings in photographic media for conferences, improved quality assurance by porting control stains across the network, and a multiplicity of other advantages that enhance image and information management in pathology.

Automatic detection of referral patients due to retinal pathologies through data mining.

PubMed

Quellec, Gwenolé; Lamard, Mathieu; Erginay, Ali; Chabouis, Agnès; Massin, Pascale; Cochener, Béatrice; Cazuguel, Guy

2016-04-01

With the increased prevalence of retinal pathologies, automating the detection of these pathologies is becoming more and more relevant. In the past few years, many algorithms have been developed for the automated detection of a specific pathology, typically diabetic retinopathy, using eye fundus photography. No matter how good these algorithms are, we believe many clinicians would not use automatic detection tools focusing on a single pathology and ignoring any other pathology present in the patient's retinas. To solve this issue, an algorithm for characterizing the appearance of abnormal retinas, as well as the appearance of the normal ones, is presented. This algorithm does not focus on individual images: it considers examination records consisting of multiple photographs of each retina, together with contextual information about the patient. Specifically, it relies on data mining in order to learn diagnosis rules from characterizations of fundus examination records. The main novelty is that the content of examination records (images and context) is characterized at multiple levels of spatial and lexical granularity: 1) spatial flexibility is ensured by an adaptive decomposition of composite retinal images into a cascade of regions, 2) lexical granularity is ensured by an adaptive decomposition of the feature space into a cascade of visual words. This multigranular representation allows for great flexibility in automatically characterizing normality and abnormality: it is possible to generate diagnosis rules whose precision and generalization ability can be traded off depending on data availability. A variation on usual data mining algorithms, originally designed to mine static data, is proposed so that contextual and visual data at adaptive granularity levels can be mined. This framework was evaluated in e-ophtha, a dataset of 25,702 examination records from the OPHDIAT screening network, as well as in the publicly-available Messidor dataset. It was successfully applied to the detection of patients that should be referred to an ophthalmologist and also to the specific detection of several pathologies. Copyright © 2016 Elsevier B.V. All rights reserved.

Depressive-like behavioral profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

PubMed Central

Camus, Sandrine M. J.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

2014-01-01

Background: To unravel the causes of major depressive disorder (MDD), the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament, or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored. Methods: Behavioral data (including body postures, orientations, gaze directions, inter-individual distances, and locations in the cage) were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys. Results: Consistent with our previous studies, we found depressive-like characteristics (e.g., inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall) among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles. Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a “spontaneous” model of depressive disorders. PMID:24600363

Urethral calculi in young-adult Nigerian males: a case series.

PubMed

Gali, B M; Ali, N; Agbese, G O; Garba, I I; Musa, K

2011-01-01

Urethral calculi are rare and usually encountered in males with urethral pathology. To present our experience managing urethral calculi in a resource limited centre and review the literature. We did a chart review of management of patients with urethral calculi between January and April 2009, at Federal Medical Centre (FMC) Azare, Nigeria. We also reviewed the literature on this rare condition. Four young adult male Nigerians between the ages of 17 and 27 years presented with varying degrees of urethral pain and palpable calculi in the anterior urethra. Two presented with acute retention of urine, but none had haematuria. The calculi were radio-opaque, located in the anterior urethra with no associated urethral pathology. Three were solitary and one multiple. The composition of the urethral calculi was a mixture of calcium oxalate calcium carbonate, magnesium phosphate, one has additional cystine but none had struvite or uric acid. Their sizes ranged between 1cm ×1.5cm and 1.5cm × 5.5cm. External urethrotomy was the method of treatment. Urethral calculi are rare in our setting, with no clear identifiable aetiological factors which suggests urinary schistosomiasisbeing associsted. The occurrence of urethral calculi appears to have a relationship with childhood urinary schistosomasis.

The role of noninvasive and invasive diagnostic imaging techniques for detection of extra-cranial venous system anomalies and developmental variants

PubMed Central

2013-01-01

The extra-cranial venous system is complex and not well studied in comparison to the peripheral venous system. A newly proposed vascular condition, named chronic cerebrospinal venous insufficiency (CCSVI), described initially in patients with multiple sclerosis (MS) has triggered intense interest in better understanding of the role of extra-cranial venous anomalies and developmental variants. So far, there is no established diagnostic imaging modality, non-invasive or invasive, that can serve as the “gold standard” for detection of these venous anomalies. However, consensus guidelines and standardized imaging protocols are emerging. Most likely, a multimodal imaging approach will ultimately be the most comprehensive means for screening, diagnostic and monitoring purposes. Further research is needed to determine the spectrum of extra-cranial venous pathology and to compare the imaging findings with pathological examinations. The ability to define and reliably detect noninvasively these anomalies is an essential step toward establishing their incidence and prevalence. The role for these anomalies in causing significant hemodynamic consequences for the intra-cranial venous drainage in MS patients and other neurologic disorders, and in aging, remains unproven. PMID:23806142

[Sexuality and trans experiences: from the hospital to the bedroom].

PubMed

Bento, Berenice

2012-10-01

In the aftermath of studies on masculinity, it is impossible to consider the production of gender identities without linking them to the relationship aspect. This change was due to the incorporation of the relationship perspective in this field of study and criticism of the concept of gender founded upon an alleged concept of femininity and masculinity to create interpretations of the place of bodies in the gender order. The objectives of this paper are: 1) to show how a given concept of gender can render multiple expressions of gender visible, like the trans identities (transsexuals, transvestites, cross dressers, drag queens, drag kings, transgenders) or sublimate them and contribute to their pathologization. The second objective will be to present narratives of trans men and trans women, who will tell us about their sexual experiences. Psycho-physicians contend the non-existence of sexuality in their bodies as being one of the indicators to lead to a diagnosis of transsexualism. I will attempt to argue that the theoretical basis that supports the pathologization of trans identities and the assertion that trans people are asexual is based on a conception that links and renders gender identities conditional upon biological structures.

Effects of chalcone derivatives on players of the immune system

PubMed Central

Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

2015-01-01

The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells. PMID:26316713

Personality and its Relation to Mental and Psychosocial Health in Emerging Adult Sexual Minority Men: The P18 Cohort Study.

PubMed

D'Avanzo, Paul A; Barton, Staci C; Kapadia, Farzana; Halkitis, Perry N

2017-01-01

Personality disorder and personality pathology encompass a dimension of psychological dysfunction known to severely impact multiple domains of functioning. However, there is a notable dearth of research regarding both the pervasiveness and correlates of personality pathology among young sexual minority males who themselves experience heightened mental health burdens. Using the self-report version of the Standardized Assessment of Personality-Abbreviated Scale we tested associations between distinct personality characteristics with sociodemographic and psychosocial factors as well as mental health states in a sample of 528 young (aged 21-25 years) sexual minority men. In multivariate analysis, personality traits varied significantly by race/ethnicity. Personality traits were also positively associated with psychosocial states, specifically, internalized anti-homosexual bias, level of connection with the gay community, and male body dissatisfaction, as well as mental health in the form of recent depressive and anxious symptomatology. These findings support the complex synergy which exists between personality characteristics, psychosocial conditions, and mental health burdens present among sexual minority men and support the need for an all-encompassing approach to both the study and care of this population that addresses the influences of both internal and external factors on well-being.

The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

PubMed Central

2012-01-01

Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases. PMID:23259712

The biophysical bases of will-less behaviors

PubMed Central

Perez Velazquez, José L.

2012-01-01

Are there distinctions at the neurophysiological level that correlate with voluntary and involuntary actions? Whereas the wide variety of involuntary behaviors (and here mostly the deviant or pathological ones will be considered) will necessarily be represented at some biophysical level in nervous system activity–for after all those cellular activity patterns manifest themselves as behaviors and thus there will be a multiplicity of them–there could be some general tendencies to be discerned amongst that assortment. Collecting observations derived from neurophysiological activity associated with several pathological conditions characterized by presenting will-less actions such as Parkinson's disease, seizures, alien hand syndrome and tics, it is proposed that a general neurophysiologic tendency of brain activity that correlates with involuntary actions is higher than normal synchrony in specific brain cell networks, depending upon the behavior in question. Wilful, considered normal behavior, depends on precise coordination of the collective activity in cell ensembles that may be lost, or diminished, when there are tendencies toward more than normal or aberrant synchronization of cellular activity. Hence, rapid fluctuations in synchrony is associated with normal actions and cognition while less variability in brain recordings particularly with regards to synchronization could be a signature of unconscious and deviant behaviors in general. PMID:23109920

Art and the teaching of pathological anatomy at the University of Florence since the nineteenth century.

PubMed

Nesi, Gabriella; Santi, Raffaella; Taddei, Gian Luigi

2009-07-01

In 1840, the University of Florence was the first university in Italy to confer a Professorship in Pathological Anatomy. The origin of this teaching post is linked to the history of the Pathology Museum founded in 1824 by the Florentine Accademia Medico-Fisica. The Museum houses anatomical specimens and waxworks depicting pathological conditions in the nineteenth century. Both the need to instruct medical students in pathology without resorting to corpse dissection and the difficulty of the lengthy preservation of anatomical preparations made it necessary to produce life-sized wax duplicates of diseased parts of the body. Through the history of the Pathology Museum of Florence, we describe how pathology developed and, in particular, how pathologists from a literary circle laid the foundations of modern surgical pathology in Italy. Museum visits for the medical students guided by lecturers are still today a component of the course of Pathological Anatomy.

Human conditions of insulin-like growth factor-I (IGF-I) deficiency

PubMed Central

2012-01-01

Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range. PMID:23148873

Plasticity and Maintenance of Hematopoietic Stem Cells During Development

PubMed Central

Kanji, Suman; Pompili, Vincent J.; Das, Hiranmoy

2012-01-01

Maintenance of hematopoietic stem cells (HSCs) pool depends on fine balance between self-renewal and differentiation of HSCs. HSCs normally reside within the bone marrow niche of an adult mammal. The embryonic development of HSCs is a complex process that involves the migration of developing HSCs in multiple anatomical sites. Throughout the process, developing HSCs receive internal (transcriptional program) and external (HSC niche) signals, which direct them to maintain balance between self-renewal and differentiation, also to generate a pool of HSCs. In physiological condition HSCs differentiate into all mature cell types present in the blood. However, in pathological condition they may differentiate into non-hematological cells according to the need of the body. It was shown that HSCs can transdifferentiate into cell types that do not belong to the hematopoietic system suggests a complete paradigm shift of the hierarchical hematopoietic tree. This review describes the developmental origins and regulation of HSCs focusing on developmental signals that induce the adult hematopoietic stem cell program, as these informations are very critical for manipulating conditions for expansion of HSCs in ex vivo condition. This review also states clinical application and related patents using HSC. PMID:21517745

The Added Diagnostic Value of 18F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

PubMed

Addeo, Pietro; Poncet, Gilles; Goichot, Bernard; Leclerc, Loic; Brigand, Cécile; Mutter, Didier; Romain, Benoit; Namer, Izzie-Jacques; Bachellier, Philippe; Imperiale, Alessio

2018-04-01

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs. Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18 F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18 F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology. There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18 F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18 F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003). 18 F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18 F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

Insular Alzheimer disease pathology and the psychometric correlates of mortality.

PubMed

Royall, Donald R

2008-03-01

Right hemisphere dysfunction is associated with mortality in Alzheimer's disease (AD) and other neurologic conditions. These associations may be mediated by insular pathology, as insular lesions result in demonstrable changes in cardiovascular and autonomic control. AD affects the insulae at a preclinical stage, and insular AD pathology may be present in up to 40% of nondemented septuagenarians and octogenarians. This pathology can affect in vivo cardiac conduction and thereby dispose to cardiac arrhythmias and sudden death. Thus, AD pathology should be considered as a possible explanation for autonomic morbidity and mortality in nondemented elderly persons.

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis subjects had diffusely lower intracellular volume fractions than the white matter in controls (P = 0.029 by unpaired t-test). Cortical thickness did not differ significantly between multiple sclerosis subjects and controls. Higher orientation dispersion in the left primary motor-somatosensory cortex was associated with increased Expanded Disability Status Scale scores in surface-based general linear modelling (P < 0.05). Microstructural pathology was frequent in early multiple sclerosis, and present mainly focally in cortical lesions, whereas more diffusely in white matter. These results suggest early demyelination with loss of cells and/or cell volumes in cortical and white matter lesions, with additional axonal dispersion in white matter lesions. In the cortex, focal lesion changes might precede diffuse atrophy with cortical thinning. Findings in the normal-appearing white matter reveal early axonal pathology outside inflammatory demyelinating lesions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Wide field of view CT and acromioclavicular joint instability: A technical innovation.

PubMed

Dyer, David R; Troupis, John M; Kamali Moaveni, Afshin

2015-06-01

A 21-year-old female with a traumatic shoulder injury is investigated and managed for symptoms relating to this injury. Pathology at the acromioclavicular joint is detected clinically; however, clinical examination and multiple imaging modalities do not reach a unified diagnosis on the grading of this acromioclavicular joint injury. When management appropriate to that suggested injury grading fail to help the patient's symptoms, further investigation methods were utilised. Wide field of view, dynamic CT (4D CT) is conducted on the patient's affected shoulder using a 320 × 0.5 mm detector multislice CT. Scans were conducted with a static table as the patient completed three movements of the affected shoulder. Capturing multiple data sets per second over a z-axis of 16 cm, measurements of the acromioclavicular joint were made, to show dynamic changes at the joint. Acromioclavicular (AC) joint translations were witnessed in three planes (a previously unrecognised pathology in the grading of acromioclavicular joint injuries). Translation in multiple planes was also not evident on careful clinical examination of this patient. AC joint width, anterior-posterior translation, superior-inferior translation and coracoclavicular width were measured with planar reconstructions while volume-rendered images and dynamic sequences aiding visual understanding of the pathology. Wide field of view dynamic CT (4D CT) is an accurate and quick modality to diagnose complex acromioclavicular joint injury. It provides dynamic information that no other modality can; 4D CT shows future benefits for clinical approach to diagnosis and management of acromioclavicular joint injury, and other musculoskeletal pathologies. © 2015 The Royal Australian and New Zealand College of Radiologists.

THE REGULATION ROLE OF CAROTID BODY PERIPHERAL CHEMORECEPTORS IN PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS.

PubMed

Lazovic, Biljana; Zlatkovic Svenda, Mirjana; Durmic, Tijana; Stajic, Zoran; Duric, Vesna; Zugic, Vladimir

2016-11-01

The major oxygen sensors in the human body are peripheral chemoreceptors. also known as interoreceptors- as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae, homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors. responsible for carbon dioxide changes . and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sy mpatholysis ultimately determine the peripheral chemorcceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

Empirical evaluation of the inter-relationship of articular elements involved in the pathoanatomy of knee osteoarthritis using magnetic resonance imaging.

PubMed

Meredith, Dennis S; Losina, Elena; Neumann, Gesa; Yoshioka, Hiroshi; Lang, Philipp K; Katz, Jeffrey N

2009-10-29

In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis. Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table. Data from 140 patients were available for review. The cohort had a median age of 61 years (range 45-89) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend < 0.0001). Comparison of CDS to change in the severity of pathology of individual articular elements showed statistically significant trends towards more severe pathology as CDS worsened for osteophytes (p-value for trend < 0.0001), bone marrow lesions (p = 0.0003), and subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion. Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these findings to clinically relevant outcomes such as pain and function.

Integrating multiple aspects of mitochondrial dynamics in neurons: Age-related differences and dynamic changes in a chronic rotenone model

PubMed Central

Arnold, Beth; Cassady, Steven J.; Van Laar, Victor S.; Berman, Sarah B.

2010-01-01

Changes in dynamic properties of mitochondria are increasingly implicated in neurodegenerative diseases, particularly Parkinson’s disease (PD). Static changes in mitochondrial morphology, often under acutely toxic conditions, are commonly utilized as indicators of changes in mitochondrial fission and fusion. However, in neurons, mitochondrial fission and fusion occur in a dynamic system of axonal/dendritic transport, biogenesis and degradation, and thus, likely interact and change over time. We sought to explore this using a chronic neuronal model (nonlethal low-concentration rotenone over several weeks), examining distal neurites, which may give insight into the earliest changes occurring in PD. Using this model, in live primary neurons, we directly quantified mitochondrial fission, fusion, and transport over time and integrated multiple aspects of mitochondrial dynamics, including morphology and growth/mitophagy. We found that rates of mitochondrial fission and fusion change as neurons age. In addition, we found that chronic rotenone exposure initially increased the ratio of fusion to fission, but later, this was reversed. Surprisingly, despite changes in rates of fission and fusion, mitochondrial morphology was minimally affected, demonstrating that morphology can be an inaccurate indicator of fission/fusion changes. In addition, we found evidence of subcellular compartmentalization of compensatory changes, as mitochondrial density increased in distal neurites first, which may be important in PD, where pathology may begin distally. We propose that rotenone-induced early changes such as in mitochondrial fusion are compensatory, accompanied later by detrimental fission. As evidence, in a dopaminergic neuronal model, in which chronic rotenone caused loss of neurites before cell death (like PD pathology), inhibiting fission protected against the neurite loss. This suggests that aberrant mitochondrial dynamics may contribute to the earliest neuropathologic mechanisms in PD. These data also emphasize that mitochondrial fission and fusion do not occur in isolation, and highlight the importance of analysis and integration of multiple mitochondrial dynamic functions in neurons. PMID:20850532

Pathology Competencies for Medical Education and Educational Cases.

PubMed

Knollmann-Ritschel, Barbara E C; Regula, Donald P; Borowitz, Michael J; Conran, Richard; Prystowsky, Michael B

2017-01-01

Current medical school curricula predominantly facilitate early integration of basic science principles into clinical practice to strengthen diagnostic skills and the ability to make treatment decisions. In addition, they promote life-long learning and understanding of the principles of medical practice. The Pathology Competencies for Medical Education (PCME) were developed in response to a call to action by pathology course directors nationwide to teach medical students pathology principles necessary for the practice of medicine. The PCME are divided into three competencies: 1) Disease Mechanisms and Processes, 2) Organ System Pathology, and 3) Diagnostic Medicine and Therapeutic Pathology. Each of these competencies is broad and contains multiple learning goals with more specific learning objectives. The original competencies were designed to be a living document, meaning that they will be revised and updated periodically, and have undergone their first revision with this publication. The development of teaching cases, which have a classic case-based design, for the learning objectives is the next step in providing educational content that is peer-reviewed and readily accessible for pathology course directors, medical educators, and medical students. Application of the PCME and cases promotes a minimum standard of exposure of the undifferentiated medical student to pathophysiologic principles. The publication of the PCME and the educational cases will create a current educational resource and repository published through Academic Pathology .

Evaluation of nucleus segmentation in digital pathology images through large scale image synthesis

NASA Astrophysics Data System (ADS)

Zhou, Naiyun; Yu, Xiaxia; Zhao, Tianhao; Wen, Si; Wang, Fusheng; Zhu, Wei; Kurc, Tahsin; Tannenbaum, Allen; Saltz, Joel; Gao, Yi

2017-03-01

Digital histopathology images with more than 1 Gigapixel are drawing more and more attention in clinical, biomedical research, and computer vision fields. Among the multiple observable features spanning multiple scales in the pathology images, the nuclear morphology is one of the central criteria for diagnosis and grading. As a result it is also the mostly studied target in image computing. Large amount of research papers have devoted to the problem of extracting nuclei from digital pathology images, which is the foundation of any further correlation study. However, the validation and evaluation of nucleus extraction have yet been formulated rigorously and systematically. Some researches report a human verified segmentation with thousands of nuclei, whereas a single whole slide image may contain up to million. The main obstacle lies in the difficulty of obtaining such a large number of validated nuclei, which is essentially an impossible task for pathologist. We propose a systematic validation and evaluation approach based on large scale image synthesis. This could facilitate a more quantitatively validated study for current and future histopathology image analysis field.

Risk factors for antepartum fetal death.

PubMed

Oron, T; Sheiner, E; Shoham-Vardi, I; Mazor, M; Katz, M; Hallak, M

2001-09-01

To determine the demographic, maternal, pregnancy-related and fetal risk factors for antepartum fetal death (APFD). From our perinatal database between the years 1990 and 1997, 68,870 singleton birth files were analyzed. Fetuses weighing < 1,000 g at birth and those with structural malformations and/or known chromosomal anomalies were excluded from the study. In order to determine independent factors contributing to APFD, a multiple logistic regression model was constructed. During the study period there were 246 cases of APFD (3.6 per 1,000 births). The following obstetric factors significantly correlated with APFD in a multiple logistic regression model: preterm deliveries: small size for gestational age (SGA), multiparity (> 5 deliveries), oligohydramnios, placental abruption, umbilical cord complications (cord around the neck and true knot of cord), pathologic presentations (nonvertex) and meconium-stained amniotic fluid. APFD was not significantly associated with advanced maternal age. APFD was significantly associated with several risk factors. Placental and umbilical cord pathologies might be the direct cause of death. Grand multiparity, oligohydramnios, meconium-stained amniotic fluid, pathologic presentations and suspected SGA should be carefully evaluated during pregnancy in order to decrease the incidence of APFD.

Locally adaptive MR intensity models and MRF-based segmentation of multiple sclerosis lesions

NASA Astrophysics Data System (ADS)

Galimzianova, Alfiia; Lesjak, Žiga; Likar, Boštjan; Pernuš, Franjo; Špiclin, Žiga

2015-03-01

Neuroimaging biomarkers are an important paraclinical tool used to characterize a number of neurological diseases, however, their extraction requires accurate and reliable segmentation of normal and pathological brain structures. For MR images of healthy brains the intensity models of normal-appearing brain tissue (NABT) in combination with Markov random field (MRF) models are known to give reliable and smooth NABT segmentation. However, the presence of pathology, MR intensity bias and natural tissue-dependent intensity variability altogether represent difficult challenges for a reliable estimation of NABT intensity model based on MR images. In this paper, we propose a novel method for segmentation of normal and pathological structures in brain MR images of multiple sclerosis (MS) patients that is based on locally-adaptive NABT model, a robust method for the estimation of model parameters and a MRF-based segmentation framework. Experiments on multi-sequence brain MR images of 27 MS patients show that, compared to whole-brain model and compared to the widely used Expectation-Maximization Segmentation (EMS) method, the locally-adaptive NABT model increases the accuracy of MS lesion segmentation.

Wnt Signaling in Cardiac Disease.

PubMed

Hermans, Kevin C M; Blankesteijn, W Matthijs

2015-07-01

Wnt signaling encompasses multiple and complex signaling cascades and is involved in many developmental processes such as tissue patterning, cell fate specification, and control of cell division. Consequently, accurate regulation of signaling activities is essential for proper embryonic development. Wnt signaling is mostly silent in the healthy adult organs but a reactivation of Wnt signaling is generally observed under pathological conditions. This has generated increasing interest in this pathway from a therapeutic point of view. In this review article, the involvement of Wnt signaling in cardiovascular development will be outlined, followed by its implication in myocardial infarct healing, cardiac hypertrophy, heart failure, arrhythmias, and atherosclerosis. The initial experiments not always offer consensus on the effects of activation or inactivation of the pathway, which may be attributed to (i) the type of cardiac disease, (ii) timing of the intervention, and (iii) type of cells that are targeted. Therefore, more research is needed to determine the exact implication of Wnt signaling in the conditions mentioned above to exploit it as a powerful therapeutic target. © 2015 American Physiological Society.

Biomechanical Phenotyping of the Murine Aorta: What Is the Best Control?

PubMed

Bellini, C; Caulk, A W; Li, G; Tellides, G; Humphrey, J D

2017-04-01

The availability of diverse mouse models is revealing increasingly greater information on arterial mechanics, including homeostatic adaptations and pathologic maladaptations to genetic, pharmacological, and surgical manipulations. Fundamental to understanding such biomechanical changes, however, is reliable information on appropriate control vessels. In this paper, we contrast 15 different geometrical and mechanical metrics of biaxial wall mechanics for the ascending aorta across seven different types of possible control mice. We show that there is a comforting similarity across these multiple controls for most, though not all, metrics. In particular, three potential controls, namely, noninduced conditional mice, exhibit higher values of distensibility, an important clinical metric of structural stiffness, and two of these potential controls also have higher values of intrinsic circumferential material stiffness. There is motivation, therefore, to understand better the biomechanical changes that can arise with noninduced Cre-lox or similar approaches for generating mutations conditionally. In cases of germline mutations generated by breeding heterozygous +/- mice, however, the resulting homozygous +/+ mice tend to exhibit properties similar to traditional (C57BL/6) controls.

Antiphospholipid antibodies: Paradigm in transition

PubMed Central

Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Ahn, Yeon S; Kelley, Roger E; Zivadinov, Robert; Maghzi, Amir H; Etemadifar, Masoud; Mousavi, Seyed Ali; Minagar, Alireza

2009-01-01

Objectives This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP. Organization After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed. Conclusion The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology. PMID:19154576

[Nutritional support and risk factors of appearance of enterocutaneous fistulas].

PubMed

Llop, J M; Cobo, S; Padullés, A; Farran, L; Jódar, R; Badia, M B

2012-01-01

Among the different factors described, nutritional support has been associated to prevention and management of enterocutaneous fistulae (ECF). To assess the influence that the parameters related to nutritional, clinical status, and surgical variables have on the occurrence of ECF. An observational case/control retrospective study was performed on patients admitted to the General and Digestive Surgery Department. The parameters analyzed were: diagnosis, body mass index (BMI), pathologic personal history, number of surgical interventions (SI) and complications (previous infection, bleeding, and ischemia). In patients with SI, we analyzed: number and type of SI, time until onset of nutritional support, and type of nutritional support. We performed a multiple logistic uni- and multivariate regression analysis by using the SPSSv.19.0 software. The primary diagnoses related to the occurrence of ECF were pancreatic pathology (OR = 5.346) and inflammatory bowel disease (IBD) (OR = 9.329). The surgical variables associated to higher prevalence of ECF emergency SI (OR = 5.79) and multiple SI (OR = 4.52). Regarding the nutritional variables, the late onset of nutrition (more than three days after SI) was associated to the occurrence of ECF (OR = 3.82). In surgical patients, early nutritional support , independently of the route of administration, decreases the occurrence of fistulae. Pancreatic pathology, IBD, emergency SI, and multiple SI were associated to higher prevalence of ECF. The variable hyponutrition appears as a risk factor that should be confirmed in further studies.

Wives of pathological gamblers: personality traits, depressive symptoms and social adjustment.

PubMed

Mazzoleni, Maria Helena B; Gorenstein, Clarice; Fuentes, Daniel; Tavares, Hermano

2009-12-01

Wives of pathological gamblers tend to endure long marriages despite financial and emotional burden. Difficulties in social adjustment, personality psychopathology, and comorbidity with psychiatric disorders are pointed as reasons for remaining on such overwhelming relationships. The goal was to examine the social adjustment, personality and negative emotionality of wives of pathological gamblers. The sample consisted of 25 wives of pathological gamblers, mean age 40.6, SD = 9.1 from a Gambling Outpatient Unit and at GAM-ANON, and 25 wives of non-gamblers, mean age 40.8, SD = 9.1, who answered advertisements placed at the Universidade de São Paulo hospital and medical school complex. They were selected in order to approximately match demographic characteristics of the wives of pathological gamblers. Subjects were assessed by the Social Adjustment Scale, Temperament and Character Inventory, Beck Depression Inventory and State-Trait Anxiety Inventory. Three variables remained in the final Multiple Logistic Regression model, wives of pathological gamblers presented greater dissatisfaction with their marital bond, and higher scores on Reward Dependence and Persistence temperament factors. Both, Wives of pathological gamblers and wives of non-gamblers presented well-structured character factors excluding personality disorders. This personality profile may explain wives of pathological gamblers emotional resilience and their marriage longevity. Co-dependence and other labels previously used to describe them may work as a double edged sword, legitimating wives of pathological gamblers problems, while stigmatizing them as inapt and needy.

The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging.

PubMed

Ladiges, Warren; Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A; Ciol, Marcia A; Ritchey, Jerry; Liggitt, Denny

2016-04-01

Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eco-Doppler evaluation of intestinal peristalsis in normal and in some pathological conditions: preliminary data.

PubMed

La Bella, A; Gimondo, P; Camboni, M

1993-01-01

Duplex-Doppler sonography could be employed in the quantitative investigation of intestinal motility. Preliminary data indicate reproductivity of the method in normal subjects and possible clinical applications in some pathological conditions affecting intestinal transit. Particularly, the possibility to discriminate between segments at different peristaltic activity seems to be very useful in intestinal obstruction. Further studies are necessary to validate this method.

Medicolegal issues in multiple pregnancy.

PubMed

Gersell, Deborah J

2007-02-01

Any discussion of multiple pregnancy figures prominently in the consideration of the medicolegal aspects of placental pathology. Multiple gestations are common and becoming more so with assisted reproductive techniques, and multiples are associated with a disproportionate share of complications that may result in disputes over quality of care. Higher rates of intrauterine growth retardation, prematurity, stillbirth, morbidity, mortality, cerebral palsy, anomalous development, and malformation as compared with singletons are well documented in multiple pregnancy and should be anticipated. Monochorionic placentation and complications of vascular anastomosis are important factors contributing to poor outcome. Other factors, although occurring in all gestations, are relevant because they are more common in multiple gestations.

Effect of Common Neuropathologies on Progression of Late Life Cognitive Impairment

PubMed Central

Yu, Lei; Boyle, Patricia A.; Leurgans, Sue; Schneider, Julie A.; Kryscio, Richard J.; Wilson, Robert S.; Bennett, David A.

2015-01-01

Brain pathologies of Alzheimer’s, cerebrovascular and Lewy body diseases are common in old age, but the relationship of these pathologies with progression from normal cognitive function to the various stages of cognitive impairment is unknown. In this study, we fit latent Markov models from longitudinal cognitive data to empirically derive three latent stages corresponding to no impairment, mild impairment, and moderate impairment; then, we examined the associations of common neuropathologies with the rates of transition among these stages. Cognitive and neuropathological data were available from 653 autopsied participants in two ongoing cohort studies of aging who were cognitively healthy at baseline (mean baseline age 79.1 years) and had longitudinal cognitive data. On average, participants in these analyses developed mild impairment 5 years after enrollment, progressed to moderate impairment after an additional 3.4 years, and stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts were associated with a higher risk of progression to mild impairment and subsequently to moderate impairment. By contrast, Lewy bodies were associated only with progression from mild to moderate impairment. The 5-year probability of progression to mild or moderate impairment was 20% for persons without any of these three pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and 56% for AD, infarcts and Lewy bodies. Thus, the presence of AD pathology alone nearly doubles the risk of developing cognitive impairment in late life, and the presence of multiple pathologies further increases this risk over multiple years prior to death. PMID:25976345

Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space.

PubMed

Howell, Owain W; Schulz-Trieglaff, Elena Katharina; Carassiti, Daniele; Gentleman, Steven M; Nicholas, Richard; Roncaroli, Federico; Reynolds, Richard

2015-10-01

Multiple sclerosis (MS) is a progressive inflammatory neurological disease affecting myelin, neurons and glia. Demyelination and neurodegeneration of cortical grey matter contribute to a more severe disease, and inflammation of the forebrain meninges associates with pathology of the underlying neocortical grey matter, particularly in deep sulci. We assessed the extent of meningeal inflammation of the cerebellum, another structure with a deeply folded anatomy, to better understand the association between subarachnoid inflammation and grey matter pathology in progressive MS. We examined demyelinating and neuronal pathology in the context of meningeal inflammation in cerebellar tissue blocks from a cohort of 27 progressive MS cases previously characterized on the basis of the absence/presence of lymphoid-like aggregates in the forebrain meninges, in comparison with 11 non-neurological controls. Demyelination and meningeal inflammation of the cerebellum was greatest in those cases previously characterized as harbouring lymphoid-like structures in the forebrain regions. Meningeal inflammation was mild to moderate in cerebellar tissue blocks, and no lymphoid-like structures were seen. Quantification of meningeal macrophages, CD4+, CD8+ T lymphocytes, B cells and plasma cells revealed that the density of meningeal macrophages associated with microglial activation in the grey matter, and the extent of grey matter demyelination correlated with the density of macrophages and plasma cells in the overlying meninges, and activated microglia of the parenchyma. These data suggest that chronic inflammation is widespread throughout the subarachnoid space and contributes to a more severe subpial demyelinating pathology in the cerebellum. © 2014 British Neuropathological Society.

Clinical image and pathology of hypertrophic cranial pachymeningitis.

PubMed

Shi, C H; Niu, S T; Zhang, Z Q

2014-12-12

The objective of this study was to examine the clinical findings, magnetic resonance imaging (MRI), pathological features, and treatment experiments of patients with hypertrophic cranial pachymeningitis (HCP). The clinical findings, MRI, and pathological appearances of 9 patients with HCP were analyzed retrospectively. The thickened dura mater was markedly enhanced after contrast media injection. The lesion near the brain hemisphere presented long regions of T1- and T2-weighted abnormal signal intensities. The abnormal signal intensities of the brain tissue were decreased significantly. Pathological examination demonstrated chronic inflammation changes, with cerebral dura mater fibrous tissue showing obvious hyperplasia, and the periphery of the blood vessel showing a great quantity of infiltrating phlegmonosis cells. HCP mainly presents headache and paralysis of multiple cranial nerves. The distinctive signs on brain MRIs involve strengthening the signal in the cerebral dura.

[Future challenges in multiple sclerosis].

PubMed

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

42 CFR 482.56 - Condition of participation: Rehabilitation services.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-language pathology or audiology services, if provided, must be provided by qualified physical therapists, physical therapist assistants, occupational therapists, occupational therapy assistants, speech-language... provides rehabilitation, physical therapy, occupational therapy, audiology, or speech pathology services...

42 CFR 482.56 - Condition of participation: Rehabilitation services.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-language pathology or audiology services, if provided, must be provided by qualified physical therapists, physical therapist assistants, occupational therapists, occupational therapy assistants, speech-language... provides rehabilitation, physical therapy, occupational therapy, audiology, or speech pathology services...

42 CFR 482.56 - Condition of participation: Rehabilitation services.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-language pathology or audiology services, if provided, must be provided by qualified physical therapists, physical therapist assistants, occupational therapists, occupational therapy assistants, speech-language... provides rehabilitation, physical therapy, occupational therapy, audiology, or speech pathology services...

Memory complaints are related to Alzheimer disease pathology in older persons.

PubMed

Barnes, L L; Schneider, J A; Boyle, P A; Bienias, J L; Bennett, D A

2006-11-14

To study the relationship between Alzheimer disease (AD) pathology and memory complaints proximate to death. A group of 90 older persons underwent detailed clinical evaluations and brain autopsy at death. The evaluations included administration of questions on subjective memory complaints and clinical classification of dementia and AD. On postmortem examination, neuritic plaques, diffuse plaques, and neurofibrillary tangles in tissue samples from five cortical regions were counted, and a summary measure of overall AD pathology was derived. In addition, amyloid load and tau tangles were quantified in eight regions. In multiple linear regression models adjusted for age, sex, and education, memory complaints were associated with AD pathology, including both amyloid and tau tangles. Subsequent analyses demonstrated that the relationship between memory complaints and AD pathology was present in those with and without dementia, and could not be explained by the potentially confounding effects of depressive symptoms or coexisting common chronic health problems. Memory complaints in older persons may indicate self awareness of a degenerative process.

An Exploration of the Associations Among Multiple Aspects of Religiousness, Body Image, Eating Pathology, and Appearance Investment.

PubMed

Goulet, Carol; Henrie, James; Szymanski, Lynda

2017-04-01

The purpose of this study was to investigate the influence of positive and negative aspects of religiousness on eating pathology, body satisfaction, and appearance investment beyond previously established variables (age, BMI, exercise frequency, weight stability, and self-esteem). Data collected from 168 adult females at a Catholic-affiliated university were analyzed using hierarchical linear regressions. As expected, some religiousness variables (spirituality and seeing one's body as having sacred qualities) were associated with eating pathology, body satisfaction, and appearance investment in potentially beneficial ways, and others (negative interaction with one's religious community) were associated in potentially harmful ways. Interestingly, greater religious meaning, or the importance of religion in one's life, was associated with greater eating pathology, and some variables (religious coping, participation in and support from one's religious community) expected to be associated with greater body satisfaction were unrelated. Results are discussed in terms of mechanisms through which the aspects of religiousness may influence body satisfaction, appearance investment, and eating pathology.

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.

PubMed

Recks, Mascha S; Stormanns, Eva R; Bader, Jonas; Arnhold, Stefan; Addicks, Klaus; Kuerten, Stefanie

2013-10-01

Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantitative Imaging In Pathology (QUIP) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

This site hosts web accessible applications, tools and data designed to support analysis, management, and exploration of whole slide tissue images for cancer research. The following tools are included: caMicroscope: A digital pathology data management and visualization plaform that enables interactive viewing of whole slide tissue images and segmentation results. caMicroscope can be also used independently of QUIP. FeatureExplorer: An interactive tool to allow patient-level feature exploration across multiple dimensions.

Describing the silent human virome with an emphasis on giant viruses.

PubMed

Popgeorgiev, Nikolay; Temmam, Sarah; Raoult, Didier; Desnues, Christelle

2013-01-01

Viruses are the most abundant obligate intracellular entities in our body. Until recently, they were only considered to be pathogens that caused a broad array of pathologies, ranging from mild disease to deaths in the most severe cases. However, recent advances in unbiased mass sequencing techniques as well as increasing epidemiological evidence have indicated that the human body is home to diverse viral species under non-pathological conditions. Despite these studies, the description of the presumably healthy viral flora, i.e. the normal human virome, is still in its infancy regarding viral composition and dynamics. This review summarizes our current knowledge of the human virome under non-pathological conditions.

Fully-relativistic full-potential multiple scattering theory: A pathology-free scheme

NASA Astrophysics Data System (ADS)

Liu, Xianglin; Wang, Yang; Eisenbach, Markus; Stocks, G. Malcolm

2018-03-01

The Green function plays an essential role in the Korringa-Kohn-Rostoker(KKR) multiple scattering method. In practice, it is constructed from the regular and irregular solutions of the local Kohn-Sham equation and robust methods exist for spherical potentials. However, when applied to a non-spherical potential, numerical errors from the irregular solutions give rise to pathological behaviors of the charge density at small radius. Here we present a full-potential implementation of the fully-relativistic KKR method to perform ab initio self-consistent calculation by directly solving the Dirac differential equations using the generalized variable phase (sine and cosine matrices) formalism Liu et al. (2016). The pathology around the origin is completely eliminated by carrying out the energy integration of the single-site Green function along the real axis. By using an efficient pole-searching technique to identify the zeros of the well-behaved Jost matrices, we demonstrated that this scheme is numerically stable and computationally efficient, with speed comparable to the conventional contour energy integration method, while free of the pathology problem of the charge density. As an application, this method is utilized to investigate the crystal structures of polonium and their bulk properties, which is challenging for a conventional real-energy scheme. The noble metals are also calculated, both as a test of our method and to study the relativistic effects.

Fully-relativistic full-potential multiple scattering theory: A pathology-free scheme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xianglin; Wang, Yang; Eisenbach, Markus

The Green function plays an essential role in the Korringa–Kohn–Rostoker(KKR) multiple scattering method. In practice, it is constructed from the regular and irregular solutions of the local Kohn–Sham equation and robust methods exist for spherical potentials. However, when applied to a non-spherical potential, numerical errors from the irregular solutions give rise to pathological behaviors of the charge density at small radius. Here we present a full-potential implementation of the fully-relativistic KKR method to perform ab initio self-consistent calculation by directly solving the Dirac differential equations using the generalized variable phase (sine and cosine matrices) formalism Liu et al. (2016). Themore » pathology around the origin is completely eliminated by carrying out the energy integration of the single-site Green function along the real axis. Here, by using an efficient pole-searching technique to identify the zeros of the well-behaved Jost matrices, we demonstrated that this scheme is numerically stable and computationally efficient, with speed comparable to the conventional contour energy integration method, while free of the pathology problem of the charge density. As an application, this method is utilized to investigate the crystal structures of polonium and their bulk properties, which is challenging for a conventional real-energy scheme. The noble metals are also calculated, both as a test of our method and to study the relativistic effects.« less

Fully-relativistic full-potential multiple scattering theory: A pathology-free scheme

DOE PAGES

Liu, Xianglin; Wang, Yang; Eisenbach, Markus; ...

2017-10-28

The Green function plays an essential role in the Korringa–Kohn–Rostoker(KKR) multiple scattering method. In practice, it is constructed from the regular and irregular solutions of the local Kohn–Sham equation and robust methods exist for spherical potentials. However, when applied to a non-spherical potential, numerical errors from the irregular solutions give rise to pathological behaviors of the charge density at small radius. Here we present a full-potential implementation of the fully-relativistic KKR method to perform ab initio self-consistent calculation by directly solving the Dirac differential equations using the generalized variable phase (sine and cosine matrices) formalism Liu et al. (2016). Themore » pathology around the origin is completely eliminated by carrying out the energy integration of the single-site Green function along the real axis. Here, by using an efficient pole-searching technique to identify the zeros of the well-behaved Jost matrices, we demonstrated that this scheme is numerically stable and computationally efficient, with speed comparable to the conventional contour energy integration method, while free of the pathology problem of the charge density. As an application, this method is utilized to investigate the crystal structures of polonium and their bulk properties, which is challenging for a conventional real-energy scheme. The noble metals are also calculated, both as a test of our method and to study the relativistic effects.« less

Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models.

PubMed

Burkitt, Michael D; Duckworth, Carrie A; Williams, Jonathan M; Pritchard, D Mark

2017-02-01

Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems. © 2017. Published by The Company of Biologists Ltd.

Ultrasonic evaluation of the neonatal brain.

PubMed

Johnson, M L; Rumack, C M

1980-04-01

Ultrasound examination of the infant brain has been performed in selected medical centers for many years. However, the equipment necessary for obtaining satisfactory visualization of the brain has only recently become commercially available. Currently, ultrasonography is an excellent, noninvasive, inexpensive, rapid, and safe imaging modality for the evaluation of hydrocephalus and other pathologic conditions of the neonatal brain. Ventricular size can often be evaluated in infants up to two or three years of age, but a detailed image of the brain parenchyma becomes more difficult to obtain in a term infant after the first two to three months of life. With the use of the water path and high resolution, real-time systems and with the delineation of structures by multiple projections, (axial, coronal, sagittal and occipital), complex abnormalities may be delineated.

Bone and mineral disorders after kidney transplantation: therapeutic strategies

PubMed Central

Molnar, Miklos Z.; Naser, Mohamed S.; Rhee, Connie M.; Kalantar-Zadeh, Kamyar; Bunnapradist, Suphamai

2017-01-01

Mineral and bone diseases (MBD) are common in patients with chronic kidney disease who undergo kidney transplantation. The incidence, types and severity of MBD varies according to the duration of chronic kidney disease, presence of comorbid conditions and intake of certain medications. Moreover, multiple types of pathology may be responsible for MBD. After successful reversal of uremia by kidney transplantation, many bone and mineral disorders improve, while immunosuppression, other medications, and new and existing comorbidities may result in new or worsening MBD. Chronic kidney disease is also common after kidney transplantation and may impact bone and mineral disease. In this article, we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant outcomes. We also discussed the diagnostic approach; immunosuppression management and potential treatment of MBD in kidney transplant recipients. PMID:24462303

Preterm labor: one syndrome, many causes.

PubMed

Romero, Roberto; Dey, Sudhansu K; Fisher, Susan J

2014-08-15

Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment. Copyright © 2014, American Association for the Advancement of Science.

Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

PubMed

Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

2013-07-01

Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases

PubMed Central

Kim, Min-Hyun; Kim, Hyeyoung

2017-01-01

Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases. PMID:28498331

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

PubMed

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Systemic candidiasis and mesenteric mast cell tumor with multiple metastases in a dog.

PubMed

Matsuda, Kazuya; Sakaguchi, Kanako; Kobayashi, Shintaro; Tominaga, Makiko; Hirayama, Kazuko; Kadosawa, Tsuyoshi; Taniyama, Hiroyuki

2009-02-01

A 5-year-old female miniature dachshund presenting with persistent vomiting and diarrhea had two concurrent rare pathological conditions: systemic candidiasis and mesenteric mast cell tumor with multiorgan metastases. Neoplastic mast cells formed mass in the mesentery of the cecal-colonic region and were also found in the liver, spleen, kidneys, lungs, adrenal grands, ovaries, bone marrow and other tissues. The cells had intracytoplasmic granules with metachromasia and were immunohistochemically positive for c-kit and histamine. Granulomatous lesions with fungal organisms were present in the heart, lungs, kidneys, pancreas, subserosal and surrounding adipose tissue of the duodenum, thyroid glands and mesenteric mass, and phagocytosed organisms were detected in the liver and bone marrow. Bacteriologically and immunohistochemically, the fungi were consistent with Candida albicans.

WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies.

PubMed

Aldaz, C Marcelo; Ferguson, Brent W; Abba, Martin C

2014-08-01

WWOX was cloned as a putative tumor suppressor gene mapping to chromosomal fragile site FRA16D. Deletions affecting WWOX accompanied by loss of expression are frequent in various epithelial cancers. Translocations and deletions affecting WWOX are also common in multiple myeloma and are associated with worse prognosis. Metanalysis of gene expression datasets demonstrates that low WWOX expression is significantly associated with shorter relapse-free survival in ovarian and breast cancer patients. Although somatic mutations affecting WWOX are not frequent, analysis of TCGA tumor datasets led to identifying 44 novel mutations in various tumor types. The highest frequencies of mutations were found in head and neck cancers and uterine and gastric adenocarcinomas. Mouse models of gene ablation led us to conclude that Wwox does not behave as a highly penetrant, classical tumor suppressor gene since its deletion is not tumorigenic in most models and its role is more likely to be of relevance in tumor progression rather than in initiation. Analysis of signaling pathways associated with WWOX expression confirmed previous in vivo and in vitro observations linking WWOX function with the TGFβ/SMAD and WNT signaling pathways and with specific metabolic processes. Supporting these conclusions recently we demonstrated that indeed WWOX behaves as a modulator of TGFβ/SMAD signaling by binding and sequestering SMAD3 in the cytoplasmic compartment. As a consequence progressive loss of WWOX expression in advanced breast cancer would contribute to the pro-metastatic effects resulting from TGFβ/SMAD3 hyperactive signaling in breast cancer. Recently, GWAS and resequencing studies have linked the WWOX locus with familial dyslipidemias and metabolic syndrome related traits. Indeed, gene expression studies in liver conditional KO mice confirmed an association between WWOX expression and lipid metabolism. Finally, very recently the first human pedigrees with probands carrying homozygous germline loss of function WWOX mutations have been identified. These patients are characterized by severe CNS related pathology that includes epilepsy, ataxia and mental retardation. In summary, WWOX is a highly conserved and tightly regulated gene throughout evolution and when defective or deregulated the consequences are important and deleterious as demonstrated by its association not only with poor prognosis in cancer but also with other important human pathologies such as metabolic syndrome and CNS related pathologic conditions. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Oxygen uptake/oxygen supply dependency: fact or fiction?

PubMed

Vincent, J L; De Backer, D

1995-01-01

More than a decade ago, observations of co-variance between VO2 and DO2 led to the identification of a condition known as pathological O2 supply dependency. This condition was subsequently observed in critically ill patients with sepsis and acute circulatory failure. More recently, other authors have challenged the existence of this condition, often citing methodologic problems or mathematical coupling to account for spurious observations in the earlier studies. Here, we review the evidence for and against pathological O2 supply dependency. We find that many of the arguments have some validity but only in specific circumstances. We conclude, therefore, that pathological O2 supply dependency is a hallmark of acute circulatory failure and that an effective therapeutic approach should be based on an evaluation of organ system function in each individual case. Parameters such as blood lactate, pHi and veno-arterial PCO2 may be useful in this respect.

Astrocytic IL-6 Influences the Clinical Symptoms of EAE in Mice.

PubMed

Erta, Maria; Giralt, Mercedes; Jiménez, Silvia; Molinero, Amalia; Comes, Gemma; Hidalgo, Juan

2016-05-17

Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females.

Application of immunogold-silver staining and immunoenzymatic methods in multiple labelling of human pancreatic Langerhans islet cells.

PubMed

Krenács, T; Lászik, Z; Dobó, E

1989-01-01

The use of immunogold-silver staining (IGSS) combined with immunoperoxidase and/or immunoalkaline phosphatase methods for the simultaneous demonstration of pancreatic islet cell hormones on routinely fixed paraffin-embedded human tissue sections was examined. If IGSS was applied first, the black colour of silver-enhanced colloidal gold on doubly immunostained sections contrasted with the colours of most of the chromogens used generally in the 2 immunoenzymatic methods. If IGSS was followed by immunoalkaline phosphatase and immunoperoxidase techniques in optional sequence, 3 different hormone-containing cell types could be stained simultaneously without non-specific cross-reactions. IGSS and immunoalkaline phosphatase methods, together with 2 kinds of non-cross-reacting immunoperoxidase systems, permitted the detection of 4 distinct antigens on the same tissue section. Multiple immunohistochemical labelling of the endocrine pancreas provides an opportunity for the correct and rapid analysis of the topographic and morphometric relationships between different hormone-producing cell populations under both normal and pathological conditions. IGSS is of great potential for the simultaneous immunolabelling of antigens situated within separate cells.

Rare inflammatory diseases of the white matter and mimics of multiple sclerosis and related disorders.

PubMed

Tardieu, Marc; Deiva, Kumaran

2013-12-01

The spectra of white matter neuroinflammatory diseases and pathological processes inducing inflammatory lesions in the white matter of the central nervous system are wider in children than in adults. The definitions of multiple sclerosis (MS) and of the related clinically isolated syndromes (CIS) and acute disseminated encephalomyelitis (ADEM) have been recently revised leading to a new consensus definition. However, other entities with similarities to these diseases may also develop with monophasic or relapsing white matter inflammation. These conditions include congenital immunogenetic diseases (such as hemophagocytic lymphohistiocytosis), vasculitis, and autoantibody-mediated encephalopathies (Hashimoto encephalopathy, encephalitis with anti-N-methyl-D-aspartate receptor antibodies and neuromyelitis optica). Moreover, infectious diseases, such as Lyme disease, tumors (oligodendroglioma and lymphoma), and even genetic or metabolic diseases should also be considered if the clinical course of the disease does not follow the typical pattern for ADEM or MS. This short review describes these different entities and provides information for the differential diagnosis of inflammatory diseases of the white matter. Georg Thieme Verlag KG Stuttgart · New York.

Basic Proteins of Plant Nuclei during Normal and Pathological Cell Growth

PubMed Central

Rasch, Ellen; Woodard, John W.

1959-01-01

Histone proteins were studied by microphotometry of plant tissue sections stained with fast green at pH 8.1. For comparative purposes the Feulgen reaction was used for deoxyribose nuclei acid (DNA); the Sakaguchi reaction for arginine; and the Millon reaction for estimates of total protein. Analysis of Tradescantia tissues indicated that amounts of nuclear histone fell into approximate multiples of the gametic (egg or sperm) quantity except in dividing tissues, where amounts intermediate between multiples were found. In differentiated tissues of lily, corn, onion, and broad bean, histones occurred in constant amounts per nucleus, characteristic of the species, as was found also for DNA. Unlike the condition in several animal species, the basic proteins of sperm nuclei in these higher plants were of the histone type; no evidence of protamine was found. In a plant neoplasm, crown gall of broad bean, behavior of the basic nuclear proteins closely paralleled that of DNA. Thus, alterations of DNA levels in tumor tissues were accompanied by quantitatively similar changes in histone levels to maintain the same Feulgen/fast green ratios found in homologous normal tissues. PMID:14436319

Enhanced interlaminar excitation or reduced superficial layer inhibition in neocortex generates different spike-and-wave-like electrographic events in vitro

PubMed Central

Hall, Stephen P.; Traub, Roger D.; Adams, Natalie E.; Cunningham, Mark O.; Schofield, Ian; Jenkins, Alistair J.

2018-01-01

Acute in vitro models have revealed a great deal of information about mechanisms underlying many types of epileptiform activity. However, few examples exist that shed light on spike-and-wave (SpW) patterns of pathological activity. SpW are seen in many epilepsy syndromes, both generalized and focal, and manifest across the entire age spectrum. They are heterogeneous in terms of their severity, symptom burden, and apparent anatomical origin (thalamic, neocortical, or both), but any relationship between this heterogeneity and underlying pathology remains elusive. In this study we demonstrate that physiological delta-frequency rhythms act as an effective substrate to permit modeling of SpW of cortical origin and may help to address this issue. For a starting point of delta activity, multiple subtypes of SpW could be modeled computationally and experimentally by either enhancing the magnitude of excitatory synaptic events ascending from neocortical layer 5 to layers 2/3 or selectively modifying superficial layer GABAergic inhibition. The former generated SpW containing multiple field spikes with long interspike intervals, whereas the latter generated SpW with short-interval multiple field spikes. Both types had different laminar origins and each disrupted interlaminar cortical dynamics in a different manner. A small number of examples of human recordings from patients with different diagnoses revealed SpW subtypes with the same temporal signatures, suggesting that detailed quantification of the pattern of spikes in SpW discharges may be a useful indicator of disparate underlying epileptogenic pathologies. NEW & NOTEWORTHY Spike-and-wave-type discharges (SpW) are a common feature in many epilepsies. Their electrographic manifestation is highly varied, as are available genetic clues to associated underlying pathology. Using computational and in vitro models, we demonstrate that distinct subtypes of SpW are generated by lamina-selective disinhibition or enhanced interlaminar excitation. These subtypes could be detected in at least some noninvasive patient recordings, suggesting more detailed analysis of SpW may be useful in determining clinical pathology. PMID:28954894

Enhanced interlaminar excitation or reduced superficial layer inhibition in neocortex generates different spike-and-wave-like electrographic events in vitro.

PubMed

Hall, Stephen P; Traub, Roger D; Adams, Natalie E; Cunningham, Mark O; Schofield, Ian; Jenkins, Alistair J; Whittington, Miles A

2018-01-01

Acute in vitro models have revealed a great deal of information about mechanisms underlying many types of epileptiform activity. However, few examples exist that shed light on spike-and-wave (SpW) patterns of pathological activity. SpW are seen in many epilepsy syndromes, both generalized and focal, and manifest across the entire age spectrum. They are heterogeneous in terms of their severity, symptom burden, and apparent anatomical origin (thalamic, neocortical, or both), but any relationship between this heterogeneity and underlying pathology remains elusive. In this study we demonstrate that physiological delta-frequency rhythms act as an effective substrate to permit modeling of SpW of cortical origin and may help to address this issue. For a starting point of delta activity, multiple subtypes of SpW could be modeled computationally and experimentally by either enhancing the magnitude of excitatory synaptic events ascending from neocortical layer 5 to layers 2/3 or selectively modifying superficial layer GABAergic inhibition. The former generated SpW containing multiple field spikes with long interspike intervals, whereas the latter generated SpW with short-interval multiple field spikes. Both types had different laminar origins and each disrupted interlaminar cortical dynamics in a different manner. A small number of examples of human recordings from patients with different diagnoses revealed SpW subtypes with the same temporal signatures, suggesting that detailed quantification of the pattern of spikes in SpW discharges may be a useful indicator of disparate underlying epileptogenic pathologies. NEW & NOTEWORTHY Spike-and-wave-type discharges (SpW) are a common feature in many epilepsies. Their electrographic manifestation is highly varied, as are available genetic clues to associated underlying pathology. Using computational and in vitro models, we demonstrate that distinct subtypes of SpW are generated by lamina-selective disinhibition or enhanced interlaminar excitation. These subtypes could be detected in at least some noninvasive patient recordings, suggesting more detailed analysis of SpW may be useful in determining clinical pathology.

Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

PubMed Central

Li, Jie; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Fu, Zhongjie; Evans, Lucy P.; Tian, Katherine T.; Juan, Aimee M.; Hurst, Christian G.; Mammoto, Akiko; Chen, Jing

2014-01-01

Purpose. Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. Methods. Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). Results. TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. Conclusions. Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases. PMID:25414194

How does it feel to be a pathology resident? Results of a survey on experiences and job satisfaction during pathology residency.

PubMed

Pehlivanoglu, Burcin; Hassoy, Hur; Calle, Catarina; Dendooven, Amelie; Nalbantoglu, ILKe; Reshchikova, Lidiya; Gul, Gulen; Doganavsargil, Basak

2017-09-01

Residents' career choices and professional motivation can be affected from perception of their role and recognition within a medical team as well as their educational and workplace experiences. To evaluate pathology trainees' perceptions of their pathology residency, we conducted a 42-item survey via a web-based link questioning respondents' personal and institutional background, workplace, training conditions, and job satisfaction level. For the 208 residents from different European countries who responded, personal expectations in terms of quality of life (53%) and scientific excitement (52%) were the most common reasons why they chose and enjoy pathology. Sixty-six percent were satisfied about their relationship with other people working in their department, although excessive time spent on gross examination appeared less satisfactory. A set residency training program (core curriculum), a set annual scientific curriculum, and a residency program director existed in the program of 58, 60, and 69% respondents, respectively. Most respondents (76%) considered that pathologists have a direct and high impact on patient management, but only 32% agreed that pathologists cooperate with clinicians/surgeons adequately. Most (95%) found that patients barely know what pathologists do. Only 22% considered pathology and pathologists to be adequately positioned in their country's health care system. Almost 84% were happy to have chosen pathology, describing it as "puzzle solving," "a different fascinating world," and "challenging while being crucial for patient management." More than two thirds (72%) considered pathology and pathologists to face a bright future. However, a noticeable number of respondents commented on the need for better physical working conditions, a better organized training program, more interaction with experienced pathologists, and deeper knowledge on molecular pathology.

Knee osteoarthritis, degenerative meniscal lesion and osteonecrosis of the knee: Can a simple gait test direct us to a better clinical diagnosis.

PubMed

Debi, R; Elbaz, A; Mor, A; Kahn, G; Peskin, B; Beer, Y; Agar, G; Morag, G; Segal, G

2017-06-01

The purpose of the current study was to compare the gait patterns in patients with three differing knee pathologies - knee osteoarthritis (OA), degenerative meniscal lesion (DML) and spontaneous osteonecrosis of the knee (SONK) and a group of healthy controls. A simple gait test will detect differences between different knee pathologies. Forty-seven patients with bilateral knee OA, 47 patients with DML, 28 patients with SONK and 27 healthy controls were included in this analysis. Patients underwent a spatiotemporal gait assessment and were asked to complete the Western Ontario and McMaster University (WOMAC) Index and the Short-Form (SF)-36 Health Survey. ANOVA tests, followed by Bonferroni multiple comparison tests and the Chi 2 tests were performed for continuous and categorical variables, respectively. Significant differences were found for all gait measures and clinical questionnaires between healthy controls and all knee conditions. Patients with SONK differed from patients with bilateral knee OA and DML in all gait measures and clinical questionnaires, except for WOMAC subscales. There were no significant differences between patients with bilateral knee OA and patients with DML. Symmetry was also examined and revealed asymmetry in some gait parameters in patients with SONK and DML. Based on the differences in gait parameters that were found in the current study, adding an objective functional spatiotemporal gait test may assist in the diagnostic process of knee pathologies. Case Control study Level III. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Relationships Between Problem-Gambling Severity and Psychopathology as Moderated by Income

PubMed Central

Sanacora, Rachel L.; Whiting, Seth W.; Pilver, Corey E.; Hoff, Rani A.; Potenza, Marc N.

2016-01-01

Background and aims Problem and pathological gambling have been associated with elevated rates of both Axis-I and Axis-II psychiatric disorders. Although both problem gambling and psychiatric disorders have been reported as being more prevalent among lower income vs. middle/higher income groups, how income might moderate the relationship between problem-gambling severity and psychopathology is incompletely understood. To examine the associations between problem-gambling severity and psychopathology in lower income and middle/higher income groups. Methods Data from the first wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093) were analyzed in adjusted logistic regression models to investigate the relationships between problem-gambling severity and psychiatric disorders within and across income groups. Results Greater problem-gambling severity was associated with increased odds of multiple psychiatric disorders for both lower income and middle/higher income groups. Income moderated the association between problem/pathological gambling and alcohol abuse/dependence, with a stronger association seen among middle/higher income respondents than among lower income respondents. Discussion and conclusions The findings that problem-gambling severity is related to psychopathology across income groups suggest a need for public health initiatives across social strata to reduce the impact that problem/pathological gambling may have in relation to psychopathology. Middle/higher income populations, perhaps owing to the availability of more “disposable income,” may be at greater risk for co-occurring gambling and alcohol-use psychopathology and may benefit preferentially from interventions targeting both gambling and alcohol use. PMID:27440475

Efficacy evaluation of educational sessions for patients with asthma and COPD.

PubMed

van Zeller, M; Vaz, A P; Soares Pires, F; Neves, I; Drummond, M; Carvalho, A M; Moura Relvas, P

2012-01-01

Asthma and COPD are respiratory diseases in which a better knowledge and understanding of the pathology allows the patients to be more involved, which is crucial in their treatment. Holding educational sessions is a good way of imparting information to the patients. To determine the efficacy of educational sessions in helping patients with Asthma and COPD to acquire a better understanding of their condition. Following a Portuguese Lung Foundation initiative to improve knowledge about respiratory health, educational sessions for patients suffering from Asthma or COPD were organized. 25 randomized patients with the disease were invited to participate. Each session lasted 60 minutes. Patient knowledge was tested by means of a multiple choice questionnaire before and after the session. Fifteen patients with asthma attended the sessions, they had an average age of 36 years, of which 60% were female. Within the group 60% were able to name their pathology correctly. Seventeen patients with COPD attended the sessions, they had an average age of 69 years, of which 70% were males and only 3 (17,6%) patients were able to correctly name their pathology. In both groups, there was a statistically positive improvement (p<0,05) of correct answers to the questionnaire the end of each educational session. Patient knowledge increased in each educational session. Patients with COPD were less well informed about their disease than patients with asthma and they also had more difficulty in correctly naming their disease. Copyright © 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Concomitant intramedullary arteriovenous malformation and a vertebral hemangioma of cervical spine discovered by a pathologic fracture during bicycle accident.

PubMed

Ayhan, Selim; Palaoglu, Selcuk; Geyik, Serdar; Saatci, Isil; Onal, Mehmet Bulent

2015-01-01

Spinal intramedullary arteriovenous malformations are uncommon and a challenging type of neurosurgical entities. They are rarely located to cervical segment. On the other hand, although hemangiomas are relatively common bone tumors, cervical involvement is again rare and clinically significant ones are infrequent. A 14 year-old-male patient referred to an academic tertiary care unit and presented with neck pain and left hand weakness. Neurological examination revealed motor strength deficit at intrinsic muscles and hyperesthesia at the left hand. Furthermore the pathological reflexes were positive on the left hand side. Imaging studies showed compression fracture, lytic changes resembling a hemangioma at C7 vertebra, and also an intramedullary vascular pathology at C5-6 level which was shown to be an intradural-intramedullary arteriovenous malformation (AVM) on digital subtraction angiography. Based on neurological and radiological findings, the decision was to treat the patient. After embolization of the AVM, the neurological condition of the patient deteriorated and immediate MRI scan of the cervical spine revealed edema of the spinal cord at the C5-6 level. Thus an emergent surgery was performed and C5-6-7 laminectomies with C5-T2 posterior fixation and arthrodesis were implemented. A second stage operation was carried out as C7 corpectomy with a distractable titanium cage 2 weeks after initial surgery. A follow-up evaluation at five years revealed 4/5 motor strength on his left intrinsic hand muscles and mild hyperactive deep tendon reflexes. Imaging studies at the postoperative period showed stable placement of the construct and no evidence of contrast enhancement at the C5-6 level inside the spinal cord. A rare case of multiple pathologies affecting the cervical spine, coincidentally diagnosed after a pathological fracture during a bicycle accident as vertebral hemangioma and intradural-intramedullary AVM that was successfully treated with early detection, have been presented. One should assess such patients under multidisciplinary fashion and treat on a case-by-case basis for achieving the best results in patient care.

Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a caucasian family

PubMed Central

Tommasi, Stefania; Strippoli, Sabino; Pellegrini, Cristina; Concetta Fargnoli, Maria; Pilato, Brunella; Natalicchio, Iole; Guida, Gabriella; Pinto, Rosamaria

2017-01-01

Multiple primary melanoma (MPM) is a rare condition, whose genetic basis has not yet been clarified. Only 8-12% of MPM are due to germline mutations of CDKN2A. However, other genes (POT1, BRCA1/2, MC1R, MGMT) have been demonstrated to be involved in predisposition to this pathology. To our knowledge, this is the first family study based on two siblings with the rare coexistence of MPM and oculocutaneous albinism (OCA), an autosomal recessive disease characterized by the absence or decrease in pigmentation in the skin, hair, and eyes. In this study, we evaluated genes involved in melanoma predisposition (CDKN2A, CDK4, MC1R, MITF, POT1, RB1, MGMT, BRCA1, BRCA2), pathogenesis (BRAF, NRAS, PIK3CA, KIT, PTEN), skin/hair pigmentation (MC1R, MITF) and in immune pathways (CTLA4) to individuate alterations able to explain the rare onset of MPM and OCA in indexes and the transmission in their pedigree. From the analysis of the pedigree, we were able to identify a “protective” haplotype with respect to MPM, including MGMT p.I174V alteration. The second generation offspring is under strict follow up as some of them have a higher risk of developing MPM according to our model. PMID:27776349

First diagnosis of septic arthritis in a dinosaur

NASA Astrophysics Data System (ADS)

Anné, Jennifer; Hedrick, Brandon P.; Schein, Jason P.

2016-08-01

Identification and interpretation of pathologies in the fossil record allows for unique insights into the life histories of extinct organisms. However, the rarity of such finds limits not only the sample size for palaeopathologic studies, but also the types of analyses that may be performed. In this study, we present the first occurrence of a palaeopathology in a vertebrate from the Mesozoic of the East Coast of North America (Appalachia), a pathologic ulna and radius of an indeterminate hadrosaur from the Navesink Formation (New Jersey). X-ray microtomography allowed for both detailed and more accurate diagnosis of the pathologic condition as well as virtual conservation of the specimen. Based on extant archosaurian comparisons, the hadrosaur was diagnosed with severe septic arthritis affecting the proximal ulna and radius. Diagnosis was based on erosion of the joint and highly reactive periosteal bone growth and fusion of the elements. To the best of our knowledge, this is the first recorded account of septic arthritis in dinosaurs. The severity of the pathology suggests the animal suffered with this condition for some time before death. Unfortunately, only the ulna and radius were found. Thus, the extent to which the condition spread to other parts of the body is unknown.

First diagnosis of septic arthritis in a dinosaur.

PubMed

Anné, Jennifer; Hedrick, Brandon P; Schein, Jason P

2016-08-01

Identification and interpretation of pathologies in the fossil record allows for unique insights into the life histories of extinct organisms. However, the rarity of such finds limits not only the sample size for palaeopathologic studies, but also the types of analyses that may be performed. In this study, we present the first occurrence of a palaeopathology in a vertebrate from the Mesozoic of the East Coast of North America (Appalachia), a pathologic ulna and radius of an indeterminate hadrosaur from the Navesink Formation (New Jersey). X-ray microtomography allowed for both detailed and more accurate diagnosis of the pathologic condition as well as virtual conservation of the specimen. Based on extant archosaurian comparisons, the hadrosaur was diagnosed with severe septic arthritis affecting the proximal ulna and radius. Diagnosis was based on erosion of the joint and highly reactive periosteal bone growth and fusion of the elements. To the best of our knowledge, this is the first recorded account of septic arthritis in dinosaurs. The severity of the pathology suggests the animal suffered with this condition for some time before death. Unfortunately, only the ulna and radius were found. Thus, the extent to which the condition spread to other parts of the body is unknown.

Can orthodontic relapse be blamed on the temporomandibular joint?

PubMed Central

Wolford, Larry M

2014-01-01

There are many temporomandibular joint (TMJ) conditions that can cause orthodontic treatment instability and relapse. These conditions are often associated with dentofacial deformities, malocclusion, TMJ pain, headaches, myofascial pain, TMJ and jaw functional impairment, ear symptoms, etc., Many of these TMJ conditions can cause progressive and continuous changes in the occlusion and jaw relationships. Patients with these conditions may benefit from corrective orthodontic and surgical intervention. The difficulty for many clinicians may lie in identifying the presence of a TMJ condition, diagnosing the specific TMJ pathology, and selecting the proper treatment for that condition. This paper will discuss the most common TMJ pathologies that can adversely affect orthodontic stability and outcomes as well as present the treatment considerations to correct the specific TMJ conditions and associated jaw deformities to provide stable and predictable treatment results. PMID:25426452

Ultrasound guided therapeutic injections of the cervical spine and brachial plexus.

PubMed

Cormick, Wes

2014-02-01

Introduction : Recent applications in ultrasound imaging include ultrasound assessment and ultrasound guided therapeutic injections of the spine and brachial plexus. Discussion : Ultrasound is an ideal modality for these regions as it allows accurate safe and quick injection of single or multiple sites. It has the added advantages of lack of ionising radiation, and can be done without requiring large expensive radiology equipment. Conclusion : Brachial plexus pathology may be present in patients presenting for shoulder symptoms where very little is found at imaging the shoulder. It is important to understand the anatomy and normal variants that may exist to be able to recognise when pathology is present. When pathology is demonstrated it is easy to do a trial of therapy with ultrasound guided injection of steroid around the nerve lesion. This review will outline the normal anatomy and variants and common pathology, which can be amenable to ultrasound guided injection of steroid.

Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

PubMed

Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Bert, Robert; Gilden, Don

2013-12-15

We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 μm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA. © 2013.

Of von Willebrand factor and platelets.

PubMed

Bryckaert, Marijke; Rosa, Jean-Philippe; Denis, Cécile V; Lenting, Peter J

2015-01-01

Hemostasis and pathological thrombus formation are dynamic processes that require multiple adhesive receptor-ligand interactions, with blood platelets at the heart of such events. Many studies have contributed to shed light on the importance of von Willebrand factor (VWF) interaction with its platelet receptors, glycoprotein (GP) Ib-IX-V and αIIbβ3 integrin, in promoting primary platelet adhesion and aggregation following vessel injury. This review will recapitulate our current knowledge on the subject from the rheological aspect to the spatio-temporal development of thrombus formation. We will also discuss the signaling events generated by VWF/GPIb-IX-V interaction, leading to platelet activation. Additionally, we will review the growing body of evidence gathered from the recent development of pathological mouse models suggesting that VWF binding to GPIb-IX-V is a promising target in arterial and venous pathological thrombosis. Finally, the pathological aspects of VWF and its impact on platelets will be addressed.

Childhood Maltreatment as Predictor of Pathological Personality Traits Using PSY-5 in an Adult Psychiatric Sample.

PubMed

Choi, Ji Young; Park, Soo Hyun

2018-02-01

Extant literature indicates that childhood maltreatment is significantly associated with personality disorders. With the recent call for a more dimensional approach to understanding personality and pathological personality traits, the aim of the present study was to examine whether the experience of childhood maltreatment is associated with pathological personality traits as measured by the Personality Psychopathology Five (PSY-5). We analyzed data from 557 adult psychiatric patients with diverse psychiatric diagnoses, including mood disorders, schizophrenia spectrum disorders, and anxiety disorders. Hierarchical multiple regression analyses were conducted to determine the degree to which childhood maltreatment explained the five trait dimensions after controlling for demographic variables, presence of psychotic symptoms, and degree of depressive symptoms. Childhood maltreatment significantly predicted all of the five trait dimensions of the PSY-5. This suggests that childhood maltreatment may negatively affect the development of an adaptive adjustment system, thereby potentially contributing to the emergence of pathological personality traits.

Ankle pain and peroneal tendon pathology.

PubMed

Baumhauer, Judith F; Nawoczenski, Deborah A; DiGiovanni, Benedict F; Flemister, A Samuel

2004-01-01

Chronic ankle pain can be due to multiple causes. A thorough review of the patient's history with a physical examination concentrating on anatomic structures surrounding the ankle is imperative. The most common of causes have been presented. The addition of provocative testing and radiographic examinations can aid in elucidating the pathology. After treatment of the injury, attention to training technique, shoe and insert usage as well as individual gait abnormalities are integrated into global patient education to decrease the incidence of injury recurrence.

TeleProbe: design and development of an efficient system for telepathology

NASA Astrophysics Data System (ADS)

Ahmed, Wamiq M.; Robinson, J. Paul; Ghafoor, Arif

2005-10-01

This paper describes an internet-based system for telepathology. This system provides support for multiple users and exploits the opportunities for optimization that arise in multi-user environment. Techniques for increasing system responsiveness by improving resource utilization and lowering network traffic are explored. Some of the proposed optimizations include an auto-focus module, client and server side caching, and request reordering. These systems can be an economic solution not only for remote pathology consultation but also for pathology and biology education.

Design and Implementation of the Retinoblastoma Collaborative Laboratory.

PubMed

Qaiser, Seemi; Limo, Alice; Gichana, Josiah; Kimani, Kahaki; Githanga, Jessie; Waweru, Wairimu; Dimba, Elizabeth A O; Dimaras, Helen

2017-01-01

The purpose of this work was to describe the design and implementation of a digital pathology laboratory, the Retinoblastoma Collaborative Laboratory (RbCoLab) in Kenya. The RbCoLab is a central lab in Nairobi that receives retinoblastoma specimens from all over Kenya. Specimens were processed using evidence-based standard operating procedures. Images were produced by a digital scanner, and pathology reports were disseminated online. The lab implemented standard operating procedures aimed at improving the accuracy, completeness, and timeliness of pathology reports, enhancing the care of Kenyan retinoblastoma patients. Integration of digital technology to support pathology services supported knowledge transfer and skills transfer. A bidirectional educational network of local pathologists and other clinicians in the circle of care of the patients emerged and served to emphasize the clinical importance of cancer pathology at multiple levels of care. A 'Robin Hood' business model of health care service delivery was developed to support sustainability and scale-up of cancer pathology services. The application of evidence-based protocols, comprehensive training, and collaboration were essential to bring improvements to the care of retinoblastoma patients in Kenya. When embraced as an integrated component of retinoblastoma care, digital pathology offers the opportunity for frequent connection and consultation for development of expertise over time.

Effects of vehicle-ride exposure on cervical pathology: a meta-analysis

PubMed Central

KOLLOCK, Roger; GAMES, Kenneth; WILSON, Alan E.; SEFTON, JoEllen M.

2015-01-01

Research to date on the effect vehicle-ride exposure has on the development of cervical pathologies in mounted Warfighters is conflicting. The purpose of this study was to determine if the literature suggests a definite effect of vehicle-ride exposure on cervical pathology. Databases were searched using multiple combinations of select terms. Twelve studies meeting the inclusion criteria were included in the meta-analysis. The results of the meta-analysis revealed that overall vehicle-ride exposure was likely to increase cervical pathology (p=0.01, odds ratio=1.59, 95% CI=1.16−2.17). Using vehicle type as a moderator it was found that vehicle-ride exposure in ground-based vehicles (p=0.01, odds ratio=2.33, 95% CI=1.41−3.85) and fixed-wing aircraft (p=0.01, odds ratio =1.59, 95% CI=1.13−2.23) were likely to increase cervical pathology. Using operator/other personnel moderator it was found that in the populations tested, fighter pilots or fighter jet weapons systems operators were more likely to develop a cervical pathology (p<0.001, odds ratio=1.78, 95% CI=1.26−2.50). The available studies indicate an increase in cervical pathology for personnel exposed to ground-based vehicles and fixed-wing aircraft. PMID:25739897

Design and Implementation of the Retinoblastoma Collaborative Laboratory

PubMed Central

Qaiser, Seemi; Limo, Alice; Gichana, Josiah; Kimani, Kahaki; Githanga, Jessie; Waweru, Wairimu; Dimba, Elizabeth A.O.; Dimaras, Helen

2017-01-01

Purpose The purpose of this work was to describe the design and implementation of a digital pathology laboratory, the Retinoblastoma Collaborative Laboratory (RbCoLab) in Kenya. Method The RbCoLab is a central lab in Nairobi that receives retinoblastoma specimens from all over Kenya. Specimens were processed using evidence-based standard operating procedures. Images were produced by a digital scanner, and pathology reports were disseminated online. Results The lab implemented standard operating procedures aimed at improving the accuracy, completeness, and timeliness of pathology reports, enhancing the care of Kenyan retinoblastoma patients. Integration of digital technology to support pathology services supported knowledge transfer and skills transfer. A bidirectional educational network of local pathologists and other clinicians in the circle of care of the patients emerged and served to emphasize the clinical importance of cancer pathology at multiple levels of care. A ‘Robin Hood’ business model of health care service delivery was developed to support sustainability and scale-up of cancer pathology services. Discussion The application of evidence-based protocols, comprehensive training, and collaboration were essential to bring improvements to the care of retinoblastoma patients in Kenya. When embraced as an integrated component of retinoblastoma care, digital pathology offers the opportunity for frequent connection and consultation for development of expertise over time. PMID:28275608

Social network media exposure and adolescent eating pathology in Fiji

PubMed Central

Becker, Anne E.; Fay, Kristen E.; Agnew-Blais, Jessica; Khan, A. Nisha; Striegel-Moore, Ruth H.; Gilman, Stephen E.

2011-01-01

Background Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure – such as the proliferation of media exposure in an individual’s social network – is also associated with eating disorders. Aims To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji. Method We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n = 523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE–Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors. Results Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR = 1.60, 95% CI 1.15–2.23 relating social network media exposure to upper-quartile EDE–Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association. Conclusions Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations. PMID:21200076

Social network media exposure and adolescent eating pathology in Fiji.

PubMed

Becker, Anne E; Fay, Kristen E; Agnew-Blais, Jessica; Khan, A Nisha; Striegel-Moore, Ruth H; Gilman, Stephen E

2011-01-01

Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure--such as the proliferation of media exposure in an individual's social network--is also associated with eating disorders. To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji. We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n=523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE-Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors. Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR=1.60, 95% CI 1.15-2.23 relating social network media exposure to upper-quartile EDE-Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association. Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations.

Dementia Resulting From Traumatic Brain Injury

PubMed Central

Shively, Sharon; Scher, Ann I.; Perl, Daniel P.; Diaz-Arrastia, Ramon

2013-01-01

Traumatic brain injury (TBI) is among the earliest illnesses described in human history and remains a major source of morbidity and mortality in the modern era. It is estimated that 2% of the US population lives with long-term disabilities due to a prior TBI, and incidence and prevalence rates are even higher in developing countries. One of the most feared long-term consequences of TBIs is dementia, as multiple epidemiologic studies show that experiencing a TBI in early or midlife is associated with an increased risk of dementia in late life. The best data indicate that moderate and severe TBIs increase risk of dementia between 2-and 4-fold. It is less clear whether mild TBIs such as brief concussions result in increased dementia risk, in part because mild head injuries are often not well documented and retrospective studies have recall bias. However, it has been observed for many years that multiple mild TBIs as experienced by professional boxers are associated with a high risk of chronic traumatic encephalopathy (CTE), a type of dementia with distinctive clinical and pathologic features. The recent recognition that CTE is common in retired professional football and hockey players has rekindled interest in this condition, as has the recognition that military personnel also experience high rates of mild TBIs and may have a similar syndrome. It is presently unknown whether dementia in TBI survivors is pathophysiologically similar to Alzheimer disease, CTE, or some other entity. Such information is critical for developing preventive and treatment strategies for a common cause of acquired dementia. Herein, we will review the epidemiologic data linking TBI and dementia, existing clinical and pathologic data, and will identify areas where future research is needed. PMID:22776913

Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury.

PubMed

Saber, Maha; Kokiko-Cochran, Olga; Puntambekar, Shweta S; Lathia, Justin D; Lamb, Bruce T

2017-01-15

Traumatic brain injury (TBI) affects 1.7 million persons annually in the United States (Centers for Disease Control and Prevention). There is increasing evidence that persons exposed to TBI have increased risk of the development of multiple neurodegenerative conditions, including Alzheimer disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, and infiltration of peripheral monocytes. Recent evidence suggests that alterations in innate immunity promote neurodegeneration. This includes genetic studies demonstrating that mutations in triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but also multiple neurodegenerative diseases. To examine whether TREM2 deficiency affects pathological outcomes of TBI, Trem2 knockout (Trem2 -/- ) and C57BL/6J (B6) mice were given a lateral fluid percussion injury (FPI) and sacrificed at 3 and 120 days post-injury (DPI) to look at both acute and chronic consequences of TREM2 deficiency. Notably, at 3 DPI, B6 mice exposed to TBI exhibited increased expression of TREM2 in the brain. Further, Trem2 -/- mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared with B6 mice exposed to TBI. In addition, at 120 DPI, Trem2 -/- mice exposed to TBI demonstrated reduced hippocampal atrophy and rescue of TBI-induced behavioral changes when compared with B6 mice exposed to TBI. Taken together, this study suggests that TREM2 deficiency influences both acute and chronic responses to TBI, leading to an altered macrophage response at early time points, and improved pathological and functional outcomes at later time points.

Positive surgical margins in robot-assisted partial nephrectomy: a multi-institutional analysis of oncologic outcomes (leave no tumor behind).

PubMed

Khalifeh, Ali; Kaouk, Jihad H; Bhayani, Sam; Rogers, Craig; Stifelman, Michael; Tanagho, Youssef S; Kumar, Ramesh; Gorin, Michael A; Sivarajan, Ganesh; Samarasekera, Dinesh; Allaf, Mohamad E

2013-11-01

Expanding indications for robot-assisted partial nephrectomy raise major oncologic concerns for positive surgical margins. Previous reports showed no correlation between positive surgical margins and oncologic outcomes. We report a multi-institutional experience with the oncologic outcomes of positive surgical margins on robot-assisted partial nephrectomy. Pathological and clinical followup data were reviewed from an institutional review board approved, prospectively maintained joint database from 5 institutions. Tumors with malignant pathology were isolated and statistically analyzed for demographics and oncologic followup. The log rank test was used to compare recurrence-free and metastasis-free survival between patients with positive and negative surgical margins. The proportional hazards method was used to assess the influence of multiple factors, including positive surgical margins, on recurrence and metastasis. A total of 943 robot-assisted partial nephrectomies for malignant tumors were successfully completed. Of the patients 21 (2.2%) had positive surgical margins on final pathological assessment, resulting in 2 groups, including the 21 with positive surgical margins and 922 with negative surgical margins. Positive surgical margin cases had higher recurrence and metastasis rates (p<0.001). As projected by the Kaplan-Meier method in the population as a whole at followup out to 63.6 months, 5-year recurrence-free and metastasis-free survival was 94.8% and 97.5%, respectively. There was a statistically significant difference in recurrence-free and metastasis-free survival between patients with positive and negative surgical margins (log rank test<0.001), which favored negative surgical margins. Positive surgical margins showed an 18.4-fold higher HR for recurrence when adjusted for multiple tumors, tumor size, tumor growth pattern and pathological stage. Positive surgical margins on final pathological evaluation increase the HR of recurrence and metastasis. In addition to pathological and molecular tumor characteristics, this should be considered to plan appropriate management. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Digital angiography and lipiodol computerized tomography in the anatomopathological framework of hepatocarcinoma].

PubMed

Pozzi-Mucelli, R; Pozzi-Mucelli, R; Pagnan, L; Dalla Palma, L

1994-12-01

The introduction of therapies other than conventional surgery of hepatocellular carcinoma (HCC) requires an accurate pathologic classification, which is important because it is well known that HCC may have multicentric growth. The Liver Cancer Study Group of Japan has proposed a classification dividing HCCs into three macroscopic forms from the pathologic point of view: nodular, massive and infiltrating HCCs. The nodular type is subdivided into four types: single nodular type, single nodular type with surrounding proliferation, multinodular fused type and multinodular type. Forty-six HCC patients were examined with Lipiodol Computed Tomography (LCT) to investigate the agreement between pathologic and imaging findings. LCT proved to be in close agreement with pathologic findings. Sixteen cases were classified as type I (single nodular type), 8 as type II (single nodular type with limited foci), 1 as type III (multinodular fused type), 18 as type IV (multiple nodular type with diffuse foci) and 3 cases as type V (massive form). No cases of infiltrative forms were observed in our series. Based on LCT findings, the capabilities of digital subtraction angiography (DSA) were studied in the pathologic classification of HCCs. DSA exhibited some limitations in the pathologic classification of HCCs in 5 of 16 patients with type I lesions. In these cases DSA suggested false-positive diagnoses because of regenerative nodules in cirrhotic liver in 3 cases and of daughter nodules (not confirmed at LCT) in 2 cases. In 7 of 8 patients with type II HCCs, DSA failed to show the daughter nodules surrounding the main nodule. In the 18 patients with multiple distant nodules (type IV), DSA was less sensitive in defining nodule number and site. In the massive form, the information obtained with LCT and DSA was comparable. In conclusion, LCT should be considered a basic examination in the study of HCC extent. Based on LCT findings, the most appropriate treatment can be selected, be it surgery, alcohol injection, or intraarterial chemoembolization.

Macrophages and depression - a misalliance or well-arranged marriage?

PubMed

Roman, Adam; Kreiner, Grzegorz; Nalepa, Irena

2013-01-01

Depression is a severe medical condition with multiple manifestations and diverse, largely unknown etiologies. The immune system, particularly macrophages, plays an important role in the pathology of the illness. Macrophages represent a heterogeneous population of immune cells that is dispersed throughout the body. The central nervous system is populated by several types of macrophages, including microglia, perivascular cells, meningeal and choroid plexus macrophages and pericytes. These cells occupy different brain compartments and have various functions. Under basal conditions, brain macrophages support the proper function of neural cells, organize and preserve the neuronal network and maintain homeostasis. As cells of the innate immune system, they recognize and react to any disturbances in homeostasis, eliminating pathogens or damaged cells, terminating inflammation and proceeding to initiate tissue reconstruction. Disturbances in these processes result in diverse pathologies. In particular, tissue stress or malfunction, both in the brain and in the periphery, produce sustained inflammatory states, which may cause depression. Excessive release of proinflammatory mediators is responsible for alterations of neurotransmitter systems and the occurrence of depressive symptoms. Almost all antidepressive drugs target monoamine or serotonin neurotransmission and also have anti-inflammatory or immunosuppressive properties. In addition, non-pharmacological treatments, such as electroconvulsive shock, can also exert anti-inflammatory effects. Recent studies have shown that antidepressive therapies can affect the functional properties of peripheral and brain macrophages and skew them toward the anti-inflammatory M2 phenotype. Because macrophages can affect outcome of inflammatory diseases, alleviate sickness behavior and improve cognitive function, it is possible that the effects of antidepressive treatments may be, at least in part, mediated by changes in macrophage activity.

How does Reactivity to Frustrative Non-Reward Increase Risk for Externalizing Symptoms?

PubMed Central

Gatzke-Kopp, Lisa M.; Willner, Cynthia J.; Jetha, Michelle K.; Abenavoli, Rachel M.; DuPuis, David; Segalowitz, Sidney J.

2015-01-01

Frustration is a normative affective response with adaptive value in motivating behavior. However, excessive anger in response to frustration characterizes multiple forms of externalizing psychopathology. How a given trait subserves both normative and pathological behavioral profiles is not entirely clear. One hypothesis is that the magnitude of response to frustration differentiates normative versus maladaptive reactivity. Disproportionate increases in arousal in response to frustration may exceed normal regulatory capacity, thus precipitating aggressive or antisocial responses. Alternatively, pathology may arise when reactivity to frustration interferes with other cognitive systems, impairing the individual’s ability to respond to frustration adaptively. In this paper we examine these two hypotheses in a sample of kindergarten children. First we examine whether children with conduct problems (CP; n = 105) are differentiated from comparison children (n = 135) with regard to magnitude of autonomic reactivity (cardiac and electrodermal) across a task that includes a frustrative non-reward block flanked by two reward blocks. Second we examine whether cognitive processing, as reflected by magnitude of the P3b brain response, is disrupted in the context of frustrative non-reward. Results indicate no differences in skin conductance, but a greater increase in heart rate during the frustration block among children in the CP group. Additionally, the CP group was characterized by a pronounced decrement in P3b amplitude during the frustration condition compared with both reward conditions. No interaction between cardiac and P3b measures was observed, suggesting that each system independently reflects a greater sensitivity to frustration in association with externalizing symptom severity. PMID:25937209

Neurobiological correlates of internet gaming disorder: Similarities to pathological gambling.

PubMed

Fauth-Bühler, M; Mann, K

2017-01-01

The number of massively multiplayer online games (MMOs) is on the rise worldwide along with the fascination that they inspire. Problems occur when the use of MMOs becomes excessive at the expense of other life domains. Although not yet formally included as disorder in common diagnostic systems, internet gaming disorder (IGD) is considered a "condition for further study" in section III of the DSM-5. The current review aims to provide an overview of cognitive and neurobiological data currently available on IGD, with a particular focus on impulsivity, compulsivity, and sensitivity to reward and punishment. Additionally, we also compare these findings on IGD with data from studies on pathological gambling (PG)-so far the only condition officially classified as a behavioral addiction in the DSM-5. Multiple similarities have been observed in the neurobiology of IGD and PG, as measured by alterations in brain function and behavior. Both patients with IGD and those with PG exhibited decreased loss sensitivity; enhanced reactivity to gaming and gambling cues, respectively; enhanced impulsive choice behavior; aberrant reward-based learning; and no changes in cognitive flexibility. In conclusion, the evidence base on the neurobiology of gaming and gambling disorders is beginning to illuminate the similarities between the two. However, as only a few studies have addressed the neurobiological basis of IGD, and some of these studies suffer from significant limitations, more research is required before IGD's inclusion as a second behavioral addiction in the next versions of the ICD and DSM can be justified. Copyright © 2015 Elsevier Ltd. All rights reserved.

AQP5 is differentially regulated in astrocytes during metabolic and traumatic injuries.

PubMed

Chai, Rui Chao; Jiang, Jiao Hua; Wong, Ann Yuen Kwan; Jiang, Feng; Gao, Kai; Vatcher, Greg; Hoi Yu, Albert Cheung

2013-10-01

Water movement plays vital roles in both physiological and pathological conditions in the brain. Astrocytes are responsible for regulating this water movement and are the major contributors to brain edema in pathological conditions. Aquaporins (AQPs) in astrocytes play critical roles in the regulation of water movement in the brain. AQP1, 3, 4, 5, 8, and 9 have been reported in the brain. Compared with AQP1, 4, and 9, AQP3, 5, and 8 are less studied. Among the lesser known AQPs, AQP5, which has multiple functions identified outside the central nervous system, is also indicated to be involved in hypoxia injury in astrocytes. In our study, AQP5 expression could be detected both in primary cultures of astrocytes and neurons, and AQP5 expression in astrocytes was confirmed in 1- to 4-week old primary cultures of astrocytes. AQP5 was localized on the cytoplasmic membrane and in the cytoplasm of astrocytes. AQP5 expression was downregulated during ischemia treatment and upregulated after scratch-wound injury, which was also confirmed in a middle cerebral artery occlusion model and a stab-wound injury model in vivo. The AQP5 increased after scratch injury was polarized to the migrating processes and cytoplasmic membrane of astrocytes in the leading edge of the scratch-wound, and AQP5 over-expression facilitated astrocyte process elongation after scratch injury. Taken together, these results indicate that AQP5 might be an important water channel in astrocytes that is differentially expressed during various brain injuries. Copyright © 2013 Wiley Periodicals, Inc.

How does reactivity to frustrative non-reward increase risk for externalizing symptoms?

PubMed

Gatzke-Kopp, Lisa M; Willner, Cynthia J; Jetha, Michelle K; Abenavoli, Rachel M; DuPuis, David; Segalowitz, Sidney J

2015-11-01

Frustration is a normative affective response with an adaptive value in motivating behavior. However, excessive anger in response to frustration characterizes multiple forms of externalizing psychopathology. How a given trait subserves both normative and pathological behavioral profiles is not entirely clear. One hypothesis is that the magnitude of response to frustration differentiates normative versus maladaptive reactivity. Disproportionate increases in arousal in response to frustration may exceed normal regulatory capacity, thus precipitating aggressive or antisocial responses. Alternatively, pathology may arise when reactivity to frustration interferes with other cognitive systems, impairing the individual's ability to respond to frustration adaptively. In this paper we examine these two hypotheses in a sample of kindergarten children. First we examine whether children with conduct problems (CP; n=105) are differentiated from comparison children (n=135) with regard to magnitude of autonomic reactivity (cardiac and electrodermal) across a task that includes a frustrative non-reward block flanked by two reward blocks. Second we examine whether cognitive processing, as reflected by magnitude of the P3b brain response, is disrupted in the context of frustrative non-reward. Results indicate no differences in skin conductance, but a greater increase in heart rate during the frustration block among children in the CP group. Additionally, the CP group was characterized by a pronounced decrement in P3b amplitude during the frustration condition compared with both reward conditions. No interaction between cardiac and P3b measures was observed, suggesting that each system independently reflects a greater sensitivity to frustration in association with externalizing symptom severity. Copyright © 2015 Elsevier B.V. All rights reserved.

Ocular ultrasonography focused on the posterior eye segment: what radiologists should know.

PubMed

De La Hoz Polo, Marcela; Torramilans Lluís, Anna; Pozuelo Segura, Oscar; Anguera Bosque, Albert; Esmerado Appiani, Catalina; Caminal Mitjana, Josep Maria

2016-06-01

Ocular B-mode ultrasonography (US) is an important adjuvant for the clinical assessment of a variety of ocular diseases. When ophthalmoscopy is not possible, mainly due to opacification of the transparent media (e.g., mature cataract or vitreous haemorrhage), US can guide the ophthalmologist in diagnosing disease and choosing treatment. The superficial location and cystic structure of the eye make US ideal for imaging of the eye. Moreover, dynamic study helps distinguish between various conditions that would otherwise be difficult to differentiate in some clinical setting, such as vitreous, retinal, and choroidal detachment. US is also good technique for detecting other pathologic conditions such as lens dislocation, vitreous haemorrhage, asteroid hyalosis, optic disc drusen, and tumors (e.g., choroidal melanoma, metastases, hemangioma). An understanding of the basic anatomy of the eye, the US technique, and common entities that affect the ocular globe will allow radiologists to offer this valuable imaging modality to patients and referring clinicians. This article focuses on the US anatomy and pathologic conditions that affect the posterior ocular segment. • US is specially indicated when ocular fundus cannot be assessed on ophthalmoscopy. • Multipurpose equipment with high-frequency transducers is optimal for imaging the eye. • Ultrasound can reliably depict ocular anatomy and pathology as detachments and tumours. • Dynamic examination is vital for distinguishing certain pathologic conditions as detachments.

Macrostructural and Microstructural Brain Lesions Relate to Gait Pathology in Children With Cerebral Palsy.

PubMed

Meyns, Pieter; Van Gestel, Leen; Leunissen, Inge; De Cock, Paul; Sunaert, Stefan; Feys, Hilde; Duysens, Jacques; Desloovere, Kaat; Ortibus, Els

2016-10-01

Background Even though lower-limb motor disorders are core features of spastic cerebral palsy (sCP), the relationship with brain lesions remains unclear. Unraveling the relation between gait pathology, lower-limb function, and brain lesions in sCP is complex for several reasons; wide heterogeneity in brain lesions, ongoing brain maturation, and gait depends on a number of primary motor functions/deficits (eg, muscle strength, spasticity). Objective To use a comprehensive approach combining conventional MRI and diffusion tensor imaging (DTI) in children with sCP above 3 years old to relate quantitative parameters of brain lesions in multiple brain areas to gait performance. Methods A total of 50 children with sCP (25 bilateral, 25 unilateral involvement) were enrolled. The investigated neuroradiological parameters included the following: (1) volumetric measures of the corpus callosum (CC) and lateral ventricles (LVs), and (2) DTI parameters of the corticospinal tract (CST). Gait pathology and primary motor deficits, including muscle strength and spasticity, were evaluated by 3D gait analysis and clinical examination. Results In bilateral sCP (n = 25), volume of the LV and the subparts of the CC connecting frontal, (pre)motor, and sensory areas were most related to lower-limb functioning and gait pathology. DTI measures of the CST revealed additional relations with the primary motor deficits (n = 13). In contrast, in unilateral sCP, volumetric (n = 25) and diffusion measures (n = 14) were only correlated to lower-limb strength. Conclusions These results indicate that the combined influence of multiple brain lesions and their impact on the primary motor deficits might explain a large part of the gait pathology in sCP. © The Author(s) 2016.

Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

PubMed

Shulman, Joshua M; Chen, Kewei; Keenan, Brendan T; Chibnik, Lori B; Fleisher, Adam; Thiyyagura, Pradeep; Roontiva, Auttawut; McCabe, Cristin; Patsopoulos, Nikolaos A; Corneveaux, Jason J; Yu, Lei; Huentelman, Matthew J; Evans, Denis A; Schneider, Julie A; Reiman, Eric M; De Jager, Philip L; Bennett, David A

2013-09-01

While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single-nucleotide polymorphisms and genome-wide association study in a joint clinicopathologic cohort, including 725 deceased subjects from the Religious Orders Study and the Rush Memory and Aging Project (2 prospective, community-based studies), followed by targeted validation in an independent neuroimaging cohort, including 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid positron emission tomographic imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our genome-wide association study, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P = 3.3 × 10-6). This polymorphism was associated with postmortem β-amyloid load as well as fibrillar β-amyloid in 2 independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, presymptomatic stages of AD.

Optimal conditions of LDR to protect the kidney from diabetes

PubMed Central

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-01-01

Aims We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day via suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Main methods Type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic mice received whole body X-irradiation at dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th week of the study. Key findings Diabetes induced renal dysfunction, shown by the decreased creatinine and increased microalbumin in urinary. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best preventive effect on the kidney of diabetic mice. Significance Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. PMID:24631139

Effect of intra-aortic balloon pump on coronary blood flow during different balloon cycles support: A computer study.

PubMed

Aye, Thin Pa Pa; Htet, Zwe Lin; Singhavilai, Thamvarit; Naiyanetr, Phornphop

2015-01-01

Intra-aortic balloon pump (IABP) has been used in clinical treatment as a mechanical circulatory support device for patients with heart failure. A computer model is used to study the effect on coronary blood flow (CBF) with different balloon cycles under both normal and pathological conditions. The model of cardiovascular and IABP is developed by using MATLAB SIMULINK. The effect on coronary blood flow has been studied under both normal and pathological conditions using different balloon cycles (balloon off; 1:4; 1:2; 1:1). A pathological heart is implemented by reducing the left ventricular contractility. The result of this study shows that the rate of balloon cycles is related to the level of coronary blood flow.

Extra-articular hip impingement: a narrative review of the literature

PubMed Central

Cheatham, Scott W.

2016-01-01

There is growing subgroup of patients with poor outcomes after hip arthroscopy for intra-articular pathology suggesting unrecognized cause(s) of impingement may exist. Extra-articular hip impingement (EHI) is an emerging group of conditions that have been associated with intra-articular causes of impingement and may be an unrecognized source of pain. EHI is caused by abnormal contact between the extra-articular regions of the proximal femur and pelvis. This review discusses the most common forms for EHI including: central iliopsoas impingement, subspine impingement, ischiofemoral impingement, and greater trochanteric-pelvic impingement. The clinical presentation of each pathology will be discussed since EHI conditions share similar clinical features as the intra-articular pathology but also contain some unique characteristics. PMID:27069266

Reflective practice in speech-language pathology: a scoping review.

PubMed

Caty, Marie-Ève; Kinsella, Elizabeth Anne; Doyle, Philip C

2015-01-01

Within the profession of speech-language pathology, there is limited information related to both conceptual and empirical perspectives of reflective practice. This review considers the key concepts and approaches to reflection and reflective practice that have been published in the speech-language pathology literature in order to identify potential research gaps. A scoping review was conducted using Arksey and O'Malley's (2005) framework. A total of 42 relevant publications were selected for review. The resulting literature mapping revealed that scholarship on reflection and reflective practice in speech-language pathology is limited. Our conceptual mapping pointed to the use of both multiple and generic terms and a lack of conceptual clarity about reflection and reflective practice in speech-language pathology. Two predominant approaches to reflection and reflective practice were identified: written reflection and reflective discussion. Both educational and clinical practice contexts were associated with reflection and reflective practice. Publications reviewed were primarily concerned with reflection and reflective practice by novices and expert practitioners. Based on this review, we posit that there is considerable need for conceptual and empirical work with a goal to support university- and work-based educational initiatives involving reflection and reflective practice in speech-language pathology.

[Internet use and pathological internet engagement in a sample of college students].

PubMed

Tsouvelas, G; Giotakos, O

2011-01-01

Recent studies indicate multiple consequences of pathologically excessive internet use. This study investigated the correlate of internet usage, with pathological internet engagement. Participants were 514 college students from the University of Athens who completed a questionnaire covering various aspects of internet use, Young's Internet Addiction Test, scales investigating online gambling addiction and cybersexual addiction and scales investigating suicidal ideation and the use of psychoactive substances. We found that the daily Internet use (b=0,38, t=10,38, p<0,001), the use of interactive online games (b=0,21, t=5,15, p<0,001), making acquaintances on the internet (b=0,20, t=5,11, p<0,001) and the participation in online forums (b=0,15, t=3,64, p<0,001) account for 42% of the variance of pathological internet engagement. Subjects at risk for developing pathological internet engagement had significantly higher levels of online gambling addiction, cybersexual addiction, suicidal ideation and alcohol abuse, compared with other groups. Pathological internet engagement, particularly in young people, is a new psychopathological parameter that should be incorporated in the diagnostic and therapeutic horizon of mental health professionals.

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017.

PubMed

Clunie, David; Hosseinzadeh, Dan; Wintell, Mikael; De Mena, David; Lajara, Nieves; Garcia-Rojo, Marcial; Bueno, Gloria; Saligrama, Kiran; Stearrett, Aaron; Toomey, David; Abels, Esther; Apeldoorn, Frank Van; Langevin, Stephane; Nichols, Sean; Schmid, Joachim; Horchner, Uwe; Beckwith, Bruce; Parwani, Anil; Pantanowitz, Liron

2018-01-01

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products.

Predictive value of seven preoperative prognostic scoring systems for spinal metastases.

PubMed

Leithner, Andreas; Radl, Roman; Gruber, Gerald; Hochegger, Markus; Leithner, Katharina; Welkerling, Heike; Rehak, Peter; Windhager, Reinhard

2008-11-01

Predicting prognosis is the key factor in selecting the proper treatment modality for patients with spinal metastases. Therefore, various assessment systems have been designed in order to provide a basis for deciding the course of treatment. Such systems have been proposed by Tokuhashi, Sioutos, Tomita, Van der Linden, and Bauer. The scores differ greatly in the kind of parameters assessed. The aim of this study was to evaluate the prognostic value of each score. Eight parameters were assessed for 69 patients (37 male, 32 female): location, general condition, number of extraspinal bone metastases, number of spinal metastases, visceral metastases, primary tumour, severity of spinal cord palsy, and pathological fracture. Scores according to Tokuhashi (original and revised), Sioutos, Tomita, Van der Linden, and Bauer were assessed as well as a modified Bauer score without scoring for pathologic fracture. Nineteen patients were still alive as of September 2006 with a minimum follow-up of 12 months. All other patients died after a mean period of 17 months after operation. The mean overall survival period was only 3 months for lung cancer, followed by prostate (7 months), kidney (23 months), breast (35 months), and multiple myeloma (51 months). At univariate survival analysis, primary tumour and visceral metastases were significant parameters, while Karnofsky score was only significant in the group including myeloma patients. In multivariate analysis of all seven parameters assessed, primary tumour and visceral metastases were the only significant parameters. Of all seven scoring systems, the original Bauer score and a Bauer score without scoring for pathologic fracture had the best association with survival (P < 0.001). The data of the present study emphasize that the original Bauer score and a modified Bauer score without scoring for pathologic fracture seem to be practicable and highly predictive preoperative scoring systems for patients with spinal metastases. However, decision for or against surgery should never be based alone on a prognostic score but should take symptoms like pain or neurological compromise into account.

Nutraceuticals in hypercholesterolaemia: an overview

PubMed Central

Santini, Antonello

2016-01-01

Growing attention is now being given to the possible preventive/alternative ways to avoid illness onset. Changes in lifestyle and food habits are taking over from the conventional pharmaceutical‐based approach, especially for chronic pathologies. Nutraceuticals have been proposed as key tools for the prevention and cure of some pathological conditions. This is leading research to develop new formulations based on these pharma‐foods addressed in a specific way to prevent and cure health issues, which, in turn, will have an effect on therapy‐related costs sustained by any National Health Organization. According to existing regulations, nutraceuticals cannot be categorized as either food or drugs but, by definition, often inhabit a grey area in between the two, being assimilated into food supplements, notwithstanding the beneficial properties that they can provide for some pathological conditions. A nutraceuticals‐based approach for health management, in particular for some pathological conditions, has resulted in a worldwide growing ‘nutraceutical’ revolution. An outstanding example is the approach to the ‘metabolic syndrome’, which includes overweight, obesity and cardiovascular‐related diseases, causing a sort of cascade of chronic health conditions, which is becoming a norm in modern life. Hypercholesterolaemia is one of these. It represents an example of a pathology that can be linked to both a poor lifestyle and dietary habits. The nutraceutical approach to hypercholesterolaemia is described in the present review as a possible alternative to the conventional drug‐based therapy. Linked Articles This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc PMID:27685833

Nutraceuticals in hypercholesterolaemia: an overview.

PubMed

Santini, Antonello; Novellino, Ettore

2017-06-01

Growing attention is now being given to the possible preventive/alternative ways to avoid illness onset. Changes in lifestyle and food habits are taking over from the conventional pharmaceutical-based approach, especially for chronic pathologies. Nutraceuticals have been proposed as key tools for the prevention and cure of some pathological conditions. This is leading research to develop new formulations based on these pharma-foods addressed in a specific way to prevent and cure health issues, which, in turn, will have an effect on therapy-related costs sustained by any National Health Organization. According to existing regulations, nutraceuticals cannot be categorized as either food or drugs but, by definition, often inhabit a grey area in between the two, being assimilated into food supplements, notwithstanding the beneficial properties that they can provide for some pathological conditions. A nutraceuticals-based approach for health management, in particular for some pathological conditions, has resulted in a worldwide growing 'nutraceutical' revolution. An outstanding example is the approach to the 'metabolic syndrome', which includes overweight, obesity and cardiovascular-related diseases, causing a sort of cascade of chronic health conditions, which is becoming a norm in modern life. Hypercholesterolaemia is one of these. It represents an example of a pathology that can be linked to both a poor lifestyle and dietary habits. The nutraceutical approach to hypercholesterolaemia is described in the present review as a possible alternative to the conventional drug-based therapy. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Improving appropriateness of blood utilization through prospective review of requests for blood products: the role of pathology residents as consultants.

PubMed

Haldiman, Lindsey; Zia, Hamid; Singh, Gurmukh

2014-01-01

To evaluate the effectiveness of prospective review of orders for fresh-frozen plasma (FFP) and platelets in reducing blood-product use, and of the effectiveness of preparing pathology residents to serve as clinical consultants. At our 572-bed tertiary-care hospital, we developed guidelines for the use of blood products in collaboration with a variety of departments. For patients whose condition(s) met generally accepted criteria, we identified trigger points to allow for quick release by blood bank staff of blood products. For patients whose condition(s) did not meet the applicable criteria, the on-call pathology resident reviewed the medical record of that patient to determine whether there were any extenuating circumstances; consulted with the ordering physician and attending pathologist, as needed; and advised the house staff on appropriate use of blood products. We evaluated the change in use of blood products between the years 2009 and 2012 to assess the effectiveness of the program. We observed a decrease of 38.8% and 31.4% in the use of FFP and platelets, respectively (29.7% and 21.1%, respectively, when normalized for the number of discharges). If projected to the national level, this improvement would translate to an annual cost reduction of approximately $130 million. Prospective review of orders for blood products can significantly improve use of these products, thereby reducing risk to patients and avoiding unnecessary healthcare costs. The involvement of pathology residents in the prospective review process provides an excellent opportunity for their training as laboratory consultants. Copyright© by the American Society for Clinical Pathology (ASCP).

Interesting images: Multiple coronary artery aneurysms.

PubMed

Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field.

Interesting Images: Multiple Coronary Artery Aneurysms

PubMed Central

Howard, Jonathon M; Viswanath, Omar; Armas, Alfredo; Santana, Orlando; Rosen, Gerald P

2017-01-01

We present the case of a 65-year-old male who presented with stable angina and dyspnea on exertion. His initial workup yielded a positive treadmill stress test for reversible apical ischemia, and transthoracic echocardiogram demonstrated impaired systolic function. Cardiac catheterization was then performed, revealing severe atherosclerotic disease including multiple coronary artery aneurysms. As a result, the patient was advised to and subsequently underwent a coronary artery bypass graft. This case highlights the presence of multiple coronary artery aneurysms and the ability to appreciate these pathologic findings on multiple imaging modalities, including coronary angiogram, transesophageal echocardiography, and direct visualization through the surgical field. PMID:28701599

Inflammatory pathways in cervical cancer - the UCT contribution.

PubMed

Sales, Kurt Jason; Katz, Arieh Anthony

2012-03-23

Cervical cancer is the leading gynaecological malignancy in Southern Africa. The main causal factor for development of the disease is infection of the cervix with human papillomavirus. It is a multi-step disease with several contributing co-factors including multiple sexual partners, a compromised immune system and cervical inflammation caused by infections with Chlamydia trachomatis or Neisseria gonorrhoeae. Inflammation involves extensive tissue remodelling events which are orchestrated by complex networks of cytokines, chemokines and bio-active lipids working across multiple cellular compartments to maintain tissue homeostasis. Many pathological disorders or diseases, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways. In this review we highlight our findings pertaining to activation of inflammatory pathways in cervical cancers, addressing their potential role in pathological changes of the cervix and the significance of these findings for intervention strategies.

Causes, effects and connectivity changes in MS-related cognitive decline.

PubMed

Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik

2016-01-01

Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.

Altered neural reward representations in pathological gamblers revealed by delay and probability discounting.

PubMed

Miedl, Stephan F; Peters, Jan; Büchel, Christian

2012-02-01

The neural basis of excessive delay discounting and reduced risk sensitivity of pathological gamblers with a particular focus on subjective neural reward representations has not been previously examined. To examine how pathological gamblers represent subjective reward value at a neural level and how this is affected by gambling severity. Model-based functional magnetic resonance imaging study with patients and control subjects. Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf. Participants were recruited from the local community by advertisement and through self-help groups. A sample of 16 pathological gamblers (according to the DSM-IV definition) was matched by age, sex, smoking status, income, educational level, and handedness to 16 healthy controls. Pathological gamblers showed increased discounting of delayed rewards and a trend toward decreased discounting of probabilistic rewards compared with matched controls. At the neural level, a significant group × condition interaction indicated that reward representations in the gamblers were modulated in a condition-specific manner, such that they exhibited increased (delay discounting) and decreased (probability discounting) neural value correlations in the reward system. In addition, throughout the reward system, neuronal value signals for delayed rewards were negatively correlated with gambling severity. The results extend previous reports of a generally hypoactive reward system in pathological gamblers by showing that, even when subjective reward valuation is accounted for, gamblers still show altered reward representations. Furthermore, results point toward a gradual degradation of mesolimbic reward representations for delayed rewards during the course of pathological gambling.

Decorin and biglycan of normal and pathologic human corneas

NASA Technical Reports Server (NTRS)

Funderburgh, J. L.; Hevelone, N. D.; Roth, M. R.; Funderburgh, M. L.; Rodrigues, M. R.; Nirankari, V. S.; Conrad, G. W.

1998-01-01

PURPOSE: Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring. METHODS: Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan. RESULTS: Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas. CONCLUSIONS: The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.

Development of a computerized atlas of neonatal surgery

NASA Astrophysics Data System (ADS)

Gill, Brijesh S.; Hardin, William D., Jr.

1995-05-01

Digital imaging is an evolving technology with significant potential for enhancing medical education and practice. Current teaching methodologies still rely on the time-honored traditions of group lectures, small group discussions, and clinical preceptorships. Educational content and value are variable. Utilization of electronic media is in its infancy but offers significant potential for enhancing if not replacing current teaching methodologies. This report details our experience with the creation of an interactive atlas on neonatal surgical conditions. The photographic atlas has been one of the classic tools of practice, reference, and especially of education in surgery. The major limitations on current atlases all stem from the fact that they are produced in book form. The limiting factors in the inclusion of large numbers of images in these volumes include the desire to limit the physical size of the book and the costs associated with high quality color reproduction of print images. The structure of the atlases usually makes them reference tools, rather than teaching tools. We have digitized a large number of clinical images dealing with the diagnosis and surgical management of all of the most common neonatal surgical conditions. The flexibility of the computer presentation environment allows the images to be organized in a number of different ways. In addition to a standard captioned atlas, the user may choose to review case histories of several of the more common conditions in neonates, complete with presenting conditions, imaging studies, surgery and pathology. Use of the computer offers the ability to choose multiple views of the images, including comparison views and transparent overlays that point out important anatomical and histopathological structures, and the ability to perform user self-tests. This atlas thus takes advantage of several aspects of data management unique to computerized digital imaging, particularly the ability to combine all aspects of medical imaging related to a single case for easy retrieval. This facet unique to digital imaging makes it the obvious choice for new methods of teaching such complex subjects as the clinical management of neonatal surgical conditions. We anticipate that many more subjects in the surgical, pathologic, and radiologic realms will eventually be presented in a similar manner.

Multiple-time scales analysis of physiological time series under neural control

NASA Technical Reports Server (NTRS)

Peng, C. K.; Hausdorff, J. M.; Havlin, S.; Mietus, J. E.; Stanley, H. E.; Goldberger, A. L.

1998-01-01

We discuss multiple-time scale properties of neurophysiological control mechanisms, using heart rate and gait regulation as model systems. We find that scaling exponents can be used as prognostic indicators. Furthermore, detection of more subtle degradation of scaling properties may provide a novel early warning system in subjects with a variety of pathologies including those at high risk of sudden death.

Genetically diagnosed Birt-Hogg-Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report.

PubMed

Whitworth, James; Stausbøl-Grøn, Brian; Skytte, Anne-Bine

2017-01-01

When faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation. Intracranial vascular pathologies (but not cerebral cavernous malformation) have recently been described in a number of individuals with BHD (Kapoor et al. in Fam Cancer 14:595-597, 10.1007/s10689-015-9807-y , 2015) but it is not yet clear whether they represent a genuine part of that conditions' phenotypic spectrum. We suggest that in such instances of potentially novel clinical features, more extensive genetic testing to consider co-existing conditions should be considered where available. The increased use of next generation sequencing applications in diagnostic settings is likely to lead more cases such as this being revealed.

Toll-like receptor-4 signaling pathway in aorta aging and diseases: "its double nature".

PubMed

Balistreri, Carmela Rita; Ruvolo, Giovanni; Lio, Domenico; Madonna, Rosalinda

2017-09-01

Recent advances in the field of innate immunity have revealed a complex role of innate immune signaling pathways in both tissue homeostasis and disease. Among them, the Toll-like receptor 4 (TLR-4) pathways has been linked to various pathophysiological conditions, such as cardiovascular diseases (CVDs). This has been interrogated by developing multiple laboratory tools that have shown in animal models and clinical conditions, the involvement of the TLR-4 signaling pathway in the pathophysiology of different CVDs, such as atherosclerosis, ischemic heart disease, heart failure, ischemia-reperfusion injury and aorta aneurysm. Among these, aorta aneurysm, a very complex pathological condition with uncertain etiology and fatal complications (i.e. dissection and rupture), has been associated with the occurrence of high risk cardiovascular conditions, including thrombosis and embolism. In this review, we discuss the possible role of TLR-4 signaling pathway in the development of aorta aneurysm, considering the emerging evidence from ongoing investigations. Our message is that emphasizing the role of TLR-4 signaling pathway in aorta aneurysm may serve as a starting point for future studies, leading to a better understanding of the pathophysiological basis and perhaps the effective treatment of this difficult human disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Post-translational quantitation by SRM/MRM: applications in cardiology.

PubMed

Gianazza, Erica; Banfi, Cristina

2018-06-04

Post-translational modifications (PTMs) have an important role in the regulation of protein function, localization and interaction with other molecules. PTMs apply a dynamic control of proteins both in physiological and pathological conditions. The study of disease-specific PTMs allows identifying potential biomarkers and developing effective drugs. Enrichment techniques combined with high-resolution MS/MS analysis provide attractive results on PTMs characterization. Selected reaction monitoring/multiple reaction monitoring (SRM/MRM) is a powerful targeted assay for the quantitation and validation of PTMs in complex biological samples. Areas covered: The most frequent PTMs are described in terms of biological role and analytical methods commonly used to detect them. The applications of SRM/MRM for the absolute quantitation of PTMs are reported and a specific section is focused on PTMs detection in proteins that are involved in cardiovascular system and heart diseases. Expert commentary: PTMs characterization in relation to disease pathology is still in progress, but targeted proteomics by LC-MS/MS has significantly upgraded the knowledge in the last years. Advances in enrichment strategies and software tools will facilitate the interpretation of high PTMs complexity. Promising studies confirm the great potentiality of SRM/MRM to study PTMs in cardiovascular field and PTMomics could be very useful in a clinical perspective.

The New York Brain Bank of Columbia University: practical highlights of 35 years of experience.

PubMed

Ramirez, Etty Paola Cortes; Keller, Christian Ernst; Vonsattel, Jean Paul

2018-01-01

The New York Brain Bank processes brains and organs of clinically well-characterized patients with age-related neurodegenerative diseases, and for comparison, from individuals without neurologic or psychiatric impairments. The donors, either patients or individuals, were evaluated at healthcare facilities of the Columbia University of New York. Each source brain yields four categories of samples: fresh frozen blocks and crushed parenchyma, and formalin-fixed wet blocks and histology sections. A source brain is thoroughly evaluated to determine qualitatively and quantitatively any changes it might harbor using conventional neuropathologic techniques. The clinical and pathologic diagnoses are integrated to determine the distributive diagnosis assigned to the samples obtained from a source brain. The gradual standardization of the protocol was developed in 1981 in response to the evolving requirements of basic investigations on neurodegeneration. The methods assimilate long-standing experience from multiple centers. The resulting and current protocol includes a constant central core applied to all brains with conditional flexibility around it. The New York Brain Bank is an integral part of the department of pathology, where the expertise, teaching duties, and hardware are shared. Since details of the protocols are available online, this chapter focuses on practical issues in professionalizing brain banking. Copyright © 2018 Elsevier B.V. All rights reserved.

Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

PubMed

Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

2015-01-01

The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

Predictive factors for intrauterine growth restriction

PubMed Central

Albu, AR; Anca, AF; Horhoianu, VV; Horhoianu, IA

2014-01-01

Abstract Reduced fetal growth is seen in about 10% of the pregnancies but only a minority has a pathological background and is known as intrauterine growth restriction or fetal growth restriction (IUGR / FGR). Increased fetal and neonatal mortality and morbidity as well as adult pathologic conditions are often associated to IUGR. Risk factors for IUGR are easy to assess but have poor predictive value. For the diagnostic purpose, biochemical serum markers, ultrasound and Doppler study of uterine and spiral arteries, placental volume and vascularization, first trimester growth pattern are object of assessment today. Modern evaluations propose combined algorithms using these strategies, all with the goal of a better prediction of risk pregnancies. Abbreviations: SGA = small for gestational age; IUGR = intrauterine growth restriction; FGR = fetal growth restriction; IUFD = intrauterine fetal demise; HIV = human immunodeficiency virus; PAPP-A = pregnancy associated plasmatic protein A; β-hCG = beta human chorionic gonadotropin; MoM = multiple of median; ADAM-12 = A-disintegrin and metalloprotease 12; PP-13 = placental protein 13; VEGF = vascular endothelial growth factor; PlGF = placental growth factor; sFlt-1 = soluble fms-like tyrosine kinase-1; UAD = uterine arteries Doppler ultrasound; RI = resistence index; PI = pulsatility index; VOCAL = Virtual Organ Computer–Aided Analysis software; VI = vascularization index; FI = flow index; VFI = vascularization flow index; PQ = placental quotient PMID:25408721

Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS.

PubMed

Drechsel, Derek A; Estévez, Alvaro G; Barbeito, Luis; Beckman, Joseph S

2012-11-01

Oxidative damage is a common and early feature of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders. Dr. Mark Smith and his colleagues have built the case for oxidative stress being a primary progenitor rather than a secondary end-stage epiphenomenon of neurodegeneration. They proposed that reactive oxygen species contribute to the "age-related cascade of neurodegeneration," whereby accumulative oxidative damage with age promotes other characteristic pathological changes in afflicted brain regions, including protein aggregation, metabolic deficiencies, and inflammation. Nitric oxide (NO) likely plays a critical role in this age-related cascade. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through stimulating cyclic GMP synthesis. However, the same physiological concentrations of NO, relevant in cellular signaling, may also initiate and amplify oxidative damage by diffusion-limited reactions with superoxide (O(2)(•-)) to produce peroxynitrite (ONOO(-)). This is perhaps best illustrated in ALS where physiological levels of NO promote survival of motor neurons, but the same concentrations can stimulate motor neuron apoptosis and glial cell activation under pathological conditions. While these changes represent a complex mechanism involving multiple cell types in the pathogenesis of ALS, they also reveal general processes underlying neurodegeneration.

The lethal form of Cushing's in 7B2 null mice is caused by multiple metabolic and hormonal abnormalities.

PubMed

Sarac, Miroslav S; Zieske, Arthur W; Lindberg, Iris

2002-06-01

The neuroendocrine-specific protein 7B2, which serves as a molecular escort for proPC2 in the secretory pathway, promotes the production of enzymatically active PC2 and may have non-PC2 related endocrine roles. Mice null for 7B2 exhibit a lethal phenotype with a complex Cushing's-like pathology, which develops from intermediate lobe ACTH hypersecretion as a consequences of interruption of PC2-mediated peptide processing as well as undefined consequences of the loss of 7B2. In this study we investigated the endocrine and metabolic alterations of 7B2 null mice from pathological and biochemical points of view. Our results show that 7B2 nulls exhibit a multisystem disorder that includes severe pathoanatomical and histopathologic alterations of vital organs, including the heart and spleen but most notably the liver, in which massive steatosis and necrosis are observed. Metabolic derangements in glucose metabolism result in glycogen and fat deposition in liver under conditions of chronic hypoglycemia. Liver failure is also likely to contribute to abnormalities in blood coagulation and blood chemistry, such as lactic acidosis. A hypoglycemic crisis coupled with respiratory distress and intensive internal thrombosis most likely results in rapid deterioration and death of the 7B2 null.

[Embryo-fetal diseases in multiple pregnancies].

PubMed

Colla, F; Alba, E; Grio, R

2001-04-01

Embryo-fetal diseases are the consequence of prenatal (progenetic and metagenetic or environmental) and intranatal (of a traumatic, infective, toxic nature) pathological factors. In multiple pregnancies this complex etiopathogenesis also includes an altered didymous embriogenesis. This study aimed to evaluate the pathologies affecting the fetus in multiple pregnancy, a special biological situation leading to the potential onset of severe fetal and neonatal damage. The authors studied 205 patients with multiple pregnancies, including 199 bigeminal, 5 trigeminal and 1 quadrigeminal, admitted to the Department B of the Obstetrics and Gynecological Clinic of Turin University between 1989-1999. Possible embyro-fetal damage was examined using a chronological criterion: namely following the development of the multiple fetuses from the zygotic to the neonatal phase. Pregnancies were biamniotic bichorionic in 54% of cases, biamniotic monochorionic in 45% and monochorionic monoamniotic in 1%. There were a total of 154 (79.38%) premature births out of 194 and neonatal birth weight was always SGA (small for gestational age). 66.84% of newborns were LBW (<2500 g) and 7.14% were VLBW (<1500 g). Fetal mortality (2.29%) was higher than early neonatal mortality (1.53%). Perinatal mortality (3.82%) was three times higher than in all neonates from the same period (1.03%). The severe embryo-fetal and neonatal damage found in multiple pregnancies is a clinical reality that calls for adequate diagnostic and therapeutic measures, and above all specific medical and social prevention to limit maternal pathogenic risks.

Evaluation of Hands-On Clinical Exam Performance Using Marker-less Video Tracking.

PubMed

Azari, David; Pugh, Carla; Laufer, Shlomi; Cohen, Elaine; Kwan, Calvin; Chen, Chia-Hsiung Eric; Yen, Thomas Y; Hu, Yu Hen; Radwin, Robert

2014-09-01

This study investigates the potential of using marker-less video tracking of the hands for evaluating hands-on clinical skills. Experienced family practitioners attending a national conference were recruited and asked to conduct a breast examination on a simulator that simulates different clinical presentations. Videos were made of the clinician's hands during the exam and video processing software for tracking hand motion to quantify hand motion kinematics was used. Practitioner motion patterns indicated consistent behavior of participants across multiple pathologies. Different pathologies exhibited characteristic motion patterns in the aggregate at specific parts of an exam, indicating consistent inter-participant behavior. Marker-less video kinematic tracking therefore shows promise in discriminating between different examination procedures, clinicians, and pathologies.

Masculine Process/Masculine Pathology: A New Psychodynamic Approach.

ERIC Educational Resources Information Center

Goldberg, Herb

1993-01-01

Notes that traditional masculine conditioning and its underlying unconscious defenses are a major unrecognized cause of psychopathology for men today. Discusses psychodynamics of gender and manifestations of the masculine experience, and illustrates symptoms of male pathology. Hopes that this awareness provides important insights for effective…

The normal and pathologic renal medulla: a comprehensive overview.

PubMed

López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

[Morphological structure of suprarenal glands in experimental vibration-induced pathology].

PubMed

Kapanadze, N A; Abzianidze, E N; Sumbadze, Ts M; Korkiia, I I; Amiranidze, M V

2009-01-01

Technical progress has caused development of vibration-induced pathology, which is determined by harmful factors or environmental effects. The harmful factors include physical factors--noise, mechanical vibrations, low temperature, high humidity of the air and incorrect lighting. The aim of our study was the investigation of morphological changes in suprarenal glands under condition of vibration-induced pathology. The experiment was conducted on 20 grown-up white male rats weighting 180-200 g. The animals were daily under an hour vibration during 2 months. The vibration frequency was modulated by means of a general vibration. After an experiment, animals were decapitated in condition of general anesthesia. The experiment revealed important changes in the morphological structure of suprarenal glands. The vibration pathology causes following changes: vessels' and sinusoid capillaries' uneven widening, develop the infiltrate cells, bleeding areas, necrosis and other changes. Based on above-stated it is supposed that technical progress and introduction of new technologies is one of the risk factors, which can cause neurohumoral disorders.

MRI of the stomach: a pictorial review with a focus on oncological applications and gastric motility.

PubMed

Sheybani, Arman; Menias, Christine O; Luna, Antonio; Fowler, Kathryn J; Hara, Amy Kiyo; Silva, Alvin C; Yano, Motoyo; Sandrasegaran, Kumar

2015-04-01

The purpose of this pictorial review is to demonstrate gastric pathology seen on magnetic resonance imaging (MRI) and discuss the essential MRI sequences for the evaluation of benign and malignant gastric pathologies. Common tumors of the stomach, polyposis syndromes, iatrogenic conditions, as well as other conditions of the stomach will be reviewed. The utility of MRI in the evaluation of patients with gastric malignancies and disorders of gastric motility will also be discussed.

Lumbar vertebral pedicles: radiologic anatomy and pathology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, N.P.; Kumar, R.; Kinkhabwala, M.

1988-01-01

With the advancement of high-resolution computed tomography (CT) scanning the spine has added new knowledge to the various conditions affecting the pedicles. We wish to review the entire spectrum of pedicular lesions: the embryology, normal anatomy, normal variants, pitfalls, congenital anomalies, and pathological conditions are discussed. Different imaging modalities involving CT, isotope bone scanning, and Magnetic Resonance Imaging (MRI) are used to complement plain films of the lumbar spine. This subject review is an excellent source for future reference to lumbar pedicular lesions. 27 references.

[SYNERGISM OF PRECONCEPTIVE RADIATION EXPOSURE AND PARENTS' ONCO-PATHOLOGY IN THE RISE OF CARCINOGENIC RISK IN THE OFFSPRINGS OF PROFESSIONAL EMPLOYEES].

PubMed

Telnov, V I; Kabirova, N R; Okatenko, P V

2015-01-01

The problem of carcinogenic risk in offsprings of individuals exposed to radiation is challenging and insufficiently studied. In that there are no evaluations of the interaction between radiation and non-radiation factors. The aim of the study was the analysis of interaction of preconceptive radiation exposure and parents' onco-pathology in cancer mortality in offsprings (F1) of workers (fathers) of the Mayak Production Association exposed to a wide range of doses of radiation over a year prior conception. The number of offspring is 8191 individuals (4180 men and 4011 women). The analysis was performed with the use of fourfold table and eightfold tables. The interaction offactors was estimated on the base of the additive and multiplicative models. The studied factors were independent. The odds ratio (OR) of cancer mortality in the offspring with parents' oncopathology (1.43) was insignificant. OR of cancer mortality in preconceptive radiation exposure in a dose over 110 mGy and without parents' onco-pathology was 2.61 (1.52-4.49), and in their combination--3.86 (1.93-7.71). Index of synergism of preconceptive radiation exposure and parents' onco-patholog in the rise of carcinogenic risk in the offspring was 1.34 and the character of their interaction was multiplicative. Thus, for the first time there was established the interaction between radiation and non-radiation factors in the synergism sort in the increase of carcinogenic risk in the offspring of people exposed to radiation.

Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis

PubMed Central

Lin, Tsen-Hsuan; Spees, William M.; Chiang, Chia-Wen; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

Optic neuritis is a frequent and early symptom of multiple sclerosis (MS). Conventional magnetic resonance (MR) techniques provide means to assess multiple MS-related pathologies, including axonal injury, demyelination, and inflammation. A method to directly and non-invasively probe white-matter function could further elucidate the interplay of underlying pathologies and functional impairments. Previously, we demonstrated a significant 27% activation-associated decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) in normal C57BL/6 mouse optic nerve with visual stimulation using diffusion fMRI. Here we apply this approach to explore the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis. Visual stimulation produced a significant 25% (vs. baseline) ADC⊥ decrease in sham EAE optic nerves, while only a 7% (vs. baseline) ADC⊥ decrease was seen in EAE mice with acute optic neuritis. The reduced activation-associated ADC⊥ response correlated with post-MRI immunohistochemistry determined pathologies (including inflammation, demyelination, and axonal injury). The negative correlation between activation-associated ADC⊥ response and visual acuity was also found when pooling EAE-affected and sham groups under our experimental criteria. Results suggest that reduction in diffusion fMRI directly reflects impaired axonal-activation in EAE mice with optic neuritis. Diffusion fMRI holds promise for directly gauging in vivo white-matter dysfunction or therapeutic responses in MS patients. PMID:24632420

Recent advances in standards for collaborative Digital Anatomic Pathology

PubMed Central

2011-01-01

Context Collaborative Digital Anatomic Pathology refers to the use of information technology that supports the creation and sharing or exchange of information, including data and images, during the complex workflow performed in an Anatomic Pathology department from specimen reception to report transmission and exploitation. Collaborative Digital Anatomic Pathology can only be fully achieved using medical informatics standards. The goal of the international integrating the Healthcare Enterprise (IHE) initiative is precisely specifying how medical informatics standards should be implemented to meet specific health care needs and making systems integration more efficient and less expensive. Objective To define the best use of medical informatics standards in order to share and exchange machine-readable structured reports and their evidences (including whole slide images) within hospitals and across healthcare facilities. Methods Specific working groups dedicated to Anatomy Pathology within multiple standards organizations defined standard-based data structures for Anatomic Pathology reports and images as well as informatic transactions in order to integrate Anatomic Pathology information into the electronic healthcare enterprise. Results The DICOM supplements 122 and 145 provide flexible object information definitions dedicated respectively to specimen description and Whole Slide Image acquisition, storage and display. The content profile “Anatomic Pathology Structured Report” (APSR) provides standard templates for structured reports in which textual observations may be bound to digital images or regions of interest. Anatomic Pathology observations are encoded using an international controlled vocabulary defined by the IHE Anatomic Pathology domain that is currently being mapped to SNOMED CT concepts. Conclusion Recent advances in standards for Collaborative Digital Anatomic Pathology are a unique opportunity to share or exchange Anatomic Pathology structured reports that are interoperable at an international level. The use of machine-readable format of APSR supports the development of decision support as well as secondary use of Anatomic Pathology information for epidemiology or clinical research. PMID:21489187

Diverticular disease of the right colon.

PubMed

Radhi, Jasim M; Ramsay, Jennifer A; Boutross-Tadross, Odette

2011-10-06

The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. Single true diverticular disease of the right colon is usually of congenital type and affects younger age group and may be associated with angiodysplasia in some cases. Multiple false diverticuli are more seen in association with caecal carcinoma or large adenomas. These are usually asymptomatic and are more seen in older patients. However this study dose not reflects the true incidence of the disease in the general population.

Profiling pathological narcissism according to DSM-5 domains and traits: A study on consecutively admitted Italian psychotherapy patients.

PubMed

Fossati, Andrea; Somma, Antonella; Borroni, Serena; Pincus, Aaron L; Markon, Kristian E; Krueger, Robert F

2017-11-01

[Correction Notice: An Erratum for this article was reported in Vol 29(11) of Psychological Assessment (see record 2016-56886-001). In the article, several values were reversed and the mean was misreported in Table 2. The corrected table is present in the erratum.] Pathological narcissism represents a clinically relevant, albeit controversial personality construct, with multiple conceptualizations that are operationalized by different measures. Even in the recently published Diagnostic and Statistical Manual for Mental Disorders-Fifth Edition (DSM-5), 2 different views of narcissistic personality disorder (NPD) are formulated (i.e., Section II and Section III). The DSM-5 Section III alternative PD model diagnosis of NPD is based on self and interpersonal dysfunction (Criterion A) and a profile of maladaptive personality traits (Criterion B), specifically elevated scores on Attention Seeking and Grandiosity. Given the diversity of conceptualizations of pathological narcissism, we evaluated the convergences and divergences in DSM-5 trait profiles characterizing multiple measures of narcissism in a clinical sample of 278 consecutively admitted Italian psychotherapy patients. Patients were administered the Italian versions of the Personality Inventory for DSM-5 (PID-5) and 4 measures of NPD, (a) the Narcissistic Personality Inventory (NPI); (b) the NPD scale of the Personality Diagnostic Questionnaire-4+; (c) the Structured Clinical Interview for Axis II Personality Disorders, Version 2.0 (SCID-II) as an observer-rated measure of NPD; and (d) the Pathological Narcissism Inventory (PNI). Multiple regression analyses showed that PID-5 traits explained from 13% to more than 60% of the variance in the different NPD measures. Attention Seeking was consistently associated with all measures of NPD, whereas Grandiosity was associated with some of the NPD measures. All measures of NPD were also significantly related to additional DSM-5 maladaptive traits. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis

PubMed Central

Abrahamsson, Sofia V.; Angelini, Daniela F.; Dubinsky, Amy N.; Morel, Esther; Oh, Unsong; Jones, Joanne L.; Carassiti, Daniele; Reynolds, Richard; Salvetti, Marco; Calabresi, Peter A.; Coles, Alasdair J.; Battistini, Luca; Martin, Roland; Burt, Richard K.

2013-01-01

Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating the immune repertoire by sequentially mobilizing and harvesting haematopoietic stem cells, administering an immunosuppressive conditioning regimen, and re-infusing the autologous haematopoietic cell product. ‘Non-myeloablative’ conditioning regimens to achieve lymphocytic ablation without marrow suppression have been proposed to improve safety and tolerability. One trial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement and inflammatory stabilization in treated patients with highly active multiple sclerosis. The aim of the present study was to understand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action. Peripheral blood was obtained from 12 patients with multiple sclerosis participating in the aforementioned trial and longitudinally followed for 2 years. We examined the phenotype and function of peripheral blood lymphocytes by cell surface or intracellular staining and multi-colour fluorescence activated cell sorting alone or in combination with proliferation assays. During immune reconstitution post-transplantation we observed significant though transient increases in the proportion of CD4+FoxP3+ T cells and CD56high natural killer cell subsets, which are cell subsets associated with immunoregulatory function. CD8+CD57+ cytotoxic T cells were persistently increased after therapy and were able to suppress CD4+ T cell proliferation with variable potency. In contrast, a CD161high proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating in the gut mucosa but expressing the central nervous system-homing receptor CCR6. Detection of mucosal-associated invariant T cells in post-mortem multiple sclerosis brain white matter active lesions confirmed their involvement in the disease pathology. Intracellular cytokine staining demonstrated interferon γ and interleukin 17 production and lack of interleukin 10 production, a pro-inflammatory profile. Mucosal-associated invariant T cell frequency did not change in patients treated with interferon β; and was more depleted after autologous haematopoietic stem cell transplantation than in patients who had received high-dose cyclophosphamide (n = 7) or alemtuzumab (n = 21) treatment alone, suggesting an additive or synergistic effect of the conditioning regime components. We propose that a favourably modified balance of regulatory and pro-inflammatory lymphocytes underlies the suppression of central nervous system inflammation in patients with multiple sclerosis following non-myeloablative autologous haematopoietic stem cell transplantation with a conditioning regimen consisting of cyclophosphamide and alemtuzumab. PMID:23864273

Diagnostic Evaluation of the Knee in the Office Setting Using Small-Bore Needle Arthroscopy.

PubMed

Patel, Karan A; Hartigan, David E; Makovicka, Justin L; Dulle, Donald L; Chhabra, Anikar

2018-01-01

Arthroscopy is currently the gold standard for diagnosing intra-articular knee pathology. Magnetic resonance imaging (MRI) can be a clinical adjunct for diagnosis; however, it is not without its shortcomings. Although highly accurate, even advanced imaging misdiagnoses the condition in 1 in 14 patients with regard to anterior cruciate ligament pathology. Previous studies have indicated that MRI fails to identify meniscal pathology when one exists in 1 of every 10 cases, and diagnoses pathology when pathology truly does not exist in 1 of every 5 patients. In-office arthroscopy offers an alternative to formal diagnostic arthroscopy, with reduced cost and risk of complications. This is a technique article that discusses the use of small-bore needle arthroscopy in the office setting.

Identifying associations between pig pathologies using a multi-dimensional machine learning methodology.

PubMed

Sanchez-Vazquez, Manuel J; Nielen, Mirjam; Edwards, Sandra A; Gunn, George J; Lewis, Fraser I

2012-08-31

Abattoir detected pathologies are of crucial importance to both pig production and food safety. Usually, more than one pathology coexist in a pig herd although it often remains unknown how these different pathologies interrelate to each other. Identification of the associations between different pathologies may facilitate an improved understanding of their underlying biological linkage, and support the veterinarians in encouraging control strategies aimed at reducing the prevalence of not just one, but two or more conditions simultaneously. Multi-dimensional machine learning methodology was used to identify associations between ten typical pathologies in 6485 batches of slaughtered finishing pigs, assisting the comprehension of their biological association. Pathologies potentially associated with septicaemia (e.g. pericarditis, peritonitis) appear interrelated, suggesting on-going bacterial challenges by pathogens such as Haemophilus parasuis and Streptococcus suis. Furthermore, hepatic scarring appears interrelated with both milk spot livers (Ascaris suum) and bacteria-related pathologies, suggesting a potential multi-pathogen nature for this pathology. The application of novel multi-dimensional machine learning methodology provided new insights into how typical pig pathologies are potentially interrelated at batch level. The methodology presented is a powerful exploratory tool to generate hypotheses, applicable to a wide range of studies in veterinary research.

Mechanisms of protein-folding diseases at a glance.

PubMed

Valastyan, Julie S; Lindquist, Susan

2014-01-01

For a protein to function appropriately, it must first achieve its proper conformation and location within the crowded environment inside the cell. Multiple chaperone systems are required to fold proteins correctly. In addition, degradation pathways participate by destroying improperly folded proteins. The intricacy of this multisystem process provides many opportunities for error. Furthermore, mutations cause misfolded, nonfunctional forms of proteins to accumulate. As a result, many pathological conditions are fundamentally rooted in the protein-folding problem that all cells must solve to maintain their function and integrity. Here, to illustrate the breadth of this phenomenon, we describe five examples of protein-misfolding events that can lead to disease: improper degradation, mislocalization, dominant-negative mutations, structural alterations that establish novel toxic functions, and amyloid accumulation. In each case, we will highlight current therapeutic options for battling such diseases.

New Roles of the Primary Cilium in Autophagy

PubMed Central

Ávalos, Yenniffer; Peña-Oyarzun, Daniel; Budini, Mauricio

2017-01-01

The primary cilium is a nonmotile organelle that emanates from the surface of multiple cell types and receives signals from the environment to regulate intracellular signaling pathways. The presence of cilia, as well as their length, is important for proper cell function; shortened, elongated, or absent cilia are associated with pathological conditions. Interestingly, it has recently been shown that the molecular machinery involved in autophagy, the process of recycling of intracellular material to maintain cellular and tissue homeostasis, participates in ciliogenesis. Cilium-dependent signaling is necessary for autophagosome formation and, conversely, autophagy regulates both ciliogenesis and cilium length by degrading specific ciliary proteins. Here, we will discuss the relationship that exists between the two processes at the cellular and molecular level, highlighting what is known about the effects of ciliary dysfunction in the control of energy homeostasis in some ciliopathies. PMID:28913352

New Roles of the Primary Cilium in Autophagy.

PubMed

Ávalos, Yenniffer; Peña-Oyarzun, Daniel; Budini, Mauricio; Morselli, Eugenia; Criollo, Alfredo

2017-01-01

The primary cilium is a nonmotile organelle that emanates from the surface of multiple cell types and receives signals from the environment to regulate intracellular signaling pathways. The presence of cilia, as well as their length, is important for proper cell function; shortened, elongated, or absent cilia are associated with pathological conditions. Interestingly, it has recently been shown that the molecular machinery involved in autophagy, the process of recycling of intracellular material to maintain cellular and tissue homeostasis, participates in ciliogenesis. Cilium-dependent signaling is necessary for autophagosome formation and, conversely, autophagy regulates both ciliogenesis and cilium length by degrading specific ciliary proteins. Here, we will discuss the relationship that exists between the two processes at the cellular and molecular level, highlighting what is known about the effects of ciliary dysfunction in the control of energy homeostasis in some ciliopathies.

The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice

PubMed Central

Tang, Wei; Lu, Yi; Tian, Qing-Yun; Zhang, Yan; Guo, Feng-Jin; Liu, Guang-Yi; Syed, Nabeel Muzaffar; Lai, Yongjie; Lin, Edward Alan; Kong, Li; Su, Jeffrey; Yin, Fangfang; Ding, Ai-Hao; Zanin-Zhorov, Alexandra; Dustin, Michael L.; Tao, Jian; Craft, Joseph; Yin, Zhinan; Feng, Jian Q.; Abramson, Steven B.; Yu, Xiu-Ping; Liu, Chuan-ju

2011-01-01

The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFR), and disturbed the TNFα/TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis. PMID:21393509

Extension of echinococcal spinal infestation extra- and intradurally after a decade of extinction.

PubMed

Samadian, M; Alavi, E; Sharifi, G; Rezaee, O; Faramarzi, F

2010-12-01

Simultaneous intradural, extradural, vertebral and paravetebral invasion of hydatid cyst, pathologic fracture, and multiple vertebral involvement are all rare encountered conditions in echinococcal infestation. A 48-year-old man who had experienced a falling down trauma, 10 years ago, and at that time, because of L1 burst fracture, undergone on Harrington rod placement, admitted in our ward for newly started urinary retention and mild paresis of lower extremities. With imaging analysis and during surgery, we discovered the extension of echinococcal spinal infestation extra- and intradurally after a decade of extinction. We performed a double stage circumferential reconstruction and adjuvant long term chemotherapy. We closely monitor our patient neurologically and radiologically and believe that aggressive surgical treatment and sustained cyclical albendazole therapy can increase the quality of life and life expectancy.

Historical evidence supports El Greco's depiction of a neurological condition in his attributed self-portrait.

PubMed

Bianucci, R; Marías Franco, F; Appenzeller, O

2017-01-15

Icono-diagnosis, the retrospective image-based diagnosis of pathologies, was applied to the canvas "Portrait of an Old Man" (1595-1600), an attributed self-portrait painted by El Greco. The presence of congenital enophthalmos, strabismus, probable amblyopia and signs of left neglect were found. We assume these sign may be consistent an ischemic event affecting the right middle cerebral artery supply territory. Historically, motor activity was not compromised and the painter was able to return to portraiture. Documental evidence indicates, that a few years later (1608), El Greco suffered another cerebrovascular event resulting in agraphia. The pictorial and historical evidence is consistent with multiple ischemic events resulting in progressive disabilities with fluctuating course characterized by temporary improvements and worsening before his death in 1614. Copyright © 2016 Elsevier B.V. All rights reserved.

A large dataset of protein dynamics in the mammalian heart proteome.

PubMed

Lau, Edward; Cao, Quan; Ng, Dominic C M; Bleakley, Brian J; Dincer, T Umut; Bot, Brian M; Wang, Ding; Liem, David A; Lam, Maggie P Y; Ge, Junbo; Ping, Peipei

2016-03-15

Protein stability is a major regulatory principle of protein function and cellular homeostasis. Despite limited understanding on mechanisms, disruption of protein turnover is widely implicated in diverse pathologies from heart failure to neurodegenerations. Information on global protein dynamics therefore has the potential to expand the depth and scope of disease phenotyping and therapeutic strategies. Using an integrated platform of metabolic labeling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the in vivo half-life of 3,228 and the expression of 8,064 cardiac proteins, quantified under healthy and hypertrophic conditions across six mouse genetic strains commonly employed in biomedical research. We anticipate these data will aid in understanding key mitochondrial and metabolic pathways in heart diseases, and further serve as a reference for methodology development in dynamics studies in multiple organ systems.

Occipital neuralgia: anatomic considerations.

PubMed

Cesmebasi, Alper; Muhleman, Mitchel A; Hulsberg, Paul; Gielecki, Jerzy; Matusz, Petru; Tubbs, R Shane; Loukas, Marios

2015-01-01

Occipital neuralgia is a debilitating disorder first described in 1821 as recurrent headaches localized in the occipital region. Other symptoms that have been associated with this condition include paroxysmal burning and aching pain in the distribution of the greater, lesser, or third occipital nerves. Several etiologies have been identified in the cause of occipital neuralgia and include, but are not limited to, trauma, fibrositis, myositis, fracture of the atlas, and compression of the C-2 nerve root, C1-2 arthrosis syndrome, atlantoaxial lateral mass osteoarthritis, hypertrophic cervical pachymeningitis, cervical cord tumor, Chiari malformation, and neurosyphilis. The management of occipital neuralgia can include conservative approaches and/or surgical interventions. Occipital neuralgia is a multifactorial problem where multiple anatomic areas/structures may be involved with this pathology. A review of these etiologies may provide guidance in better understanding occipital neuralgia. © 2014 Wiley Periodicals, Inc.

Pulmonary Foreign Body Granulomatosis in Dental Technician.

PubMed

Chung, Sung Jun; Koo, Gun Woo; Park, Dong Won; Kwak, Hyun Jung; Yhi, Ji Young; Moon, Ji-Yong; Kim, Sang-Heon; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Park, Sung Soo; Pyo, Ju Yeon; Oh, Young-Ha; Kim, Tae-Hyung

2015-10-01

Occupational lung diseases are caused by several toxic substances including heavy metals; however, the exact pathologic mechanisms remain unknown. In the workplace, dental technicians are often exposed to heavy metals such as cobalt, nickel, or beryllium and occasionally develop occupational lung diseases. We described a case of occupational lung disease in a patient who was employed as a dental technician for over a decade. A 31-year-old, non-smoking woman presented with productive cough and shortness of breath of several weeks duration. Chest computed tomography revealed a large number of scattered, bilateral small pulmonary nodules throughout the lung field, and multiple mediastinal lymph nodes enlargement. Percutaneous needle biopsy showed multifocal small granulomas with foreign body type giant cells suggestive of heavy metals inhalation. The patient's condition improved on simple avoidance strategy for several months. This case highlighted the importance of proper workplace safety.

Cytokines and the immune-neuroendocrine network: What did we learn from infection and autoimmunity?

PubMed

Correa, Silvia G; Maccioni, Mariana; Rivero, Virginia E; Iribarren, Pablo; Sotomayor, Claudia E; Riera, Clelia M

2007-01-01

The initial view of the neuroendocrine-immune communication as the brake of immune activation is changing. Recent evidence suggests that the optimization of the body's overall response to infection could be actually the role of the immune-endocrine network. In gradually more complex organisms, the multiplicity of host-pathogen interfaces forced the development of efficient and protective responses. Molecules such as cytokines and Toll-like receptors (TLRs) are distributed both in the periphery and in the brain to participate in a coordinated adaptive function. When sustained release of inflammatory mediators occurs, as in autoimmune diseases, undesirable pathological consequences become evident with different manifestations and outcomes. Clearly, organisms are not well adapted to that disregulated condition yet, suggesting that additional partners within neuroendocrine-immune interactions might emerge from the evolutionary road.

Treatment of enamel hypoplasia in a patient with Usher syndrome.

PubMed

de la Peña, Victor Alonso; Valea, Martín Caserío

2011-08-01

Usher syndrome (USH) is a group of autosomal recessive diseases characterized by the association of retinitis pigmentosa with sensorineural hearing loss. There are three types of USH. In addition, in people with USH and hypoplasia, the thickness of the enamel is reduced. The authors describe a case of a patient with USH type II associated with severe enamel hypoplasia and multiple unerupted teeth. The authors placed direct composite crowns and extracted severely affected and impacted molars. There is little information available on the oral pathologies of USH. Because the authors did not know how the patient's condition would progress and the patient still was growing, the authors treated the patient conservatively by placing direct composite crowns. The treatment has met both esthetic and functional expectations for 10 years. Copyright © 2011 American Dental Association. All rights reserved.

Mind/body dualism in medicine: The case of chronic pelvic pain without organic pathology: a critical review of the literature.

PubMed

Grace, V M

1998-01-01

Chronic pelvic pain in the absence of organic pathology identifiable in medical terms is considered one of the most perplexing conditions that gynecologists confront. A critical analysis of the medical, psychiatric, and psychological literature on chronic pelvic pain without organic pathology reveals that the dichotomous construct of mind and body underpinning medical research and understanding is a barrier to the successful diagnosis and treatment of this condition, and indeed to the productive engagement of the health professional with the patient. The strict duality of the condition's etiology being understood in either physiological or psychogenic terms has been questioned at times over the last 40 years, but only recently has an "integrative model" been proposed. However, it is argued here that although the development of a multidisciplinary approach is important, only a radical deconstruction of the medical paradigm will truly address the problem and enable a real change in practice.

[Coincidence of juvenile idiopathic arthritis and multiple sclerosis: case report].

PubMed

Puszczewicz, Mariusz J; Tuchocka-Piotrowska, Aleksandra; Majewski, Dominik; Kołczewska, Aleksandra

2006-01-01

Juvenile idiopathic arthritis is a systemic pathology of connective tissue characterized by a chronic inflammatory process with an autoimmune background whereas multiple sclerosis is a demyelination disease with an important role of immune disorders in its pathogenesis. The etiology in both cases remains unknown. The coincidence of juvenile idiopathic arthritis and multiple sclerosis was described a just a few patients. We now report on a 31-year-old woman with juvenile idiopathic arthritis and multiple sclerosis. In the present case, the main problem was to find the right proper medication for a very, aggressive course of multiple sclerosis and for arthritis. Treatment with interferon-beta and methylprednisolone led to remission with just minor side-effects.

Association of Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 with pathological diagnosis of Alzheimer disease.

PubMed

Yu, Lei; Chibnik, Lori B; Srivastava, Gyan P; Pochet, Nathalie; Yang, Jingyun; Xu, Jishu; Kozubek, James; Obholzer, Nikolaus; Leurgans, Sue E; Schneider, Julie A; Meissner, Alexander; De Jager, Philip L; Bennett, David A

2015-01-01

Recent large-scale genome-wide association studies have discovered several genetic variants associated with Alzheimer disease (AD); however, the extent to which DNA methylation in these AD loci contributes to the disease susceptibility remains unknown. To examine the association of brain DNA methylation in 28 reported AD loci with AD pathologies. Ongoing community-based clinical pathological cohort studies of aging and dementia (the Religious Orders Study and the Rush Memory and Aging Project) among 740 autopsied participants 66.0 to 108.3 years old. DNA methylation levels at individual CpG sites generated from dorsolateral prefrontal cortex tissue using a bead assay. Pathological diagnosis of AD by National Institute on Aging-Reagan criteria following a standard postmortem examination. Overall, 447 participants (60.4%) met the criteria for pathological diagnosis of AD. Brain DNA methylation in SORL1, ABCA7, HLA-DRB5, SLC24A4, and BIN1 was associated with pathological AD. The association was robustly retained after replacing the binary trait of pathological AD with 2 quantitative and molecular specific hallmarks of AD, namely, Aβ load and paired helical filament tau tangle density. Furthermore, RNA expression of transcripts of SORL1 and ABCA7 was associated with paired helical filament tau tangle density, and the expression of BIN1 was associated with Aβ load. Brain DNA methylation in multiple AD loci is associated with AD pathologies. The results provide further evidence that disruption of DNA methylation is involved in the pathological process of AD.

A team-based approach to autopsy education: integrating anatomic and clinical pathology at the rotation level.

PubMed

Hébert, Tiffany Michele; Maleki, Sara; Vasovic, Ljiljana V; Arnold, Jeffrey L; Steinberg, Jacob J; Prystowsky, Michael B

2014-03-01

Pathology residency training programs should aim to teach residents to think beyond the compartmentalized data of specific rotations and synthesize data in order to understand the whole clinical picture when interacting with clinicians. To test a collaborative autopsy procedure at Montefiore Medical Center (Bronx, New York), linking residents and attending physicians from anatomic and clinical pathology in the autopsy process from the initial chart review to the final report. Residents consult with clinical pathology colleagues regarding key clinical laboratory findings during the autopsy. This new procedure serves multiple functions: creating a team-based, mutually beneficial educational experience; actively teaching consultative skills; and facilitating more in-depth analysis of the clinical laboratory findings in autopsies. An initial trial of the team-based autopsy system was done from November 2010 to December 2012. Residents were then surveyed via questionnaire to evaluate the frequency and perceived usefulness of clinical pathology autopsy consultations. Senior residents were the most frequent users of clinical pathology autopsy consultation. The most frequently consulted services were microbiology and chemistry. Eighty-nine percent of the residents found the clinical pathology consultation to be useful in arriving at a final diagnosis and clinicopathologic correlation. The team-based autopsy is a novel approach to integration of anatomic and clinical pathology curricula at the rotation level. Residents using this approach develop a more holistic approach to pathology, better preparing them for meaningful consultative interaction with clinicians. This paradigm shift in training positions us to better serve in our increasing role as arbiters of outcomes measures in accountable care organizations.

Physical frailty in older persons is associated with Alzheimer disease pathology.

PubMed

Buchman, Aron S; Schneider, Julie A; Leurgans, Sue; Bennett, David A

2008-08-12

We examined the extent to which physical frailty in older persons is associated with common age-related brain pathology, including cerebral infarcts, Lewy body pathology, and Alzheimer disease (AD) pathology. We studied brain autopsies from 165 deceased participants from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study of aging. Physical frailty, based on four components, including grip strength, time to walk 8 feet, body composition, and fatigue, was assessed at annual clinical evaluations. Multiple regression analyses were used to examine the relation of postmortem neuropathologic findings to frailty proximate to death, controlling for age, sex, and education. The mean age at death was 88.1 years (SD = 5.7 years). The level of AD pathology was associated with frailty proximate to death ( = 0.252, SE = 0.077, p = 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( = -0.121, SE = 0.115, p = 0.294) nor Lewy body disease pathology ( = 0.07, SE = 0.156, p = 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications. Physical frailty in old age is associated with Alzheimer disease pathology in older persons with and without dementia.

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity

PubMed Central

Affirul, C.A.; Qisti, F.N.; Zamri, Z.; Azlanuddin, A.; Hairol, A.O.; Razman, J.

2014-01-01

INTRODUCTION Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. PRESENTATION OF CASE This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. DISCUSSION We discuss the presentations, diagnosis and pathology findings of this rare pathology. CONCLUSION The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. PMID:25462046

Pancreatic pseudopapillary tumour: A rare misdiagnosed entity.

PubMed

Affirul, C A; Qisti, F N; Zamri, Z; Azlanuddin, A; Hairol, A O; Razman, J

2014-01-01

Solid pseudo papillary pancreatic tumour is a rare entity. The atypical presentation causes a delayed or misdiagnosis of these pathology. It commonly affects the female population in the 2nd and 3rd decade of life. The presentation varies from non-specific abdominal pain to incidental findings in asymptomatic patients. It is a low-grade premalignant condition that is curable by excision of the tumour. This paper presents a 17-year-old girl with intra-abdominal mass diagnosed with solid pseudo papillary tumour that underwent Whipple's procedure. We discuss the presentations, diagnosis and pathology findings of this rare pathology. The diagnosis remains an enigma in view of the nature and location of the tumour. Resection is still the best choice remains for this condition. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Standards to support information systems integration in anatomic pathology.

PubMed

Daniel, Christel; García Rojo, Marcial; Bourquard, Karima; Henin, Dominique; Schrader, Thomas; Della Mea, Vincenzo; Gilbertson, John; Beckwith, Bruce A

2009-11-01

Integrating anatomic pathology information- text and images-into electronic health care records is a key challenge for enhancing clinical information exchange between anatomic pathologists and clinicians. The aim of the Integrating the Healthcare Enterprise (IHE) international initiative is precisely to ensure interoperability of clinical information systems by using existing widespread industry standards such as Digital Imaging and Communication in Medicine (DICOM) and Health Level Seven (HL7). To define standard-based informatics transactions to integrate anatomic pathology information to the Healthcare Enterprise. We used the methodology of the IHE initiative. Working groups from IHE, HL7, and DICOM, with special interest in anatomic pathology, defined consensual technical solutions to provide end-users with improved access to consistent information across multiple information systems. The IHE anatomic pathology technical framework describes a first integration profile, "Anatomic Pathology Workflow," dedicated to the diagnostic process including basic image acquisition and reporting solutions. This integration profile relies on 10 transactions based on HL7 or DICOM standards. A common specimen model was defined to consistently identify and describe specimens in both HL7 and DICOM transactions. The IHE anatomic pathology working group has defined standard-based informatics transactions to support the basic diagnostic workflow in anatomic pathology laboratories. In further stages, the technical framework will be completed to manage whole-slide images and semantically rich structured reports in the diagnostic workflow and to integrate systems used for patient care and those used for research activities (such as tissue bank databases or tissue microarrayers).

Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein

PubMed Central

2013-01-01

Background α-Synuclein (αS) is the major component of several types of brain inclusions including Lewy bodies, a hallmark of Parkinson’s disease. Aberrant aggregation of αS also is associated with cellular demise in multiple neurologic disorders collectively referred to as synucleinopathies. Recent studies demonstrate the induction of αS pathology by a single intracerebral injection of exogenous amyloidogenic αS in adult non-transgenic and transgenic mice expressing human αS. To further investigate the mechanism of pathology induction and evaluate an experimental paradigm with potential for higher throughput, we performed similar studies in neonatal mice injected with αS. Results In non-transgenic mice, we observed limited induction of neuronal αS inclusions predominantly 8 months after brain injection of aggregated, amyloidogenic human αS. More robust inclusion pathology was induced in transgenic mice expressing wild-type human αS (line M20), and inclusion pathology was observed at earlier time points. Injection of a non-amyloidogenic (Δ71-82) deletion protein of αS was also able to induce similar pathology in a subset of M20 transgenic mice. M20 transgenic mice injected with amyloidogenic or non-amyloidogenic αS demonstrated a delayed and robust induction of brain neuroinflammation that occurs in mice with or without αS pathological inclusions implicating this mechanism in aggregate formation. Conclusions The finding that a non-amyloidogenic Δ71-82 αS can induce pathology calls into question the simple interpretation that exogenous αS catalyzes aggregation and spread of intracellular αS pathology solely through a nucleation dependent conformational templating mechanism. These results indicate that several mechanisms may act synergistically or independently to promote the spread of αS pathology. PMID:24252149

An Investigation of Multidimensional Voice Program Parameters in Three Different Databases for Voice Pathology Detection and Classification.

PubMed

Al-Nasheri, Ahmed; Muhammad, Ghulam; Alsulaiman, Mansour; Ali, Zulfiqar; Mesallam, Tamer A; Farahat, Mohamed; Malki, Khalid H; Bencherif, Mohamed A

2017-01-01

Automatic voice-pathology detection and classification systems may help clinicians to detect the existence of any voice pathologies and the type of pathology from which patients suffer in the early stages. The main aim of this paper is to investigate Multidimensional Voice Program (MDVP) parameters to automatically detect and classify the voice pathologies in multiple databases, and then to find out which parameters performed well in these two processes. Samples of the sustained vowel /a/ of normal and pathological voices were extracted from three different databases, which have three voice pathologies in common. The selected databases in this study represent three distinct languages: (1) the Arabic voice pathology database; (2) the Massachusetts Eye and Ear Infirmary database (English database); and (3) the Saarbruecken Voice Database (German database). A computerized speech lab program was used to extract MDVP parameters as features, and an acoustical analysis was performed. The Fisher discrimination ratio was applied to rank the parameters. A t test was performed to highlight any significant differences in the means of the normal and pathological samples. The experimental results demonstrate a clear difference in the performance of the MDVP parameters using these databases. The highly ranked parameters also differed from one database to another. The best accuracies were obtained by using the three highest ranked MDVP parameters arranged according to the Fisher discrimination ratio: these accuracies were 99.68%, 88.21%, and 72.53% for the Saarbruecken Voice Database, the Massachusetts Eye and Ear Infirmary database, and the Arabic voice pathology database, respectively. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Parasites and pathological condition in Green mussel Perna viridis Linnaeus, 1758 from western Johor Straits, Malaysia

NASA Astrophysics Data System (ADS)

Azmi, Nur-Fauzana; Ghaffar, Mazlan Abd.; Cob, Zaidi Che

2018-04-01

This study describes the parasites and pathological condition of infected organ of the green mussel Perna viridis from Merambong Shoal, Western Johor Straits, Malaysia. Samples were collected randomly in November and December 2013. Histopathology techniques using Masson's Trichrome staining protocol were performed and the thin sections were observed under light microscope. Result showed that gonad was the most infected organ followed by the digestive tubule, adductor muscle, intestine and mantle tissue. The parasites (apicomplexa) such as spore-like Nematopsis, macrogamont-like coccidian, mature oocyst-like coccidian, unidentified coccidian and protozoan were found in the adductor muscle, gonad and mantle. Meanwhile, the pathological conditions were found in all infected organs except the gill, such as particular melanin deposits in cytoplasm, Rickettsia-like or Chlamydiae organism and bacteria-like inclusions. Haemocytic infiltrations were found in the surrounding connective tissues of all infected organs. However, these light infections are not causing morbidity and mortalityof the green mussel P.viridis. This study provides baseline information on health profile of the green mussel P.viridis. Further investigations are needed particularly on parasite species identification and their ecology. Understanding of the morphology and pathology of parasites infecting mollusks are very important for management of the resources.

Endoscopic ultrasound in common bile duct dilatation with normal liver enzymes

PubMed Central

De Angelis, Claudio; Marietti, Milena; Bruno, Mauro; Pellicano, Rinaldo; Rizzetto, Mario

2015-01-01

In recent years, the description of isolated bile duct dilatation has been increasingly observed in subjects with normal liver function tests and nonspecific abdominal symptoms, probably due to the widespread use of high-resolution imaging techniques. However, there is scant literature about the evolution of this condition and the impact of endoscopic ultrasound (EUS) in the diagnostic work up. When noninvasive imaging tests (transabdominal ultrasound, computed tomography or magnetic resonance cholangiopancreatography) fail to identify the cause of dilatation and clinical or biochemical alarm signs are absent, the probability of having biliary disease is considered low. In this setting, using EUS, the presence of pathologic findings (choledocholithiasis, strictures, chronic pancreatitis, ampullary or pancreatic tumors, cholangiocarcinoma), not always with a benign course, has been observed. The aim of this review has been to evaluate the prevalence of disease among non-jaundiced patients without signs of cytolysis and/or cholestasis and the assessment of EUS yield. Data point out to a promising role of EUS in the identification of a potential biliary pathology. EUS is a low invasive technique, with high accuracy, that could play a double cost-effective role: identifying pathologic conditions with dismal prognosis, in asymptomatic patients with negative prior imaging tests, and excluding pathologic conditions and further follow-up in healthy subjects. PMID:26191344

Visceral larva migrans presenting as multiple intracranial and intraspinal abscesses.

PubMed

Moiyadi, Alefia; Mahadevan, Anita; Anandh, Balasubramaniam; Shivashankar, Ravi Shankar; Chickabasavaiah, Yasha Thagadur; Shankar, Susarla Krishna

2007-08-01

Involvement of nervous system by toxocariasis is rare and can produce a spectrum of pathology that includes eosinophillic meningoencephalitis, meningomyelitis, space occupying lesions, vasculitis causing seizures or behavioral abnormalities posing diagnostic dilemmas. We describe a 38-year-old man who presented with multiple intracranial and intramedullary abscesses caused by visceral larva migrans. Neurohelminthiasis as a cause of multiple abscesses, though rare, should be entertained as a differential diagnosis particularly in tropical South-east Asian countries where helminthiasis is still an epidemiological concern prevalent in the pediatric age group.

42 CFR 485.711 - Condition of participation: Plan of care and physician involvement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Agencies as Providers of Outpatient Physical Therapy and Speech-Language Pathology Services § 485.711... physical therapy or speech pathology services, there is a written plan of care established and periodically reviewed by a physician, or by a physical therapist or speech pathologist respectively. (a) Standard...

Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia

PubMed Central

Gao, Kun; Swarup, Vivek; Versano, Revital; Dong, Hongmei; Jordan, Maria C

2017-01-01

Friedreich's ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model of Fxn deficiency that enabled us to control the onset and progression of disease phenotypes by the modulation of Fxn levels. Systemic knockdown of Fxn in adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease. PMID:29257745

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

PubMed

Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

2017-04-01

Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

[On practicability of implementing the speciality "podiatry" in traumatology and orthopedics].

PubMed

2011-01-01

The absence of single opinion concerning the classification of foot and ankle joint pathology does not permit to formulate universal and practical approach to the identification of pathological syndromes in case of patient foot lesion. The situation is aggravated by the unsolved issues related to the terminological definition of podiatry as a direction in orthopedics to solve the issues of foot and ankle joint pathology. In actual conditions the implementation of new technologies into the structure of traumatological orthopedics care is needed. This approach permits to combine the qualities of models of effective and optimized care to patients with foot and ankle joint pathology. The study of issue related to the systematization of podiatric pathology revealed that actually no single universal classification easy-to-use in practice exists. Hence the development of original applied working scheme of foot and ankle joint pathology is proposed.

ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

NASA Astrophysics Data System (ADS)

Nouriziabari, Seyed Berdia

Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis.

PubMed

Olney, Nicholas T; Goodkind, Madeleine S; Lomen-Hoerth, Catherine; Whalen, Patrick K; Williamson, Craig A; Holley, Deborah E; Verstaen, Alice; Brown, Laurel M; Miller, Bruce L; Kornak, John; Levenson, Robert W; Rosen, Howard J

2011-12-01

Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and 14 with amyotrophic lateral sclerosis but no pathological laughing and crying were studied. Emotional measures included self-reported emotional experience, video recordings of facial reactivity and peripheral physiological responses (skin conductance, heart rate and somatic activity). Nineteen of the 21 patients with histories of pathological laughing and crying had at least one episode in the laboratory that they agreed constituted pathological laughing or crying (a total of 56 episodes were documented). Compared with viewing sad and amusing films, the episodes were associated with greater facial and physiological activation. Contrary to many clinical descriptions, episodes were often induced by contextually appropriate stimuli and associated with strong experiences of emotion that were consistent with the display. When instructed to regulate their facial responses to emotion-eliciting films, patients with pathological laughing and crying showed impairments compared with patients who did not have a history of this disorder. These findings support the idea that pathological laughing and crying represents activation of all channels of emotional responding (i.e. behavioural, physiological and subjective). Furthermore, they support previously advanced theories that, rather than being associated with general emotional hyperreactivity, this disorder may be due to dysfunction in frontal neural systems that support voluntary regulation of emotion.

Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis

PubMed Central

Olney, Nicholas T.; Goodkind, Madeleine S.; Lomen-Hoerth, Catherine; Whalen, Patrick K.; Williamson, Craig A.; Holley, Deborah E.; Verstaen, Alice; Brown, Laurel M.; Miller, Bruce L.; Kornak, John; Levenson, Robert W.

2011-01-01

Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and 14 with amyotrophic lateral sclerosis but no pathological laughing and crying were studied. Emotional measures included self-reported emotional experience, video recordings of facial reactivity and peripheral physiological responses (skin conductance, heart rate and somatic activity). Nineteen of the 21 patients with histories of pathological laughing and crying had at least one episode in the laboratory that they agreed constituted pathological laughing or crying (a total of 56 episodes were documented). Compared with viewing sad and amusing films, the episodes were associated with greater facial and physiological activation. Contrary to many clinical descriptions, episodes were often induced by contextually appropriate stimuli and associated with strong experiences of emotion that were consistent with the display. When instructed to regulate their facial responses to emotion-eliciting films, patients with pathological laughing and crying showed impairments compared with patients who did not have a history of this disorder. These findings support the idea that pathological laughing and crying represents activation of all channels of emotional responding (i.e. behavioural, physiological and subjective). Furthermore, they support previously advanced theories that, rather than being associated with general emotional hyperreactivity, this disorder may be due to dysfunction in frontal neural systems that support voluntary regulation of emotion. PMID:22155983

Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias.

PubMed

Timmerman, Vincent; Clowes, Virginia E; Reid, Evan

2013-08-01

In this review we focus on Charcot-Marie-Tooth (CMT) neuropathies and hereditary spastic paraplegias (HSPs). Although these diseases differ in whether they primarily affect the peripheral or central nervous system, both are genetically determined, progressive, long axonopathies that affect motor and sensory pathways. This commonality suggests that there might be similarities in the molecular pathology underlying these conditions, and here we compare the molecular genetics and cellular pathology of the two groups. Copyright © 2012 Elsevier Inc. All rights reserved.

Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities

NASA Astrophysics Data System (ADS)

El Houssaini, Kenza; Ivanov, Anton I.; Bernard, Christophe; Jirsa, Viktor K.

2015-01-01

Epilepsy, refractory status epilepticus, and depolarization block are pathological brain activities whose mechanisms are poorly understood. Using a generic mathematical model of seizure activity, we show that these activities coexist under certain conditions spanning the range of possible brain activities. We perform a detailed bifurcation analysis and predict strategies to escape from some of the pathological states. Experimental results using rodent data provide support of the model, highlighting the concept that these pathological activities belong to the endogenous repertoire of brain activities.

[Secondary osteoporosis].

PubMed

Lafita, J; Pineda, J; Fuentes, C; Martínez, J P

2003-01-01

Secondary osteoporosis is caused by pathologies or medications, differing from the bone loss explainable by the post-menopausal stage or by ageing. The possible pathologies that can condition the loss of bone mass are very varied: endocrinological, digestive, genetic, haematological, rheumatic, post-transplant, pharmacological and a wide miscellaneous group. This article essentially reviews the endocrinological causes, with special emphasis on the more controversial aspects, followed by a clinical approach for the systematic diagnosis of these pathologies, which are frequent in cases initially labelled as primary osteoporosis

The Matter of Disability.

PubMed

Mitchell, David T; Snyder, Sharon L

2016-12-01

By ruling out questions of impairment from the social critique of disability, Disability Studies (DS) analyses establish a limit point in the field. Of course the setting of "limits" enables possibilities in multiple directions as well as fortifies boundaries of refusal. For instance, impairment (the biological conditions of an organism's inefficient attachment to the world) becomes in DS simultaneously a productive refusal to interpret disabled bodies as inferior to non-disabled bodies (i.e. pathologized) and a bar to thinking through more active engagements with disability as materiality. Disability materiality such as conditions produced by ecological toxicities serve as active switch-points for creative corporeal navigations of the interaction between bodies and environments.In fact in this paper we want to propose a more "lively" definition of disability materiality to existing definitions of impairment as limiting expressions of non-normative bodies. We have no useful ways of explaining disability as adaptation and it's time we begin the process of theorizing more active ideas of materiality that extend existing ideas of disability beyond simplistic conceptions of socially rejected biologies made available by social constructivist thought.

[Disseminated cryptococcosis in an immunocompetent patient].

PubMed

Elkhihal, B; Hasnaoui, A; Ghfir, I; Moustachi, A; Aoufi, S; Lyagoubi, M

2015-09-01

Disseminated cryptococcosis is a serious opportunistic fungal infection caused by a yeast-encapsulated fungus of the genus Cryptococcus neoformans. It occurs most often in patients with a significant deficit of cellular immunity and preferentially affects the central nervous system. The skin and the lungs are the most commonly affected sites outside the neuro-subarachnoid location. We report the case of a patient apparently immunocompetent who had a disseminated cryptococcosis. The disease started with the multiple purplish skin lesions, large umbilicated on the face, groin, forearm and leg with progressively increasing volume. This symptomatology had evolved in the context of weight loss and poor general condition. The diagnosis was established by the presence of cryptococcal at the skin biopsy and cerebrospinal fluid. Research of immunosuppression common pathologies were negative. Treatment was initiated based on amphotericin B for 40 days. The patient's condition deteriorates onset of paraplegia and swallowing disorders causing death in an array of cachexia. This observation points out that disseminated cryptococcosis can occur in an immunocompetent patient. The skin lesions may be the first sign of the disease. Copyright © 2015. Published by Elsevier Masson SAS.

Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions

PubMed Central

Weber, Daniela; Davies, Michael J.; Grune, Tilman

2015-01-01

Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples. PMID:26141921

Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions.

PubMed

Weber, Daniela; Davies, Michael J; Grune, Tilman

2015-08-01

Protein oxidation is involved in regulatory physiological events as well as in damage to tissues and is thought to play a key role in the pathophysiology of diseases and in the aging process. Protein-bound carbonyls represent a marker of global protein oxidation, as they are generated by multiple different reactive oxygen species in blood, tissues and cells. Sample preparation and stabilization are key steps in the accurate quantification of oxidation-related products and examination of physiological/pathological processes. This review therefore focuses on the sample preparation processes used in the most relevant methods to detect protein carbonyls after derivatization with 2,4-dinitrophenylhydrazine with an emphasis on measurement in plasma, cells, organ homogenates, isolated proteins and organelles. Sample preparation, derivatization conditions and protein handling are presented for the spectrophotometric and HPLC method as well as for immunoblotting and ELISA. An extensive overview covering these methods in previously published articles is given for researchers who plan to measure protein carbonyls in different samples. © 2015 Published by Elsevier Ltd.

Soluble HLA-G: Are They Clinically Relevant?

PubMed Central

Pistoia, Vito; Morandi, Fabio; Wang, Xinhui; Ferrone, Soldano

2007-01-01

HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main function in physiological conditions is to abrogate maternal NK cell activity against foetal tissue and to establish immune tolerance at maternal-foetal interface. HLA-G is expressed not only as a membrane bound molecule on the surface of cells, but also as a soluble moiety in body fluids. The major isoforms of HLA-G present in serum are soluble HLA-G1 and HLA-G5 which are generated by shedding or proteolytic cleavage of the membrane bound isoform and by secretion of a soluble isoform, respectively. Here we review the data about soluble HLA-G (sHLA-G) serum levels in different pathological conditions, including immune-mediated disorders, transplantation, and malignancies. In particular, we focus on sHLA-G expression and function in human neuroblastoma, a pediatric tumor, with special emphasis on a novel potential immuno escape mechanism utilized by NB to instruct monocytes to produce and release sHLA-G. Finally, the potential clinical relevance of sHLA-G serum levels is discussed. PMID:17825579

Rationale for hospital-based rehabilitation in obesity with comorbidities.

PubMed

Capodaglio, P; Lafortuna, C; Petroni, M L; Salvadori, A; Gondoni, L; Castelnuovo, G; Brunani, A

2013-06-01

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to-date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.

Laser applications in surgery

PubMed Central

Azadgoli, Beina

2016-01-01

In modern medicine, lasers are increasingly utilized for treatment of a variety of pathologies as interest in less invasive treatment modalities intensifies. The physics behind lasers allows the same basic principles to be applied to a multitude of tissue types using slight modifications of the system. Multiple laser systems have been studied within each field of medicine. The term “laser” was combined with “surgery,” “ablation,” “lithotripsy,” “cancer treatment,” “tumor ablation,” “dermatology,” “skin rejuvenation,” “lipolysis,” “cardiology,” “atrial fibrillation (AF),” and “epilepsy” during separate searches in the PubMed database. Original articles that studied the application of laser energy for these conditions were reviewed and included. A review of laser therapy is presented. Laser energy can be safely and effectively used for lithotripsy, for the treatment of various types of cancer, for a multitude of cosmetic and reconstructive procedures, and for the ablation of abnormal conductive pathways. For each of these conditions, management with lasers is comparable to, and potentially superior to, management with more traditional methods. PMID:28090508

Pathology and pathophysiology of inhalational anthrax in a guinea pig model.

PubMed

Savransky, Vladimir; Sanford, Daniel C; Syar, Emily; Austin, Jamie L; Tordoff, Kevin P; Anderson, Michael S; Stark, Gregory V; Barnewall, Roy E; Briscoe, Crystal M; Lemiale-Biérinx, Laurence; Park, Sukjoon; Ionin, Boris; Skiadopoulos, Mario H

2013-04-01

Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's "Animal Rule." However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 10(4) spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans.

Pathology and Pathophysiology of Inhalational Anthrax in a Guinea Pig Model

PubMed Central

Savransky, Vladimir; Sanford, Daniel C.; Syar, Emily; Austin, Jamie L.; Tordoff, Kevin P.; Anderson, Michael S.; Stark, Gregory V.; Barnewall, Roy E.; Briscoe, Crystal M.; Lemiale-Biérinx, Laurence; Park, Sukjoon; Ionin, Boris

2013-01-01

Nonhuman primates (NHPs) and rabbits are the animal models most commonly used to evaluate the efficacy of medical countermeasures against anthrax in support of licensure under the FDA's “Animal Rule.” However, a need for an alternative animal model may arise in certain cases. The development of such an alternative model requires a thorough understanding of the course and manifestation of experimental anthrax disease induced under controlled conditions in the proposed animal species. The guinea pig, which has been used extensively for anthrax pathogenesis studies and anthrax vaccine potency testing, is a good candidate for such an alternative model. This study was aimed at determining the median lethal dose (LD50) of the Bacillus anthracis Ames strain in guinea pigs and investigating the natural history, pathophysiology, and pathology of inhalational anthrax in this animal model following nose-only aerosol exposure. The inhaled LD50 of aerosolized Ames strain spores in guinea pigs was determined to be 5.0 × 104 spores. Aerosol challenge of guinea pigs resulted in inhalational anthrax with death occurring between 46 and 71 h postchallenge. The first clinical signs appeared as early as 36 h postchallenge. Cardiovascular function declined starting at 20 h postexposure. Hematogenous dissemination of bacteria was observed microscopically in multiple organs and tissues as early as 24 h postchallenge. Other histopathologic findings typical of disseminated anthrax included suppurative (heterophilic) inflammation, edema, fibrin, necrosis, and/or hemorrhage in the spleen, lungs, and regional lymph nodes and lymphocyte depletion and/or lymphocytolysis in the spleen and lymph nodes. This study demonstrated that the course of inhalational anthrax disease and the resulting pathology in guinea pigs are similar to those seen in rabbits and NHPs, as well as in humans. PMID:23357384

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017

PubMed Central

Clunie, David; Hosseinzadeh, Dan; Wintell, Mikael; De Mena, David; Lajara, Nieves; Garcia-Rojo, Marcial; Bueno, Gloria; Saligrama, Kiran; Stearrett, Aaron; Toomey, David; Abels, Esther; Apeldoorn, Frank Van; Langevin, Stephane; Nichols, Sean; Schmid, Joachim; Horchner, Uwe; Beckwith, Bruce; Parwani, Anil; Pantanowitz, Liron

2018-01-01

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products. PMID:29619278

Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report.

PubMed

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Unlu, Serkan; Ertem, Kadir; Nizam, Ilknur

2014-08-01

Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. Copyright © 2014. Published by Elsevier Ltd.

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis.

PubMed

Loeffler, Jean-Philippe; Picchiarelli, Gina; Dupuis, Luc; Gonzalez De Aguilar, Jose-Luis

2016-03-01

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets. © 2016 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Narcissism and relational representations among psychiatric outpatients.

PubMed

Kealy, David; Ogrodniczuk, John S; Joyce, Anthony S; Steinberg, Paul I; Piper, William E

2015-06-01

Pathological narcissism is associated with maladaptive interpersonal behavior, although less is known regarding the internal relational representations of narcissistic patients. The authors examined the relationship between pathological narcissism and two constructs that reflect internal representations of relational patterns: quality of object relations and attachment style. Patients attending a psychiatric day treatment program (N = 218) completed measures of narcissism, general psychiatric distress, and attachment style in terms of attachment avoidance and anxiety. A semistructured interview was used to assess quality of object relations. Multiple regression analysis was conducted, controlling for general psychiatric distress. Pathological narcissism was associated with anxious attachment, but not with avoidant attachment. Narcissism was also associated with lower levels of quality of object relations. The implications of these results are discussed in terms of internal representations of self-other relations.

Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

PubMed

Sun, Li; Li, Weiping; Li, Weizu; Xiong, Li; Li, Guiping; Ma, Rong

2014-07-01

Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

Somatic symptoms of generalized anxiety disorder from the DSM-IV: associations with pathological worry and depression symptoms in a nonclinical sample.

PubMed

Joormann, J; Stöber, J

1999-01-01

The present study investigates specificity of the six somatic symptoms that are associated with generalized anxiety disorder (GAD), according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. A nonclinical sample of 183 students provided severity ratings for (a) restlessness, (b) easily fatigued, (c) difficulty concentrating, (d) irritability, (e) muscle tension, and (f) sleep disturbance. In addition, they responded to questionnaires assessing pathological worry and depression symptoms. Partial correlations and multiple regression analyses indicated that only muscle tension showed a unique relation to pathological worry. In contrast, difficulty concentrating was exclusively related to depression symptoms. Present findings corroborate psychophysiological findings that elevated muscle tension is a specific characteristic of pathological worriers. Moreover, they suggest that the problem of unclear boundaries between GAD and major depression may be reduced if future revisions of the somatic symptom list for GAD emphasize muscle tension while de-emphasizing difficulty concentrating.

Pathological implications of cell cycle re-entry in Alzheimer disease.

PubMed

Bonda, David J; Lee, Hyun-pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2010-06-29

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Ex-vivo UV autofluorescence imaging and fluorescence spectroscopy of atherosclerotic pathology in human aorta

NASA Astrophysics Data System (ADS)

Lewis, William; Williams, Maura; Franco, Walfre

2017-02-01

The aim of our study was to identify fluorescence excitation-emission pairs correlated with atherosclerotic pathology in ex-vivo human aorta. Wide-field images of atherosclerotic human aorta were captured using UV and visible excitation and emission wavelength pairs of several known fluorophores to investigate correspondence with gross pathologic features. Fluorescence spectroscopy and histology were performed on 21 aortic samples. A matrix of Pearson correlation coefficients were determined for the relationship between relevant histologic features and the intensity of emission for 427 wavelength pairs. A multiple linear regression analysis indicated that elastin (370/460 nm) and tryptophan (290/340 nm) fluorescence predicted 58% of the variance in intima thickness (R-squared = 0.588, F(2,18) = 12.8, p=.0003), and 48% of the variance in media thickness (R-squared = 0.483, F(2,18) = 8.42, p=.002), suggesting that endogenous fluorescence intensity at these wavelengths can be utilized for improved pathologic characterization of atherosclerotic plaques.

Prevalence and risk factors related to preterm birth in Brazil.

PubMed

Leal, Maria do Carmo; Esteves-Pereira, Ana Paula; Nakamura-Pereira, Marcos; Torres, Jacqueline Alves; Theme-Filha, Mariza; Domingues, Rosa Maria Soares Madeira; Dias, Marcos Augusto Bastos; Moreira, Maria Elizabeth; Gama, Silvana Granado

2016-10-17

The rate of preterm birth has been increasing worldwide, including in Brazil. This constitutes a significant public health challenge because of the higher levels of morbidity and mortality and long-term health effects associated with preterm birth. This study describes and quantifies factors affecting spontaneous and provider-initiated preterm birth in Brazil. Data are from the 2011-2012 "Birth in Brazil" study, which used a national population-based sample of 23,940 women. We analyzed the variables following a three-level hierarchical methodology. For each level, we performed non-conditional multiple logistic regression for both spontaneous and provider-initiated preterm birth. The rate of preterm birth was 11.5 %, (95 % confidence 10.3 % to 12.9 %) 60.7 % spontaneous - with spontaneous onset of labor or premature preterm rupture of membranes - and 39.3 % provider-initiated, with more than 90 % of the last group being pre-labor cesarean deliveries. Socio-demographic factors associated with spontaneous preterm birth were adolescent pregnancy, low total years of schooling, and inadequate prenatal care. Other risk factors were previous preterm birth (OR 3.74; 95 % CI 2.92-4.79), multiple pregnancy (OR 16.42; 95 % CI 10.56-25.53), abruptio placentae (OR 2.38; 95 % CI 1.27-4.47) and infections (OR 4.89; 95 % CI 1.72-13.88). In contrast, provider-initiated preterm birth was associated with private childbirth healthcare (OR 1.47; 95 % CI 1.09-1.97), advanced-age pregnancy (OR 1.27; 95 % CI 1.01-1.59), two or more prior cesarean deliveries (OR 1.64; 95 % CI 1.19-2.26), multiple pregnancy (OR 20.29; 95 % CI 12.58-32.72) and any maternal or fetal pathology (OR 6.84; 95 % CI 5.56-8.42). The high proportion of provider-initiated preterm birth and its association with prior cesarean deliveries and all of the studied maternal/fetal pathologies suggest that a reduction of this type of prematurity may be possible. The association of spontaneous preterm birth with socially-disadvantaged groups reaffirms that the reduction of social and health inequalities should continue to be a national priority.

Imaging in short stature

PubMed Central

Chaudhary, Vikas; Bano, Shahina

2012-01-01

Short stature can be a sign of disease, disability, and social stigma causing psychological stress. It is important to have an early diagnosis and treatment. Short stature may result from skeletal dysplasias, endocrine disorders, may be familial, or may be the result of malnutrition and chronic illnesses. A team effort of the healthcare professionals like pediatricians, endocrinologists, radiologists, and pathologists is required to diagnose, treat and monitor various pathological conditions associated with growth abnormality. In this review, we have discussed the role of imaging in diagnosing and characterizing various pathological conditions associated with short stature. PMID:23087851

Imaging in short stature.

PubMed

Chaudhary, Vikas; Bano, Shahina

2012-09-01

Short stature can be a sign of disease, disability, and social stigma causing psychological stress. It is important to have an early diagnosis and treatment. Short stature may result from skeletal dysplasias, endocrine disorders, may be familial, or may be the result of malnutrition and chronic illnesses. A team effort of the healthcare professionals like pediatricians, endocrinologists, radiologists, and pathologists is required to diagnose, treat and monitor various pathological conditions associated with growth abnormality. In this review, we have discussed the role of imaging in diagnosing and characterizing various pathological conditions associated with short stature.

Cerebral Ketone Metabolism During Development and Injury

PubMed Central

Prins, Mayumi L.

2011-01-01

Cerebral metabolism of ketones is a normal part of the process of brain development. While the mature brain relies on glucose as a primary fuel source, metabolism of ketone bodies remains an alternative energy source under conditions of starvation. The neuroprotective properties of brain ketone metabolism make this alternative substrate a viable therapeutic option for various pathologies. Since the ability to revert to utilizing ketones as an alternative substrate is greatest in the younger post-weaned brain, this particular therapeutic approach remains an untapped resource particularly for pediatric pathological conditions. PMID:22104087

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015.

PubMed

Shamim, Thorakkal

2016-01-01

There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal.

The Oral Pathology Related Articles Published in Iranian Journal of Pathology from 2006 to 2015

PubMed Central

Shamim, Thorakkal

2016-01-01

Background: There is a paucity of information about the oral pathology related articles published in a pathology journal. This study aimed to audit the oral pathology related articles published in Iranian Journal of Pathology (Iran J Pathol) from 2006 to 2015. Methods: Bibliometric analysis of issues of Iran J Pathol from 2006 to 2015 was performed using web-based search. The articles published were analyzed for type of article and individual topic of oral pathology. The articles published were also checked for authorship trends. Results: Out of the total 49 published articles related to oral pathology, case reports (21) and original articles (18) contributed the major share. The highest number of oral pathology related articles was published in 2011, 2014 and 2015 with 8 articles each and the least published year was 2012 with 1 article. Among the oral pathology related articles published, spindle cell neoplasms (7) followed by salivary gland tumors (5), jaw tumors (4), oral granulomatous conditions (4), lymphomas (4), oral cancer (3) and odontogenic cysts (3) form the major attraction of the contributors. The largest numbers of published articles related to oral pathology were received from Tehran University of Medical Sciences; Tehran (7) followed by Mashhad University of Medical Sciences, Mashhad (6) and Shahid Beheshti University of Medical Sciences, Tehran (5). Conclusion: This paper may be considered as a baseline study for the bibliometric information regarding oral pathology related articles published in a pathology journal. PMID:27799973

NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome.

PubMed

Whitmore, Laura C; Goss, Kelli L; Newell, Elizabeth A; Hilkin, Brieanna M; Hook, Jessica S; Moreland, Jessica G

2014-07-01

Systemic inflammatory response syndrome (SIRS) is a common clinical condition in patients in intensive care units that can lead to complications, including multiple organ dysfunction syndrome (MODS). MODS carries a high mortality rate, and it is unclear why some patients resolve SIRS, whereas others develop MODS. Although oxidant stress has been implicated in the development of MODS, several recent studies have demonstrated a requirement for NADPH oxidase 2 (NOX2)-derived oxidants in limiting inflammation. We recently demonstrated that NOX2 protects against lung injury and mortality in a murine model of SIRS. In the present study, we investigated the role of NOX2-derived oxidants in the progression from SIRS to MODS. Using a murine model of sterile systemic inflammation, we observed significantly greater illness and subacute mortality in gp91(phox-/y) (NOX2-deficient) mice compared with wild-type mice. Cellular analysis revealed continued neutrophil recruitment to the peritoneum and lungs of the NOX2-deficient mice and altered activation states of both neutrophils and macrophages. Histological examination showed multiple organ pathology indicative of MODS in the NOX2-deficient mice, and several inflammatory cytokines were elevated in lungs of the NOX2-deficient mice. Overall, these data suggest that NOX2 function protects against the development of MODS and is required for normal resolution of systemic inflammation. Copyright © 2014 the American Physiological Society.

Workplace accident-related finger-fracture at the Mexican Institute of Social Security. Resolution time, economic impact and sequelae.

PubMed

Salinas-Tovar, Santiago; Hernández-Leyva, Blanca E; Marín-Cotoñieto, Irma Araceli; Santos-Celis, Rafael; Luna-Pizarro, Daniel; López-Rojas, Pablo

2007-01-01

To identify resolution time and economic impact of occupational finger fracture with permanent disability. A cross-sectional study was conducted in 2004; the main variables were age; sex; disability days and sequelae. The International Classification of Diseases (ICD 10) was used for the study. The analysis included frequency, exceeded disability days and estimation of cost of disabilities, pensions and direct costs. Chi square test was used to identify the differences. 13,410 Fractures occurred nationwide: multiple finger fractures (803); thumb fractures (1982) and other finger fractures (10,625). Days of resolution time were: 70.5 days for multiple finger fractures and 51.1 days for another finger fractures. Permanent disability partial rate of thumb fracture was 5.3/100, 15.8/100 multiple finger fractures and 5.9 fractures of other finger. The estimated cost by temporary disability in the Instituto Mexicano del Seguro Social was on $10,669,000 U.S., while permanent disability costs in cases of settlements and annual pension payments were $758,536 U.S. Finger-fracture is a prevalent pathology whichever needs that medical procedures are review, also identify factors that decrease resolution time and establish improve actions that create boundaries on the workers damage health. It must be considered that this condition affects enterprise' productivity and decrease the quality of life from workers.

Kupffer Cell Metabolism and Function

PubMed Central

Nguyen-Lefebvre, Anh Thu; Horuzsko, Anatolij

2015-01-01

Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions. PMID:26937490

[Hashimoto Thyroiditis and Periodontal Disease: A Narrative Review].

PubMed

Morais, Ana; Resende, Marta; Pereira, José

2016-10-31

Currently there is a growing interest in studying systemic conditions with impact on the periodontium. The aim of this article is to determinate if there is a relation between Hashimoto's thyroiditis and periodontal disease. Founded on periodontology based on evidence and in the combination of the keywords: 'Hashimoto disease'; 'Hypothyroidism'; 'Periodontal disease'; 'Systemic Diseases'; a search and evaluation of articles was conducted in Medline, Scopus and Thomson Reuters databases, selecting 30 articles for integral analysis. There have been developed several studies, searching for a better comprehension about the complexity and pathogenesis of periodontal diseases, associated them to multiple systemic conditions. Actually, the relationship that is best described in the literature is the one with rheumatoid arthritis; however, other relations have been pointed, such as Hashimoto's thyroiditis. The identification of multiple etiopathogenic mechanisms common to Hashimoto's thyroiditis and periodontal disease allow to suspect of a relation between them. Some of these mechanisms include the proliferation of lymphocytes T helper 1 and T helper 17 and their impact on the periodontium, the dysfunction of vascular endothelium in gingival microcirculation and the influence of hypothyroidism on bone metabolism, namely on the alveolar bone. There is biological plausibility to support the establishment of an association between Hashimoto's thyroiditis and periodontal disease. However, there are not enough studies to support the existence of a causal nexus between these two pathologies, so, in the future, more studies should be conducted to determinate there relation and interaction.

Iron chelation and multiple sclerosis

PubMed Central

Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.

2014-01-01

Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen. PMID:24397846

Stability, Consistency and Performance of Distribution Entropy in Analysing Short Length Heart Rate Variability (HRV) Signal.

PubMed

Karmakar, Chandan; Udhayakumar, Radhagayathri K; Li, Peng; Venkatesh, Svetha; Palaniswami, Marimuthu

2017-01-01

Distribution entropy ( DistEn ) is a recently developed measure of complexity that is used to analyse heart rate variability (HRV) data. Its calculation requires two input parameters-the embedding dimension m , and the number of bins M which replaces the tolerance parameter r that is used by the existing approximation entropy ( ApEn ) and sample entropy ( SampEn ) measures. The performance of DistEn can also be affected by the data length N . In our previous studies, we have analyzed stability and performance of DistEn with respect to one parameter ( m or M ) or combination of two parameters ( N and M ). However, impact of varying all the three input parameters on DistEn is not yet studied. Since DistEn is predominantly aimed at analysing short length heart rate variability (HRV) signal, it is important to comprehensively study the stability, consistency and performance of the measure using multiple case studies. In this study, we examined the impact of changing input parameters on DistEn for synthetic and physiological signals. We also compared the variations of DistEn and performance in distinguishing physiological (Elderly from Young) and pathological (Healthy from Arrhythmia) conditions with ApEn and SampEn . The results showed that DistEn values are minimally affected by the variations of input parameters compared to ApEn and SampEn. DistEn also showed the most consistent and the best performance in differentiating physiological and pathological conditions with various of input parameters among reported complexity measures. In conclusion, DistEn is found to be the best measure for analysing short length HRV time series.

Stability, Consistency and Performance of Distribution Entropy in Analysing Short Length Heart Rate Variability (HRV) Signal

PubMed Central

Karmakar, Chandan; Udhayakumar, Radhagayathri K.; Li, Peng; Venkatesh, Svetha; Palaniswami, Marimuthu

2017-01-01

Distribution entropy (DistEn) is a recently developed measure of complexity that is used to analyse heart rate variability (HRV) data. Its calculation requires two input parameters—the embedding dimension m, and the number of bins M which replaces the tolerance parameter r that is used by the existing approximation entropy (ApEn) and sample entropy (SampEn) measures. The performance of DistEn can also be affected by the data length N. In our previous studies, we have analyzed stability and performance of DistEn with respect to one parameter (m or M) or combination of two parameters (N and M). However, impact of varying all the three input parameters on DistEn is not yet studied. Since DistEn is predominantly aimed at analysing short length heart rate variability (HRV) signal, it is important to comprehensively study the stability, consistency and performance of the measure using multiple case studies. In this study, we examined the impact of changing input parameters on DistEn for synthetic and physiological signals. We also compared the variations of DistEn and performance in distinguishing physiological (Elderly from Young) and pathological (Healthy from Arrhythmia) conditions with ApEn and SampEn. The results showed that DistEn values are minimally affected by the variations of input parameters compared to ApEn and SampEn. DistEn also showed the most consistent and the best performance in differentiating physiological and pathological conditions with various of input parameters among reported complexity measures. In conclusion, DistEn is found to be the best measure for analysing short length HRV time series. PMID:28979215